Trial Outcomes & Findings for Pharmacokinetics and Safety Study of Omecamtiv Mecarbil in Healthy Japanese Adults (NCT NCT02601001)
NCT ID: NCT02601001
Last Updated: 2021-07-27
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
50 participants
Primary outcome timeframe
Day 1 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose. Day 8 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours after the morning dose.
Results posted on
2021-07-27
Participant Flow
This study was conducted at a single center in Japan. Participants were enrolled from 13 November 2015 to 24 November 2015.
Participants were randomly assigned to one of three treatment groups in a 1:2:2 ratio. The study consisted of a screening period, two 8-day treatment periods with an 11-day drug holiday in between, and an end of study (EOS) visit on day 35.
Participant milestones
| Measure |
Placebo
Participants received placebo tablets twice a day (BID) in dosing period 1 (days 1 to 8) and in dosing period 2 (days 20 to 27).
|
Period 1 Group A: Omecamtiv Mecarbil 25 mg
Participants received omecamtiv mecarbil (OM) 25 mg BID in dosing period 1 (days 1 to 8).
|
Period 1 Group B: Omecamtiv Mecarbil 25 mg
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8).
|
Period 2 Group A: Omecamtiv Mecarbil 25 mg
Participants who received omecamtiv mecarbil 25 mg BID in dosing period 1 then received omecamtiv mecarbil 25 mg BID in dosing period 2 (days 20 to 27) based on their day 8 predose omecamtiv mecarbil plasma concentration (Cpredose).
|
Period 2 Group A: Omecamtiv Mecarbil 37.5 mg
Participants who received omecamtiv mecarbil 25 mg BID in dosing period 1 then received omecamtiv mecarbil 37.5 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
Period 2 Group B: Omecamtiv Mecarbil 25 mg
Participants who received omecamtiv mecarbil 25 mg BID in dosing period 1 then received omecamtiv mecarbil 25 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
Period 2 Group B: Omecamtiv Mecarbil 50 mg
Participants who received omecamtiv mecarbil 25 mg BID in dosing period 1 then received omecamtiv mecarbil 50 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
|---|---|---|---|---|---|---|---|
|
Dosing Period 1
STARTED
|
10
|
20
|
20
|
0
|
0
|
0
|
0
|
|
Dosing Period 1
COMPLETED
|
10
|
20
|
20
|
0
|
0
|
0
|
0
|
|
Dosing Period 1
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Dosing Period 2
STARTED
|
10
|
0
|
0
|
7
|
13
|
7
|
13
|
|
Dosing Period 2
COMPLETED
|
10
|
0
|
0
|
7
|
13
|
7
|
12
|
|
Dosing Period 2
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
Reasons for withdrawal
| Measure |
Placebo
Participants received placebo tablets twice a day (BID) in dosing period 1 (days 1 to 8) and in dosing period 2 (days 20 to 27).
|
Period 1 Group A: Omecamtiv Mecarbil 25 mg
Participants received omecamtiv mecarbil (OM) 25 mg BID in dosing period 1 (days 1 to 8).
|
Period 1 Group B: Omecamtiv Mecarbil 25 mg
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8).
|
Period 2 Group A: Omecamtiv Mecarbil 25 mg
Participants who received omecamtiv mecarbil 25 mg BID in dosing period 1 then received omecamtiv mecarbil 25 mg BID in dosing period 2 (days 20 to 27) based on their day 8 predose omecamtiv mecarbil plasma concentration (Cpredose).
|
Period 2 Group A: Omecamtiv Mecarbil 37.5 mg
Participants who received omecamtiv mecarbil 25 mg BID in dosing period 1 then received omecamtiv mecarbil 37.5 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
Period 2 Group B: Omecamtiv Mecarbil 25 mg
Participants who received omecamtiv mecarbil 25 mg BID in dosing period 1 then received omecamtiv mecarbil 25 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
Period 2 Group B: Omecamtiv Mecarbil 50 mg
Participants who received omecamtiv mecarbil 25 mg BID in dosing period 1 then received omecamtiv mecarbil 50 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
|---|---|---|---|---|---|---|---|
|
Dosing Period 2
Adverse Event
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
Baseline Characteristics
Pharmacokinetics and Safety Study of Omecamtiv Mecarbil in Healthy Japanese Adults
Baseline characteristics by cohort
| Measure |
Placebo
n=10 Participants
Participants received placebo tablets twice a day (BID) in dosing period 1 (days 1 to 8) and in dosing period 2 (days 20 to 27).
|
Group A: Omecamtiv Mecarbil 25 mg / 37.5 mg
n=20 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 25 mg or 37.5 mg BID in dosing period 2 (days 20 to 27) based on their day 8 predose omecamtiv mecarbil plasma concentration (Cpredose): If day 8 Cpredose was \< 200 ng/mL, participants received 37.5 mg BID; if day 8 Cpredose was ≥ 200 ng/mL participants continued to receive 25 mg BID.
|
Group B: Omecamtiv Mecarbil 25 mg / 50 mg
n=20 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 25 mg or 50 mg BID in dosing period 2 (days 20 to 27) based on their day 8 predose omecamtiv mecarbil plasma concentration (Cpredose): If day 8 Cpredose was \< 200 ng/mL, participants received 50 mg BID; if day 8 Cpredose was ≥ 200 ng/mL participants continued to receive 25 mg BID.
|
Total
n=50 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
29.2 years
STANDARD_DEVIATION 4.2 • n=113 Participants
|
35.5 years
STANDARD_DEVIATION 7.6 • n=163 Participants
|
27.3 years
STANDARD_DEVIATION 4.6 • n=160 Participants
|
31.0 years
STANDARD_DEVIATION 7.0 • n=483 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=113 Participants
|
6 Participants
n=163 Participants
|
6 Participants
n=160 Participants
|
15 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=113 Participants
|
14 Participants
n=163 Participants
|
14 Participants
n=160 Participants
|
35 Participants
n=483 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=113 Participants
|
0 Participants
n=163 Participants
|
0 Participants
n=160 Participants
|
0 Participants
n=483 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
10 Participants
n=113 Participants
|
20 Participants
n=163 Participants
|
20 Participants
n=160 Participants
|
50 Participants
n=483 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=113 Participants
|
0 Participants
n=163 Participants
|
0 Participants
n=160 Participants
|
0 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
0 Participants
n=113 Participants
|
0 Participants
n=163 Participants
|
0 Participants
n=160 Participants
|
0 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
Asian
|
10 Participants
n=113 Participants
|
20 Participants
n=163 Participants
|
20 Participants
n=160 Participants
|
50 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
0 Participants
n=113 Participants
|
0 Participants
n=163 Participants
|
0 Participants
n=160 Participants
|
0 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=113 Participants
|
0 Participants
n=163 Participants
|
0 Participants
n=160 Participants
|
0 Participants
n=483 Participants
|
|
Race/Ethnicity, Customized
White
|
0 Participants
n=113 Participants
|
0 Participants
n=163 Participants
|
0 Participants
n=160 Participants
|
0 Participants
n=483 Participants
|
PRIMARY outcome
Timeframe: Day 1 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose. Day 8 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours after the morning dose.Population: The pharmacokinetic (PK) analysis set included all randomized participants who received at least 1 dose of omecamtiv mecarbil and had at least 1 evaluable omecamtiv mecarbil PK parameter.
Outcome measures
| Measure |
Group A: Omecamtiv Mecarbil 25 mg
n=20 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8).
|
Group B: Omecamtiv Mecarbil 25 mg
n=20 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8).
|
Group B: Omecamtiv Mecarbil 25 mg / 25 mg
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 25 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
Group B: Omecamtiv Mecarbil 25 mg / 50 mg
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 50 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
Group B: Omecamtiv Mecarbil 25 mg / 50 mg
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 50 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
|---|---|---|---|---|---|
|
Dosing Period 1: Maximum Observed Plasma Concentration (Cmax) of Omecamtiv Mecarbil After First and Last Dose in Period 1
After first dose on day 1
|
77.4 ng/mL
Standard Deviation 21.6
|
79.5 ng/mL
Standard Deviation 18.9
|
—
|
—
|
—
|
|
Dosing Period 1: Maximum Observed Plasma Concentration (Cmax) of Omecamtiv Mecarbil After First and Last Dose in Period 1
After last dose on day 8
|
256 ng/mL
Standard Deviation 71.2
|
259 ng/mL
Standard Deviation 59.2
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Day 1 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose. Day 8 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours after the morning dose.Population: PK analysis set
Outcome measures
| Measure |
Group A: Omecamtiv Mecarbil 25 mg
n=20 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8).
|
Group B: Omecamtiv Mecarbil 25 mg
n=20 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8).
|
Group B: Omecamtiv Mecarbil 25 mg / 25 mg
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 25 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
Group B: Omecamtiv Mecarbil 25 mg / 50 mg
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 50 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
Group B: Omecamtiv Mecarbil 25 mg / 50 mg
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 50 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
|---|---|---|---|---|---|
|
Dosing Period 1: Time to Maximum Observed Plasma Concentration (Tmax) of Omecamtiv Mecarbil After First and Last Dose in Period 1
After first dose on day 1
|
4.0 hours
Interval 0.5 to 8.0
|
3.0 hours
Interval 0.5 to 8.0
|
—
|
—
|
—
|
|
Dosing Period 1: Time to Maximum Observed Plasma Concentration (Tmax) of Omecamtiv Mecarbil After First and Last Dose in Period 1
After last dose on day 8
|
2.0 hours
Interval 0.5 to 4.0
|
2.0 hours
Interval 0.5 to 8.0
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Day 1 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose. Day 8 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose.Population: The PK analysis set with available AUC data at each time point
Outcome measures
| Measure |
Group A: Omecamtiv Mecarbil 25 mg
n=20 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8).
|
Group B: Omecamtiv Mecarbil 25 mg
n=20 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8).
|
Group B: Omecamtiv Mecarbil 25 mg / 25 mg
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 25 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
Group B: Omecamtiv Mecarbil 25 mg / 50 mg
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 50 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
Group B: Omecamtiv Mecarbil 25 mg / 50 mg
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 50 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
|---|---|---|---|---|---|
|
Dosing Period 1: Area Under the Concentration-time Curve for a Dosing Interval of 12 Hours (AUC0-12) for Omecamtiv Mecarbil After First and Last Dose in Period 1
After first dose on day 1
|
687 ng*hr/mL
Standard Deviation 210
|
677 ng*hr/mL
Standard Deviation 163
|
—
|
—
|
—
|
|
Dosing Period 1: Area Under the Concentration-time Curve for a Dosing Interval of 12 Hours (AUC0-12) for Omecamtiv Mecarbil After First and Last Dose in Period 1
After last dose on day 8
|
2570 ng*hr/mL
Standard Deviation 739
|
2670 ng*hr/mL
Standard Deviation 699
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Day 8 predosePopulation: PK analysis set
Outcome measures
| Measure |
Group A: Omecamtiv Mecarbil 25 mg
n=20 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8).
|
Group B: Omecamtiv Mecarbil 25 mg
n=20 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8).
|
Group B: Omecamtiv Mecarbil 25 mg / 25 mg
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 25 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
Group B: Omecamtiv Mecarbil 25 mg / 50 mg
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 50 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
Group B: Omecamtiv Mecarbil 25 mg / 50 mg
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 50 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
|---|---|---|---|---|---|
|
Dosing Period 1: Predose Omecamtiv Mecarbil Plasma Concentration
|
190 ng/mL
Standard Deviation 58.5
|
192 ng/mL
Standard Deviation 55.1
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Day 1 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose. Day 8 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose.Population: The PK analysis set with available AUC data at both time points
Accumulation ratio calculated as the ratio of day 8 AUC(0-12) / day 1 AUC(0-12)
Outcome measures
| Measure |
Group A: Omecamtiv Mecarbil 25 mg
n=10 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8).
|
Group B: Omecamtiv Mecarbil 25 mg
n=14 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8).
|
Group B: Omecamtiv Mecarbil 25 mg / 25 mg
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 25 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
Group B: Omecamtiv Mecarbil 25 mg / 50 mg
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 50 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
Group B: Omecamtiv Mecarbil 25 mg / 50 mg
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 50 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
|---|---|---|---|---|---|
|
Dosing Period 1: Accumulation Ratio
|
3.66 ratio
Standard Deviation 0.89
|
3.79 ratio
Standard Deviation 0.77
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Day 20 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose. Day 27 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours after the morning dose.Population: Pharmacokinetic analysis set with available data at each time point
Outcome measures
| Measure |
Group A: Omecamtiv Mecarbil 25 mg
n=7 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8).
|
Group B: Omecamtiv Mecarbil 25 mg
n=13 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8).
|
Group B: Omecamtiv Mecarbil 25 mg / 25 mg
n=7 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 25 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
Group B: Omecamtiv Mecarbil 25 mg / 50 mg
n=13 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 50 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
Group B: Omecamtiv Mecarbil 25 mg / 50 mg
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 50 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
|---|---|---|---|---|---|
|
Dosing Period 2: Maximum Observed Plasma Concentration (Cmax) of Omecamtiv Mecarbil After First and Last Dose in Period 2
After first dose on day 20
|
96.5 ng/mL
Standard Deviation 27.2
|
107 ng/mL
Standard Deviation 30.4
|
84.9 ng/mL
Standard Deviation 30.0
|
154 ng/mL
Standard Deviation 22.0
|
—
|
|
Dosing Period 2: Maximum Observed Plasma Concentration (Cmax) of Omecamtiv Mecarbil After First and Last Dose in Period 2
After last dose on day 27
|
335 ng/mL
Standard Deviation 32.0
|
341 ng/mL
Standard Deviation 48.8
|
311 ng/mL
Standard Deviation 54.2
|
537 ng/mL
Standard Deviation 91.7
|
—
|
PRIMARY outcome
Timeframe: Day 20 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose. Day 27 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours after the morning dose.Population: Pharmacokinetic analysis set with available data at each time point
Outcome measures
| Measure |
Group A: Omecamtiv Mecarbil 25 mg
n=7 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8).
|
Group B: Omecamtiv Mecarbil 25 mg
n=13 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8).
|
Group B: Omecamtiv Mecarbil 25 mg / 25 mg
n=7 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 25 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
Group B: Omecamtiv Mecarbil 25 mg / 50 mg
n=13 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 50 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
Group B: Omecamtiv Mecarbil 25 mg / 50 mg
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 50 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
|---|---|---|---|---|---|
|
Dosing Period 2: Time to Maximum Observed Plasma Concentration (Tmax) of Omecamtiv Mecarbil After First and Last Dose in Period 2
After first dose on day 20
|
4.0 hours
Interval 2.0 to 11.0
|
2.0 hours
Interval 0.5 to 6.0
|
4.0 hours
Interval 1.0 to 11.0
|
3.0 hours
Interval 0.5 to 6.0
|
—
|
|
Dosing Period 2: Time to Maximum Observed Plasma Concentration (Tmax) of Omecamtiv Mecarbil After First and Last Dose in Period 2
After last dose on day 27
|
2.0 hours
Interval 0.5 to 4.0
|
3.0 hours
Interval 0.5 to 4.0
|
4.0 hours
Interval 0.5 to 4.0
|
3.0 hours
Interval 0.5 to 4.0
|
—
|
PRIMARY outcome
Timeframe: Day 20 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose. Day 27 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose.Population: Pharmacokinetic analysis set with available AUC data at each time point
Outcome measures
| Measure |
Group A: Omecamtiv Mecarbil 25 mg
n=7 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8).
|
Group B: Omecamtiv Mecarbil 25 mg
n=13 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8).
|
Group B: Omecamtiv Mecarbil 25 mg / 25 mg
n=7 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 25 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
Group B: Omecamtiv Mecarbil 25 mg / 50 mg
n=13 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 50 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
Group B: Omecamtiv Mecarbil 25 mg / 50 mg
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 50 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
|---|---|---|---|---|---|
|
Dosing Period 2: AUC(0-12) for Omecamtiv Mecarbil After First and Last Dose in Period 2
After first dose on day 20
|
902 ng*hr/mL
Standard Deviation 220
|
950 ng*hr/mL
Standard Deviation 228
|
841 ng*hr/mL
Standard Deviation 403
|
1330 ng*hr/mL
Standard Deviation 217
|
—
|
|
Dosing Period 2: AUC(0-12) for Omecamtiv Mecarbil After First and Last Dose in Period 2
After last dose on day 27
|
3520 ng*hr/mL
Standard Deviation 505
|
3500 ng*hr/mL
Standard Deviation 519
|
3290 ng*hr/mL
Standard Deviation 662
|
5490 ng*hr/mL
Standard Deviation 1000
|
—
|
PRIMARY outcome
Timeframe: Day 27 predosePopulation: PK analysis set
Outcome measures
| Measure |
Group A: Omecamtiv Mecarbil 25 mg
n=7 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8).
|
Group B: Omecamtiv Mecarbil 25 mg
n=13 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8).
|
Group B: Omecamtiv Mecarbil 25 mg / 25 mg
n=7 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 25 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
Group B: Omecamtiv Mecarbil 25 mg / 50 mg
n=12 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 50 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
Group B: Omecamtiv Mecarbil 25 mg / 50 mg
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 50 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
|---|---|---|---|---|---|
|
Dosing Period 2: Predose Omecamtiv Mecarbil Plasma Concentration
|
271 ng/mL
Standard Deviation 44.8
|
256 ng/mL
Standard Deviation 42.1
|
245 ng/mL
Standard Deviation 43.3
|
401 ng/mL
Standard Deviation 77.8
|
—
|
PRIMARY outcome
Timeframe: Day 20 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose. Day 27 at 0 hours and 0.5, 1, 2, 3, 4, 6, 8, and 12 hours after the morning dose.Population: Pharmacokinetic analysis set with available AUC data at both time points
Accumulation ratio calculated as the ratio of day 27 AUC(0-12) / day 20 AUC(0-12).
Outcome measures
| Measure |
Group A: Omecamtiv Mecarbil 25 mg
n=4 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8).
|
Group B: Omecamtiv Mecarbil 25 mg
n=10 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8).
|
Group B: Omecamtiv Mecarbil 25 mg / 25 mg
n=4 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 25 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
Group B: Omecamtiv Mecarbil 25 mg / 50 mg
n=9 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 50 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
Group B: Omecamtiv Mecarbil 25 mg / 50 mg
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 50 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
|---|---|---|---|---|---|
|
Dosing Period 2: Accumulation Ratio
|
4.12 ratio
Standard Deviation 1.28
|
3.81 ratio
Standard Deviation 0.83
|
4.53 ratio
Standard Deviation 1.19
|
4.11 ratio
Standard Deviation 1.15
|
—
|
SECONDARY outcome
Timeframe: 35 daysPopulation: All randomized participants who received at least one dose of study treatment (omecamtiv mecarbil or placebo).
An adverse event is defined as any untoward medical occurrence in a clinical trial participant, including worsening of a preexisting medical condition. The event does not necessarily have a causal relationship with study treatment. A serious adverse event is defined as an adverse event that met at least 1 of the following serious criteria: * fatal * life threatening * required in patient hospitalization or prolongation of existing hospitalization * resulted in persistent or significant disability/incapacity * congenital anomaly/birth defect * other medically important serious event. Adverse events were graded for severity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Outcome measures
| Measure |
Group A: Omecamtiv Mecarbil 25 mg
n=10 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8).
|
Group B: Omecamtiv Mecarbil 25 mg
n=7 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8).
|
Group B: Omecamtiv Mecarbil 25 mg / 25 mg
n=13 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 25 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
Group B: Omecamtiv Mecarbil 25 mg / 50 mg
n=7 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 50 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
Group B: Omecamtiv Mecarbil 25 mg / 50 mg
n=13 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 50 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
|---|---|---|---|---|---|
|
Number of Participants With Treatment-emergent Adverse Events
Any treatment-emergent adverse event
|
6 Participants
|
4 Participants
|
7 Participants
|
4 Participants
|
3 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events
Serious adverse events
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events
TEAE leading to discontinuation of study drug
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events
Severe adverse events
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events
Life-threatening adverse events
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events
Fatal adverse events
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 35 daysPopulation: All randomized participants who received at least one dose of study treatment (omecamtiv mecarbil or placebo).
Abnormal laboratory findings were graded for severity according to the NCI CTCAE version 4.0 according to the following guideline: * Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. * Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL). * Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. * Grade 4: Life-threatening consequences; urgent intervention indicated. * Grade 5: Death related to AE.
Outcome measures
| Measure |
Group A: Omecamtiv Mecarbil 25 mg
n=10 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8).
|
Group B: Omecamtiv Mecarbil 25 mg
n=7 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8).
|
Group B: Omecamtiv Mecarbil 25 mg / 25 mg
n=13 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 25 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
Group B: Omecamtiv Mecarbil 25 mg / 50 mg
n=7 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 50 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
Group B: Omecamtiv Mecarbil 25 mg / 50 mg
n=13 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 50 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
|---|---|---|---|---|---|
|
Number of Participants With Grade 3 or Higher Laboratory Toxicities
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Day 1 predose and day 8Population: All randomized participants who received at least one dose of study treatment (omecamtiv mecarbil or placebo).
QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle as measured by electrocardiogram (ECG). Maximum increase from Period 1 baseline was categorized as: ≤ 30 milliseconds (ms) \> 30 to 60 ms \> 60 ms
Outcome measures
| Measure |
Group A: Omecamtiv Mecarbil 25 mg
n=10 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8).
|
Group B: Omecamtiv Mecarbil 25 mg
n=7 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8).
|
Group B: Omecamtiv Mecarbil 25 mg / 25 mg
n=13 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 25 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
Group B: Omecamtiv Mecarbil 25 mg / 50 mg
n=7 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 50 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
Group B: Omecamtiv Mecarbil 25 mg / 50 mg
n=13 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 50 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
|---|---|---|---|---|---|
|
Maximum Increase From Baseline in Fridericia-Corrected QT Interval (QTcF) In Dosing Period 1
≤ 30 ms
|
10 Participants
|
7 Participants
|
13 Participants
|
7 Participants
|
13 Participants
|
|
Maximum Increase From Baseline in Fridericia-Corrected QT Interval (QTcF) In Dosing Period 1
> 30 to 60 ms
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Maximum Increase From Baseline in Fridericia-Corrected QT Interval (QTcF) In Dosing Period 1
> 60 ms
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Day 20 predose and Day 27Population: Randomized participants who received at least one dose of study treatment (omecamtiv mecarbil or placebo), with available data.
QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle as measured by ECG. Maximum increase from Period 2 baseline was categorized as: ≤ 30 ms \> 30 to 60 ms \> 60 ms
Outcome measures
| Measure |
Group A: Omecamtiv Mecarbil 25 mg
n=10 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8).
|
Group B: Omecamtiv Mecarbil 25 mg
n=7 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8).
|
Group B: Omecamtiv Mecarbil 25 mg / 25 mg
n=13 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 25 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
Group B: Omecamtiv Mecarbil 25 mg / 50 mg
n=7 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 50 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
Group B: Omecamtiv Mecarbil 25 mg / 50 mg
n=12 Participants
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8) and 50 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
|---|---|---|---|---|---|
|
Maximum Increase From Baseline in Fridericia-Corrected QT Interval (QTcF) In Dosing Period 2
≤ 30 ms
|
10 Participants
|
7 Participants
|
13 Participants
|
7 Participants
|
12 Participants
|
|
Maximum Increase From Baseline in Fridericia-Corrected QT Interval (QTcF) In Dosing Period 2
> 30 to 60 ms
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Maximum Increase From Baseline in Fridericia-Corrected QT Interval (QTcF) In Dosing Period 2
> 60 ms
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
Adverse Events
Period 1: Placebo
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Period 1 Group A: OM 25 mg BID
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Period 1 Group B: OM 25 mg BID
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Period 2: Placebo
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Period 2 Group A: OM 25 mg BID
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Period 2 Group A: OM 37.5 mg BID
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Period 2 Group B: OM 25 mg BID
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Period 2 Group B: OM 50 mg BID
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Period 1: Placebo
n=10 participants at risk
Participants received placebo tablets twice a day (BID) in dosing period 1 (days 1 to 8).
|
Period 1 Group A: OM 25 mg BID
n=20 participants at risk
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8).
|
Period 1 Group B: OM 25 mg BID
n=20 participants at risk
Participants received omecamtiv mecarbil 25 mg BID in dosing period 1 (days 1 to 8).
|
Period 2: Placebo
n=10 participants at risk
Participants received placebo tablets BID in dosing period 2 (days 20 to 27).
|
Period 2 Group A: OM 25 mg BID
n=7 participants at risk
Participants received omecamtiv mecarbil 25 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
Period 2 Group A: OM 37.5 mg BID
n=13 participants at risk
Participants received omecamtiv mecarbil 37.5 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
Period 2 Group B: OM 25 mg BID
n=7 participants at risk
Participants received omecamtiv mecarbil 25 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
Period 2 Group B: OM 50 mg BID
n=13 participants at risk
Participants received omecamtiv mecarbil 50 mg BID in dosing period 2 (days 20 to 27) based on their day 8 omecamtiv mecarbil Cpredose.
|
|---|---|---|---|---|---|---|---|---|
|
Cardiac disorders
Ventricular tachycardia
|
0.00%
0/10 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/20 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/20 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/10 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/7 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/13 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/7 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
7.7%
1/13 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Nausea
|
10.0%
1/10 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/20 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/20 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/10 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/7 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/13 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/7 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/13 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
|
General disorders
Chest pain
|
0.00%
0/10 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/20 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/20 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
10.0%
1/10 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/7 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/13 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/7 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/13 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
|
General disorders
Injection site nerve damage
|
0.00%
0/10 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/20 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/20 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/10 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/7 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/13 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
14.3%
1/7 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/13 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
|
Infections and infestations
Chronic tonsillitis
|
0.00%
0/10 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/20 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/20 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/10 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/7 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/13 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/7 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
7.7%
1/13 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
|
Infections and infestations
Herpes zoster
|
0.00%
0/10 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/20 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
5.0%
1/20 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/10 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/7 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/13 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/7 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/13 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
|
Infections and infestations
Pharyngitis
|
0.00%
0/10 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/20 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/20 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/10 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/7 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/13 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/7 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
7.7%
1/13 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/10 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
10.0%
2/20 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/20 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
20.0%
2/10 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
14.3%
1/7 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
23.1%
3/13 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/7 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
7.7%
1/13 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/10 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
5.0%
1/20 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/20 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
10.0%
1/10 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/7 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/13 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/7 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
7.7%
1/13 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/10 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
5.0%
1/20 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/20 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/10 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/7 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/13 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/7 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/13 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
|
Investigations
Protein urine present
|
0.00%
0/10 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/20 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/20 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/10 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
14.3%
1/7 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/13 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/7 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/13 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/10 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/20 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/20 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
10.0%
1/10 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/7 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/13 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/7 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/13 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
10.0%
1/10 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/20 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/20 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/10 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/7 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/13 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/7 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/13 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
|
Nervous system disorders
Headache
|
0.00%
0/10 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/20 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
5.0%
1/20 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/10 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/7 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/13 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/7 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/13 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
10.0%
1/10 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/20 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/20 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/10 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/7 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/13 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/7 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/13 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract inflammation
|
0.00%
0/10 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
10.0%
2/20 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/20 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/10 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
14.3%
1/7 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/13 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/7 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/13 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
0.00%
0/10 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/20 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
10.0%
2/20 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/10 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/7 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/13 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/7 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/13 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
|
Vascular disorders
Orthostatic hypotension
|
0.00%
0/10 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/20 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/20 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/10 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
14.3%
1/7 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/13 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/7 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
0.00%
0/13 • Period 1: Day 1 to day 19 Period 2: Day 20 to day 35
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
- Publication restrictions are in place
Restriction type: OTHER