Trial Outcomes & Findings for Proof of Concept Study to Assess Activity and Safety of SMT C1100 (Ezutromid) in Boys With Duchenne Muscular Dystrophy (DMD) (NCT NCT02858362)
NCT ID: NCT02858362
Last Updated: 2020-01-02
Results Overview
MRS FF was analysed for vastus lateralis and soleus leg muscles. The endpoints were measured for Cohorts 1 and 2 only. Results for Cohorts 1 and 2 are pooled as specified in the protocol.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
43 participants
Primary outcome timeframe
Baseline, Week 12, Week 24, Week 36 and Week 48
Results posted on
2020-01-02
Participant Flow
Participants were enrolled in 16 sites across the United Kingdom (UK) and United States (US) between the dates of 16 June 2016 (First Patient In) and 11 September 2018 (Last Patient Out). Cohort 1 was conducted in the UK and US, Cohort 2 was conducted in the US only, and Cohort 3 was conducted in the UK only.
Participant milestones
| Measure |
Cohort 1: SMT C1100 Formulation 1
Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.
|
Cohort 2: SMT C1100 Formulation 2
Participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 3: SMT C1100 Formulation 1
Participants in this cohort had previously received SMT C1100, but were not eligible for Cohorts 1 or 2. Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.
|
|---|---|---|---|
|
Overall Study
STARTED
|
30
|
10
|
3
|
|
Overall Study
Did Not Enter Extension Phase
|
1
|
2
|
0
|
|
Overall Study
COMPLETED
|
28
|
9
|
0
|
|
Overall Study
NOT COMPLETED
|
2
|
1
|
3
|
Reasons for withdrawal
| Measure |
Cohort 1: SMT C1100 Formulation 1
Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.
|
Cohort 2: SMT C1100 Formulation 2
Participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 3: SMT C1100 Formulation 1
Participants in this cohort had previously received SMT C1100, but were not eligible for Cohorts 1 or 2. Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.
|
|---|---|---|---|
|
Overall Study
Protocol Violation
|
0
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
0
|
|
Overall Study
Early Study Termination
|
0
|
0
|
3
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
0
|
Baseline Characteristics
Efficacy measurements were planned and performed for Cohorts 1 and 2 only. One participant in Cohort 1 did not have analyzable results for MRS FF vastus lateralis at the baseline visit.
Baseline characteristics by cohort
| Measure |
Cohort 1: SMT C1100 Formulation 1
n=30 Participants
Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.
|
Cohort 2: SMT C1100 Formulation 2
n=10 Participants
Participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 3: SMT C1100 Formulation 1
n=3 Participants
Participants in this cohort had previously received SMT C1100, but were not eligible for Cohorts 1 or 2. Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.
|
Total
n=43 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Customized
Children (2-11 years)
|
30 Participants
n=30 Participants
|
10 Participants
n=10 Participants
|
1 Participants
n=3 Participants
|
41 Participants
n=43 Participants
|
|
Age, Customized
Adolescents (12-17 years)
|
0 Participants
n=30 Participants
|
0 Participants
n=10 Participants
|
2 Participants
n=3 Participants
|
2 Participants
n=43 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=30 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=3 Participants
|
0 Participants
n=43 Participants
|
|
Sex: Female, Male
Male
|
30 Participants
n=30 Participants
|
10 Participants
n=10 Participants
|
3 Participants
n=3 Participants
|
43 Participants
n=43 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=30 Participants
|
2 Participants
n=10 Participants
|
0 Participants
n=3 Participants
|
3 Participants
n=43 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
29 Participants
n=30 Participants
|
8 Participants
n=10 Participants
|
3 Participants
n=3 Participants
|
40 Participants
n=43 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=30 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=3 Participants
|
0 Participants
n=43 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=30 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=3 Participants
|
0 Participants
n=43 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=30 Participants
|
1 Participants
n=10 Participants
|
0 Participants
n=3 Participants
|
2 Participants
n=43 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=30 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=3 Participants
|
0 Participants
n=43 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=30 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=3 Participants
|
0 Participants
n=43 Participants
|
|
Race (NIH/OMB)
White
|
26 Participants
n=30 Participants
|
9 Participants
n=10 Participants
|
3 Participants
n=3 Participants
|
38 Participants
n=43 Participants
|
|
Race (NIH/OMB)
More than one race
|
2 Participants
n=30 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=3 Participants
|
2 Participants
n=43 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=30 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=3 Participants
|
1 Participants
n=43 Participants
|
|
Magnetic Resonance Spectroscopy (MRS) Fat Fraction (FF) Vastus Lateralis
|
13.78 Percentage of fat in the muscle
STANDARD_DEVIATION 13.317 • n=29 Participants • Efficacy measurements were planned and performed for Cohorts 1 and 2 only. One participant in Cohort 1 did not have analyzable results for MRS FF vastus lateralis at the baseline visit.
|
18.36 Percentage of fat in the muscle
STANDARD_DEVIATION 13.664 • n=10 Participants • Efficacy measurements were planned and performed for Cohorts 1 and 2 only. One participant in Cohort 1 did not have analyzable results for MRS FF vastus lateralis at the baseline visit.
|
—
|
14.95 Percentage of fat in the muscle
STANDARD_DEVIATION 13.379 • n=39 Participants • Efficacy measurements were planned and performed for Cohorts 1 and 2 only. One participant in Cohort 1 did not have analyzable results for MRS FF vastus lateralis at the baseline visit.
|
|
Magnetic Resonance Spectroscopy (MRS) Fat Fraction (FF) Soleus
|
8.57 Percentage of fat in the muscle
STANDARD_DEVIATION 8.240 • n=30 Participants • Efficacy measurements were planned and performed for Cohorts 1 and 2 only.
|
10.79 Percentage of fat in the muscle
STANDARD_DEVIATION 9.996 • n=10 Participants • Efficacy measurements were planned and performed for Cohorts 1 and 2 only.
|
—
|
9.12 Percentage of fat in the muscle
STANDARD_DEVIATION 8.631 • n=40 Participants • Efficacy measurements were planned and performed for Cohorts 1 and 2 only.
|
|
Magnetic Resonance Spectroscopy (MRS) Water Transverse Relaxation Time (WTRT) Vastus Lateralis
|
32.24 Milliseconds
STANDARD_DEVIATION 1.980 • n=29 Participants • Efficacy measurements were planned and performed for Cohorts 1 and 2 only. One participant in Cohort 1 did not have analyzable results for MRS WTRT vastus lateralis at the baseline visit.
|
32.17 Milliseconds
STANDARD_DEVIATION 2.146 • n=10 Participants • Efficacy measurements were planned and performed for Cohorts 1 and 2 only. One participant in Cohort 1 did not have analyzable results for MRS WTRT vastus lateralis at the baseline visit.
|
—
|
32.23 Milliseconds
STANDARD_DEVIATION 1.995 • n=39 Participants • Efficacy measurements were planned and performed for Cohorts 1 and 2 only. One participant in Cohort 1 did not have analyzable results for MRS WTRT vastus lateralis at the baseline visit.
|
|
Magnetic Resonance Spectroscopy (MRS) Water Transverse Relaxation Time (WTRT) Soleus
|
31.88 Milliseconds
STANDARD_DEVIATION 1.936 • n=30 Participants • Efficacy measurements were planned and performed for Cohorts 1 and 2 only.
|
31.87 Milliseconds
STANDARD_DEVIATION 1.988 • n=10 Participants • Efficacy measurements were planned and performed for Cohorts 1 and 2 only.
|
—
|
31.88 Milliseconds
STANDARD_DEVIATION 1.923 • n=40 Participants • Efficacy measurements were planned and performed for Cohorts 1 and 2 only.
|
|
Development Heavy Chain Myosin (MHCd) Expression in Muscle Fibres
|
12.185 Percent of muscle fibres expressing MHCd
STANDARD_DEVIATION 3.8454 • n=29 Participants • Efficacy measurements were planned and performed for Cohorts 1 and 2 only. One participant in Cohort 1 did not have analyzable results for MHCd expression at the baseline visit.
|
11.587 Percent of muscle fibres expressing MHCd
STANDARD_DEVIATION 4.1344 • n=10 Participants • Efficacy measurements were planned and performed for Cohorts 1 and 2 only. One participant in Cohort 1 did not have analyzable results for MHCd expression at the baseline visit.
|
—
|
12.032 Percent of muscle fibres expressing MHCd
STANDARD_DEVIATION 3.8748 • n=39 Participants • Efficacy measurements were planned and performed for Cohorts 1 and 2 only. One participant in Cohort 1 did not have analyzable results for MHCd expression at the baseline visit.
|
|
Muscle Fibre Diameter
|
43.662 Micrometer
STANDARD_DEVIATION 5.3837 • n=29 Participants • Efficacy measurements were planned and performed for Cohorts 1 and 2 only. One participant in Cohort 1 did not have analyzable results for muscle fibre diameter at the baseline visit.
|
42.086 Micrometer
STANDARD_DEVIATION 6.1878 • n=10 Participants • Efficacy measurements were planned and performed for Cohorts 1 and 2 only. One participant in Cohort 1 did not have analyzable results for muscle fibre diameter at the baseline visit.
|
—
|
43.258 Micrometer
STANDARD_DEVIATION 5.5598 • n=39 Participants • Efficacy measurements were planned and performed for Cohorts 1 and 2 only. One participant in Cohort 1 did not have analyzable results for muscle fibre diameter at the baseline visit.
|
|
Utrophin Intensity
|
0.368 Arbitrary Units
STANDARD_DEVIATION 0.0480 • n=30 Participants • Efficacy measurements were planned and performed for Cohorts 1 and 2 only. One participant in Cohort 2 did not have analyzable results for utrophin expression at the baseline visit.
|
0.349 Arbitrary Units
STANDARD_DEVIATION 0.0507 • n=9 Participants • Efficacy measurements were planned and performed for Cohorts 1 and 2 only. One participant in Cohort 2 did not have analyzable results for utrophin expression at the baseline visit.
|
—
|
0.364 Arbitrary Units
STANDARD_DEVIATION 0.0486 • n=39 Participants • Efficacy measurements were planned and performed for Cohorts 1 and 2 only. One participant in Cohort 2 did not have analyzable results for utrophin expression at the baseline visit.
|
PRIMARY outcome
Timeframe: Baseline, Week 12, Week 24, Week 36 and Week 48Population: All participants who received at least one dose of study medication and had at least one assessment of the endpoint (which could be their baseline assessment).
MRS FF was analysed for vastus lateralis and soleus leg muscles. The endpoints were measured for Cohorts 1 and 2 only. Results for Cohorts 1 and 2 are pooled as specified in the protocol.
Outcome measures
| Measure |
Cohorts 1 and 2: SMT C1100
n=40 Participants
Cohort 1 participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks. Cohort 2 participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 2: SMT C1100 Formulation 2
Participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 3: SMT C1100 Formulation 1
Participants in this cohort had previously received SMT C1100, but were not eligible for Cohorts 1 or 2. Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.
|
|---|---|---|---|
|
Change From Baseline in Magnetic Resonance Spectroscopy (MRS) Fat Fraction (FF) for Leg Muscles
Vastus Lateralis: Week 12 Change from Baseline
|
1.779 Percentage of fat in the muscle
Interval 0.939 to 2.62
|
—
|
—
|
|
Change From Baseline in Magnetic Resonance Spectroscopy (MRS) Fat Fraction (FF) for Leg Muscles
Vastus Lateralis: Week 24 Change from Baseline
|
3.914 Percentage of fat in the muscle
Interval 2.695 to 5.132
|
—
|
—
|
|
Change From Baseline in Magnetic Resonance Spectroscopy (MRS) Fat Fraction (FF) for Leg Muscles
Vastus Lateralis: Week 36 Change from Baseline
|
5.238 Percentage of fat in the muscle
Interval 3.563 to 6.913
|
—
|
—
|
|
Change From Baseline in Magnetic Resonance Spectroscopy (MRS) Fat Fraction (FF) for Leg Muscles
Vastus Lateralis: Week 48 Change from Baseline
|
7.142 Percentage of fat in the muscle
Interval 4.866 to 9.417
|
—
|
—
|
|
Change From Baseline in Magnetic Resonance Spectroscopy (MRS) Fat Fraction (FF) for Leg Muscles
Soleus: Week 12 Change from Baseline
|
0.615 Percentage of fat in the muscle
Interval 0.068 to 1.162
|
—
|
—
|
|
Change From Baseline in Magnetic Resonance Spectroscopy (MRS) Fat Fraction (FF) for Leg Muscles
Soleus: Week 24 Change from Baseline
|
1.108 Percentage of fat in the muscle
Interval 0.35 to 1.865
|
—
|
—
|
|
Change From Baseline in Magnetic Resonance Spectroscopy (MRS) Fat Fraction (FF) for Leg Muscles
Soleus: Week 36 Change from Baseline
|
2.384 Percentage of fat in the muscle
Interval 1.287 to 3.481
|
—
|
—
|
|
Change From Baseline in Magnetic Resonance Spectroscopy (MRS) Fat Fraction (FF) for Leg Muscles
Soleus: Week 48 Change from Baseline
|
2.584 Percentage of fat in the muscle
Interval 1.258 to 3.909
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Week 12, Week 24, Week 36 and Week 48Population: All participants who received at least one dose of study medication and had at least one assessment of the endpoint (which could be their baseline assessment).
MRS WTRT was analysed for the vastus lateralis and soleus leg muscles. The endpoints were measured for Cohorts 1 and 2 only. Results for Cohorts 1 and 2 are pooled as specified in the protocol.
Outcome measures
| Measure |
Cohorts 1 and 2: SMT C1100
n=40 Participants
Cohort 1 participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks. Cohort 2 participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 2: SMT C1100 Formulation 2
Participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 3: SMT C1100 Formulation 1
Participants in this cohort had previously received SMT C1100, but were not eligible for Cohorts 1 or 2. Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.
|
|---|---|---|---|
|
Change From Baseline for Magnetic Resonance Spectroscopy (MRS) Water Transverse Relaxation Time (WTRT) for Leg Muscles
Vastus Lateralis: Week 12 Change from Baseline
|
-0.559 Milliseconds
Interval -1.19 to 0.072
|
—
|
—
|
|
Change From Baseline for Magnetic Resonance Spectroscopy (MRS) Water Transverse Relaxation Time (WTRT) for Leg Muscles
Vastus Lateralis: Week 24 Change from Baseline
|
-0.486 Milliseconds
Interval -1.193 to 0.221
|
—
|
—
|
|
Change From Baseline for Magnetic Resonance Spectroscopy (MRS) Water Transverse Relaxation Time (WTRT) for Leg Muscles
Vastus Lateralis: Week 36 Change from Baseline
|
-0.849 Milliseconds
Interval -1.454 to -0.244
|
—
|
—
|
|
Change From Baseline for Magnetic Resonance Spectroscopy (MRS) Water Transverse Relaxation Time (WTRT) for Leg Muscles
Vastus Lateralis: Week 48 Change from Baseline
|
-0.822 Milliseconds
Interval -1.673 to 0.028
|
—
|
—
|
|
Change From Baseline for Magnetic Resonance Spectroscopy (MRS) Water Transverse Relaxation Time (WTRT) for Leg Muscles
Soleus: Week 12 Change from Baseline
|
-0.655 Milliseconds
Interval -1.209 to -0.101
|
—
|
—
|
|
Change From Baseline for Magnetic Resonance Spectroscopy (MRS) Water Transverse Relaxation Time (WTRT) for Leg Muscles
Soleus: Week 24 Change from Baseline
|
-0.861 Milliseconds
Interval -1.44 to -0.281
|
—
|
—
|
|
Change From Baseline for Magnetic Resonance Spectroscopy (MRS) Water Transverse Relaxation Time (WTRT) for Leg Muscles
Soleus: Week 36 Change from Baseline
|
-0.447 Milliseconds
Interval -1.085 to 0.19
|
—
|
—
|
|
Change From Baseline for Magnetic Resonance Spectroscopy (MRS) Water Transverse Relaxation Time (WTRT) for Leg Muscles
Soleus: Week 48 Change from Baseline
|
-0.119 Milliseconds
Interval -0.747 to 0.509
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose at Weeks 1, 4, 8, 12, 24, 36 and 48Population: All participants in Cohorts 1 or 2 who received at least one dose of study medication and had at least one concentration measurement (which could be below the limit of quantification). No evaluable data was collected from Cohort 3 participants due to early study termination.
Pharmacokinetic analysis is presented by cohort due to the use of different formulations. The median pre-dose concentration was derived for each participant and then summarized across participants.
Outcome measures
| Measure |
Cohorts 1 and 2: SMT C1100
n=30 Participants
Cohort 1 participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks. Cohort 2 participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 2: SMT C1100 Formulation 2
n=10 Participants
Participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 3: SMT C1100 Formulation 1
Participants in this cohort had previously received SMT C1100, but were not eligible for Cohorts 1 or 2. Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.
|
|---|---|---|---|
|
Observed Trough Plasma Concentration (Ctrough) for SMT C1100, Dihydrodiol 1 (DHD1) and Dihydrodiol III (DHD 3)
DHD 1
|
155 ng/mL
Geometric Coefficient of Variation 61
|
365 ng/mL
Geometric Coefficient of Variation 55
|
—
|
|
Observed Trough Plasma Concentration (Ctrough) for SMT C1100, Dihydrodiol 1 (DHD1) and Dihydrodiol III (DHD 3)
SMT C1100
|
17 ng/mL
Geometric Coefficient of Variation 140
|
80 ng/mL
Geometric Coefficient of Variation 83.1
|
—
|
|
Observed Trough Plasma Concentration (Ctrough) for SMT C1100, Dihydrodiol 1 (DHD1) and Dihydrodiol III (DHD 3)
DHD 3
|
484 ng/mL
Geometric Coefficient of Variation 67
|
1206 ng/mL
Geometric Coefficient of Variation 68
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 3 to 10 hours post-dose at Weeks 1, 4, 8, 12, 24, 36 and 48Population: All participants in Cohorts 1 or 2 who received at least one dose of study medication and had at least one concentration measurement (which could be below the limit of quantification). No evaluable data was collected from Cohort 3 participants due to early study termination.
Pharmacokinetic analysis is presented by cohort due to the use of different formulations.
Outcome measures
| Measure |
Cohorts 1 and 2: SMT C1100
n=30 Participants
Cohort 1 participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks. Cohort 2 participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 2: SMT C1100 Formulation 2
n=10 Participants
Participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 3: SMT C1100 Formulation 1
Participants in this cohort had previously received SMT C1100, but were not eligible for Cohorts 1 or 2. Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.
|
|---|---|---|---|
|
Simulated Maximum Plasma Concentration (Cmax) for SMT C1100, Dihydrodiol 1 (DHD1) and Dihydrodiol III (DHD 3)
SMT C1100
|
135 ng/mL
Interval 97.0 to 185.0
|
415 ng/mL
Interval 303.0 to 640.0
|
—
|
|
Simulated Maximum Plasma Concentration (Cmax) for SMT C1100, Dihydrodiol 1 (DHD1) and Dihydrodiol III (DHD 3)
DHD 1
|
1897 ng/mL
Interval 1690.0 to 2158.0
|
2829 ng/mL
Interval 2597.0 to 3072.0
|
—
|
|
Simulated Maximum Plasma Concentration (Cmax) for SMT C1100, Dihydrodiol 1 (DHD1) and Dihydrodiol III (DHD 3)
DHD 3
|
3162 ng/mL
Interval 2392.0 to 4053.0
|
4652 ng/mL
Interval 3802.0 to 6116.0
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 3 to 10 hours post-dose at Weeks 1, 4, 8, 12, 24, 36 and 48Population: All participants in Cohorts 1 or 2 who received at least one dose of study medication and had at least one concentration measurement (which could be below the limit of quantification). No evaluable data was collected from Cohort 3 participants due to early study termination.
Pharmacokinetic analysis is presented by cohort due to the use of different formulations.
Outcome measures
| Measure |
Cohorts 1 and 2: SMT C1100
n=30 Participants
Cohort 1 participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks. Cohort 2 participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 2: SMT C1100 Formulation 2
n=10 Participants
Participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 3: SMT C1100 Formulation 1
Participants in this cohort had previously received SMT C1100, but were not eligible for Cohorts 1 or 2. Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.
|
|---|---|---|---|
|
Simulated Average Plasma Concentration (Cav) for SMT C1100, Dihydrodiol 1 (DHD1) and Dihydrodiol III (DHD 3)
SMT C1100
|
54 ng/mL
Interval 37.0 to 82.0
|
163 ng/mL
Interval 114.0 to 272.0
|
—
|
|
Simulated Average Plasma Concentration (Cav) for SMT C1100, Dihydrodiol 1 (DHD1) and Dihydrodiol III (DHD 3)
DHD 1
|
742 ng/mL
Interval 685.0 to 836.0
|
1109 ng/mL
Interval 1028.0 to 1217.0
|
—
|
|
Simulated Average Plasma Concentration (Cav) for SMT C1100, Dihydrodiol 1 (DHD1) and Dihydrodiol III (DHD 3)
DHD 3
|
1359 ng/mL
Interval 972.0 to 1790.0
|
2211 ng/mL
Interval 1707.0 to 3066.0
|
—
|
PRIMARY outcome
Timeframe: Day 1 to a maximum of Week 96Population: All participants who received at least one dose of study medication.
An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. A TEAE is defined as any event not present before exposure to study drug or any event already present that worsens in either intensity or frequency after exposure to study drug.
Outcome measures
| Measure |
Cohorts 1 and 2: SMT C1100
n=30 Participants
Cohort 1 participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks. Cohort 2 participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 2: SMT C1100 Formulation 2
n=10 Participants
Participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 3: SMT C1100 Formulation 1
n=3 Participants
Participants in this cohort had previously received SMT C1100, but were not eligible for Cohorts 1 or 2. Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.
|
|---|---|---|---|
|
Number of Participants Reporting One or More Treatment-Emergent Adverse Events (TEAEs)
|
30 Participants
|
10 Participants
|
3 Participants
|
SECONDARY outcome
Timeframe: Baseline, Week 24 and Week 48Population: All participants who received at least one dose of study medication and had at least one assessment of the endpoint (which could be their baseline assessment). For the summaries of changes from baseline only those participants in this population who had measurements at both baseline and the relevant post-baseline visit were included.
A maximum of two muscle biopsies were taken, one at baseline and the other at Week 24 or Week 48. Utrophin intensity was analyzed using a semiautomated quantitative assay on the biopsy samples. A positive change from baseline represents an increase in utrophin expression, no change from baseline represents maintenance of utrophin expression and a negative change from baseline represents a reduction in utrophin expression. The endpoint was measured for Cohorts 1 and 2 only. Results for Cohorts 1 and 2 are pooled as specified in the protocol.
Outcome measures
| Measure |
Cohorts 1 and 2: SMT C1100
n=37 Participants
Cohort 1 participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks. Cohort 2 participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 2: SMT C1100 Formulation 2
Participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 3: SMT C1100 Formulation 1
Participants in this cohort had previously received SMT C1100, but were not eligible for Cohorts 1 or 2. Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.
|
|---|---|---|---|
|
Change From Baseline in Utrophin Intensity
Change from baseline at Week 24
|
0.0232 Arbitrary units
Standard Deviation 0.0601
|
—
|
—
|
|
Change From Baseline in Utrophin Intensity
Change from baseline at Week 48
|
0.0114 Arbitrary units
Standard Deviation 0.0574
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 24 and Week 48Population: All participants who received at least one dose of study medication and had at least one assessment of the endpoint (which could be their baseline assessment). For the summaries of changes from baseline only those participants in this population who had measurements at both baseline and the relevant post-baseline visit were included.
A maximum of two muscle biopsies were taken, one at baseline and the other at Week 24 or Week 48. MHCd expression was analyzed using a semiautomated quantitative assay on the biopsy samples. A positive change from baseline represents an increase in MHCd expression, no change from baseline represents maintenance of MHCd expression and a negative change from baseline represents a reduction in MHCd expression. The endpoint was measured for Cohorts 1 and 2 only. Results for Cohorts 1 and 2 are pooled as specified in the protocol.
Outcome measures
| Measure |
Cohorts 1 and 2: SMT C1100
n=38 Participants
Cohort 1 participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks. Cohort 2 participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 2: SMT C1100 Formulation 2
Participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 3: SMT C1100 Formulation 1
Participants in this cohort had previously received SMT C1100, but were not eligible for Cohorts 1 or 2. Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.
|
|---|---|---|---|
|
Change From Baseline in Developmental Heavy Chain Myosin (MHCd) Expression
Change from baseline at Week 24
|
-2.3166 Percent of muscle fibres expressing MHCd
Standard Deviation 3.9180
|
—
|
—
|
|
Change From Baseline in Developmental Heavy Chain Myosin (MHCd) Expression
Change from baseline at Week 48
|
1.2248 Percent of muscle fibres expressing MHCd
Standard Deviation 4.2596
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 24 and Week 48Population: All participants who received at least one dose of study medication and had at least one assessment of the endpoint (which could be their baseline assessment). For the summaries of changes from baseline only those participants in this population who had measurements at both baseline and the relevant post-baseline visit were included.
A maximum of two muscle biopsies were taken, one at baseline and the other at Week 24 or Week 48. Muscle fibre diameter was analyzed using a semiautomated quantitative assay on the biopsy samples. The endpoint was measured for Cohorts 1 and 2 only. Results for Cohorts 1 and 2 are pooled as specified in the protocol.
Outcome measures
| Measure |
Cohorts 1 and 2: SMT C1100
n=38 Participants
Cohort 1 participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks. Cohort 2 participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 2: SMT C1100 Formulation 2
Participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 3: SMT C1100 Formulation 1
Participants in this cohort had previously received SMT C1100, but were not eligible for Cohorts 1 or 2. Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.
|
|---|---|---|---|
|
Change From Baseline in Muscle Fibre Diameter
Change from baseline at Week 24
|
-1.9205 Micrometers (μm)
Standard Deviation 4.7250
|
—
|
—
|
|
Change From Baseline in Muscle Fibre Diameter
Change from baseline at Week 48
|
2.0636 Micrometers (μm)
Standard Deviation 4.1267
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 12, Week 24, Week 36 and Week 48Population: All participants who received at least one dose of study medication. No evaluable data was collected from Cohort 3 participants due to early study termination.
Results for Cohorts 1, 2 and 3 are pooled as specified in the protocol.
Outcome measures
| Measure |
Cohorts 1 and 2: SMT C1100
n=38 Participants
Cohort 1 participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks. Cohort 2 participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 2: SMT C1100 Formulation 2
Participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 3: SMT C1100 Formulation 1
Participants in this cohort had previously received SMT C1100, but were not eligible for Cohorts 1 or 2. Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.
|
|---|---|---|---|
|
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)
Week 12 Change from Baseline
|
-3.4 Percentage of FEV1
Standard Deviation 20.86
|
—
|
—
|
|
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)
Week 24 Change from Baseline
|
-2.5 Percentage of FEV1
Standard Deviation 24.88
|
—
|
—
|
|
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)
Week 36 Change from Baseline
|
-7.3 Percentage of FEV1
Standard Deviation 24.26
|
—
|
—
|
|
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)
Week 48 Change from Baseline
|
2.0 Percentage of FEV1
Standard Deviation 18.31
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 12, Week 24, Week 36 and Week 48Population: All participants who received at least one dose of study medication. No evaluable data was collected from Cohort 3 participants due to early study termination.
Results for Cohorts 1, 2 and 3 are pooled as specified in the protocol.
Outcome measures
| Measure |
Cohorts 1 and 2: SMT C1100
n=39 Participants
Cohort 1 participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks. Cohort 2 participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 2: SMT C1100 Formulation 2
Participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 3: SMT C1100 Formulation 1
Participants in this cohort had previously received SMT C1100, but were not eligible for Cohorts 1 or 2. Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.
|
|---|---|---|---|
|
Change From Baseline in Forced Vital Capacity (FVC)
Week 12 Change from Baseline
|
-4.0 Percentage of FVC
Standard Deviation 16.31
|
—
|
—
|
|
Change From Baseline in Forced Vital Capacity (FVC)
Week 24 Change from Baseline
|
1.1 Percentage of FVC
Standard Deviation 16.75
|
—
|
—
|
|
Change From Baseline in Forced Vital Capacity (FVC)
Week 36 Change from Baseline
|
-3.4 Percentage of FVC
Standard Deviation 18.39
|
—
|
—
|
|
Change From Baseline in Forced Vital Capacity (FVC)
Week 48 Change from Baseline
|
1.1 Percentage of FVC
Standard Deviation 16.29
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 12, Week 24, Week 36 and Week 48Population: All participants who received at least one dose of study medication. No evaluable data was collected from Cohort 3 participants due to early study termination.
Results for Cohorts 1, 2 and 3 are pooled as specified in the protocol.
Outcome measures
| Measure |
Cohorts 1 and 2: SMT C1100
n=36 Participants
Cohort 1 participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks. Cohort 2 participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 2: SMT C1100 Formulation 2
Participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 3: SMT C1100 Formulation 1
Participants in this cohort had previously received SMT C1100, but were not eligible for Cohorts 1 or 2. Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.
|
|---|---|---|---|
|
Change From Baseline in Maximum Inspiratory Pressure (MIP)
Week 12 Change from Baseline
|
3.6 cm H2O
Standard Deviation 32.68
|
—
|
—
|
|
Change From Baseline in Maximum Inspiratory Pressure (MIP)
Week 24 Change from Baseline
|
3.0 cm H2O
Standard Deviation 25.00
|
—
|
—
|
|
Change From Baseline in Maximum Inspiratory Pressure (MIP)
Week 36 Change from Baseline
|
9.0 cm H2O
Standard Deviation 18.40
|
—
|
—
|
|
Change From Baseline in Maximum Inspiratory Pressure (MIP)
Week 48 Change from Baseline
|
8.7 cm H2O
Standard Deviation 20.30
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 12, Week 24, Week 36 and Week 48Population: All participants who received at least one dose of study medication. No evaluable data was collected from Cohort 3 participants due to early study termination.
Results for Cohorts 1, 2 and 3 are pooled as specified in the protocol.
Outcome measures
| Measure |
Cohorts 1 and 2: SMT C1100
n=35 Participants
Cohort 1 participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks. Cohort 2 participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 2: SMT C1100 Formulation 2
Participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 3: SMT C1100 Formulation 1
Participants in this cohort had previously received SMT C1100, but were not eligible for Cohorts 1 or 2. Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.
|
|---|---|---|---|
|
Change From Baseline in Maximum Expiratory Pressure (MEP)
Week 12 Change from Baseline
|
1.8 cm H2O
Standard Deviation 17.97
|
—
|
—
|
|
Change From Baseline in Maximum Expiratory Pressure (MEP)
Week 24 Change from Baseline
|
2.5 cm H2O
Standard Deviation 22.95
|
—
|
—
|
|
Change From Baseline in Maximum Expiratory Pressure (MEP)
Week 36 Change from Baseline
|
-1.0 cm H2O
Standard Deviation 23.53
|
—
|
—
|
|
Change From Baseline in Maximum Expiratory Pressure (MEP)
Week 48 Change from Baseline
|
6.5 cm H2O
Standard Deviation 20.09
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 12, Week 24, Week 36 and Week 48Population: All participants who received at least one dose of study medication. No evaluable data was collected from Cohort 3 participants due to early study termination.
Results for Cohorts 1, 2 and 3 are pooled as specified in the protocol.
Outcome measures
| Measure |
Cohorts 1 and 2: SMT C1100
n=34 Participants
Cohort 1 participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks. Cohort 2 participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 2: SMT C1100 Formulation 2
Participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 3: SMT C1100 Formulation 1
Participants in this cohort had previously received SMT C1100, but were not eligible for Cohorts 1 or 2. Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.
|
|---|---|---|---|
|
Change From Baseline in Peak Expiratory Flow (PEF)
Week 12 Change from Baseline
|
0.5 Percentage of PEF
Standard Deviation 20.65
|
—
|
—
|
|
Change From Baseline in Peak Expiratory Flow (PEF)
Week 24 Change from Baseline
|
-0.1 Percentage of PEF
Standard Deviation 23.86
|
—
|
—
|
|
Change From Baseline in Peak Expiratory Flow (PEF)
Week 36 Change from Baseline
|
-0.4 Percentage of PEF
Standard Deviation 23.46
|
—
|
—
|
|
Change From Baseline in Peak Expiratory Flow (PEF)
Week 48 Change from Baseline
|
9.6 Percentage of PEF
Standard Deviation 30.09
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 12, Week 24, Week 36 and Week 48Population: No evaluable data was collected from Cohort 3 participants due to early study termination.
Analysis of PCF was planned for Cohort 3 only.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, Week 12, Week 24, Week 36 and Week 48Population: No evaluable data was collected from Cohort 3 participants due to early study termination.
Analysis of SNIP was planned for Cohort 3 only.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline to Week 48Population: All participants who received at least one dose of study medication. No evaluable data was collected from Cohort 3 participants due to early study termination.
Systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse will be disclosed with the following categories: * All values within 20% of change from baseline (\< 20% change). * At least one value ≥ 20% reduction from baseline, but no increases ≥ 20% from baseline (≥ 20% reduction and no \< 20% increase). * At least one value ≥ 20% increase from baseline, but no reductions ≥ 20% from baseline (≥ 20% Increase and no \< 20% reduction). * At least one value ≥ 20% reduction from baseline and at least one value ≥ 20% increase from baseline (≥ 20% reduction and ≥ 20% increase). Results for Cohorts 1, 2 and 3 are pooled as specified in the protocol.
Outcome measures
| Measure |
Cohorts 1 and 2: SMT C1100
n=40 Participants
Cohort 1 participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks. Cohort 2 participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 2: SMT C1100 Formulation 2
Participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 3: SMT C1100 Formulation 1
Participants in this cohort had previously received SMT C1100, but were not eligible for Cohorts 1 or 2. Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.
|
|---|---|---|---|
|
Number of Participants That Experienced a Clinically Significant Change in Vital Signs Measurements
SBP · < 20% change
|
28 Participants
|
—
|
—
|
|
Number of Participants That Experienced a Clinically Significant Change in Vital Signs Measurements
SBP · ≥ 20% reduction and no < 20% increase
|
2 Participants
|
—
|
—
|
|
Number of Participants That Experienced a Clinically Significant Change in Vital Signs Measurements
SBP · ≥ 20% Increase and no < 20% reduction
|
10 Participants
|
—
|
—
|
|
Number of Participants That Experienced a Clinically Significant Change in Vital Signs Measurements
SBP · ≥ 20% reduction and ≥ 20% increase
|
0 Participants
|
—
|
—
|
|
Number of Participants That Experienced a Clinically Significant Change in Vital Signs Measurements
DBP · < 20% change
|
19 Participants
|
—
|
—
|
|
Number of Participants That Experienced a Clinically Significant Change in Vital Signs Measurements
DBP · ≥ 20% reduction and no < 20% increase
|
11 Participants
|
—
|
—
|
|
Number of Participants That Experienced a Clinically Significant Change in Vital Signs Measurements
DBP · ≥ 20% Increase and no < 20% reduction
|
10 Participants
|
—
|
—
|
|
Number of Participants That Experienced a Clinically Significant Change in Vital Signs Measurements
DBP · ≥ 20% reduction and ≥ 20% increase
|
0 Participants
|
—
|
—
|
|
Number of Participants That Experienced a Clinically Significant Change in Vital Signs Measurements
Pulse · < 20% change
|
21 Participants
|
—
|
—
|
|
Number of Participants That Experienced a Clinically Significant Change in Vital Signs Measurements
Pulse · ≥ 20% reduction and no < 20% increase
|
6 Participants
|
—
|
—
|
|
Number of Participants That Experienced a Clinically Significant Change in Vital Signs Measurements
Pulse · ≥ 20% Increase and no < 20% reduction
|
13 Participants
|
—
|
—
|
|
Number of Participants That Experienced a Clinically Significant Change in Vital Signs Measurements
Pulse · ≥ 20% reduction and ≥ 20% increase
|
0 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 to Week 48Population: All participants who received at least one dose of study medication.
Examinations included: ear, nose and throat, cardiovascular system, pulmonary system, skin, abdomen, neurological system, height and weight. Results for Cohorts 1, 2 and 3 are pooled as specified in the protocol.
Outcome measures
| Measure |
Cohorts 1 and 2: SMT C1100
n=43 Participants
Cohort 1 participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks. Cohort 2 participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 2: SMT C1100 Formulation 2
Participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 3: SMT C1100 Formulation 1
Participants in this cohort had previously received SMT C1100, but were not eligible for Cohorts 1 or 2. Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.
|
|---|---|---|---|
|
Number of Participants That Experienced a Clinically Significant in Physical Examination Result
|
1 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline to Week 48Population: All participants who received at least one dose of study medication. No evaluable data was collected from Cohort 3 participants due to early study termination.
PR interval (PRI), heart rate (HR), QTcF and increase from baseline in QTcF (IQTcF) were summarized categorically. Results for Cohorts 1, 2 and 3 are pooled as specified in the protocol.
Outcome measures
| Measure |
Cohorts 1 and 2: SMT C1100
n=40 Participants
Cohort 1 participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks. Cohort 2 participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 2: SMT C1100 Formulation 2
Participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 3: SMT C1100 Formulation 1
Participants in this cohort had previously received SMT C1100, but were not eligible for Cohorts 1 or 2. Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.
|
|---|---|---|---|
|
Number of Participants That Experienced a Potentially Clinically Significant Electrocardiogram Measurements
PRI: <170 ms
|
37 Participants
|
—
|
—
|
|
Number of Participants That Experienced a Potentially Clinically Significant Electrocardiogram Measurements
PRI: ≥170 ms
|
3 Participants
|
—
|
—
|
|
Number of Participants That Experienced a Potentially Clinically Significant Electrocardiogram Measurements
PRI: < 20% change
|
35 Participants
|
—
|
—
|
|
Number of Participants That Experienced a Potentially Clinically Significant Electrocardiogram Measurements
PRI: ≥ 20% reduction and no < 20% increase
|
2 Participants
|
—
|
—
|
|
Number of Participants That Experienced a Potentially Clinically Significant Electrocardiogram Measurements
PRI: ≥ 20% increase and no < 20% reduction
|
3 Participants
|
—
|
—
|
|
Number of Participants That Experienced a Potentially Clinically Significant Electrocardiogram Measurements
PRI: ≥ 20% reduction and ≥ 20% increase
|
0 Participants
|
—
|
—
|
|
Number of Participants That Experienced a Potentially Clinically Significant Electrocardiogram Measurements
HR: < 20% change
|
7 Participants
|
—
|
—
|
|
Number of Participants That Experienced a Potentially Clinically Significant Electrocardiogram Measurements
HR: ≥ 20% reduction and no < 20% increase
|
6 Participants
|
—
|
—
|
|
Number of Participants That Experienced a Potentially Clinically Significant Electrocardiogram Measurements
HR: ≥ 20% increase and no < 20% reduction
|
22 Participants
|
—
|
—
|
|
Number of Participants That Experienced a Potentially Clinically Significant Electrocardiogram Measurements
HR: ≥ 20% reduction and ≥ 20% increase
|
5 Participants
|
—
|
—
|
|
Number of Participants That Experienced a Potentially Clinically Significant Electrocardiogram Measurements
QTcF: < 450 ms
|
40 Participants
|
—
|
—
|
|
Number of Participants That Experienced a Potentially Clinically Significant Electrocardiogram Measurements
QTcF: ≥ 450 ms
|
0 Participants
|
—
|
—
|
|
Number of Participants That Experienced a Potentially Clinically Significant Electrocardiogram Measurements
IQTcF: < 30 ms
|
32 Participants
|
—
|
—
|
|
Number of Participants That Experienced a Potentially Clinically Significant Electrocardiogram Measurements
IQTcF: 30 - 59 ms
|
8 Participants
|
—
|
—
|
|
Number of Participants That Experienced a Potentially Clinically Significant Electrocardiogram Measurements
IQTcF: >= 60 ms
|
0 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 24 and Week 48Population: All participants who received at least one dose of study medication. No evaluable data was collected from Cohort 3 participants due to early study termination.
Participants were at rest in a supine position for 10 minutes before the measurements were performed. Results for Cohorts 1, 2 and 3 are pooled as specified in the protocol.
Outcome measures
| Measure |
Cohorts 1 and 2: SMT C1100
n=40 Participants
Cohort 1 participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks. Cohort 2 participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 2: SMT C1100 Formulation 2
Participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 3: SMT C1100 Formulation 1
Participants in this cohort had previously received SMT C1100, but were not eligible for Cohorts 1 or 2. Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.
|
|---|---|---|---|
|
Number of Participants That Experienced a Potentially Clinically Significant Echocardiogram Measurement
Baseline · Normal
|
38 Participants
|
—
|
—
|
|
Number of Participants That Experienced a Potentially Clinically Significant Echocardiogram Measurement
Baseline · Abnormal, Not Clinically Significant
|
2 Participants
|
—
|
—
|
|
Number of Participants That Experienced a Potentially Clinically Significant Echocardiogram Measurement
Baseline · Abnormal, Clinically Significant
|
0 Participants
|
—
|
—
|
|
Number of Participants That Experienced a Potentially Clinically Significant Echocardiogram Measurement
Week 24 · Normal
|
33 Participants
|
—
|
—
|
|
Number of Participants That Experienced a Potentially Clinically Significant Echocardiogram Measurement
Week 24 · Abnormal, Not Clinically Significant
|
5 Participants
|
—
|
—
|
|
Number of Participants That Experienced a Potentially Clinically Significant Echocardiogram Measurement
Week 24 · Abnormal, Clinically Significant
|
0 Participants
|
—
|
—
|
|
Number of Participants That Experienced a Potentially Clinically Significant Echocardiogram Measurement
Week 48 · Normal
|
33 Participants
|
—
|
—
|
|
Number of Participants That Experienced a Potentially Clinically Significant Echocardiogram Measurement
Week 48 · Abnormal, Not Clinically Significant
|
2 Participants
|
—
|
—
|
|
Number of Participants That Experienced a Potentially Clinically Significant Echocardiogram Measurement
Week 48 · Abnormal, Clinically Significant
|
1 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 to Week 48Population: All participants who received at least one dose of study medication.
Parameters included: haemoglobin, haematocrit, mean corpuscular volume, white blood cells, red blood cells, neutrophils (percentage and absolute), lymphocytes (percentage and absolute), monocytes (percentage and absolute), eosinophils (percentage and absolute), basophils (percentage and absolute) and platelets. Results for Cohorts 1, 2 and 3 are pooled as specified in the protocol.
Outcome measures
| Measure |
Cohorts 1 and 2: SMT C1100
n=43 Participants
Cohort 1 participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks. Cohort 2 participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 2: SMT C1100 Formulation 2
Participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 3: SMT C1100 Formulation 1
Participants in this cohort had previously received SMT C1100, but were not eligible for Cohorts 1 or 2. Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.
|
|---|---|---|---|
|
Number of Participants That Experienced a Clinically Significant Haematology Result (Investigator's Assessment)
|
0 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 to Week 48Population: All participants who received at least one dose of study medication.
Parameters included: calcium, potassium, sodium, albumin, urea nitrogen, uric acid, creatinine, creatine kinase, fasting glucose, cystatin C, lactate dehydrogenase, amylase, lipase, low density lipoprotein cholesterol, high density lipoprotein (HDL) cholesterol, cholesterol, non-HDL cholesterol, total HDL cholesterol ratio, total bilirubin, direct bilirubin, indirect bilirubin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase and glutamate dehydrogenase. Results for Cohorts 1, 2 and 3 are pooled as specified in the protocol.
Outcome measures
| Measure |
Cohorts 1 and 2: SMT C1100
n=43 Participants
Cohort 1 participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks. Cohort 2 participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 2: SMT C1100 Formulation 2
Participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 3: SMT C1100 Formulation 1
Participants in this cohort had previously received SMT C1100, but were not eligible for Cohorts 1 or 2. Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.
|
|---|---|---|---|
|
Number of Participants Who Experienced a Clinically Significant Biochemistry Result (Investigator's Assessment)
|
3 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline to Week 48Population: All participants who received at least one dose of study medication.
Laboratory measurements for alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TB), alkaline phosphatase (ALP), and glutamate dehydrogenase (GLDH). Hy's Law is defined as an increase in ALT, AST and TB, indicating hepatocyte necrosis and functional deficit. Results for Cohorts 1, 2 and 3 are pooled as specified in the protocol.
Outcome measures
| Measure |
Cohorts 1 and 2: SMT C1100
n=43 Participants
Cohort 1 participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks. Cohort 2 participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 2: SMT C1100 Formulation 2
Participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 3: SMT C1100 Formulation 1
Participants in this cohort had previously received SMT C1100, but were not eligible for Cohorts 1 or 2. Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.
|
|---|---|---|---|
|
Number of Participants That Experienced a Potentially Clinically Significant Liver Function Result
ALT >= upper limit of normal (ULN)
|
43 Participants
|
—
|
—
|
|
Number of Participants That Experienced a Potentially Clinically Significant Liver Function Result
ALT >= 2*ULN
|
43 Participants
|
—
|
—
|
|
Number of Participants That Experienced a Potentially Clinically Significant Liver Function Result
ALT >= 3*ULN
|
42 Participants
|
—
|
—
|
|
Number of Participants That Experienced a Potentially Clinically Significant Liver Function Result
AST >= ULN
|
43 Participants
|
—
|
—
|
|
Number of Participants That Experienced a Potentially Clinically Significant Liver Function Result
AST >= 2*ULN
|
42 Participants
|
—
|
—
|
|
Number of Participants That Experienced a Potentially Clinically Significant Liver Function Result
AST >= 3*ULN
|
42 Participants
|
—
|
—
|
|
Number of Participants That Experienced a Potentially Clinically Significant Liver Function Result
TB >= ULN
|
0 Participants
|
—
|
—
|
|
Number of Participants That Experienced a Potentially Clinically Significant Liver Function Result
TB >= 2*ULN
|
0 Participants
|
—
|
—
|
|
Number of Participants That Experienced a Potentially Clinically Significant Liver Function Result
ALP >= 1.5*ULN
|
0 Participants
|
—
|
—
|
|
Number of Participants That Experienced a Potentially Clinically Significant Liver Function Result
GLDH >= ULN excluding haemolysed samples
|
27 Participants
|
—
|
—
|
|
Number of Participants That Experienced a Potentially Clinically Significant Liver Function Result
GLDH >= ULN including haemolysed samples
|
30 Participants
|
—
|
—
|
|
Number of Participants That Experienced a Potentially Clinically Significant Liver Function Result
GLDH >= 2.5*ULN Excluding Haemolysed Samples
|
2 Participants
|
—
|
—
|
|
Number of Participants That Experienced a Potentially Clinically Significant Liver Function Result
GLDH >= 2.5*ULN including haemolysed samples
|
2 Participants
|
—
|
—
|
|
Number of Participants That Experienced a Potentially Clinically Significant Liver Function Result
Participants meeting Hy's law
|
0 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 to Week 48Population: All participants who received at least one dose of study medication.
Parameters included: glucose, bilirubin, ketones, specific gravity, blood, pH, protein, urobilinogen, nitrites and leucocytes. Results for Cohorts 1, 2 and 3 are pooled as specified in the protocol.
Outcome measures
| Measure |
Cohorts 1 and 2: SMT C1100
n=43 Participants
Cohort 1 participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks. Cohort 2 participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 2: SMT C1100 Formulation 2
Participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 3: SMT C1100 Formulation 1
Participants in this cohort had previously received SMT C1100, but were not eligible for Cohorts 1 or 2. Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.
|
|---|---|---|---|
|
Number of Participants That Experienced a Clinically Significant Urinalysis Result (Investigator's Assessment)
|
0 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 to Week 48Population: All participants who received at least one dose of study medication in Cohorts 2 and 3 only.
Parameters included: activated partial thromboplastin time, prothrombin time and international normalised ratio. Coagulation was only assessed for Cohorts 2 and 3. Results for Cohorts 2 and 3 are pooled as specified in the protocol.
Outcome measures
| Measure |
Cohorts 1 and 2: SMT C1100
n=13 Participants
Cohort 1 participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks. Cohort 2 participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 2: SMT C1100 Formulation 2
Participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 3: SMT C1100 Formulation 1
Participants in this cohort had previously received SMT C1100, but were not eligible for Cohorts 1 or 2. Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.
|
|---|---|---|---|
|
Number of Participants That Experienced a Clinically Significant Coagulation Result (Investigator's Assessment)
|
0 Participants
|
—
|
—
|
Adverse Events
Cohort 1: SMT C1100 Formulation 1
Serious events: 4 serious events
Other events: 30 other events
Deaths: 0 deaths
Cohort 2: SMT C1100 Formulation 2
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Cohort 3: SMT C1100 Formulation 1
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Cohort 1: SMT C1100 Formulation 1
n=30 participants at risk
Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.
|
Cohort 2: SMT C1100 Formulation 2
n=10 participants at risk
Participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 3: SMT C1100 Formulation 1
n=3 participants at risk
Participants in this cohort had previously received SMT C1100, but were not eligible for Cohorts 1 or 2. Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.
|
|---|---|---|---|
|
Injury, poisoning and procedural complications
Femur fracture
|
3.3%
1/30 • Number of events 1 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
General disorders
Peripheral swelling
|
3.3%
1/30 • Number of events 1 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
3.3%
1/30 • Number of events 1 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Renal and urinary disorders
Chromaturia
|
3.3%
1/30 • Number of events 1 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Gastrointestinal disorders
Abdominal pain
|
3.3%
1/30 • Number of events 1 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Gastrointestinal disorders
Vomiting
|
3.3%
1/30 • Number of events 1 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
General disorders
Non-cardiac chest pain
|
3.3%
1/30 • Number of events 1 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Infections and infestations
Viral infection
|
3.3%
1/30 • Number of events 1 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Infections and infestations
Tonsillitis bacterial
|
3.3%
1/30 • Number of events 1 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Musculoskeletal and connective tissue disorders
Rhabdomyolysis
|
3.3%
1/30 • Number of events 1 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Infections and infestations
Gastritis viral
|
3.3%
1/30 • Number of events 1 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Injury, poisoning and procedural complications
Spinal compression fracture
|
3.3%
1/30 • Number of events 1 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
Other adverse events
| Measure |
Cohort 1: SMT C1100 Formulation 1
n=30 participants at risk
Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.
|
Cohort 2: SMT C1100 Formulation 2
n=10 participants at risk
Participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
|
Cohort 3: SMT C1100 Formulation 1
n=3 participants at risk
Participants in this cohort had previously received SMT C1100, but were not eligible for Cohorts 1 or 2. Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.
|
|---|---|---|---|
|
Gastrointestinal disorders
Faeces pale
|
60.0%
18/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
30.0%
3/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
100.0%
3/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Gastrointestinal disorders
Vomiting
|
56.7%
17/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
60.0%
6/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Gastrointestinal disorders
Diarrhoea
|
40.0%
12/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
40.0%
4/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
66.7%
2/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
26.7%
8/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
30.0%
3/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
33.3%
1/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Gastrointestinal disorders
Abdominal pain
|
23.3%
7/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Gastrointestinal disorders
Nausea
|
16.7%
5/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
10.0%
1/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
33.3%
1/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Gastrointestinal disorders
Constipation
|
6.7%
2/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
10.0%
1/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
33.3%
1/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Gastrointestinal disorders
Abdominal discomfort
|
6.7%
2/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
10.0%
1/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Gastrointestinal disorders
Toothache
|
10.0%
3/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Gastrointestinal disorders
Faeces discoloured
|
3.3%
1/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
10.0%
1/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Gastrointestinal disorders
Gastritis
|
6.7%
2/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Infections and infestations
Nasopharyngitis
|
20.0%
6/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
50.0%
5/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Infections and infestations
Rhinitis
|
10.0%
3/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
10.0%
1/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Infections and infestations
Upper respiratory tract infection
|
13.3%
4/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Infections and infestations
Ear infection
|
3.3%
1/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
20.0%
2/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Infections and infestations
Gastroenteritis
|
6.7%
2/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
10.0%
1/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Infections and infestations
Otitis media
|
10.0%
3/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Infections and infestations
Sinusitis
|
6.7%
2/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Infections and infestations
Viral upper respiratory tract infection
|
6.7%
2/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Infections and infestations
Campylobacter gastroenteritis
|
0.00%
0/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
10.0%
1/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Infections and infestations
Gastroenteritis viral
|
0.00%
0/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
10.0%
1/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Infections and infestations
Pharyngitis
|
0.00%
0/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
10.0%
1/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Injury, poisoning and procedural complications
Fall
|
23.3%
7/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
10.0%
1/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Injury, poisoning and procedural complications
Procedural pain
|
23.3%
7/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Injury, poisoning and procedural complications
Contusion
|
10.0%
3/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Injury, poisoning and procedural complications
Head injury
|
6.7%
2/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Injury, poisoning and procedural complications
Joint injury
|
6.7%
2/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Injury, poisoning and procedural complications
Ligament sprain
|
6.7%
2/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Injury, poisoning and procedural complications
Skin abrasion
|
6.7%
2/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Injury, poisoning and procedural complications
Spinal fracture
|
6.7%
2/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Injury, poisoning and procedural complications
Foot fracture
|
0.00%
0/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
10.0%
1/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
General disorders
Pyrexia
|
23.3%
7/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
10.0%
1/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
General disorders
Fatigue
|
13.3%
4/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
10.0%
1/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
General disorders
Catheter site bruise
|
6.7%
2/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
General disorders
Chest pain
|
6.7%
2/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
26.7%
8/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
40.0%
4/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
26.7%
8/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
20.0%
2/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
6.7%
2/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
10.0%
1/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
3.3%
1/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
10.0%
1/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
0.00%
0/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
10.0%
1/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
33.3%
10/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
23.3%
7/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
10.0%
1/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
10.0%
3/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
10.0%
1/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
33.3%
1/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
6.7%
2/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Nervous system disorders
Headache
|
30.0%
9/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
10.0%
1/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
33.3%
1/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Nervous system disorders
Dizziness
|
0.00%
0/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
10.0%
1/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Skin and subcutaneous tissue disorders
Rash
|
16.7%
5/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Skin and subcutaneous tissue disorders
Swelling face
|
10.0%
3/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
6.7%
2/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Skin and subcutaneous tissue disorders
Erythema
|
6.7%
2/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
6.7%
2/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Skin and subcutaneous tissue disorders
Skin discolouration
|
3.3%
1/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
10.0%
1/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Psychiatric disorders
Aggression
|
6.7%
2/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
10.0%
1/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Psychiatric disorders
Abnormal behaviour
|
3.3%
1/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
10.0%
1/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Psychiatric disorders
Anger
|
0.00%
0/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
10.0%
1/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
33.3%
1/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Psychiatric disorders
Belligerence
|
0.00%
0/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
10.0%
1/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Psychiatric disorders
Depressed mood
|
0.00%
0/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
33.3%
1/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Psychiatric disorders
Enuresis
|
0.00%
0/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
10.0%
1/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Psychiatric disorders
Irritability
|
0.00%
0/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
10.0%
1/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Psychiatric disorders
Mood altered
|
0.00%
0/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
10.0%
1/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Investigations
Glutamate dehydrogenase increased
|
10.0%
3/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
10.0%
1/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Investigations
Gamma-glutamyltransferase increased
|
6.7%
2/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
10.0%
3/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Metabolism and nutrition disorders
Increased appetite
|
3.3%
1/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
10.0%
1/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Metabolism and nutrition disorders
Vitamin D deficiency
|
6.7%
2/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Eye disorders
Vitreous floaters
|
0.00%
0/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
10.0%
1/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma
|
10.0%
3/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Ear and labyrinth disorders
Ear pain
|
6.7%
2/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Congenital, familial and genetic disorders
Cryptorchism
|
0.00%
0/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
10.0%
1/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Renal and urinary disorders
Pollakiuria
|
0.00%
0/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
33.3%
1/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Gastrointestinal disorders
Dyspepsia
|
10.0%
3/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
10.0%
1/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
|
Gastrointestinal disorders
Lip swelling
|
10.0%
3/30 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/10 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
0.00%
0/3 • Day 1 to a maximum of 96 weeks
Treatment Emergent Adverse Events.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place