Trial Outcomes & Findings for To Assess Safety and Effect of Olaparib on the Pharmacokinetics of Anastrozole, Letrozole & Tamoxifen, and Their Effect on Olaparib, in Patients With Advanced Solid Cancer (NCT NCT02093351)
NCT ID: NCT02093351
Last Updated: 2019-10-02
Results Overview
Tamoxifen, N-desmethyl tamoxifen (N-DMT) and endoxifen Cmax ss in the presence and absence of co-administered olaparib, and associated Cmax ss treatment ratios
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
79 participants
Primary outcome timeframe
Pre-dose and at 1, 2, 4, 5, 6, 8, 12 and 24 hours post-dose on Day 26 and Day 31
Results posted on
2019-10-02
Participant Flow
First patient enrolled: 01 Sep 2014; last completed Part A: 28 Apr 2015. Last patient completed Part B: 27 Apr 2016. Part A assessed olaparib's effect on the pharmacokinetic (PK) parameters of anastrozole, letrozole and tamoxifen and vice versa; in Part B eligible patients received olaparib providing further safety data. Target accrual was met.
79 patients were assigned to study treatment and received at least 1 dose of olaparib in Part A; 18 patients did not fulfil eligibility criteria. Part A of the study consisted of 3 treatment periods preceded by a screening period. There was a 4-day washout between the first two treatment periods.
Participant milestones
| Measure |
Cohort 1 - Tamoxifen
In Part A, patients in Cohort 1 received olaparib 300 mg twice daily (bd) for 5 days in Treatment Period 1; tamoxifen 60 mg once daily (od) (loading dose) for 4 days then 20 mg od for 13 days (maintenance dose) in Treatment Period 2; and tamoxifen 20 mg od concomitantly with olaparib 300 mg bd for 5 days in Treatment Period 3.
|
Cohort 2 - Anastrozole
In Part A, patients in Cohort 2 received olaparib 300 mg bd for 5 days in Treatment Period 1; anastrozole 1 mg od for 10 days in Treatment Period 2; and anastrozole 1 mg od concomitantly with olaparib 300 mg bd for 5 days in Treatment Period 3.
|
Cohort 3 - Letrozole
In Part A, patients in Cohort 3 received olaparib 300 mg bd for 5 days in Treatment Period 1; letrozole 2.5 mg od for 29 days in Treatment Period 2; and letrozole 2.5 mg od concomitantly with olaparib 300 mg bd for 5 days in Treatment Period 3.
|
Olaparib (Part B)
In Part B, patients continued to receive olaparib 300 mg bd either as monotherapy or in combination with routine clinical regimes of letrozole, anastrazole or tamoxifen if deemed necessary by the investigator.
|
|---|---|---|---|---|
|
Part A
STARTED
|
30
|
23
|
26
|
0
|
|
Part A
Completing Treatment Period 1
|
29
|
22
|
23
|
0
|
|
Part A
Completing Treatment Period 2
|
29
|
21
|
23
|
0
|
|
Part A
Completing Treatment Period 3
|
28
|
21
|
23
|
0
|
|
Part A
COMPLETED
|
28
|
21
|
23
|
0
|
|
Part A
NOT COMPLETED
|
2
|
2
|
3
|
0
|
|
Part B
STARTED
|
0
|
0
|
0
|
69
|
|
Part B
COMPLETED
|
0
|
0
|
0
|
6
|
|
Part B
NOT COMPLETED
|
0
|
0
|
0
|
63
|
Reasons for withdrawal
| Measure |
Cohort 1 - Tamoxifen
In Part A, patients in Cohort 1 received olaparib 300 mg twice daily (bd) for 5 days in Treatment Period 1; tamoxifen 60 mg once daily (od) (loading dose) for 4 days then 20 mg od for 13 days (maintenance dose) in Treatment Period 2; and tamoxifen 20 mg od concomitantly with olaparib 300 mg bd for 5 days in Treatment Period 3.
|
Cohort 2 - Anastrozole
In Part A, patients in Cohort 2 received olaparib 300 mg bd for 5 days in Treatment Period 1; anastrozole 1 mg od for 10 days in Treatment Period 2; and anastrozole 1 mg od concomitantly with olaparib 300 mg bd for 5 days in Treatment Period 3.
|
Cohort 3 - Letrozole
In Part A, patients in Cohort 3 received olaparib 300 mg bd for 5 days in Treatment Period 1; letrozole 2.5 mg od for 29 days in Treatment Period 2; and letrozole 2.5 mg od concomitantly with olaparib 300 mg bd for 5 days in Treatment Period 3.
|
Olaparib (Part B)
In Part B, patients continued to receive olaparib 300 mg bd either as monotherapy or in combination with routine clinical regimes of letrozole, anastrazole or tamoxifen if deemed necessary by the investigator.
|
|---|---|---|---|---|
|
Part A
Adverse Event
|
0
|
1
|
1
|
0
|
|
Part A
Condition under investigation worsened
|
2
|
0
|
2
|
0
|
|
Part A
Death
|
0
|
1
|
0
|
0
|
|
Part B
Patient decision
|
0
|
0
|
0
|
3
|
|
Part B
Disease progression
|
0
|
0
|
0
|
4
|
|
Part B
Complete response
|
0
|
0
|
0
|
1
|
|
Part B
Adverse event + disease progression
|
0
|
0
|
0
|
1
|
|
Part B
Lack of therapeutic response
|
0
|
0
|
0
|
12
|
|
Part B
Condition under investigation worsened
|
0
|
0
|
0
|
39
|
|
Part B
Adverse Event
|
0
|
0
|
0
|
2
|
|
Part B
Death
|
0
|
0
|
0
|
1
|
Baseline Characteristics
To Assess Safety and Effect of Olaparib on the Pharmacokinetics of Anastrozole, Letrozole & Tamoxifen, and Their Effect on Olaparib, in Patients With Advanced Solid Cancer
Baseline characteristics by cohort
| Measure |
Cohort 1 - Tamoxifen
n=30 Participants
In Part A, patients in Cohort 1 received olaparib 300 mg twice daily (bd) for 5 days in Treatment Period 1; tamoxifen 60 mg once daily (od) (loading dose) for 4 days then 20 mg od for 13 days (maintenance dose) in Treatment Period 2; and tamoxifen 20 mg od concomitantly with olaparib 300 mg bd for 5 days in Treatment Period 3.
|
Cohort 2 - Anastrozole
n=23 Participants
In Part A, patients in Cohort 2 received olaparib 300 mg bd for 5 days in Treatment Period 1; anastrozole 1 mg od for 10 days in Treatment Period 2; and anastrozole 1 mg od concomitantly with olaparib 300 mg bd for 5 days in Treatment Period 3.
|
Cohort 3 - Letrozole
n=26 Participants
In Part A, patients in Cohort 3 received olaparib 300 mg bd for 5 days in Treatment Period 1; letrozole 2.5 mg od for 29 days in Treatment Period 2; and letrozole 2.5 mg od concomitantly with olaparib 300 mg bd for 5 days in Treatment Period 3.
|
Total
n=79 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
52.6 years
STANDARD_DEVIATION 11.32 • n=99 Participants
|
59.4 years
STANDARD_DEVIATION 11.68 • n=107 Participants
|
64.0 years
STANDARD_DEVIATION 7.79 • n=206 Participants
|
58.3 years
STANDARD_DEVIATION 11.37 • n=7 Participants
|
|
Sex: Female, Male
Female
|
26 Participants
n=99 Participants
|
18 Participants
n=107 Participants
|
20 Participants
n=206 Participants
|
64 Participants
n=7 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
15 Participants
n=7 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
30 Participants
n=99 Participants
|
23 Participants
n=107 Participants
|
26 Participants
n=206 Participants
|
79 Participants
n=7 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
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
1 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
2 Participants
n=7 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
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
2 Participants
n=7 Participants
|
|
Race (NIH/OMB)
White
|
27 Participants
n=99 Participants
|
22 Participants
n=107 Participants
|
24 Participants
n=206 Participants
|
73 Participants
n=7 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
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
1 Participants
n=7 Participants
|
PRIMARY outcome
Timeframe: Pre-dose and at 1, 2, 4, 5, 6, 8, 12 and 24 hours post-dose on Day 26 and Day 31Population: The PK Analysis set included all patients who received a study drug dose and provided evaluable PK profiles for at least 1 treatment period in Part A.
Tamoxifen, N-desmethyl tamoxifen (N-DMT) and endoxifen Cmax ss in the presence and absence of co-administered olaparib, and associated Cmax ss treatment ratios
Outcome measures
| Measure |
Cohort 1 - Tamoxifen Alone (Treatment Period 2)
n=24 Participants
Patients in Cohort 1 received tamoxifen 60 mg od from Day 10 to Day 13 (loading dose). From Day 14 to Day 26 patients received tamoxifen 20 mg od (maintenance dose). Blood sampling for PK analysis was taken on Day 26.
|
Cohort 1 - Olaparib + Tamoxifen (Treatment Period 3)
n=18 Participants
Patients in Cohort 1 received tamoxifen 20 mg od concomitantly with olaparib 300 mg bd for 5 days from Day 27 to Day 31. Blood sampling for PK analysis was taken on Day 31.
|
|---|---|---|
|
Effect of Olaparib on Exposure to Tamoxifen - Cmax ss
PK analysis of tamoxifen
|
130.3 mcg/mL
Geometric Coefficient of Variation 27.3
|
154.2 mcg/mL
Geometric Coefficient of Variation 34.9
|
|
Effect of Olaparib on Exposure to Tamoxifen - Cmax ss
PK analysis of N-DMT
|
162.9 mcg/mL
Geometric Coefficient of Variation 28.0
|
149.1 mcg/mL
Geometric Coefficient of Variation 44.8
|
|
Effect of Olaparib on Exposure to Tamoxifen - Cmax ss
PK analysis of endoxifen
|
5.923 mcg/mL
Geometric Coefficient of Variation 65.7
|
5.727 mcg/mL
Geometric Coefficient of Variation 61.2
|
PRIMARY outcome
Timeframe: Pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours post morning dose on Day 5 and Day 31Population: The PK Analysis set included all patients who received a study drug dose and provided evaluable PK profiles for at least 1 treatment period in Part A.
Olaparib Cmax ss in the presence and absence of co-administered tamoxifen, and associated Cmax ss treatment ratios
Outcome measures
| Measure |
Cohort 1 - Tamoxifen Alone (Treatment Period 2)
n=27 Participants
Patients in Cohort 1 received tamoxifen 60 mg od from Day 10 to Day 13 (loading dose). From Day 14 to Day 26 patients received tamoxifen 20 mg od (maintenance dose). Blood sampling for PK analysis was taken on Day 26.
|
Cohort 1 - Olaparib + Tamoxifen (Treatment Period 3)
n=19 Participants
Patients in Cohort 1 received tamoxifen 20 mg od concomitantly with olaparib 300 mg bd for 5 days from Day 27 to Day 31. Blood sampling for PK analysis was taken on Day 31.
|
|---|---|---|
|
Effect of Tamoxifen on Exposure to Olaparib - Cmax ss
|
9.456 mcg/mL
Geometric Coefficient of Variation 41.5
|
7.216 mcg/mL
Geometric Coefficient of Variation 43.6
|
PRIMARY outcome
Timeframe: Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 19 and Day 24Population: PK Analysis set included all patients who received a study drug dose and provided evaluable PK profiles for at least 1 treatment period in Part A.
Anastrozole maximum plasma concentration at steady state (Cmax ss) in the presence and absence of co-administered olaparib, and associated Cmax ss treatment ratios
Outcome measures
| Measure |
Cohort 1 - Tamoxifen Alone (Treatment Period 2)
n=20 Participants
Patients in Cohort 1 received tamoxifen 60 mg od from Day 10 to Day 13 (loading dose). From Day 14 to Day 26 patients received tamoxifen 20 mg od (maintenance dose). Blood sampling for PK analysis was taken on Day 26.
|
Cohort 1 - Olaparib + Tamoxifen (Treatment Period 3)
n=19 Participants
Patients in Cohort 1 received tamoxifen 20 mg od concomitantly with olaparib 300 mg bd for 5 days from Day 27 to Day 31. Blood sampling for PK analysis was taken on Day 31.
|
|---|---|---|
|
Effect of Olaparib on Exposure to Anastrozole - Cmax ss
|
40.98 micrograms per millilitre (mcg/mL)
Geometric Coefficient of Variation 36.2
|
35.83 micrograms per millilitre (mcg/mL)
Geometric Coefficient of Variation 31.9
|
PRIMARY outcome
Timeframe: Pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours post morning dose on Day 5 and Day 24Population: PK Analysis set included all patients who received a study drug dose and provided evaluable PK profiles for at least 1 treatment period in Part A.
Olaparib Cmax ss in the presence and absence of co-administered anastrozole, and associated Cmax ss treatment ratios
Outcome measures
| Measure |
Cohort 1 - Tamoxifen Alone (Treatment Period 2)
n=22 Participants
Patients in Cohort 1 received tamoxifen 60 mg od from Day 10 to Day 13 (loading dose). From Day 14 to Day 26 patients received tamoxifen 20 mg od (maintenance dose). Blood sampling for PK analysis was taken on Day 26.
|
Cohort 1 - Olaparib + Tamoxifen (Treatment Period 3)
n=20 Participants
Patients in Cohort 1 received tamoxifen 20 mg od concomitantly with olaparib 300 mg bd for 5 days from Day 27 to Day 31. Blood sampling for PK analysis was taken on Day 31.
|
|---|---|---|
|
Effect of Anastrozole on Exposure to Olaparib - Cmax ss
|
9.490 mcg/mL
Geometric Coefficient of Variation 34.3
|
8.256 mcg/mL
Geometric Coefficient of Variation 39.9
|
PRIMARY outcome
Timeframe: Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 38 and Day 43Population: PK Analysis set included all patients who received a study drug dose and provided evaluable PK profiles for at least 1 treatment period in Part A.
Letrozole Cmax ss in the presence and absence of co-administered olaparib, and associated Cmax ss treatment ratios
Outcome measures
| Measure |
Cohort 1 - Tamoxifen Alone (Treatment Period 2)
n=23 Participants
Patients in Cohort 1 received tamoxifen 60 mg od from Day 10 to Day 13 (loading dose). From Day 14 to Day 26 patients received tamoxifen 20 mg od (maintenance dose). Blood sampling for PK analysis was taken on Day 26.
|
Cohort 1 - Olaparib + Tamoxifen (Treatment Period 3)
n=23 Participants
Patients in Cohort 1 received tamoxifen 20 mg od concomitantly with olaparib 300 mg bd for 5 days from Day 27 to Day 31. Blood sampling for PK analysis was taken on Day 31.
|
|---|---|---|
|
Effect of Olaparib on Exposure to Letrozole - Cmax ss
|
118.9 mcg/mL
Geometric Coefficient of Variation 32.6
|
111.8 mcg/mL
Geometric Coefficient of Variation 30.4
|
PRIMARY outcome
Timeframe: Pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours post morning dose on Day 5 and Day 43Population: The PK Analysis set included all patients who received a study drug dose and provided evaluable PK profiles for at least 1 treatment period in Part A.
Olaparib Cmax ss in the presence and absence of co-administered letrozole, and associated Cmax ss treatment ratios
Outcome measures
| Measure |
Cohort 1 - Tamoxifen Alone (Treatment Period 2)
n=22 Participants
Patients in Cohort 1 received tamoxifen 60 mg od from Day 10 to Day 13 (loading dose). From Day 14 to Day 26 patients received tamoxifen 20 mg od (maintenance dose). Blood sampling for PK analysis was taken on Day 26.
|
Cohort 1 - Olaparib + Tamoxifen (Treatment Period 3)
n=23 Participants
Patients in Cohort 1 received tamoxifen 20 mg od concomitantly with olaparib 300 mg bd for 5 days from Day 27 to Day 31. Blood sampling for PK analysis was taken on Day 31.
|
|---|---|---|
|
Effect of Letrozole on Exposure to Olaparib - Cmax ss
|
10.05 mcg/mL
Geometric Coefficient of Variation 30.2
|
10.48 mcg/mL
Geometric Coefficient of Variation 33.6
|
PRIMARY outcome
Timeframe: Pre-dose and at 1, 2, 4, 5, 6, 8, 12 and 24 hours post-dose on Day 26 and Day 31Population: The PK Analysis set included all patients who received a study drug dose and provided evaluable PK profiles for at least 1 treatment period in Part A.
Tamoxifen, N-DMT and endoxifen AUC0-τ, in the presence and absence of co-administered olaparib, and associated AUC0-τ treatment ratios
Outcome measures
| Measure |
Cohort 1 - Tamoxifen Alone (Treatment Period 2)
n=24 Participants
Patients in Cohort 1 received tamoxifen 60 mg od from Day 10 to Day 13 (loading dose). From Day 14 to Day 26 patients received tamoxifen 20 mg od (maintenance dose). Blood sampling for PK analysis was taken on Day 26.
|
Cohort 1 - Olaparib + Tamoxifen (Treatment Period 3)
n=18 Participants
Patients in Cohort 1 received tamoxifen 20 mg od concomitantly with olaparib 300 mg bd for 5 days from Day 27 to Day 31. Blood sampling for PK analysis was taken on Day 31.
|
|---|---|---|
|
Effect of Olaparib on Exposure to Tamoxifen - AUC0-τ
PK analysis of tamoxifen
|
2233 microgram x hour/millilitre (mcg*h/mL)
Geometric Coefficient of Variation 31.9
|
2751 microgram x hour/millilitre (mcg*h/mL)
Geometric Coefficient of Variation 28.9
|
|
Effect of Olaparib on Exposure to Tamoxifen - AUC0-τ
PK analysis of N-DMT
|
3189 microgram x hour/millilitre (mcg*h/mL)
Geometric Coefficient of Variation 28.8
|
2955 microgram x hour/millilitre (mcg*h/mL)
Geometric Coefficient of Variation 37.3
|
|
Effect of Olaparib on Exposure to Tamoxifen - AUC0-τ
PK analysis of endoxifen
|
119.3 microgram x hour/millilitre (mcg*h/mL)
Geometric Coefficient of Variation 66.1
|
115.8 microgram x hour/millilitre (mcg*h/mL)
Geometric Coefficient of Variation 64.8
|
PRIMARY outcome
Timeframe: Pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours post morning dose on Day 5 and Day 31Population: The PK Analysis set included all patients who received a study drug dose and provided evaluable PK profiles for at least 1 treatment period in Part A.
Olaparib AUC0-τ, in the presence and absence of co-administered tamoxifen, and associated AUC0-τ treatment ratios
Outcome measures
| Measure |
Cohort 1 - Tamoxifen Alone (Treatment Period 2)
n=26 Participants
Patients in Cohort 1 received tamoxifen 60 mg od from Day 10 to Day 13 (loading dose). From Day 14 to Day 26 patients received tamoxifen 20 mg od (maintenance dose). Blood sampling for PK analysis was taken on Day 26.
|
Cohort 1 - Olaparib + Tamoxifen (Treatment Period 3)
n=18 Participants
Patients in Cohort 1 received tamoxifen 20 mg od concomitantly with olaparib 300 mg bd for 5 days from Day 27 to Day 31. Blood sampling for PK analysis was taken on Day 31.
|
|---|---|---|
|
Effect of Tamoxifen on Exposure to Olaparib - AUC0-τ
|
62.12 mcg*h/mL
Geometric Coefficient of Variation 51.6
|
42.27 mcg*h/mL
Geometric Coefficient of Variation 60.6
|
PRIMARY outcome
Timeframe: Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 19 and Day 24Population: The PK Analysis set included all patients who received a study drug dose and provided evaluable PK profiles for at least 1 treatment period in Part A.
Anastrozole Area under plasma concentration-time curve over the dosing interval at steady state (AUC0-τ), in the presence and absence of co-administered olaparib, and associated AUC0-τ treatment ratios
Outcome measures
| Measure |
Cohort 1 - Tamoxifen Alone (Treatment Period 2)
n=20 Participants
Patients in Cohort 1 received tamoxifen 60 mg od from Day 10 to Day 13 (loading dose). From Day 14 to Day 26 patients received tamoxifen 20 mg od (maintenance dose). Blood sampling for PK analysis was taken on Day 26.
|
Cohort 1 - Olaparib + Tamoxifen (Treatment Period 3)
n=19 Participants
Patients in Cohort 1 received tamoxifen 20 mg od concomitantly with olaparib 300 mg bd for 5 days from Day 27 to Day 31. Blood sampling for PK analysis was taken on Day 31.
|
|---|---|---|
|
Effect of Olaparib on Exposure to Anastrozole - AUC0-τ
|
696.8 mcg*h/mL
Geometric Coefficient of Variation 36.6
|
582.5 mcg*h/mL
Geometric Coefficient of Variation 31.6
|
PRIMARY outcome
Timeframe: Pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours post morning dose on Day 5 and Day 24Population: The PK Analysis set included all patients who received a study drug dose and provided evaluable PK profiles for at least 1 treatment period in Part A.
Olaparib AUC0-τ, in the presence and absence of co-administered anastrozole, and associated AUC0-τ treatment ratios
Outcome measures
| Measure |
Cohort 1 - Tamoxifen Alone (Treatment Period 2)
n=21 Participants
Patients in Cohort 1 received tamoxifen 60 mg od from Day 10 to Day 13 (loading dose). From Day 14 to Day 26 patients received tamoxifen 20 mg od (maintenance dose). Blood sampling for PK analysis was taken on Day 26.
|
Cohort 1 - Olaparib + Tamoxifen (Treatment Period 3)
n=19 Participants
Patients in Cohort 1 received tamoxifen 20 mg od concomitantly with olaparib 300 mg bd for 5 days from Day 27 to Day 31. Blood sampling for PK analysis was taken on Day 31.
|
|---|---|---|
|
Effect of Anastrozole on Exposure to Olaparib - AUC0-τ
|
55.49 mcg*h/mL
Geometric Coefficient of Variation 53.8
|
44.33 mcg*h/mL
Geometric Coefficient of Variation 63.6
|
PRIMARY outcome
Timeframe: Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 38 and Day 43Population: The PK Analysis set included all patients who received a study drug dose and provided evaluable PK profiles for at least 1 treatment period in Part A.
Letrozole AUC0-τ, in the presence and absence of co-administered olaparib, and associated AUC0-τ treatment ratios
Outcome measures
| Measure |
Cohort 1 - Tamoxifen Alone (Treatment Period 2)
n=23 Participants
Patients in Cohort 1 received tamoxifen 60 mg od from Day 10 to Day 13 (loading dose). From Day 14 to Day 26 patients received tamoxifen 20 mg od (maintenance dose). Blood sampling for PK analysis was taken on Day 26.
|
Cohort 1 - Olaparib + Tamoxifen (Treatment Period 3)
n=23 Participants
Patients in Cohort 1 received tamoxifen 20 mg od concomitantly with olaparib 300 mg bd for 5 days from Day 27 to Day 31. Blood sampling for PK analysis was taken on Day 31.
|
|---|---|---|
|
Effect of Olaparib on Exposure to Letrozole - AUC0-τ
|
2292 mcg*h/mL
Geometric Coefficient of Variation 36.7
|
2167 mcg*h/mL
Geometric Coefficient of Variation 38.0
|
PRIMARY outcome
Timeframe: Pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours post morning dose on Day 5 and Day 43Population: The PK Analysis set included all patients who received a study drug dose and provided evaluable PK profiles for at least 1 treatment period in Part A.
Olaparib AUC0-τ, in the presence and absence of co-administered letrozole, and associated AUC0-τ treatment ratios
Outcome measures
| Measure |
Cohort 1 - Tamoxifen Alone (Treatment Period 2)
n=22 Participants
Patients in Cohort 1 received tamoxifen 60 mg od from Day 10 to Day 13 (loading dose). From Day 14 to Day 26 patients received tamoxifen 20 mg od (maintenance dose). Blood sampling for PK analysis was taken on Day 26.
|
Cohort 1 - Olaparib + Tamoxifen (Treatment Period 3)
n=23 Participants
Patients in Cohort 1 received tamoxifen 20 mg od concomitantly with olaparib 300 mg bd for 5 days from Day 27 to Day 31. Blood sampling for PK analysis was taken on Day 31.
|
|---|---|---|
|
Effect of Letrozole on Exposure to Olaparib - AUC0-τ
|
61.77 mcg*h/mL
Geometric Coefficient of Variation 43.2
|
67.82 mcg*h/mL
Geometric Coefficient of Variation 44.1
|
Adverse Events
Cohort 1 - Tamoxifen
Serious events: 2 serious events
Other events: 27 other events
Deaths: 1 deaths
Cohort 2 - Anastrozole
Serious events: 0 serious events
Other events: 20 other events
Deaths: 1 deaths
Cohort 3 - Letrozole
Serious events: 0 serious events
Other events: 20 other events
Deaths: 1 deaths
Olaparib (Part B)
Serious events: 22 serious events
Other events: 66 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Cohort 1 - Tamoxifen
n=30 participants at risk
In Part A, patients in Cohort 1 received olaparib 300 mg twice daily (bd) for 5 days in Treatment Period 1; tamoxifen 60 mg once daily (od) (loading dose) for 4 days then 20 mg od for 13 days (maintenance dose) in Treatment Period 2; and tamoxifen 20 mg od concomitantly with olaparib 300 mg bd for 5 days in Treatment Period 3.
|
Cohort 2 - Anastrozole
n=23 participants at risk
In Part A, patients in Cohort 2 received olaparib 300 mg bd for 5 days in Treatment Period 1; anastrozole 1 mg od for 10 days in Treatment Period 2; and anastrozole 1 mg od concomitantly with olaparib 300 mg bd for 5 days in Treatment Period 3.
|
Cohort 3 - Letrozole
n=26 participants at risk
In Part A, patients in Cohort 3 received olaparib 300 mg bd for 5 days in Treatment Period 1; letrozole 2.5 mg od for 29 days in Treatment Period 2; and letrozole 2.5 mg od concomitantly with olaparib 300 mg bd for 5 days in Treatment Period 3.
|
Olaparib (Part B)
n=69 participants at risk
In Part B, patients continued to receive olaparib 300 mg bd either as monotherapy or in combination with routine clinical regimes of letrozole, anastrazole or tamoxifen if deemed necessary by the investigator.
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Ascites
|
3.3%
1/30 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/23 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/26 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/69 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Gastrointestinal disorders
Vomiting
|
3.3%
1/30 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/23 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/26 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
1.4%
1/69 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/30 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/23 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/26 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
7.2%
5/69 • Number of events 8 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Blood and lymphatic system disorders
Anaemia Macrocytic
|
0.00%
0/30 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/23 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/26 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
1.4%
1/69 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/30 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/23 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/26 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
1.4%
1/69 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Eye disorders
Diplopia
|
0.00%
0/30 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/23 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/26 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
1.4%
1/69 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
General disorders
Device Occlusion
|
0.00%
0/30 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/23 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/26 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
2.9%
2/69 • Number of events 8 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
General disorders
Oedema Peripheral
|
0.00%
0/30 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/23 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/26 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
1.4%
1/69 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Hepatobiliary disorders
Cholangitis
|
0.00%
0/30 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/23 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/26 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
1.4%
1/69 • Number of events 8 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Infections and infestations
Klebsiella Infection
|
0.00%
0/30 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/23 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/26 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
1.4%
1/69 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Infections and infestations
Lower Respiratory Tract Infection
|
0.00%
0/30 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/23 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/26 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
1.4%
1/69 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Infections and infestations
Pneumonia
|
0.00%
0/30 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/23 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/26 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
1.4%
1/69 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Infections and infestations
Pyelonephritis
|
0.00%
0/30 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/23 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/26 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
1.4%
1/69 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Infections and infestations
Urinary Tract Infection
|
0.00%
0/30 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/23 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/26 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
2.9%
2/69 • Number of events 3 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Infections and infestations
Urosepsis
|
0.00%
0/30 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/23 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/26 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
2.9%
2/69 • Number of events 2 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/30 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/23 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/26 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
1.4%
1/69 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder Transitional Cell Carcinoma
|
0.00%
0/30 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/23 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/26 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
1.4%
1/69 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer Pain
|
0.00%
0/30 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/23 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/26 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
1.4%
1/69 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Nervous system disorders
Cognitive Disorder
|
0.00%
0/30 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/23 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/26 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
1.4%
1/69 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.00%
0/30 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/23 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/26 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
1.4%
1/69 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Vascular disorders
Superior Vena Cava Occlusion
|
0.00%
0/30 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/23 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/26 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
1.4%
1/69 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/30 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/23 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/26 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
2.9%
2/69 • Number of events 2 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
Other adverse events
| Measure |
Cohort 1 - Tamoxifen
n=30 participants at risk
In Part A, patients in Cohort 1 received olaparib 300 mg twice daily (bd) for 5 days in Treatment Period 1; tamoxifen 60 mg once daily (od) (loading dose) for 4 days then 20 mg od for 13 days (maintenance dose) in Treatment Period 2; and tamoxifen 20 mg od concomitantly with olaparib 300 mg bd for 5 days in Treatment Period 3.
|
Cohort 2 - Anastrozole
n=23 participants at risk
In Part A, patients in Cohort 2 received olaparib 300 mg bd for 5 days in Treatment Period 1; anastrozole 1 mg od for 10 days in Treatment Period 2; and anastrozole 1 mg od concomitantly with olaparib 300 mg bd for 5 days in Treatment Period 3.
|
Cohort 3 - Letrozole
n=26 participants at risk
In Part A, patients in Cohort 3 received olaparib 300 mg bd for 5 days in Treatment Period 1; letrozole 2.5 mg od for 29 days in Treatment Period 2; and letrozole 2.5 mg od concomitantly with olaparib 300 mg bd for 5 days in Treatment Period 3.
|
Olaparib (Part B)
n=69 participants at risk
In Part B, patients continued to receive olaparib 300 mg bd either as monotherapy or in combination with routine clinical regimes of letrozole, anastrazole or tamoxifen if deemed necessary by the investigator.
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
20.0%
6/30 • Number of events 7 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
13.0%
3/23 • Number of events 3 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
11.5%
3/26 • Number of events 3 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
26.1%
18/69 • Number of events 27 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
3.3%
1/30 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/23 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
7.7%
2/26 • Number of events 2 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
7.2%
5/69 • Number of events 7 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Eye disorders
Vision Blurred
|
3.3%
1/30 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/23 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
7.7%
2/26 • Number of events 2 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
2.9%
2/69 • Number of events 2 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Gastrointestinal disorders
Abdominal Distension
|
6.7%
2/30 • Number of events 2 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
8.7%
2/23 • Number of events 2 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/26 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
7.2%
5/69 • Number of events 6 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Gastrointestinal disorders
Abdominal Pain
|
10.0%
3/30 • Number of events 3 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
8.7%
2/23 • Number of events 2 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
15.4%
4/26 • Number of events 4 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
14.5%
10/69 • Number of events 13 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
6.7%
2/30 • Number of events 2 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
13.0%
3/23 • Number of events 3 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
7.7%
2/26 • Number of events 4 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
5.8%
4/69 • Number of events 5 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Gastrointestinal disorders
Constipation
|
13.3%
4/30 • Number of events 4 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
8.7%
2/23 • Number of events 2 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
11.5%
3/26 • Number of events 3 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
15.9%
11/69 • Number of events 14 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Gastrointestinal disorders
Diarrhoea
|
16.7%
5/30 • Number of events 5 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
4.3%
1/23 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
11.5%
3/26 • Number of events 5 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
17.4%
12/69 • Number of events 13 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Gastrointestinal disorders
Dyspepsia
|
13.3%
4/30 • Number of events 4 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/23 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
3.8%
1/26 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
7.2%
5/69 • Number of events 5 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Gastrointestinal disorders
Nausea
|
53.3%
16/30 • Number of events 22 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
30.4%
7/23 • Number of events 12 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
42.3%
11/26 • Number of events 13 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
40.6%
28/69 • Number of events 32 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Gastrointestinal disorders
Vomiting
|
20.0%
6/30 • Number of events 9 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
17.4%
4/23 • Number of events 4 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
15.4%
4/26 • Number of events 5 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
31.9%
22/69 • Number of events 34 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
General disorders
Asthenia
|
0.00%
0/30 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/23 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
7.7%
2/26 • Number of events 4 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
5.8%
4/69 • Number of events 6 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
General disorders
Fatigue
|
40.0%
12/30 • Number of events 13 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
26.1%
6/23 • Number of events 7 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
34.6%
9/26 • Number of events 10 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
43.5%
30/69 • Number of events 36 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
General disorders
Non-Cardiac Chest Pain
|
6.7%
2/30 • Number of events 3 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/23 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
11.5%
3/26 • Number of events 3 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
7.2%
5/69 • Number of events 6 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
General disorders
Oedema Peripheral
|
6.7%
2/30 • Number of events 2 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
8.7%
2/23 • Number of events 3 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
7.7%
2/26 • Number of events 2 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
10.1%
7/69 • Number of events 8 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Infections and infestations
Lower Respiratory Tract Infection
|
3.3%
1/30 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
4.3%
1/23 • Number of events 2 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
11.5%
3/26 • Number of events 3 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
5.8%
4/69 • Number of events 5 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Infections and infestations
Urinary Tract Infection
|
3.3%
1/30 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/23 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
7.7%
2/26 • Number of events 2 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
2.9%
2/69 • Number of events 4 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/30 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
8.7%
2/23 • Number of events 2 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
3.8%
1/26 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
1.4%
1/69 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Investigations
Blood Alkaline Phosphatase Increased
|
6.7%
2/30 • Number of events 3 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/23 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/26 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
4.3%
3/69 • Number of events 3 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Investigations
Blood Creatinine Increased
|
10.0%
3/30 • Number of events 4 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/23 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/26 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
1.4%
1/69 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Metabolism and nutrition disorders
Decreased Appetite
|
6.7%
2/30 • Number of events 2 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
17.4%
4/23 • Number of events 5 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
11.5%
3/26 • Number of events 4 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
18.8%
13/69 • Number of events 14 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
0.00%
0/30 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
8.7%
2/23 • Number of events 2 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/26 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
1.4%
1/69 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
3.3%
1/30 • Number of events 2 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
13.0%
3/23 • Number of events 4 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
3.8%
1/26 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
11.6%
8/69 • Number of events 10 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
3.3%
1/30 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
13.0%
3/23 • Number of events 4 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
3.8%
1/26 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
8.7%
6/69 • Number of events 6 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Musculoskeletal and connective tissue disorders
Muscle Spasms
|
6.7%
2/30 • Number of events 2 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
4.3%
1/23 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
3.8%
1/26 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
7.2%
5/69 • Number of events 5 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Musculoskeletal and connective tissue disorders
Muscular Weakness
|
6.7%
2/30 • Number of events 2 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/23 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/26 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
4.3%
3/69 • Number of events 3 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain
|
0.00%
0/30 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/23 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
7.7%
2/26 • Number of events 2 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
7.2%
5/69 • Number of events 5 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Stiffness
|
0.00%
0/30 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
4.3%
1/23 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
7.7%
2/26 • Number of events 2 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/69 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
3.3%
1/30 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
13.0%
3/23 • Number of events 3 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/26 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
4.3%
3/69 • Number of events 3 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Musculoskeletal and connective tissue disorders
Pain in Extremity
|
10.0%
3/30 • Number of events 4 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/23 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
11.5%
3/26 • Number of events 5 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
5.8%
4/69 • Number of events 4 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Nervous system disorders
Dizziness
|
6.7%
2/30 • Number of events 2 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
4.3%
1/23 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
3.8%
1/26 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
13.0%
9/69 • Number of events 12 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Nervous system disorders
Dysgeusia
|
3.3%
1/30 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
4.3%
1/23 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
15.4%
4/26 • Number of events 4 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
13.0%
9/69 • Number of events 9 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Nervous system disorders
Headache
|
10.0%
3/30 • Number of events 4 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
4.3%
1/23 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
15.4%
4/26 • Number of events 4 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
17.4%
12/69 • Number of events 21 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Nervous system disorders
Peripheral Sensory Neuropathy
|
6.7%
2/30 • Number of events 2 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/23 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/26 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
2.9%
2/69 • Number of events 3 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
3.3%
1/30 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
8.7%
2/23 • Number of events 2 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
3.8%
1/26 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
17.4%
12/69 • Number of events 13 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
10.0%
3/30 • Number of events 3 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
8.7%
2/23 • Number of events 4 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
3.8%
1/26 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
26.1%
18/69 • Number of events 21 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Skin and subcutaneous tissue disorders
Dry Skin
|
0.00%
0/30 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/23 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
11.5%
3/26 • Number of events 3 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/69 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/30 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
17.4%
4/23 • Number of events 5 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
7.7%
2/26 • Number of events 2 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
4.3%
3/69 • Number of events 4 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Vascular disorders
Hot Flush
|
13.3%
4/30 • Number of events 4 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
4.3%
1/23 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
7.7%
2/26 • Number of events 2 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
5.8%
4/69 • Number of events 4 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Vascular disorders
Hypertension
|
3.3%
1/30 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
8.7%
2/23 • Number of events 2 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
3.8%
1/26 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
7.2%
5/69 • Number of events 5 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Reproductive system and breast disorders
Vaginal Discharge
|
6.7%
2/30 • Number of events 2 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/23 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/26 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
2.9%
2/69 • Number of events 2 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Gastrointestinal disorders
Abdominal Discomfort
|
3.3%
1/30 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/23 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/26 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
5.8%
4/69 • Number of events 4 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Gastrointestinal disorders
Abdominal Pain Lower
|
0.00%
0/30 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
4.3%
1/23 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
3.8%
1/26 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
5.8%
4/69 • Number of events 4 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Gastrointestinal disorders
Stomatitis
|
3.3%
1/30 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
4.3%
1/23 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/26 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
5.8%
4/69 • Number of events 6 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
General disorders
Pyrexia
|
3.3%
1/30 • Number of events 2 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/23 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
3.8%
1/26 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
14.5%
10/69 • Number of events 10 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Infections and infestations
Nasopharyngitis
|
3.3%
1/30 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/23 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
3.8%
1/26 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
8.7%
6/69 • Number of events 7 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/30 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
4.3%
1/23 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/26 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
10.1%
7/69 • Number of events 8 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Chest Pain
|
3.3%
1/30 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/23 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/26 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
7.2%
5/69 • Number of events 6 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/30 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
4.3%
1/23 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
3.8%
1/26 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
8.7%
6/69 • Number of events 7 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/30 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
4.3%
1/23 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
3.8%
1/26 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
13.0%
9/69 • Number of events 9 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Investigations
Alanine Aminotransferase Increased
|
3.3%
1/30 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/23 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
3.8%
1/26 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
5.8%
4/69 • Number of events 5 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Investigations
Aspartate Aminotransferase Increased
|
0.00%
0/30 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/23 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
3.8%
1/26 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
7.2%
5/69 • Number of events 6 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Investigations
Gamma-glutamyltransferase Increased
|
3.3%
1/30 • Number of events 2 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
4.3%
1/23 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
3.8%
1/26 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
5.8%
4/69 • Number of events 4 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
|
Cardiac disorders
Palpitations
|
0.00%
0/30 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
4.3%
1/23 • Number of events 1 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
0.00%
0/26 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
5.8%
4/69 • Number of events 6 • For Part A, adverse events (AEs) were collected from the date of first dose up to last dose of study medication in Part A for patients continuing to Part B, or up to 30 days after last dose for patients who did not enter Part B (up to approximately 2 months). For Part B, AEs were collected from date of first dose in Part B up to 30 days after last dose (up to approximately 18 months).
AE data is reported as treatment-emergent AEs. Each Part A cohort received treatment over 3 Treatment Periods. There was a washout period of 4 days between Treatment Periods 1 and 2, and no washout period between Treatment Periods 2 and 3. MedDRA v18.1 was used for Part B.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place