Trial Outcomes & Findings for A Study of Efficacy and Safety of M2951 in Participants With Relapsing Multiple Sclerosis (NCT NCT02975349)
NCT ID: NCT02975349
Last Updated: 2025-05-14
Results Overview
Analysis of T1-Gadolinium enhancing lesions was done using magnetic resonance imaging (MRI) scans. As per planned analysis, Tecfidera treatment group was not included in inferential analysis.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
267 participants
Primary outcome timeframe
Week 12 to Week 24
Results posted on
2025-05-14
Participant Flow
Participant milestones
| Measure |
Placebo (Period 1)
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
|
Placebo Then Evobrutinib 25 mg QD (Period 2)
Participants who received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1 received Evobrutinib 25 milligram (mg) orally, once daily (QD) in blinded extension (BE) period from week 25 to week 48.
|
Placebo + Evobrutinib 25 mg QD (Period 3)
Participants who received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1 received Evobrutinib 25 mg orally, QD from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 25 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg BID (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
|---|---|---|---|---|---|---|---|
|
Active Treatment Period (24 Weeks)
STARTED
|
54
|
0
|
0
|
52
|
53
|
54
|
54
|
|
Active Treatment Period (24 Weeks)
Safety Analysis Set
|
54
|
0
|
0
|
52
|
53
|
54
|
54
|
|
Active Treatment Period (24 Weeks)
COMPLETED
|
49
|
0
|
0
|
47
|
48
|
48
|
52
|
|
Active Treatment Period (24 Weeks)
NOT COMPLETED
|
5
|
0
|
0
|
5
|
5
|
6
|
2
|
|
Blinded Extension Period (24 Weeks)
STARTED
|
0
|
49
|
0
|
47
|
48
|
48
|
52
|
|
Blinded Extension Period (24 Weeks)
COMPLETED
|
0
|
42
|
0
|
43
|
44
|
46
|
52
|
|
Blinded Extension Period (24 Weeks)
NOT COMPLETED
|
0
|
7
|
0
|
4
|
4
|
2
|
0
|
|
Open-label Extension Period (336 Weeks)
STARTED
|
0
|
0
|
39
|
39
|
42
|
44
|
49
|
|
Open-label Extension Period (336 Weeks)
COMPLETED
|
0
|
0
|
28
|
25
|
33
|
35
|
39
|
|
Open-label Extension Period (336 Weeks)
NOT COMPLETED
|
0
|
0
|
11
|
14
|
9
|
9
|
10
|
Reasons for withdrawal
| Measure |
Placebo (Period 1)
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
|
Placebo Then Evobrutinib 25 mg QD (Period 2)
Participants who received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1 received Evobrutinib 25 milligram (mg) orally, once daily (QD) in blinded extension (BE) period from week 25 to week 48.
|
Placebo + Evobrutinib 25 mg QD (Period 3)
Participants who received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1 received Evobrutinib 25 mg orally, QD from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 25 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg BID (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
|---|---|---|---|---|---|---|---|
|
Active Treatment Period (24 Weeks)
Withdrawal by Subject
|
0
|
0
|
0
|
3
|
3
|
0
|
0
|
|
Active Treatment Period (24 Weeks)
Lost to Follow-up
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Active Treatment Period (24 Weeks)
Adverse Event
|
4
|
0
|
0
|
2
|
2
|
6
|
2
|
|
Blinded Extension Period (24 Weeks)
Adverse Event
|
0
|
1
|
0
|
1
|
3
|
1
|
0
|
|
Blinded Extension Period (24 Weeks)
Withdrawal by Subject
|
0
|
5
|
0
|
2
|
1
|
1
|
0
|
|
Blinded Extension Period (24 Weeks)
Lack of Efficacy
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
|
Blinded Extension Period (24 Weeks)
Progressive Disease
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
|
Open-label Extension Period (336 Weeks)
Adverse Event
|
0
|
0
|
3
|
2
|
2
|
1
|
2
|
|
Open-label Extension Period (336 Weeks)
Study reached its predefined end
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
|
Open-label Extension Period (336 Weeks)
Lack of Efficacy
|
0
|
0
|
0
|
0
|
2
|
0
|
1
|
|
Open-label Extension Period (336 Weeks)
Death
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
|
Open-label Extension Period (336 Weeks)
COVID-19 Related
|
0
|
0
|
0
|
1
|
1
|
1
|
2
|
|
Open-label Extension Period (336 Weeks)
Lost to Follow-up
|
0
|
0
|
1
|
0
|
0
|
1
|
0
|
|
Open-label Extension Period (336 Weeks)
Other
|
0
|
0
|
3
|
3
|
1
|
2
|
3
|
|
Open-label Extension Period (336 Weeks)
Withdrawal by Subject
|
0
|
0
|
4
|
7
|
2
|
4
|
2
|
Baseline Characteristics
A Study of Efficacy and Safety of M2951 in Participants With Relapsing Multiple Sclerosis
Baseline characteristics by cohort
| Measure |
Placebo (Period 1)
n=53 Participants
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
|
Evobrutinib 25 mg QD (Period 1, 2 and 3)
n=50 Participants
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg QD (Period 1, 2 and 3)
n=51 Participants
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg BID (Period 1, 2 and 3)
n=53 Participants
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
n=54 Participants
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Total
n=261 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Continuous
|
41.6 Years
STANDARD_DEVIATION 10.77 • n=99 Participants
|
42.4 Years
STANDARD_DEVIATION 9.37 • n=107 Participants
|
42.9 Years
STANDARD_DEVIATION 10.07 • n=206 Participants
|
42.2 Years
STANDARD_DEVIATION 11.50 • n=7 Participants
|
42.8 Years
STANDARD_DEVIATION 11.70 • n=31 Participants
|
42.4 Years
STANDARD_DEVIATION 10.67 • n=30 Participants
|
|
Sex: Female, Male
Female
|
39 Participants
n=99 Participants
|
32 Participants
n=107 Participants
|
35 Participants
n=206 Participants
|
36 Participants
n=7 Participants
|
39 Participants
n=31 Participants
|
181 Participants
n=30 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=99 Participants
|
18 Participants
n=107 Participants
|
16 Participants
n=206 Participants
|
17 Participants
n=7 Participants
|
15 Participants
n=31 Participants
|
80 Participants
n=30 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=31 Participants
|
5 Participants
n=30 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
52 Participants
n=99 Participants
|
49 Participants
n=107 Participants
|
51 Participants
n=206 Participants
|
52 Participants
n=7 Participants
|
52 Participants
n=31 Participants
|
256 Participants
n=30 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
0 Participants
n=30 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
0 Participants
n=30 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
0 Participants
n=30 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
0 Participants
n=30 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
0 Participants
n=30 Participants
|
|
Race (NIH/OMB)
White
|
53 Participants
n=99 Participants
|
50 Participants
n=107 Participants
|
51 Participants
n=206 Participants
|
53 Participants
n=7 Participants
|
54 Participants
n=31 Participants
|
261 Participants
n=30 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
0 Participants
n=30 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
0 Participants
n=30 Participants
|
PRIMARY outcome
Timeframe: Week 12 to Week 24Population: Modified Intent-To-Treat (mITT) analysis set included participants who belong to both Intent To Treat (ITT, consisted all participants who randomly allocated to a treatment, based on the intention to treat "as randomized" principle) and safety analysis sets (consisted all participants who receive at least 1 dose of trial treatment), and who have at least one baseline and one post-baseline magnetic resonance imaging (MRI) assessment.
Analysis of T1-Gadolinium enhancing lesions was done using magnetic resonance imaging (MRI) scans. As per planned analysis, Tecfidera treatment group was not included in inferential analysis.
Outcome measures
| Measure |
Placebo (Period 1)
n=53 Participants
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
|
Evobrutinib 25 mg QD (Period 1, 2 and 3)
n=50 Participants
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg QD (Period 1, 2 and 3)
n=51 Participants
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg BID (Period 1, 2 and 3)
n=53 Participants
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
n=54 Participants
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
|---|---|---|---|---|---|---|
|
Total Number of Gadolinium-Enhancing T1 Lesions
|
3.85 Lesions
Standard Deviation 5.436
|
4.06 Lesions
Standard Deviation 8.024
|
1.69 Lesions
Standard Deviation 4.693
|
1.15 Lesions
Standard Deviation 3.702
|
4.78 Lesions
Standard Deviation 22.045
|
—
|
SECONDARY outcome
Timeframe: Week 24Population: The modified ITT (mITT) analysis set consists of all participants who belong to both the ITT and safety analysis sets, and who have at least one baseline and one post-baseline magnetic resonance imaging (MRI) assessment.
A qualifying relapse is defined as new, worsening or recurrent neurological symptoms attributed to Multiple Sclerosis (MS) that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days. As per planned analysis, Tecfidera treatment group was not included in inferential analysis.
Outcome measures
| Measure |
Placebo (Period 1)
n=53 Participants
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
|
Evobrutinib 25 mg QD (Period 1, 2 and 3)
n=50 Participants
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg QD (Period 1, 2 and 3)
n=51 Participants
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg BID (Period 1, 2 and 3)
n=53 Participants
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
n=54 Participants
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
|---|---|---|---|---|---|---|
|
Annualized Relapse Rate (ARR) at Week 24
|
0.37 relapses per year
Interval 0.17 to 0.7
|
0.57 relapses per year
Interval 0.3 to 0.97
|
0.13 relapses per year
Interval 0.03 to 0.38
|
0.08 relapses per year
Interval 0.01 to 0.3
|
0.20 relapses per year
Interval 0.06 to 0.47
|
—
|
SECONDARY outcome
Timeframe: Week 24Population: mITT analysis set consists of all participants who belong to both the ITT and safety analysis sets, and who have at least one baseline and one post-baseline MRI assessment.
A qualifying relapse is defined as new, worsening or recurrent neurological symptoms attributed to Multiple Sclerosis (MS) that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days. Percentage of participants with qualified relapse-free status at week 24 were reported. As per planned analysis, Tecfidera treatment group was not included in inferential analysis.
Outcome measures
| Measure |
Placebo (Period 1)
n=53 Participants
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
|
Evobrutinib 25 mg QD (Period 1, 2 and 3)
n=50 Participants
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg QD (Period 1, 2 and 3)
n=51 Participants
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg BID (Period 1, 2 and 3)
n=53 Participants
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
n=54 Participants
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
|---|---|---|---|---|---|---|
|
Qualified Relapse-Free Status at Week 24
|
77.4 percentage of participants
Interval 63.8 to 87.7
|
74.0 percentage of participants
Interval 59.7 to 85.4
|
88.2 percentage of participants
Interval 76.1 to 95.6
|
86.8 percentage of participants
Interval 74.7 to 94.5
|
88.9 percentage of participants
Interval 77.4 to 95.8
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: Modified Intent-To-Treat (mITT) analysis set included participants who belong to both Intent To Treat (ITT, consisted all participants who randomly allocated to a treatment, based on the intention to treat "as randomized" principle) and safety analysis sets (consisted all participants who receive at least 1 dose of trial treatment), and who have at least one baseline and one post-baseline magnetic resonance imaging (MRI) assessment.
The EDSS is an ordinal clinical rating scale in half-point increments. It assesses the following eight functional systems, areas of the central nervous system that control bodily functions: Pyramidal (ability to walk), Cerebellar (coordination), Brain stem (speech and swallowing), Sensory (touch and pain), Bowel and bladder functions, Visual, Mental, Other (includes any other neurological findings due to Multiple Sclerosis \[MS\]). EDSS overall score ranging from 0 (normal) to 10 (death due to MS). As per planned analysis, Tecfidera treatment group was not included in inferential analysis.
Outcome measures
| Measure |
Placebo (Period 1)
n=53 Participants
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
|
Evobrutinib 25 mg QD (Period 1, 2 and 3)
n=50 Participants
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg QD (Period 1, 2 and 3)
n=51 Participants
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg BID (Period 1, 2 and 3)
n=53 Participants
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
n=54 Participants
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Expanded Disability Status Scale (EDSS) at Week 24
|
-0.03 Units on a scale
Standard Deviation 0.301
|
0.02 Units on a scale
Standard Deviation 0.622
|
-0.14 Units on a scale
Standard Deviation 0.664
|
0.04 Units on a scale
Standard Deviation 0.216
|
0.02 Units on a scale
Standard Deviation 0.274
|
—
|
SECONDARY outcome
Timeframe: Baseline up to Safety Follow-up (Week 52)Population: The safety analysis set included of all participants who received at least 1 dose of evobrutinib or placebo or Tecfidera.
An adverse event (AE) was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the study drug. An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent adverse events are defined as any adverse event with a start date on or after the date of first dose and within 28 days after the date of last dose in the study. TEAEs include both Serious TEAEs and non-serious TEAEs.
Outcome measures
| Measure |
Placebo (Period 1)
n=54 Participants
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
|
Evobrutinib 25 mg QD (Period 1, 2 and 3)
n=49 Participants
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg QD (Period 1, 2 and 3)
n=52 Participants
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg BID (Period 1, 2 and 3)
n=53 Participants
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
n=54 Participants
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
n=54 Participants
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
|---|---|---|---|---|---|---|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Death
TEAEs
|
24 Participants
|
19 Participants
|
28 Participants
|
35 Participants
|
34 Participants
|
35 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Death
Serious TEAEs
|
2 Participants
|
0 Participants
|
2 Participants
|
2 Participants
|
4 Participants
|
2 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Death
TEAEs Leading to Death
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline up to Safety Follow-up (Week 52)Population: The safety analysis set included of all participants who received at least 1 dose of evobrutinib or placebo or Tecfidera.
Vital signs, including semi supine blood pressure, pulse rate, respiratory rate, weight, and oral temperature were assessed. ECG parameters included rhythm, ventricular rate, PR interval, QRS duration, and QT interval. Number of participants with clinically significant change from baseline in vital signs and ECG were reported. Clinical Significance was decided by the investigator.
Outcome measures
| Measure |
Placebo (Period 1)
n=54 Participants
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
|
Evobrutinib 25 mg QD (Period 1, 2 and 3)
n=49 Participants
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg QD (Period 1, 2 and 3)
n=52 Participants
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg BID (Period 1, 2 and 3)
n=53 Participants
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
n=54 Participants
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
n=54 Participants
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
|---|---|---|---|---|---|---|
|
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs and Electrocardiograms (ECGs)
Vital Sign Abnormalities
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs and Electrocardiograms (ECGs)
ECG Abnormalities
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline up to Safety Follow-up (Week 52)Population: The safety analysis set included of all participants who received at least 1 dose of evobrutinib or placebo or Tecfidera.
Hematology, biochemistry, and urinalysis values were graded with National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 toxicity grades (where Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening and Grade 5 = death). For the hematology and biochemistry parameters, participants with a value grade 3 or higher were reported. For the urinalysis parameters, participants with a value grade 3 or higher, or a value \>= 2 upper limit of normal (ULN), or a value classified as ++ Increasing were reported.
Outcome measures
| Measure |
Placebo (Period 1)
n=54 Participants
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
|
Evobrutinib 25 mg QD (Period 1, 2 and 3)
n=49 Participants
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg QD (Period 1, 2 and 3)
n=52 Participants
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg BID (Period 1, 2 and 3)
n=53 Participants
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
n=54 Participants
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
n=54 Participants
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
|---|---|---|---|---|---|---|
|
Number of Participants With Grade 3 or Higher Hematology, Biochemistry and Urinalysis Values
Grade >= 3 hematology values
|
0 Participants
|
2 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Grade 3 or Higher Hematology, Biochemistry and Urinalysis Values
Grade >= 3 biochemistry values
|
2 Participants
|
8 Participants
|
6 Participants
|
9 Participants
|
16 Participants
|
9 Participants
|
|
Number of Participants With Grade 3 or Higher Hematology, Biochemistry and Urinalysis Values
Grade >= 3 or value >= 2 ULN or ++ Increasing urinalysis values
|
0 Participants
|
2 Participants
|
1 Participants
|
2 Participants
|
2 Participants
|
6 Participants
|
SECONDARY outcome
Timeframe: Baseline (Day 1), Weeks 4, 16, and 24Population: The safety analysis set included of all participants who received at least 1 dose evobrutinib or placebo or Tecfidera. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signified those participants who were evaluable for the specified category at given time points.
Absolute Concentrations serum levels of IgG, IgA, IgM were assessed.
Outcome measures
| Measure |
Placebo (Period 1)
n=54 Participants
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
|
Evobrutinib 25 mg QD (Period 1, 2 and 3)
n=52 Participants
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg QD (Period 1, 2 and 3)
n=53 Participants
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg BID (Period 1, 2 and 3)
n=54 Participants
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
n=54 Participants
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
|---|---|---|---|---|---|---|
|
Absolute Concentrations of Immunoglobulin (Ig) Levels (Active Treatment Period)
Ig A, Day 1
|
1.99 Gram per Liter
Standard Deviation 0.777
|
1.89 Gram per Liter
Standard Deviation 0.764
|
1.90 Gram per Liter
Standard Deviation 0.722
|
1.87 Gram per Liter
Standard Deviation 0.675
|
2.03 Gram per Liter
Standard Deviation 0.763
|
—
|
|
Absolute Concentrations of Immunoglobulin (Ig) Levels (Active Treatment Period)
Ig A, Week 4
|
1.98 Gram per Liter
Standard Deviation 0.777
|
1.92 Gram per Liter
Standard Deviation 0.770
|
1.93 Gram per Liter
Standard Deviation 0.762
|
1.94 Gram per Liter
Standard Deviation 0.748
|
1.90 Gram per Liter
Standard Deviation 0.699
|
—
|
|
Absolute Concentrations of Immunoglobulin (Ig) Levels (Active Treatment Period)
Ig A, Week 16
|
2.07 Gram per Liter
Standard Deviation 0.824
|
2.10 Gram per Liter
Standard Deviation 0.813
|
2.13 Gram per Liter
Standard Deviation 0.832
|
2.08 Gram per Liter
Standard Deviation 0.753
|
2.03 Gram per Liter
Standard Deviation 0.752
|
—
|
|
Absolute Concentrations of Immunoglobulin (Ig) Levels (Active Treatment Period)
Ig A, Week 24
|
1.99 Gram per Liter
Standard Deviation 0.807
|
2.12 Gram per Liter
Standard Deviation 0.833
|
2.09 Gram per Liter
Standard Deviation 0.838
|
2.09 Gram per Liter
Standard Deviation 0.793
|
1.97 Gram per Liter
Standard Deviation 0.757
|
—
|
|
Absolute Concentrations of Immunoglobulin (Ig) Levels (Active Treatment Period)
Ig G, Day 1
|
9.61 Gram per Liter
Standard Deviation 1.897
|
9.43 Gram per Liter
Standard Deviation 2.126
|
9.81 Gram per Liter
Standard Deviation 1.841
|
9.62 Gram per Liter
Standard Deviation 1.960
|
9.47 Gram per Liter
Standard Deviation 1.839
|
—
|
|
Absolute Concentrations of Immunoglobulin (Ig) Levels (Active Treatment Period)
Ig G, Week 4
|
9.64 Gram per Liter
Standard Deviation 2.094
|
9.34 Gram per Liter
Standard Deviation 1.972
|
9.79 Gram per Liter
Standard Deviation 1.910
|
9.64 Gram per Liter
Standard Deviation 1.987
|
9.05 Gram per Liter
Standard Deviation 1.922
|
—
|
|
Absolute Concentrations of Immunoglobulin (Ig) Levels (Active Treatment Period)
Ig G, Week 16
|
9.68 Gram per Liter
Standard Deviation 2.085
|
9.41 Gram per Liter
Standard Deviation 2.077
|
9.70 Gram per Liter
Standard Deviation 1.991
|
9.56 Gram per Liter
Standard Deviation 2.129
|
9.58 Gram per Liter
Standard Deviation 1.850
|
—
|
|
Absolute Concentrations of Immunoglobulin (Ig) Levels (Active Treatment Period)
Ig G, Week 24
|
9.66 Gram per Liter
Standard Deviation 2.081
|
9.46 Gram per Liter
Standard Deviation 2.123
|
9.62 Gram per Liter
Standard Deviation 2.048
|
9.36 Gram per Liter
Standard Deviation 1.988
|
9.27 Gram per Liter
Standard Deviation 1.866
|
—
|
|
Absolute Concentrations of Immunoglobulin (Ig) Levels (Active Treatment Period)
Ig M, Day 1
|
1.42 Gram per Liter
Standard Deviation 0.692
|
1.27 Gram per Liter
Standard Deviation 0.542
|
1.44 Gram per Liter
Standard Deviation 0.716
|
1.33 Gram per Liter
Standard Deviation 0.684
|
1.27 Gram per Liter
Standard Deviation 0.589
|
—
|
|
Absolute Concentrations of Immunoglobulin (Ig) Levels (Active Treatment Period)
Ig M, Week 4
|
1.40 Gram per Liter
Standard Deviation 0.668
|
1.21 Gram per Liter
Standard Deviation 0.526
|
1.32 Gram per Liter
Standard Deviation 0.654
|
1.28 Gram per Liter
Standard Deviation 0.656
|
1.23 Gram per Liter
Standard Deviation 0.603
|
—
|
|
Absolute Concentrations of Immunoglobulin (Ig) Levels (Active Treatment Period)
Ig M, Week 16
|
1.43 Gram per Liter
Standard Deviation 0.703
|
1.13 Gram per Liter
Standard Deviation 0.558
|
1.24 Gram per Liter
Standard Deviation 0.639
|
1.20 Gram per Liter
Standard Deviation 0.689
|
1.28 Gram per Liter
Standard Deviation 0.678
|
—
|
|
Absolute Concentrations of Immunoglobulin (Ig) Levels (Active Treatment Period)
Ig M, Week 24
|
1.44 Gram per Liter
Standard Deviation 0.748
|
1.03 Gram per Liter
Standard Deviation 0.499
|
1.20 Gram per Liter
Standard Deviation 0.672
|
1.08 Gram per Liter
Standard Deviation 0.494
|
1.29 Gram per Liter
Standard Deviation 0.667
|
—
|
SECONDARY outcome
Timeframe: Week 48Population: The safety analysis set included of all participants who received at least 1 dose evobrutinib or placebo or Tecfidera. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure. Results reported are for blinded extension period only and no participants took placebo during this period.
Absolute Concentrations serum levels of IgG, IgA, IgM were assessed.
Outcome measures
| Measure |
Placebo (Period 1)
n=50 Participants
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
|
Evobrutinib 25 mg QD (Period 1, 2 and 3)
n=51 Participants
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg QD (Period 1, 2 and 3)
n=54 Participants
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg BID (Period 1, 2 and 3)
n=52 Participants
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
|---|---|---|---|---|---|---|
|
Absolute Concentrations of Immunoglobulin (Ig) Levels (Blinded Extension Period)
IgA
|
2.13 Gram per Liter
Standard Deviation 0.807
|
2.18 Gram per Liter
Standard Deviation 0.790
|
2.23 Gram per Liter
Standard Deviation 0.838
|
2.06 Gram per Liter
Standard Deviation 0.695
|
—
|
—
|
|
Absolute Concentrations of Immunoglobulin (Ig) Levels (Blinded Extension Period)
IgG
|
9.53 Gram per Liter
Standard Deviation 2.070
|
9.74 Gram per Liter
Standard Deviation 1.902
|
9.38 Gram per Liter
Standard Deviation 2.189
|
9.60 Gram per Liter
Standard Deviation 1.968
|
—
|
—
|
|
Absolute Concentrations of Immunoglobulin (Ig) Levels (Blinded Extension Period)
IgM
|
1.08 Gram per Liter
Standard Deviation 0.557
|
1.13 Gram per Liter
Standard Deviation 0.639
|
1.10 Gram per Liter
Standard Deviation 0.692
|
1.28 Gram per Liter
Standard Deviation 0.635
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 1), Weeks 4, 16, and 24Population: The safety analysis set included of all participants who received at least 1 dose evobrutinib or placebo or Tecfidera. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signified those participants who were evaluable for the specified category at given time points.
Change from baseline in the serum levels of IgG, IgA, IgM were assessed.
Outcome measures
| Measure |
Placebo (Period 1)
n=54 Participants
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
|
Evobrutinib 25 mg QD (Period 1, 2 and 3)
n=50 Participants
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg QD (Period 1, 2 and 3)
n=53 Participants
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg BID (Period 1, 2 and 3)
n=54 Participants
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
n=54 Participants
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Immunoglobulin (Ig) Levels (Active Treatment Period)
Ig A, Week 4
|
-0.02 Gram per Liter
Standard Deviation 0.201
|
0.02 Gram per Liter
Standard Deviation 0.165
|
0.04 Gram per Liter
Standard Deviation 0.169
|
0.07 Gram per Liter
Standard Deviation 0.195
|
-0.13 Gram per Liter
Standard Deviation 0.238
|
—
|
|
Change From Baseline in Immunoglobulin (Ig) Levels (Active Treatment Period)
Ig A, Week 16
|
0.10 Gram per Liter
Standard Deviation 0.188
|
0.18 Gram per Liter
Standard Deviation 0.245
|
0.21 Gram per Liter
Standard Deviation 0.313
|
0.22 Gram per Liter
Standard Deviation 0.209
|
-0.02 Gram per Liter
Standard Deviation 0.274
|
—
|
|
Change From Baseline in Immunoglobulin (Ig) Levels (Active Treatment Period)
Ig A, Week 24
|
0.06 Gram per Liter
Standard Deviation 0.250
|
0.21 Gram per Liter
Standard Deviation 0.283
|
0.18 Gram per Liter
Standard Deviation 0.416
|
0.22 Gram per Liter
Standard Deviation 0.229
|
-0.06 Gram per Liter
Standard Deviation 0.207
|
—
|
|
Change From Baseline in Immunoglobulin (Ig) Levels (Active Treatment Period)
Ig G, Week 4
|
0.02 Gram per Liter
Standard Deviation 0.758
|
-0.10 Gram per Liter
Standard Deviation 0.697
|
-0.02 Gram per Liter
Standard Deviation 0.688
|
0.02 Gram per Liter
Standard Deviation 0.581
|
-0.42 Gram per Liter
Standard Deviation 0.926
|
—
|
|
Change From Baseline in Immunoglobulin (Ig) Levels (Active Treatment Period)
Ig G, Week 16
|
0.04 Gram per Liter
Standard Deviation 0.747
|
-0.07 Gram per Liter
Standard Deviation 0.964
|
-0.10 Gram per Liter
Standard Deviation 1.068
|
-0.05 Gram per Liter
Standard Deviation 0.710
|
0.07 Gram per Liter
Standard Deviation 0.961
|
—
|
|
Change From Baseline in Immunoglobulin (Ig) Levels (Active Treatment Period)
Ig G, Week 24
|
0.06 Gram per Liter
Standard Deviation 0.682
|
0.00 Gram per Liter
Standard Deviation 1.228
|
-0.15 Gram per Liter
Standard Deviation 1.058
|
-0.28 Gram per Liter
Standard Deviation 0.774
|
-0.23 Gram per Liter
Standard Deviation 0.882
|
—
|
|
Change From Baseline in Immunoglobulin (Ig) Levels (Active Treatment Period)
Ig M, Week 4
|
-0.01 Gram per Liter
Standard Deviation 0.210
|
-0.06 Gram per Liter
Standard Deviation 0.100
|
-0.12 Gram per Liter
Standard Deviation 0.233
|
-0.05 Gram per Liter
Standard Deviation 0.133
|
-0.04 Gram per Liter
Standard Deviation 0.132
|
—
|
|
Change From Baseline in Immunoglobulin (Ig) Levels (Active Treatment Period)
Ig M, Week 16
|
0.02 Gram per Liter
Standard Deviation 0.177
|
-0.12 Gram per Liter
Standard Deviation 0.184
|
-0.18 Gram per Liter
Standard Deviation 0.244
|
-0.14 Gram per Liter
Standard Deviation 0.189
|
-0.00 Gram per Liter
Standard Deviation 0.184
|
—
|
|
Change From Baseline in Immunoglobulin (Ig) Levels (Active Treatment Period)
Ig M, Week 24
|
0.04 Gram per Liter
Standard Deviation 0.163
|
-0.14 Gram per Liter
Standard Deviation 0.286
|
-0.20 Gram per Liter
Standard Deviation 0.289
|
-0.21 Gram per Liter
Standard Deviation 0.167
|
-0.00 Gram per Liter
Standard Deviation 0.186
|
—
|
SECONDARY outcome
Timeframe: Baseline (Week 25), Week 48Population: The safety analysis set included of all participants who received at least 1 dose evobrutinib or placebo or Tecfidera. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure. Results reported are for blinded extension period only and no participants took placebo during this period.
Change from baseline in the serum levels of IgG, IgA, IgM were assessed.
Outcome measures
| Measure |
Placebo (Period 1)
n=48 Participants
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
|
Evobrutinib 25 mg QD (Period 1, 2 and 3)
n=51 Participants
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg QD (Period 1, 2 and 3)
n=54 Participants
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg BID (Period 1, 2 and 3)
n=52 Participants
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Immunoglobulin (Ig) Levels (Blinded Extension Period)
IgA
|
0.26 Gram per Liter
Standard Deviation 0.248
|
0.28 Gram per Liter
Standard Deviation 0.275
|
0.36 Gram per Liter
Standard Deviation 0.320
|
0.03 Gram per Liter
Standard Deviation 0.316
|
—
|
—
|
|
Change From Baseline in Immunoglobulin (Ig) Levels (Blinded Extension Period)
IgG
|
0.11 Gram per Liter
Standard Deviation 1.024
|
-0.08 Gram per Liter
Standard Deviation 0.940
|
-0.24 Gram per Liter
Standard Deviation 0.883
|
0.10 Gram per Liter
Standard Deviation 1.244
|
—
|
—
|
|
Change From Baseline in Immunoglobulin (Ig) Levels (Blinded Extension Period)
IgM
|
-0.18 Gram per Liter
Standard Deviation 0.211
|
-0.27 Gram per Liter
Standard Deviation 0.287
|
-0.23 Gram per Liter
Standard Deviation 0.218
|
-0.01 Gram per Liter
Standard Deviation 0.198
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 1), Weeks 4, and 24Population: The safety analysis set included of all participants who received at least 1 dose evobrutinib or placebo or Tecfidera. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signified those participants who were evaluable for the specified category at given time points.
Absolute concentration of B Cells are reported.
Outcome measures
| Measure |
Placebo (Period 1)
n=52 Participants
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
|
Evobrutinib 25 mg QD (Period 1, 2 and 3)
n=52 Participants
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg QD (Period 1, 2 and 3)
n=53 Participants
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg BID (Period 1, 2 and 3)
n=53 Participants
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
n=52 Participants
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
|---|---|---|---|---|---|---|
|
Absolute Concentration of B Cells (Active Treatment Period)
Day 1
|
242 cells per micro-liter
Standard Deviation 134.2
|
208 cells per micro-liter
Standard Deviation 117.5
|
247 cells per micro-liter
Standard Deviation 131.8
|
219 cells per micro-liter
Standard Deviation 113.7
|
210 cells per micro-liter
Standard Deviation 97.4
|
—
|
|
Absolute Concentration of B Cells (Active Treatment Period)
Week 4
|
243 cells per micro-liter
Standard Deviation 130.8
|
220 cells per micro-liter
Standard Deviation 92.7
|
277 cells per micro-liter
Standard Deviation 156.2
|
270 cells per micro-liter
Standard Deviation 143.2
|
201 cells per micro-liter
Standard Deviation 114.3
|
—
|
|
Absolute Concentration of B Cells (Active Treatment Period)
Week 24
|
264 cells per micro-liter
Standard Deviation 154.9
|
230 cells per micro-liter
Standard Deviation 119.7
|
235 cells per micro-liter
Standard Deviation 115.3
|
214 cells per micro-liter
Standard Deviation 105.0
|
180 cells per micro-liter
Standard Deviation 114.3
|
—
|
SECONDARY outcome
Timeframe: Weeks 48 and 52Population: The safety analysis set included of all participants who received at least 1 dose evobrutinib or placebo or Tecfidera. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signified those participants who were evaluable for the specified category at given time points. Results reported are for blinded extension period only and no participants took placebo during this period.
Absolute concentration of B Cells were reported.
Outcome measures
| Measure |
Placebo (Period 1)
n=49 Participants
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
|
Evobrutinib 25 mg QD (Period 1, 2 and 3)
n=51 Participants
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg QD (Period 1, 2 and 3)
n=54 Participants
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg BID (Period 1, 2 and 3)
n=47 Participants
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
|---|---|---|---|---|---|---|
|
Absolute Concentration of B Cells (Blinded Extension Period)
Week 48
|
203 cells per micro-liter
Standard Deviation 111.9
|
222 cells per micro-liter
Standard Deviation 148.8
|
187 cells per micro-liter
Standard Deviation 87.1
|
181 cells per micro-liter
Standard Deviation 109.8
|
—
|
—
|
|
Absolute Concentration of B Cells (Blinded Extension Period)
Week 52
|
227 cells per micro-liter
Standard Deviation 93.7
|
206 cells per micro-liter
Standard Deviation 140.3
|
154 cells per micro-liter
Standard Deviation 73.6
|
135 cells per micro-liter
Standard Deviation 29.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 1), Weeks 4 and 24Population: The safety analysis set included of all participants who received at least 1 dose evobrutinib or placebo or Tecfidera. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signified those participants who were evaluable for the specified category at given time points.
Change from baseline in absolute B cells are reported.
Outcome measures
| Measure |
Placebo (Period 1)
n=52 Participants
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
|
Evobrutinib 25 mg QD (Period 1, 2 and 3)
n=50 Participants
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg QD (Period 1, 2 and 3)
n=53 Participants
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg BID (Period 1, 2 and 3)
n=53 Participants
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
n=52 Participants
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Absolute B Cells (Active Treatment Period)
Week 4
|
-5 cells per micro-liter
Standard Deviation 94.5
|
9 cells per micro-liter
Standard Deviation 112.2
|
31 cells per micro-liter
Standard Deviation 114.2
|
50 cells per micro-liter
Standard Deviation 86.7
|
-3 cells per micro-liter
Standard Deviation 111.0
|
—
|
|
Change From Baseline in Absolute B Cells (Active Treatment Period)
Week 24
|
7 cells per micro-liter
Standard Deviation 135.8
|
13 cells per micro-liter
Standard Deviation 98.2
|
-15 cells per micro-liter
Standard Deviation 128.5
|
-9 cells per micro-liter
Standard Deviation 85.1
|
-26 cells per micro-liter
Standard Deviation 113.9
|
—
|
SECONDARY outcome
Timeframe: Baseline (Week 25), Weeks 48 and 52Population: The safety analysis set included of all participants who received at least 1 dose evobrutinib or placebo or Tecfidera. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signified those participants who were evaluable for the specified category at given time points. Results reported are for blinded extension period only and no participants took placebo during this period.
Change from baseline in absolute B cells are reported.
Outcome measures
| Measure |
Placebo (Period 1)
n=49 Participants
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
|
Evobrutinib 25 mg QD (Period 1, 2 and 3)
n=51 Participants
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg QD (Period 1, 2 and 3)
n=54 Participants
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg BID (Period 1, 2 and 3)
n=47 Participants
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Absolute B Cells (Blinded Extension Period)
Week 48
|
-5 cells per micro-liter
Standard Deviation 116.1
|
-30 cells per micro-liter
Standard Deviation 148.2
|
-32 cells per micro-liter
Standard Deviation 97.9
|
-15 cells per micro-liter
Standard Deviation 105.7
|
—
|
—
|
|
Change From Baseline in Absolute B Cells (Blinded Extension Period)
Week 52
|
-28 cells per micro-liter
Standard Deviation 209.8
|
-25 cells per micro-liter
Standard Deviation 65.5
|
-81 cells per micro-liter
Standard Deviation 119.0
|
15 cells per micro-liter
Standard Deviation 22.6
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 12 to 24Population: Modified Intent-To-Treat (mITT) analysis set included participants who belong to both Intent To Treat (ITT, consisted all participants who randomly allocated to a treatment, based on the intention to treat "as randomized" principle) and safety analysis sets (consisted all participants who receive at least 1 dose of trial treatment), and who have at least one baseline and one post-baseline magnetic resonance imaging (MRI) assessment.
Analysis of Gadolinium-positive T1 lesions was done using magnetic resonance imaging (MRI) scans. As per planned analysis, Tecfidera treatment group was not included in inferential analysis.
Outcome measures
| Measure |
Placebo (Period 1)
n=53 Participants
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
|
Evobrutinib 25 mg QD (Period 1, 2 and 3)
n=50 Participants
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg QD (Period 1, 2 and 3)
n=51 Participants
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg BID (Period 1, 2 and 3)
n=53 Participants
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
n=54 Participants
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
|---|---|---|---|---|---|---|
|
Total Number of New Gadolinium-positive (Gd+) T1 Lesions
|
3.08 Lesions
Standard Deviation 4.371
|
3.44 Lesions
Standard Deviation 6.846
|
1.20 Lesions
Standard Deviation 3.499
|
0.98 Lesions
Standard Deviation 3.273
|
3.24 Lesions
Standard Deviation 15.320
|
—
|
SECONDARY outcome
Timeframe: Week 12 to Week 24Population: mITT analysis set consists of all participants who belong to both the ITT and safety analysis sets, and who have at least one baseline and one post-baseline magnetic resonance imaging (MRI) assessment.
Analysis of Gadolinium-positive T1 lesions was done using magnetic resonance imaging (MRI) scans. As per planned analysis, Tecfidera treatment group was not included in inferential analysis.
Outcome measures
| Measure |
Placebo (Period 1)
n=53 Participants
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
|
Evobrutinib 25 mg QD (Period 1, 2 and 3)
n=50 Participants
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg QD (Period 1, 2 and 3)
n=51 Participants
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg BID (Period 1, 2 and 3)
n=53 Participants
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
n=54 Participants
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
|---|---|---|---|---|---|---|
|
Mean Per-scan Number of Gadolinium-positive (Gd+) T1 Lesions
|
1.02 Lesions
Standard Deviation 1.439
|
1.31 Lesions
Standard Deviation 3.130
|
0.42 Lesions
Standard Deviation 1.173
|
0.34 Lesions
Standard Deviation 0.960
|
1.45 Lesions
Standard Deviation 7.293
|
—
|
SECONDARY outcome
Timeframe: Week 12 to Week 24Population: mITT analysis set consists of all participants who belong to both the ITT and safety analysis sets, and who have at least one baseline and one post-baseline magnetic resonance imaging (MRI) assessment.
Analysis of New or Enlarging T2 lesions was done using magnetic resonance imaging (MRI) scans. As per planned analysis, Tecfidera treatment group was not included in inferential analysis.
Outcome measures
| Measure |
Placebo (Period 1)
n=53 Participants
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
|
Evobrutinib 25 mg QD (Period 1, 2 and 3)
n=50 Participants
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg QD (Period 1, 2 and 3)
n=51 Participants
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg BID (Period 1, 2 and 3)
n=53 Participants
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
n=54 Participants
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
|---|---|---|---|---|---|---|
|
Total Number of New or Enlarging T2 Lesions
|
5.96 Lesions
Standard Deviation 6.994
|
6.52 Lesions
Standard Deviation 11.569
|
3.41 Lesions
Standard Deviation 10.752
|
2.19 Lesions
Standard Deviation 4.719
|
5.35 Lesions
Standard Deviation 16.667
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: mITT analysis set consists of all participants who belong to both the ITT and safety analysis sets, and who have at least one baseline and one post-baseline magnetic resonance imaging (MRI) assessment. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Analysis of volume of T2 lesions was done using magnetic resonance imaging (MRI) scans. Tecfidera treatment group was not included in inferential analysis.
Outcome measures
| Measure |
Placebo (Period 1)
n=44 Participants
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
|
Evobrutinib 25 mg QD (Period 1, 2 and 3)
n=46 Participants
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg QD (Period 1, 2 and 3)
n=48 Participants
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg BID (Period 1, 2 and 3)
n=46 Participants
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
n=50 Participants
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Volume of T2 Lesions at Week 24
|
0.42 cubic centimeter (cc)
Standard Deviation 1.009
|
0.93 cubic centimeter (cc)
Standard Deviation 1.853
|
-0.01 cubic centimeter (cc)
Standard Deviation 0.562
|
0.09 cubic centimeter (cc)
Standard Deviation 0.463
|
0.47 cubic centimeter (cc)
Standard Deviation 2.964
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 24Population: mITT analysis set consists of all participants who belong to both the ITT and safety analysis sets, and who have at least one baseline and one post-baseline magnetic resonance imaging (MRI) assessment.
Analysis of volume of Gd+ T1 lesions was done using magnetic resonance imaging (MRI) scans. As per planned analysis, Tecfidera treatment group was not included in inferential analysis.
Outcome measures
| Measure |
Placebo (Period 1)
n=53 Participants
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
|
Evobrutinib 25 mg QD (Period 1, 2 and 3)
n=50 Participants
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg QD (Period 1, 2 and 3)
n=51 Participants
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg BID (Period 1, 2 and 3)
n=53 Participants
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
n=54 Participants
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Volume of Gadolinium-positive (Gd+) T1 Lesions at Week 24
|
-0.023 cc
Standard Deviation 0.2220
|
0.057 cc
Standard Deviation 0.3479
|
-0.111 cc
Standard Deviation 0.5416
|
-0.051 cc
Standard Deviation 0.1032
|
-0.050 cc
Standard Deviation 0.4771
|
—
|
SECONDARY outcome
Timeframe: Week 48Population: mITT BE analysis set included all participants who belonged to the mITT analysis set with an MRI assessment during the 24-week blinded extension period.
Analysis of Gd+ T1 lesions was done using magnetic resonance imaging (MRI) scans.
Outcome measures
| Measure |
Placebo (Period 1)
n=44 Participants
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
|
Evobrutinib 25 mg QD (Period 1, 2 and 3)
n=44 Participants
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg QD (Period 1, 2 and 3)
n=46 Participants
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg BID (Period 1, 2 and 3)
n=45 Participants
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
n=50 Participants
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
|---|---|---|---|---|---|---|
|
Number of Gadolinium-positive (Gd+) T1 Lesions at Week 48
|
1.00 Lesions
Standard Deviation 1.614
|
1.91 Lesions
Standard Deviation 4.296
|
0.85 Lesions
Standard Deviation 2.867
|
0.49 Lesions
Standard Deviation 1.218
|
0.42 Lesions
Standard Deviation 1.444
|
—
|
SECONDARY outcome
Timeframe: Week 48Population: mITT BE analysis set included all participants who belonged to the mITT analysis set with an MRI assessment during the 24-week blinded extension period.
Analysis of new Gd+ T1 lesions was done using magnetic resonance imaging (MRI) scans.
Outcome measures
| Measure |
Placebo (Period 1)
n=44 Participants
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
|
Evobrutinib 25 mg QD (Period 1, 2 and 3)
n=44 Participants
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg QD (Period 1, 2 and 3)
n=46 Participants
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg BID (Period 1, 2 and 3)
n=45 Participants
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
n=50 Participants
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
|---|---|---|---|---|---|---|
|
Number of New Gadolinium-positive (Gd+) T1 Lesions at Week 48
|
0.95 Lesions
Standard Deviation 1.569
|
1.84 Lesions
Standard Deviation 4.154
|
0.85 Lesions
Standard Deviation 2.867
|
0.49 Lesions
Standard Deviation 1.218
|
0.42 Lesions
Standard Deviation 1.444
|
—
|
SECONDARY outcome
Timeframe: Week 0 to Week 48Population: mITT analysis set consists of all participants who belong to both the ITT and safety analysis sets, and who have at least one baseline and one post-baseline magnetic resonance imaging (MRI) assessment.
A qualifying relapse is defined as new, worsening or recurrent neurological symptoms attributed to Multiple Sclerosis (MS) that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days.
Outcome measures
| Measure |
Placebo (Period 1)
n=53 Participants
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
|
Evobrutinib 25 mg QD (Period 1, 2 and 3)
n=50 Participants
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg QD (Period 1, 2 and 3)
n=51 Participants
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg BID (Period 1, 2 and 3)
n=53 Participants
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
n=54 Participants
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
|---|---|---|---|---|---|---|
|
Annualized Relapse Rate (ARR)
|
0.37 relapses per year
Interval 0.21 to 0.59
|
0.52 relapses per year
Interval 0.33 to 0.78
|
0.25 relapses per year
Interval 0.12 to 0.44
|
0.11 relapses per year
Interval 0.04 to 0.25
|
0.14 relapses per year
Interval 0.06 to 0.29
|
—
|
SECONDARY outcome
Timeframe: Week 25 to Week 48Population: mITT BE analysis set included all participants who belonged to the mITT analysis set with an MRI assessment during the 24-week blinded extension period.
A qualifying relapse is defined as new, worsening or recurrent neurological symptoms attributed to Multiple Sclerosis (MS) that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days. Percentage of participants with qualified relapse-free status were reported.
Outcome measures
| Measure |
Placebo (Period 1)
n=44 Participants
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
|
Evobrutinib 25 mg QD (Period 1, 2 and 3)
n=44 Participants
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg QD (Period 1, 2 and 3)
n=46 Participants
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg BID (Period 1, 2 and 3)
n=45 Participants
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
n=50 Participants
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
|---|---|---|---|---|---|---|
|
Qualified Relapse-free Status
|
84.1 percentage of participants
|
86.4 percentage of participants
|
78.3 percentage of participants
|
91.1 percentage of participants
|
96.0 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: Week 24, Week 48Population: mITT BE analysis set included all participants who belonged to the mITT analysis set with an MRI assessment during the 24-week blinded extension period.
The EDSS is an ordinal clinical rating scale in half-point increments. It assesses the following eight functional systems, areas of the central nervous system that control bodily functions: Pyramidal (ability to walk), Cerebellar (coordination), Brain stem (speech and swallowing), Sensory (touch and pain), Bowel and bladder functions, Visual, Mental, Other (includes any other neurological findings due to Multiple Sclerosis \[MS\]). EDSS overall score ranging from 0 (normal) to 10 (death due to MS).
Outcome measures
| Measure |
Placebo (Period 1)
n=44 Participants
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
|
Evobrutinib 25 mg QD (Period 1, 2 and 3)
n=44 Participants
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg QD (Period 1, 2 and 3)
n=46 Participants
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg BID (Period 1, 2 and 3)
n=45 Participants
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
n=50 Participants
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
|---|---|---|---|---|---|---|
|
Change From Week 24 in Expanded Disability Status Scale (EDSS) at Week 48
|
-0.05 Units on a scale
Standard Deviation 0.260
|
-0.10 Units on a scale
Standard Deviation 0.351
|
-0.01 Units on a scale
Standard Deviation 0.619
|
0.00 Units on a scale
Standard Deviation 0.238
|
-0.10 Units on a scale
Standard Deviation 0.404
|
—
|
SECONDARY outcome
Timeframe: Week 24 to Week 48Population: mITT BE analysis set included all participants who belonged to the mITT analysis set with an MRI assessment during the 24-week blinded extension period. Here, "Number of Participants Analyzed" signified those participants who were evaluable for this outcome measure.
Analysis of New or Enlarging T2 lesions was done using magnetic resonance imaging (MRI) scans.
Outcome measures
| Measure |
Placebo (Period 1)
n=42 Participants
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
|
Evobrutinib 25 mg QD (Period 1, 2 and 3)
n=42 Participants
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg QD (Period 1, 2 and 3)
n=43 Participants
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg BID (Period 1, 2 and 3)
n=43 Participants
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
n=50 Participants
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
|---|---|---|---|---|---|---|
|
Total Number of New or Enlarging T2 Lesions at Week 48 Relative to Week 24
|
3.57 Lesions
Standard Deviation 4.346
|
5.86 Lesions
Standard Deviation 11.330
|
3.84 Lesions
Standard Deviation 10.083
|
1.60 Lesions
Standard Deviation 3.799
|
1.88 Lesions
Standard Deviation 4.796
|
—
|
SECONDARY outcome
Timeframe: Week 24, Week 48Population: mITT BE analysis set included all participants who belonged to the mITT analysis set with an MRI assessment during the 24-week blinded extension period.
Analysis of volume of Gd+ T1 lesions was done using magnetic resonance imaging (MRI) scans.
Outcome measures
| Measure |
Placebo (Period 1)
n=44 Participants
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
|
Evobrutinib 25 mg QD (Period 1, 2 and 3)
n=44 Participants
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg QD (Period 1, 2 and 3)
n=46 Participants
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg BID (Period 1, 2 and 3)
n=45 Participants
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
n=50 Participants
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
|---|---|---|---|---|---|---|
|
Change From Week 24 in Volume of Gadolinium-positive (Gd+) T1 Lesions at Week 48
|
0.092 cc
Standard Deviation 0.4626
|
0.088 cc
Standard Deviation 0.4006
|
0.045 cc
Standard Deviation 0.2285
|
0.024 cc
Standard Deviation 0.1981
|
-0.203 cc
Standard Deviation 1.1073
|
—
|
SECONDARY outcome
Timeframe: Week 24, Week 48Population: mITT BE analysis set included all participants who belonged to the mITT analysis set with an MRI assessment during the 24-week blinded extension period.
Analysis of volume of T2 lesions was done using magnetic resonance imaging (MRI) scans.
Outcome measures
| Measure |
Placebo (Period 1)
n=44 Participants
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
|
Evobrutinib 25 mg QD (Period 1, 2 and 3)
n=44 Participants
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg QD (Period 1, 2 and 3)
n=46 Participants
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg BID (Period 1, 2 and 3)
n=45 Participants
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
n=50 Participants
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
|---|---|---|---|---|---|---|
|
Change From Week 24 in Volume of T2 Lesions at Week 48
|
0.53 cc
Standard Deviation 1.360
|
0.67 cc
Standard Deviation 1.865
|
0.35 cc
Standard Deviation 1.083
|
-0.03 cc
Standard Deviation 1.031
|
-0.57 cc
Standard Deviation 2.699
|
—
|
SECONDARY outcome
Timeframe: OLE Baseline (BE period Week 48), OLE Weeks 96, 144, 192, 240, 288 and 336Population: modified ITT OLE Analysis Set (mITT-OLE) Analysis Set: participants randomly allocated to a treatment who belong to Safety OLE Analysis Set, and who have at least 1 Magnetic Resonance Imaging (MRI) assessment on or after OLE Week 0. Overall Number of Participants Analyzed= Participants evaluable for this outcome measure and Number analyzed= participants who were evaluable for the specified category. Results reported are for OLE period only and no participants took placebo during this period.
Analysis of T1-Gadolinium enhancing lesions was done using magnetic resonance imaging (MRI) scans.
Outcome measures
| Measure |
Placebo (Period 1)
n=34 Participants
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
|
Evobrutinib 25 mg QD (Period 1, 2 and 3)
n=35 Participants
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg QD (Period 1, 2 and 3)
n=37 Participants
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg BID (Period 1, 2 and 3)
n=44 Participants
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
n=37 Participants
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
|---|---|---|---|---|---|---|
|
OLE Period: Total Number of Gadolinium-Enhancing T1 Lesions
OLE Baseline (BE period Week 48)
|
0.82 Lesions
Standard Deviation 2.668
|
1.74 Lesions
Standard Deviation 4.395
|
1.46 Lesions
Standard Deviation 4.519
|
1.16 Lesions
Standard Deviation 3.050
|
2.03 Lesions
Standard Deviation 11.829
|
—
|
|
OLE Period: Total Number of Gadolinium-Enhancing T1 Lesions
Week 96
|
0.13 Lesions
Standard Deviation 0.341
|
0.63 Lesions
Standard Deviation 1.822
|
0.49 Lesions
Standard Deviation 1.121
|
0.69 Lesions
Standard Deviation 1.411
|
0.67 Lesions
Standard Deviation 2.255
|
—
|
|
OLE Period: Total Number of Gadolinium-Enhancing T1 Lesions
Week 144
|
0.76 Lesions
Standard Deviation 2.294
|
0.41 Lesions
Standard Deviation 1.217
|
0.82 Lesions
Standard Deviation 3.512
|
0.54 Lesions
Standard Deviation 1.146
|
1.29 Lesions
Standard Deviation 5.940
|
—
|
|
OLE Period: Total Number of Gadolinium-Enhancing T1 Lesions
Week 192
|
1.00 Lesions
Standard Deviation 3.367
|
0.64 Lesions
Standard Deviation 1.890
|
0.81 Lesions
Standard Deviation 2.206
|
0.84 Lesions
Standard Deviation 1.798
|
0.96 Lesions
Standard Deviation 3.130
|
—
|
|
OLE Period: Total Number of Gadolinium-Enhancing T1 Lesions
Week 240
|
1.68 Lesions
Standard Deviation 5.800
|
0.63 Lesions
Standard Deviation 1.996
|
0.37 Lesions
Standard Deviation 1.189
|
0.77 Lesions
Standard Deviation 2.417
|
0.88 Lesions
Standard Deviation 3.204
|
—
|
|
OLE Period: Total Number of Gadolinium-Enhancing T1 Lesions
Week 288
|
0.35 Lesions
Standard Deviation 0.671
|
0.35 Lesions
Standard Deviation 0.786
|
0.32 Lesions
Standard Deviation 1.090
|
1.04 Lesions
Standard Deviation 2.946
|
0.35 Lesions
Standard Deviation 1.265
|
—
|
|
OLE Period: Total Number of Gadolinium-Enhancing T1 Lesions
Week 336
|
0.83 Lesions
Standard Deviation 1.602
|
3.00 Lesions
Standard Deviation 5.745
|
1.17 Lesions
Standard Deviation 2.858
|
0.29 Lesions
Standard Deviation 0.756
|
5.60 Lesions
Standard Deviation 18.310
|
—
|
SECONDARY outcome
Timeframe: OLE Baseline (BE period Week 48), OLE Weeks 96, 144, 192, 240, 288 and 336Population: modified ITT OLE Analysis Set (mITT-OLE) Analysis Set: participants randomly allocated to a treatment who belong to Safety OLE Analysis Set, and who have at least 1 Magnetic Resonance Imaging (MRI) assessment on or after OLE Week 0. Here, "Number analyzed" signifies those participants who were evaluable for the specified category. Results reported are for OLE period only and no participants took placebo during this period.
A qualifying relapse is defined as new, worsening or recurrent neurological symptoms attributed to Multiple Sclerosis (MS) that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days.
Outcome measures
| Measure |
Placebo (Period 1)
n=39 Participants
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
|
Evobrutinib 25 mg QD (Period 1, 2 and 3)
n=38 Participants
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg QD (Period 1, 2 and 3)
n=42 Participants
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg BID (Period 1, 2 and 3)
n=44 Participants
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
n=48 Participants
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
|---|---|---|---|---|---|---|
|
OLE Period: Annualized Relapse Rate (ARR)
OLE Baseline (BE period Week 48)
|
0.29 relapses per year
Interval 0.14 to 0.53
|
0.18 relapses per year
Interval 0.06 to 0.38
|
0.14 relapses per year
Interval 0.04 to 0.32
|
0.17 relapses per year
Interval 0.07 to 0.36
|
0.12 relapses per year
Interval 0.04 to 0.28
|
—
|
|
OLE Period: Annualized Relapse Rate (ARR)
Week 96
|
0.16 relapses per year
Interval 0.05 to 0.37
|
0.13 relapses per year
Interval 0.04 to 0.34
|
0.09 relapses per year
Interval 0.02 to 0.26
|
0.08 relapses per year
Interval 0.02 to 0.22
|
0.03 relapses per year
Interval 0.0 to 0.16
|
—
|
|
OLE Period: Annualized Relapse Rate (ARR)
Week 144
|
0.07 relapses per year
Interval 0.01 to 0.25
|
0.11 relapses per year
Interval 0.02 to 0.33
|
0.03 relapses per year
Interval 0.0 to 0.17
|
0.15 relapses per year
Interval 0.05 to 0.34
|
0.16 relapses per year
Interval 0.05 to 0.37
|
—
|
|
OLE Period: Annualized Relapse Rate (ARR)
Week 192
|
0.04 relapses per year
Interval 0.0 to 0.2
|
0.08 relapses per year
Interval 0.01 to 0.29
|
0.22 relapses per year
Interval 0.09 to 0.45
|
0.16 relapses per year
Interval 0.05 to 0.38
|
0.04 relapses per year
Interval 0.0 to 0.2
|
—
|
|
OLE Period: Annualized Relapse Rate (ARR)
Week 240
|
0.16 relapses per year
Interval 0.04 to 0.41
|
0.04 relapses per year
Interval 0.0 to 0.23
|
0.10 relapses per year
Interval 0.02 to 0.28
|
0.13 relapses per year
Interval 0.04 to 0.34
|
0.00 relapses per year
Interval to 0.15
Based on pre-specified criteria, when the number of qualified relapses is zero, the lower limit of 95% confidence interval could not be calculated.
|
—
|
|
OLE Period: Annualized Relapse Rate (ARR)
Week 288
|
0.13 relapses per year
Interval 0.13 to 0.38
|
0.05 relapses per year
Interval 0.0 to 0.25
|
0.07 relapses per year
Interval 0.01 to 0.25
|
0.00 relapses per year
Interval to 0.13
Based on pre-specified criteria, when the number of qualified relapses is zero, the lower limit of 95% confidence interval could not be calculated.
|
0.04 relapses per year
Interval 0.0 to 0.24
|
—
|
|
OLE Period: Annualized Relapse Rate (ARR)
Week 336
|
0.00 relapses per year
Interval to 1.75
Based on pre-specified criteria, when the number of qualified relapses is zero, the lower limit of 95% confidence interval could not be calculated.
|
0.00 relapses per year
Interval to 1.55
Based on pre-specified criteria, when the number of qualified relapses is zero, the lower limit of 95% confidence interval could not be calculated.
|
0.31 relapses per year
Interval 0.01 to 1.7
|
0.00 relapses per year
Interval to 1.27
Based on pre-specified criteria, when the number of qualified relapses is zero, the lower limit of 95% confidence interval could not be calculated.
|
0.00 relapses per year
Interval to 7.97
Based on pre-specified criteria, when the number of qualified relapses is zero, the lower limit of 95% confidence interval could not be calculated.
|
—
|
SECONDARY outcome
Timeframe: OLE Baseline (BE period Week 48) up to OLE Week 336Population: modified ITT OLE Analysis Set (mITT-OLE) Analysis Set: participants randomly allocated to a treatment who belong to Safety OLE Analysis Set, and who have at least 1 Magnetic Resonance Imaging (MRI) assessment on or after OLE Week 0. Overall Number of Participants Analyzed= Participants evaluable for this outcome measure. Results reported are for OLE period only and no participants took placebo during this period.
A qualifying relapse is defined as new, worsening or recurrent neurological symptoms attributed to Multiple Sclerosis (MS) that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days. Percentage of participants with qualified relapse-free status from OLE Baseline (BE period Week 48) up to Week 336 were reported.
Outcome measures
| Measure |
Placebo (Period 1)
n=39 Participants
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
|
Evobrutinib 25 mg QD (Period 1, 2 and 3)
n=38 Participants
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg QD (Period 1, 2 and 3)
n=42 Participants
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg BID (Period 1, 2 and 3)
n=44 Participants
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
n=48 Participants
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
|---|---|---|---|---|---|---|
|
OLE Period: Percentage of Participants With Qualified Relapse-Free Status
|
66.7 percentage of participants
|
68.4 percentage of participants
|
71.4 percentage of participants
|
65.9 percentage of participants
|
83.3 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: OLE Baseline (BE period Week 48), OLE Weeks 96, 144, 192, 240, 288 and 336Population: modified ITT OLE Analysis Set (mITT-OLE) Analysis Set: participants randomly allocated to a treatment who belong to Safety OLE Analysis Set, and who have at least 1 Magnetic Resonance Imaging (MRI) assessment on or after OLE Week 0. Overall Number of Participants Analyzed= Participants evaluable for this outcome measure and Number analyzed = participants who were evaluable for the specified category. Results reported are for OLE period only and no participants took placebo during this period.
The EDSS is an ordinal clinical rating scale in half-point increments. It assesses the following eight functional systems, areas of the central nervous system that control bodily functions: Pyramidal (ability to walk), Cerebellar (coordination), Brain stem (speech and swallowing), Sensory (touch and pain), Bowel and bladder functions, Visual, Mental, Other (includes any other neurological findings due to Multiple Sclerosis \[MS\]). EDSS overall score ranging from 0 (normal) to 10 (death due to MS).
Outcome measures
| Measure |
Placebo (Period 1)
n=39 Participants
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
|
Evobrutinib 25 mg QD (Period 1, 2 and 3)
n=38 Participants
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg QD (Period 1, 2 and 3)
n=42 Participants
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg BID (Period 1, 2 and 3)
n=44 Participants
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
n=48 Participants
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
|---|---|---|---|---|---|---|
|
OLE Period: Change From Baseline in Expanded Disability Status Scale (EDSS) at Week 96, 144, 192, 240, 288 and 336
Week 336
|
0.0 units on a scale
Standard Deviation 0.52
|
0.5 units on a scale
Standard Deviation 1.36
|
0.7 units on a scale
Standard Deviation 1.38
|
-0.2 units on a scale
Standard Deviation 0.57
|
0.0 units on a scale
Standard Deviation 0.52
|
—
|
|
OLE Period: Change From Baseline in Expanded Disability Status Scale (EDSS) at Week 96, 144, 192, 240, 288 and 336
OLE Baseline (BE period Week 48)
|
0.1 units on a scale
Standard Deviation 0.39
|
0.0 units on a scale
Standard Deviation 0.69
|
0.1 units on a scale
Standard Deviation 0.46
|
0.0 units on a scale
Standard Deviation 0.27
|
0.0 units on a scale
Standard Deviation 0.34
|
—
|
|
OLE Period: Change From Baseline in Expanded Disability Status Scale (EDSS) at Week 96, 144, 192, 240, 288 and 336
Week 96
|
0.1 units on a scale
Standard Deviation 0.40
|
0.1 units on a scale
Standard Deviation 0.46
|
0.2 units on a scale
Standard Deviation 0.71
|
0.0 units on a scale
Standard Deviation 0.42
|
0.0 units on a scale
Standard Deviation 0.32
|
—
|
|
OLE Period: Change From Baseline in Expanded Disability Status Scale (EDSS) at Week 96, 144, 192, 240, 288 and 336
Week 144
|
0.1 units on a scale
Standard Deviation 0.79
|
0.1 units on a scale
Standard Deviation 0.61
|
0.2 units on a scale
Standard Deviation 0.79
|
0.0 units on a scale
Standard Deviation 0.44
|
0.0 units on a scale
Standard Deviation 0.28
|
—
|
|
OLE Period: Change From Baseline in Expanded Disability Status Scale (EDSS) at Week 96, 144, 192, 240, 288 and 336
Week 192
|
0.2 units on a scale
Standard Deviation 0.64
|
0.1 units on a scale
Standard Deviation 0.61
|
0.2 units on a scale
Standard Deviation 0.35
|
0.2 units on a scale
Standard Deviation 0.72
|
0.0 units on a scale
Standard Deviation 0.29
|
—
|
|
OLE Period: Change From Baseline in Expanded Disability Status Scale (EDSS) at Week 96, 144, 192, 240, 288 and 336
Week 240
|
0.3 units on a scale
Standard Deviation 0.72
|
0.3 units on a scale
Standard Deviation 0.50
|
0.2 units on a scale
Standard Deviation 0.46
|
0.2 units on a scale
Standard Deviation 0.93
|
0.1 units on a scale
Standard Deviation 0.40
|
—
|
|
OLE Period: Change From Baseline in Expanded Disability Status Scale (EDSS) at Week 96, 144, 192, 240, 288 and 336
Week 288
|
0.4 units on a scale
Standard Deviation 0.80
|
0.1 units on a scale
Standard Deviation 0.87
|
0.4 units on a scale
Standard Deviation 0.58
|
0.4 units on a scale
Standard Deviation 0.81
|
0.2 units on a scale
Standard Deviation 0.45
|
—
|
SECONDARY outcome
Timeframe: OLE Baseline (BE period Week 48) up to OLE Week 336Population: The Safety OLE Analysis Set included all participants who receive at least 1 dose of Evobrutinib during the OLE. Results reported are for OLE period only and no participants took placebo during this period.
An adverse event (AE) was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the study drug. An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent adverse events are defined as any adverse event with a start date on or after the date of first dose and within 28 days after the date of last dose in the study. TEAEs include both Serious TEAEs and non-serious TEAEs.
Outcome measures
| Measure |
Placebo (Period 1)
n=39 Participants
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
|
Evobrutinib 25 mg QD (Period 1, 2 and 3)
n=39 Participants
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg QD (Period 1, 2 and 3)
n=42 Participants
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg BID (Period 1, 2 and 3)
n=44 Participants
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
n=49 Participants
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
|---|---|---|---|---|---|---|
|
OLE Period: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
|
35 Participants
|
29 Participants
|
41 Participants
|
40 Participants
|
37 Participants
|
—
|
SECONDARY outcome
Timeframe: OLE Baseline (BE period Week 48) up to OLE Week 336Population: The Safety OLE Analysis Set included all participants who receive at least 1 dose of Evobrutinib during the OLE. Results reported are for OLE period only and no participants took placebo during this period.
Vital signs, including semi supine blood pressure, pulse rate, respiratory rate, weight, and oral temperature were assessed. Number of participants with clinically significant change from baseline in vital signs were reported. Clinical Significance was decided by the investigator.
Outcome measures
| Measure |
Placebo (Period 1)
n=39 Participants
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
|
Evobrutinib 25 mg QD (Period 1, 2 and 3)
n=39 Participants
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg QD (Period 1, 2 and 3)
n=42 Participants
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg BID (Period 1, 2 and 3)
n=44 Participants
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
n=49 Participants
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
|---|---|---|---|---|---|---|
|
OLE Period: Number of Participants With Clinically Significant Changes From Baseline in Vital Signs
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: OLE Baseline (BE period Week 48) up to OLE Week 336Population: The Safety OLE Analysis Set included all participants who receive at least 1 dose of Evobrutinib during the OLE. Results reported are for OLE period only and no participants took placebo during this period.
Laboratory parameters included hematology, biochemistry, and urinalysis. Number of participants with clinically significant change from baseline in laboratory parameters were reported. Clinical Significance was decided by the investigator.
Outcome measures
| Measure |
Placebo (Period 1)
n=39 Participants
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
|
Evobrutinib 25 mg QD (Period 1, 2 and 3)
n=39 Participants
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg QD (Period 1, 2 and 3)
n=42 Participants
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg BID (Period 1, 2 and 3)
n=44 Participants
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
n=49 Participants
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
|---|---|---|---|---|---|---|
|
OLE Period: Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: OLE Baseline (BE period Week 48) up to OLE Week 336Population: The Safety OLE Analysis Set included all participants who receive at least 1 dose of Evobrutinib during the OLE. Results reported are for OLE period only and no participants took placebo during this period.
ECG parameters included rhythm, ventricular rate, PR interval, QRS duration, and QT interval. Number of participants with clinically significant change from baseline in ECG were reported. Clinical Significance was decided by the investigator.
Outcome measures
| Measure |
Placebo (Period 1)
n=39 Participants
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
|
Evobrutinib 25 mg QD (Period 1, 2 and 3)
n=39 Participants
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg QD (Period 1, 2 and 3)
n=42 Participants
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg BID (Period 1, 2 and 3)
n=44 Participants
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
n=49 Participants
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
|---|---|---|---|---|---|---|
|
OLE Period: Number of Participants With Clinically Significant Changes From Baseline in Electrocardiograms (ECGs)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: OLE Baseline (BE period Week 48), OLE Weeks 96, 144, 192, 240 and 288Population: The Safety OLE Analysis Set included all participants who receive at least 1 dose of Evobrutinib during the OLE. Overall Number of Participants Analyzed= Participants evaluable for this outcome measure and Number analyzed = participants who were evaluable for the specified category. Results reported are for OLE period only and no participants took placebo during this period.
Absolute Concentrations serum levels of IgG, IgA, IgM were assessed.
Outcome measures
| Measure |
Placebo (Period 1)
n=37 Participants
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
|
Evobrutinib 25 mg QD (Period 1, 2 and 3)
n=37 Participants
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg QD (Period 1, 2 and 3)
n=37 Participants
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg BID (Period 1, 2 and 3)
n=44 Participants
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
n=40 Participants
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
|---|---|---|---|---|---|---|
|
OLE Period: Absolute Concentrations of Immunoglobulin (Ig) Levels
Ig A, OLE Baseline (BE period Week 48)
|
2.31 Gram per Liter
Standard Deviation 0.966
|
2.44 Gram per Liter
Standard Deviation 0.897
|
2.49 Gram per Liter
Standard Deviation 0.953
|
2.52 Gram per Liter
Standard Deviation 0.970
|
2.31 Gram per Liter
Standard Deviation 0.906
|
—
|
|
OLE Period: Absolute Concentrations of Immunoglobulin (Ig) Levels
Ig A, Week 72
|
2.38 Gram per Liter
Standard Deviation 1.084
|
2.53 Gram per Liter
Standard Deviation 1.075
|
2.72 Gram per Liter
Standard Deviation 1.137
|
2.65 Gram per Liter
Standard Deviation 1.062
|
2.43 Gram per Liter
Standard Deviation 0.865
|
—
|
|
OLE Period: Absolute Concentrations of Immunoglobulin (Ig) Levels
Ig A, Week 96
|
2.42 Gram per Liter
Standard Deviation 1.173
|
2.69 Gram per Liter
Standard Deviation 1.026
|
2.91 Gram per Liter
Standard Deviation 1.181
|
2.82 Gram per Liter
Standard Deviation 1.113
|
2.62 Gram per Liter
Standard Deviation 1.072
|
—
|
|
OLE Period: Absolute Concentrations of Immunoglobulin (Ig) Levels
Ig A, Week 144
|
2.57 Gram per Liter
Standard Deviation 1.274
|
2.73 Gram per Liter
Standard Deviation 0.918
|
2.82 Gram per Liter
Standard Deviation 1.326
|
2.91 Gram per Liter
Standard Deviation 1.233
|
2.57 Gram per Liter
Standard Deviation 1.025
|
—
|
|
OLE Period: Absolute Concentrations of Immunoglobulin (Ig) Levels
IgA, Week 192
|
2.60 Gram per Liter
Standard Deviation 1.242
|
2.71 Gram per Liter
Standard Deviation 0.987
|
2.86 Gram per Liter
Standard Deviation 1.255
|
3.15 Gram per Liter
Standard Deviation 1.185
|
2.70 Gram per Liter
Standard Deviation 1.055
|
—
|
|
OLE Period: Absolute Concentrations of Immunoglobulin (Ig) Levels
IgA, Week 240
|
2.71 Gram per Liter
Standard Deviation 1.280
|
2.85 Gram per Liter
Standard Deviation 1.095
|
3.05 Gram per Liter
Standard Deviation 1.314
|
3.13 Gram per Liter
Standard Deviation 1.269
|
2.65 Gram per Liter
Standard Deviation 0.984
|
—
|
|
OLE Period: Absolute Concentrations of Immunoglobulin (Ig) Levels
IgA, Week 288
|
2.68 Gram per Liter
Standard Deviation 1.305
|
3.08 Gram per Liter
Standard Deviation 1.276
|
3.12 Gram per Liter
Standard Deviation 1.306
|
3.30 Gram per Liter
Standard Deviation 1.347
|
2.92 Gram per Liter
Standard Deviation 1.108
|
—
|
|
OLE Period: Absolute Concentrations of Immunoglobulin (Ig) Levels
Ig G, OLE Baseline (BE period Week 48)
|
9.75 Gram per Liter
Standard Deviation 2.253
|
10.37 Gram per Liter
Standard Deviation 2.512
|
10.73 Gram per Liter
Standard Deviation 2.479
|
10.44 Gram per Liter
Standard Deviation 2.291
|
9.65 Gram per Liter
Standard Deviation 2.165
|
—
|
|
OLE Period: Absolute Concentrations of Immunoglobulin (Ig) Levels
Ig G, Week 72
|
9.63 Gram per Liter
Standard Deviation 2.335
|
10.47 Gram per Liter
Standard Deviation 2.509
|
10.69 Gram per Liter
Standard Deviation 2.515
|
10.42 Gram per Liter
Standard Deviation 2.116
|
9.93 Gram per Liter
Standard Deviation 2.131
|
—
|
|
OLE Period: Absolute Concentrations of Immunoglobulin (Ig) Levels
Ig G, Week 96
|
9.46 Gram per Liter
Standard Deviation 2.490
|
10.10 Gram per Liter
Standard Deviation 2.461
|
10.76 Gram per Liter
Standard Deviation 2.413
|
10.29 Gram per Liter
Standard Deviation 2.172
|
9.93 Gram per Liter
Standard Deviation 2.285
|
—
|
|
OLE Period: Absolute Concentrations of Immunoglobulin (Ig) Levels
Ig G, Week 144
|
9.48 Gram per Liter
Standard Deviation 2.294
|
10.43 Gram per Liter
Standard Deviation 2.304
|
10.38 Gram per Liter
Standard Deviation 2.638
|
10.21 Gram per Liter
Standard Deviation 2.552
|
9.32 Gram per Liter
Standard Deviation 2.115
|
—
|
|
OLE Period: Absolute Concentrations of Immunoglobulin (Ig) Levels
IgG, Week 192
|
9.37 Gram per Liter
Standard Deviation 2.156
|
9.99 Gram per Liter
Standard Deviation 2.197
|
10.36 Gram per Liter
Standard Deviation 2.548
|
10.46 Gram per Liter
Standard Deviation 2.135
|
9.56 Gram per Liter
Standard Deviation 2.094
|
—
|
|
OLE Period: Absolute Concentrations of Immunoglobulin (Ig) Levels
IgG, Week 240
|
9.28 Gram per Liter
Standard Deviation 2.081
|
10.33 Gram per Liter
Standard Deviation 2.422
|
10.47 Gram per Liter
Standard Deviation 2.562
|
10.47 Gram per Liter
Standard Deviation 2.562
|
9.58 Gram per Liter
Standard Deviation 2.245
|
—
|
|
OLE Period: Absolute Concentrations of Immunoglobulin (Ig) Levels
IgG, Week 288
|
9.46 Gram per Liter
Standard Deviation 2.068
|
10.48 Gram per Liter
Standard Deviation 2.541
|
10.64 Gram per Liter
Standard Deviation 2.566
|
10.36 Gram per Liter
Standard Deviation 2.273
|
9.72 Gram per Liter
Standard Deviation 2.700
|
—
|
|
OLE Period: Absolute Concentrations of Immunoglobulin (Ig) Levels
Ig M, OLE Baseline (BE period Week 48)
|
1.06 Gram per Liter
Standard Deviation 0.550
|
0.89 Gram per Liter
Standard Deviation 0.403
|
1.08 Gram per Liter
Standard Deviation 0.680
|
0.92 Gram per Liter
Standard Deviation 0.422
|
0.99 Gram per Liter
Standard Deviation 0.586
|
—
|
|
OLE Period: Absolute Concentrations of Immunoglobulin (Ig) Levels
Ig M, Week 72
|
1.03 Gram per Liter
Standard Deviation 0.551
|
0.87 Gram per Liter
Standard Deviation 0.397
|
1.05 Gram per Liter
Standard Deviation 0.758
|
0.91 Gram per Liter
Standard Deviation 0.425
|
0.94 Gram per Liter
Standard Deviation 0.561
|
—
|
|
OLE Period: Absolute Concentrations of Immunoglobulin (Ig) Levels
Ig M, Week 96
|
1.01 Gram per Liter
Standard Deviation 0.556
|
0.87 Gram per Liter
Standard Deviation 0.413
|
1.05 Gram per Liter
Standard Deviation 0.747
|
0.92 Gram per Liter
Standard Deviation 0.460
|
0.91 Gram per Liter
Standard Deviation 0.525
|
—
|
|
OLE Period: Absolute Concentrations of Immunoglobulin (Ig) Levels
Ig M, Week 144
|
0.88 Gram per Liter
Standard Deviation 0.463
|
0.88 Gram per Liter
Standard Deviation 0.468
|
0.94 Gram per Liter
Standard Deviation 0.614
|
0.89 Gram per Liter
Standard Deviation 0.377
|
0.90 Gram per Liter
Standard Deviation 0.519
|
—
|
|
OLE Period: Absolute Concentrations of Immunoglobulin (Ig) Levels
Ig M, Week 192
|
0.89 Gram per Liter
Standard Deviation 0.492
|
0.87 Gram per Liter
Standard Deviation 0.461
|
0.90 Gram per Liter
Standard Deviation 0.462
|
0.84 Gram per Liter
Standard Deviation 0.320
|
0.90 Gram per Liter
Standard Deviation 0.585
|
—
|
|
OLE Period: Absolute Concentrations of Immunoglobulin (Ig) Levels
Ig M, Week 240
|
0.85 Gram per Liter
Standard Deviation 0.420
|
0.83 Gram per Liter
Standard Deviation 0.419
|
0.87 Gram per Liter
Standard Deviation 0.468
|
0.88 Gram per Liter
Standard Deviation 0.369
|
0.87 Gram per Liter
Standard Deviation 0.611
|
—
|
|
OLE Period: Absolute Concentrations of Immunoglobulin (Ig) Levels
Ig M, Week 288
|
0.85 Gram per Liter
Standard Deviation 0.405
|
0.90 Gram per Liter
Standard Deviation 0.490
|
0.94 Gram per Liter
Standard Deviation 0.544
|
0.87 Gram per Liter
Standard Deviation 0.397
|
1.03 Gram per Liter
Standard Deviation 0.568
|
—
|
SECONDARY outcome
Timeframe: OLE Baseline (BE period Week 48), OLE Weeks 96, 144, 192, 240 and 288Population: The Safety OLE Analysis Set included all participants who receive at least 1 dose of Evobrutinib during the OLE. Overall Number of Participants Analyzed= Participants evaluable for this outcome measure and Number analyzed = participants who were evaluable for the specified category. Results reported are for OLE period only and no participants took placebo during this period.
Change from baseline in the serum levels of IgG, IgA, IgM were assessed.
Outcome measures
| Measure |
Placebo (Period 1)
n=37 Participants
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
|
Evobrutinib 25 mg QD (Period 1, 2 and 3)
n=37 Participants
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg QD (Period 1, 2 and 3)
n=37 Participants
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg BID (Period 1, 2 and 3)
n=44 Participants
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
n=40 Participants
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
|---|---|---|---|---|---|---|
|
OLE Period: Change From Baseline in Immunoglobulin (Ig) Levels
Ig A, Week 96
|
0.44 Gram per Liter
Standard Deviation 0.491
|
0.45 Gram per Liter
Standard Deviation 0.407
|
0.58 Gram per Liter
Standard Deviation 0.485
|
0.54 Gram per Liter
Standard Deviation 0.446
|
0.59 Gram per Liter
Standard Deviation 0.545
|
—
|
|
OLE Period: Change From Baseline in Immunoglobulin (Ig) Levels
Ig A, Week 144
|
0.58 Gram per Liter
Standard Deviation 0.594
|
0.41 Gram per Liter
Standard Deviation 0.347
|
0.50 Gram per Liter
Standard Deviation 0.670
|
0.57 Gram per Liter
Standard Deviation 0.589
|
0.54 Gram per Liter
Standard Deviation 0.452
|
—
|
|
OLE Period: Change From Baseline in Immunoglobulin (Ig) Levels
IgA, Week 192
|
0.60 Gram per Liter
Standard Deviation 0.597
|
0.38 Gram per Liter
Standard Deviation 0.443
|
0.55 Gram per Liter
Standard Deviation 0.667
|
0.82 Gram per Liter
Standard Deviation 0.530
|
0.67 Gram per Liter
Standard Deviation 0.492
|
—
|
|
OLE Period: Change From Baseline in Immunoglobulin (Ig) Levels
IgA, Week 240
|
0.67 Gram per Liter
Standard Deviation 0.605
|
0.55 Gram per Liter
Standard Deviation 0.471
|
0.74 Gram per Liter
Standard Deviation 0.682
|
0.78 Gram per Liter
Standard Deviation 0.621
|
0.68 Gram per Liter
Standard Deviation 0.520
|
—
|
|
OLE Period: Change From Baseline in Immunoglobulin (Ig) Levels
IgA, Week 288
|
0.68 Gram per Liter
Standard Deviation 0.934
|
0.75 Gram per Liter
Standard Deviation 0.680
|
0.91 Gram per Liter
Standard Deviation 0.915
|
1.02 Gram per Liter
Standard Deviation 0.637
|
0.93 Gram per Liter
Standard Deviation 0.724
|
—
|
|
OLE Period: Change From Baseline in Immunoglobulin (Ig) Levels
Ig G, OLE Baseline (BE period Week 48)
|
0.39 Gram per Liter
Standard Deviation 0.960
|
0.54 Gram per Liter
Standard Deviation 1.463
|
0.69 Gram per Liter
Standard Deviation 1.147
|
1.11 Gram per Liter
Standard Deviation 1.150
|
0.23 Gram per Liter
Standard Deviation 1.216
|
—
|
|
OLE Period: Change From Baseline in Immunoglobulin (Ig) Levels
Ig G, Week 72
|
0.40 Gram per Liter
Standard Deviation 1.019
|
0.56 Gram per Liter
Standard Deviation 1.364
|
0.79 Gram per Liter
Standard Deviation 1.236
|
1.07 Gram per Liter
Standard Deviation 0.994
|
0.48 Gram per Liter
Standard Deviation 1.288
|
—
|
|
OLE Period: Change From Baseline in Immunoglobulin (Ig) Levels
Ig G, Week 96
|
0.17 Gram per Liter
Standard Deviation 1.359
|
0.18 Gram per Liter
Standard Deviation 1.228
|
0.64 Gram per Liter
Standard Deviation 1.178
|
0.84 Gram per Liter
Standard Deviation 1.073
|
0.47 Gram per Liter
Standard Deviation 1.355
|
—
|
|
OLE Period: Change From Baseline in Immunoglobulin (Ig) Levels
Ig A, OLE Baseline (BE period Week 48)
|
0.26 Gram per Liter
Standard Deviation 0.237
|
0.17 Gram per Liter
Standard Deviation 0.333
|
0.19 Gram per Liter
Standard Deviation 0.283
|
0.26 Gram per Liter
Standard Deviation 0.291
|
0.28 Gram per Liter
Standard Deviation 0.355
|
—
|
|
OLE Period: Change From Baseline in Immunoglobulin (Ig) Levels
Ig A, Week 72
|
0.40 Gram per Liter
Standard Deviation 0.398
|
0.36 Gram per Liter
Standard Deviation 0.515
|
0.41 Gram per Liter
Standard Deviation 0.417
|
0.38 Gram per Liter
Standard Deviation 0.453
|
0.42 Gram per Liter
Standard Deviation 0.368
|
—
|
|
OLE Period: Change From Baseline in Immunoglobulin (Ig) Levels
Ig G, Week 144
|
0.35 Gram per Liter
Standard Deviation 1.367
|
0.17 Gram per Liter
Standard Deviation 1.451
|
0.31 Gram per Liter
Standard Deviation 1.356
|
0.68 Gram per Liter
Standard Deviation 1.458
|
-0.09 Gram per Liter
Standard Deviation 1.176
|
—
|
|
OLE Period: Change From Baseline in Immunoglobulin (Ig) Levels
IgG, Week 192
|
0.14 Gram per Liter
Standard Deviation 1.227
|
-0.13 Gram per Liter
Standard Deviation 1.141
|
0.18 Gram per Liter
Standard Deviation 1.625
|
0.84 Gram per Liter
Standard Deviation 1.384
|
0.09 Gram per Liter
Standard Deviation 1.324
|
—
|
|
OLE Period: Change From Baseline in Immunoglobulin (Ig) Levels
IgG, Week 240
|
-0.01 Gram per Liter
Standard Deviation 1.336
|
0.10 Gram per Liter
Standard Deviation 1.557
|
0.37 Gram per Liter
Standard Deviation 1.596
|
0.75 Gram per Liter
Standard Deviation 1.362
|
0.19 Gram per Liter
Standard Deviation 1.314
|
—
|
|
OLE Period: Change From Baseline in Immunoglobulin (Ig) Levels
IgG, Week 288
|
0.18 Gram per Liter
Standard Deviation 1.492
|
0.48 Gram per Liter
Standard Deviation 1.465
|
0.37 Gram per Liter
Standard Deviation 2.203
|
1.01 Gram per Liter
Standard Deviation 1.570
|
0.36 Gram per Liter
Standard Deviation 1.440
|
—
|
|
OLE Period: Change From Baseline in Immunoglobulin (Ig) Levels
Ig M, OLE Baseline (BE period Week 48)
|
-0.18 Gram per Liter
Standard Deviation 0.152
|
-0.10 Gram per Liter
Standard Deviation 0.120
|
-0.09 Gram per Liter
Standard Deviation 0.122
|
-0.05 Gram per Liter
Standard Deviation 0.099
|
-0.28 Gram per Liter
Standard Deviation 0.280
|
—
|
|
OLE Period: Change From Baseline in Immunoglobulin (Ig) Levels
IgM, Week 72
|
-0.19 Gram per Liter
Standard Deviation 0.170
|
-0.11 Gram per Liter
Standard Deviation 0.119
|
-0.10 Gram per Liter
Standard Deviation 0.147
|
-0.07 Gram per Liter
Standard Deviation 0.104
|
-0.34 Gram per Liter
Standard Deviation 0.264
|
—
|
|
OLE Period: Change From Baseline in Immunoglobulin (Ig) Levels
IgM, Week 96
|
-0.23 Gram per Liter
Standard Deviation 0.146
|
-0.13 Gram per Liter
Standard Deviation 0.141
|
-0.09 Gram per Liter
Standard Deviation 0.199
|
-0.08 Gram per Liter
Standard Deviation 0.127
|
-0.35 Gram per Liter
Standard Deviation 0.301
|
—
|
|
OLE Period: Change From Baseline in Immunoglobulin (Ig) Levels
IgM, Week 144
|
-0.28 Gram per Liter
Standard Deviation 0.323
|
-0.14 Gram per Liter
Standard Deviation 0.195
|
-0.17 Gram per Liter
Standard Deviation 0.174
|
-0.11 Gram per Liter
Standard Deviation 0.149
|
-0.40 Gram per Liter
Standard Deviation 0.327
|
—
|
|
OLE Period: Change From Baseline in Immunoglobulin (Ig) Levels
IgM, Week 192
|
-0.28 Gram per Liter
Standard Deviation 0.254
|
-0.16 Gram per Liter
Standard Deviation 0.204
|
-0.19 Gram per Liter
Standard Deviation 0.186
|
-0.18 Gram per Liter
Standard Deviation 0.197
|
-0.46 Gram per Liter
Standard Deviation 0.330
|
—
|
|
OLE Period: Change From Baseline in Immunoglobulin (Ig) Levels
IgM, Week 240
|
-0.29 Gram per Liter
Standard Deviation 0.282
|
-0.20 Gram per Liter
Standard Deviation 0.187
|
-0.19 Gram per Liter
Standard Deviation 0.205
|
-0.16 Gram per Liter
Standard Deviation 0.254
|
-0.53 Gram per Liter
Standard Deviation 0.348
|
—
|
|
OLE Period: Change From Baseline in Immunoglobulin (Ig) Levels
IgM, Week 288
|
-0.29 Gram per Liter
Standard Deviation 0.284
|
-0.11 Gram per Liter
Standard Deviation 0.313
|
-0.15 Gram per Liter
Standard Deviation 0.315
|
-0.17 Gram per Liter
Standard Deviation 0.178
|
-0.39 Gram per Liter
Standard Deviation 0.472
|
—
|
Adverse Events
Placebo (Period 1)
Serious events: 2 serious events
Other events: 14 other events
Deaths: 0 deaths
Placebo Then Evobrutinib 25 mg QD (Period 2)
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Evobrutinib 25 mg QD (Period 1 and Period 2)
Serious events: 2 serious events
Other events: 19 other events
Deaths: 0 deaths
Evobrutinib 75 mg QD (Period 1 and Period 2)
Serious events: 2 serious events
Other events: 19 other events
Deaths: 0 deaths
Evobrutinib 75 mg BID (Period 1 and Period 2)
Serious events: 4 serious events
Other events: 20 other events
Deaths: 0 deaths
Tecfidera (Period 1 and Period 2)
Serious events: 2 serious events
Other events: 30 other events
Deaths: 0 deaths
Placebo + Evobrutinib 25 mg QD (Period 3)
Serious events: 7 serious events
Other events: 30 other events
Deaths: 0 deaths
Evobrutinib 25 mg QD (Period 3)
Serious events: 12 serious events
Other events: 26 other events
Deaths: 1 deaths
Evobrutinib 75 mg QD (Period 3)
Serious events: 8 serious events
Other events: 34 other events
Deaths: 0 deaths
Evobrutinib 75 mg BID (Period 3)
Serious events: 5 serious events
Other events: 31 other events
Deaths: 1 deaths
Tecfidera (Period 3)
Serious events: 10 serious events
Other events: 26 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Placebo (Period 1)
n=54 participants at risk
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
|
Placebo Then Evobrutinib 25 mg QD (Period 2)
n=49 participants at risk
Participants who received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1 received Evobrutinib 25 milligram (mg) orally, once daily (QD) in blinded extension (BE) period from week 25 to week 48.
|
Evobrutinib 25 mg QD (Period 1 and Period 2)
n=52 participants at risk
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period.
|
Evobrutinib 75 mg QD (Period 1 and Period 2)
n=53 participants at risk
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period.
|
Evobrutinib 75 mg BID (Period 1 and Period 2)
n=54 participants at risk
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period.
|
Tecfidera (Period 1 and Period 2)
n=54 participants at risk
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period.
|
Placebo + Evobrutinib 25 mg QD (Period 3)
n=39 participants at risk
Participants who received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1 received Evobrutinib 25 mg orally, QD from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 25 mg QD (Period 3)
n=39 participants at risk
Participants received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg QD (Period 3)
n=42 participants at risk
Participants received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg BID (Period 3)
n=44 participants at risk
Participants received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 3)
n=49 participants at risk
Participants received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
|---|---|---|---|---|---|---|---|---|---|---|---|
|
Nervous system disorders
Restless legs syndrome
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
1.9%
1/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Hepatobiliary disorders
Hepatitis toxic
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
1.9%
1/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
1.9%
1/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.0%
1/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Infections and infestations
Lyme disease
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
1.9%
1/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Injury, poisoning and procedural complications
Overdose
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
1.9%
1/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Injury, poisoning and procedural complications
Lower limb fracture
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.0%
1/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
1.9%
1/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Investigations
Transaminases increased
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
1.9%
1/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
1.9%
1/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Nervous system disorders
Epilepsy
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
1.9%
1/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
1.9%
1/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Injury, poisoning and procedural complications
Lumbar vertebral fracture
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.0%
1/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Infections and infestations
Pneumonia
|
1.9%
1/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
5.1%
2/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm
|
1.9%
1/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Vascular disorders
Peripheral embolism
|
1.9%
1/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Blood and lymphatic system disorders
Microcytic anaemia
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Cardiac disorders
Myocardial ischaemia
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Cardiac disorders
Sinus tachycardia
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Cardiac disorders
Supraventricular tachycardia
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Eye disorders
Keratoconus
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.0%
1/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
General disorders
Pyrexia
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.3%
1/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.4%
1/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.0%
1/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Hepatobiliary disorders
Hepatitis
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.0%
1/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Immune system disorders
Anaphylactic shock
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Infections and infestations
COVID-19 pneumonia
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
4.1%
2/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Infections and infestations
Appendicitis
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.0%
1/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Infections and infestations
Breast abscess
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Infections and infestations
COVID-19
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.4%
1/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Infections and infestations
Cervicitis
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Infections and infestations
Endometritis
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Infections and infestations
Erysipelas
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.3%
1/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Infections and infestations
Escherichia sepsis
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.3%
1/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Infections and infestations
Gastroenteritis norovirus
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Infections and infestations
Pulmonary tuberculosis
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Infections and infestations
Pyelonephritis acute
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.0%
1/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Infections and infestations
Serratia infection
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.0%
1/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Infections and infestations
Tonsillitis
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.3%
1/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.0%
1/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Injury, poisoning and procedural complications
Femoral neck fracture
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.4%
1/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.3%
1/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Injury, poisoning and procedural complications
Fibula fracture
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.0%
1/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Injury, poisoning and procedural complications
Head injury
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Injury, poisoning and procedural complications
Post procedural complication
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.0%
1/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.3%
1/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Injury, poisoning and procedural complications
Sternal fracture
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.3%
1/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Investigations
Lipase increased
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Metabolism and nutrition disorders
Haemochromatosis
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.0%
1/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Musculoskeletal and connective tissue disorders
Osteonecrosis
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
4.8%
2/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Musculoskeletal and connective tissue disorders
Fracture pain
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.4%
1/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.0%
1/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ovarian germ cell teratoma benign
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.4%
1/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Papilloma
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Small cell lung cancer
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.4%
1/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Nervous system disorders
Cerebellar ischaemia
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.3%
1/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Nervous system disorders
Cerebral venous sinus thrombosis
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.0%
1/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Nervous system disorders
Headache
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Nervous system disorders
Ischaemic stroke
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Nervous system disorders
Multiple sclerosis pseudo relapse
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.3%
1/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Nervous system disorders
Vertebrobasilar artery dissection
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.3%
1/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Nervous system disorders
Vertigo CNS origin
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Pregnancy, puerperium and perinatal conditions
Pregnancy
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Psychiatric disorders
Confusional state
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.0%
1/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Psychiatric disorders
Mood disorder due to a general medical condition
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Renal and urinary disorders
Bladder hypertrophy
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Renal and urinary disorders
Tubulointerstitial nephritis
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.3%
1/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Reproductive system and breast disorders
Cervical dysplasia
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Reproductive system and breast disorders
Heavy menstrual bleeding
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Reproductive system and breast disorders
Uterine cervix stenosis
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Respiratory, thoracic and mediastinal disorders
Nasal polyps
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.4%
1/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Vascular disorders
Blood pressure fluctuation
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.4%
1/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
Other adverse events
| Measure |
Placebo (Period 1)
n=54 participants at risk
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
|
Placebo Then Evobrutinib 25 mg QD (Period 2)
n=49 participants at risk
Participants who received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1 received Evobrutinib 25 milligram (mg) orally, once daily (QD) in blinded extension (BE) period from week 25 to week 48.
|
Evobrutinib 25 mg QD (Period 1 and Period 2)
n=52 participants at risk
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period.
|
Evobrutinib 75 mg QD (Period 1 and Period 2)
n=53 participants at risk
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period.
|
Evobrutinib 75 mg BID (Period 1 and Period 2)
n=54 participants at risk
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period.
|
Tecfidera (Period 1 and Period 2)
n=54 participants at risk
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period.
|
Placebo + Evobrutinib 25 mg QD (Period 3)
n=39 participants at risk
Participants who received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1 received Evobrutinib 25 mg orally, QD from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 25 mg QD (Period 3)
n=39 participants at risk
Participants received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg QD (Period 3)
n=42 participants at risk
Participants received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Evobrutinib 75 mg BID (Period 3)
n=44 participants at risk
Participants received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
Tecfidera (Period 3)
n=49 participants at risk
Participants received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
|
|---|---|---|---|---|---|---|---|---|---|---|---|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
5.1%
2/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.4%
1/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.0%
1/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
3.8%
2/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
1.9%
1/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
5.6%
3/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
7.7%
3/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
6.1%
3/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Gastrointestinal disorders
Diarrhoea
|
1.9%
1/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
1.9%
1/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
7.4%
4/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.4%
1/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
6.1%
3/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Infections and infestations
Nasopharyngitis
|
9.3%
5/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.0%
1/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
17.3%
9/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
5.7%
3/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
13.0%
7/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
3.7%
2/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
17.9%
7/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
17.9%
7/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
19.0%
8/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
20.5%
9/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
8.2%
4/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
1.9%
1/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
1.9%
1/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
1.9%
1/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
5.6%
3/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
12.8%
5/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
5.1%
2/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
14.3%
6/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
9.1%
4/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
6.1%
3/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Investigations
Alanine aminotransferase increased
|
5.6%
3/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.0%
1/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
5.8%
3/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
11.3%
6/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
9.3%
5/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
5.6%
3/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
10.2%
5/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Investigations
Lipase increased
|
3.7%
2/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
6.1%
3/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
3.8%
2/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
9.4%
5/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
9.3%
5/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
5.6%
3/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
12.8%
5/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
15.4%
6/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
14.3%
6/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
18.2%
8/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
10.2%
5/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Investigations
Aspartate aminotransferase increased
|
1.9%
1/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
1.9%
1/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
3.8%
2/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
7.4%
4/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
3.7%
2/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Investigations
Blood creatinine increased
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
5.7%
3/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
5.6%
3/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
1.9%
1/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
5.1%
2/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
4.8%
2/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
6.8%
3/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.0%
1/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Investigations
Gamma-glutamyltransferase increased
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
1.9%
1/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
1.9%
1/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
5.6%
3/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
1.9%
1/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
5.1%
2/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.4%
1/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
6.1%
3/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Investigations
Lymphocyte count decreased
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
1.9%
1/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
9.3%
5/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
5.1%
2/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.3%
1/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
4.1%
2/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Investigations
White blood cell count decreased
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
1.9%
1/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
5.6%
3/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
1.9%
1/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
3.8%
2/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
5.7%
3/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
7.4%
4/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
12.8%
5/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
7.7%
3/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.4%
1/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
4.5%
2/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
4.1%
2/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Nervous system disorders
Headache
|
3.7%
2/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
5.8%
3/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
3.8%
2/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
1.9%
1/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
1.9%
1/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
7.7%
3/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
5.1%
2/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
11.9%
5/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
13.6%
6/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
8.2%
4/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Skin and subcutaneous tissue disorders
Erythema
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
13.0%
7/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Vascular disorders
Flushing
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
22.2%
12/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Investigations
Amylase increased
|
5.6%
3/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
6.1%
3/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
5.1%
2/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.4%
1/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.3%
1/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.0%
1/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Infections and infestations
Urinary tract infection
|
5.6%
3/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
3.8%
2/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
1.9%
1/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
17.9%
7/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
12.8%
5/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
16.7%
7/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
11.4%
5/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
6.1%
3/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Infections and infestations
Cystitis
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
6.1%
3/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
1.9%
1/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Blood and lymphatic system disorders
Microcytic anaemia
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
10.3%
4/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.4%
1/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.4%
1/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
6.1%
3/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
General disorders
Asthenia
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
5.1%
2/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
7.1%
3/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.3%
1/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
General disorders
Vaccination site pain
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
5.1%
2/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
4.8%
2/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.0%
1/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Infections and infestations
COVID-19
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
15.4%
6/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
20.5%
8/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
7.1%
3/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
13.6%
6/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
14.3%
7/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Infections and infestations
Pharyngitis
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
7.1%
3/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
4.5%
2/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
4.1%
2/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Infections and infestations
Respiratory tract infection
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
9.5%
4/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.3%
1/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.0%
1/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Infections and infestations
Laryngitis
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
5.1%
2/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Infections and infestations
Vulvovaginal mycotic infection
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
5.1%
2/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Injury, poisoning and procedural complications
Immunisation reaction
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
5.1%
2/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
5.1%
2/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.4%
1/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.3%
1/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
6.1%
3/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
9.1%
4/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
8.2%
4/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Investigations
Weight increased
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
5.1%
2/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.4%
1/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
5.1%
2/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.4%
1/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
12.8%
5/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
21.4%
9/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
6.8%
3/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
5.1%
2/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
10.3%
4/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
7.1%
3/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.3%
1/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
6.1%
3/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
5.1%
2/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.0%
1/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
5.1%
2/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.4%
1/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
4.5%
2/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.0%
1/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Nervous system disorders
Sciatica
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
5.1%
2/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
7.7%
3/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.0%
1/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Nervous system disorders
Balance disorder
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
5.1%
2/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.3%
1/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Nervous system disorders
Muscle spasticity
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
7.1%
3/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
5.1%
2/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
4.8%
2/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
4.1%
2/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Psychiatric disorders
Depressed mood
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
7.1%
3/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.3%
1/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Reproductive system and breast disorders
Menstruation irregular
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
5.1%
2/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.6%
1/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
7.1%
3/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
4.5%
2/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
2.0%
1/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
5.1%
2/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
7.1%
3/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
|
Vascular disorders
Hypertension
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/52 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/53 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/54 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
5.1%
2/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
0.00%
0/39 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
4.8%
2/42 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
4.5%
2/44 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
4.1%
2/49 • Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
|
Additional Information
Communication Center
Merck KGaA, Darmstadt, Germany
Phone: +49-6151-72-5200
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place