Trial Outcomes & Findings for Safety, PK, and Efficacy of Omecamtiv Mecarbil in Japanese Subjects With Heart Failure With Reduced Ejection Fraction (NCT NCT02695420)

NCT ID: NCT02695420

Last Updated: 2021-07-27

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

81 participants

Primary outcome timeframe

Before morning dose on Week 2 (Day 15), Week 4 (Day 28), Week 12 (Day 84), Week 16 (Day 112)

Results posted on

2021-07-27

Participant Flow

Participants were enrolled at 31 research centers in Japan from 14 April 2016 to 16 December 2016.

Participants were randomized at a ratio of 1:1:1:1 to twice daily (BID) placebo, 25 mg, 25 mg-\>37.5 mg Target Dose, or 25 mg-\>50 mg Target Dose, respectively. Randomization was stratified by presence or absence of atrial fibrillation/flutter.

Participant milestones

Participant milestones
Measure	Placebo BID Placebo for omecamtiv mecarbil BID	Omecamtiv Mecarbil 25 mg BID Omecamtiv mecarbil 25 mg BID	Omecamtiv Mecarbil 25 mg to 37.5 mg BID Target Dose Omecamtiv mecarbil 25 mg BID up to Week 4 or Week 8 and 25 mg or 37.5 mg BID after Week 4 or Week 8, based on Week 2 PK	Omecamtiv Mecarbil 25 mg to 50 mg BID Target Dose Omecamtiv Mecarbil 25 mg BID up to Week 4 or Week 8 and 25 mg or 50 mg BID after Week 4 or Week 8, based on Week 2 PK
Overall Study STARTED	21	21	19	20
Overall Study COMPLETED	21	20	19	20
Overall Study NOT COMPLETED	0	1	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo BID Placebo for omecamtiv mecarbil BID	Omecamtiv Mecarbil 25 mg BID Omecamtiv mecarbil 25 mg BID	Omecamtiv Mecarbil 25 mg to 37.5 mg BID Target Dose Omecamtiv mecarbil 25 mg BID up to Week 4 or Week 8 and 25 mg or 37.5 mg BID after Week 4 or Week 8, based on Week 2 PK	Omecamtiv Mecarbil 25 mg to 50 mg BID Target Dose Omecamtiv Mecarbil 25 mg BID up to Week 4 or Week 8 and 25 mg or 50 mg BID after Week 4 or Week 8, based on Week 2 PK
Overall Study Death	0	1	0	0

Baseline Characteristics

Safety, PK, and Efficacy of Omecamtiv Mecarbil in Japanese Subjects With Heart Failure With Reduced Ejection Fraction

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo BID n=21 Participants Placebo for omecamtiv mecarbil BID	Omecamtiv Mecarbil 25 mg BID n=21 Participants Omecamtiv mecarbil 25 mg BID	Omecamtiv Mecarbil 25 mg to 37.5 mg BID Target Dose n=19 Participants Omecamtiv mecarbil 25 mg BID up to Week 4 or Week 8 and 25 mg or 37.5 mg BID after Week 4 or Week 8, based on Week 2 PK	Omecamtiv Mecarbil 25 mg to 50 mg BID Target Dose n=20 Participants Omecamtiv Mecarbil 25 mg BID up to Week 4 or Week 8 and 25 mg or 50 mg BID after Week 4 or Week 8, based on Week 2 PK	Total n=81 Participants Total of all reporting groups
Age, Continuous	64.6 years STANDARD_DEVIATION 11.5 • n=5 Participants	66.9 years STANDARD_DEVIATION 10.3 • n=7 Participants	63.6 years STANDARD_DEVIATION 10.8 • n=5 Participants	66.5 years STANDARD_DEVIATION 12.2 • n=4 Participants	65.4 years STANDARD_DEVIATION 11.1 • n=21 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	13 Participants n=21 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	18 Participants n=7 Participants	19 Participants n=5 Participants	19 Participants n=4 Participants	68 Participants n=21 Participants
Race/Ethnicity, Customized Asian	21 participants n=5 Participants	21 participants n=7 Participants	19 participants n=5 Participants	20 participants n=4 Participants	81 participants n=21 Participants
Race/Ethnicity, Customized Other	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	0 participants n=21 Participants
Race/Ethnicity, Customized Japanese	21 participants n=5 Participants	21 participants n=7 Participants	19 participants n=5 Participants	20 participants n=4 Participants	81 participants n=21 Participants
Atrial Fibrillation/Flutter at Randomization Present	4 participants n=5 Participants	4 participants n=7 Participants	3 participants n=5 Participants	4 participants n=4 Participants	15 participants n=21 Participants
Atrial Fibrillation/Flutter at Randomization Absent	17 participants n=5 Participants	17 participants n=7 Participants	16 participants n=5 Participants	16 participants n=4 Participants	66 participants n=21 Participants

PRIMARY outcome

Timeframe: Before morning dose on Week 2 (Day 15), Week 4 (Day 28), Week 12 (Day 84), Week 16 (Day 112)

Population: PK Analysis Set: all randomized participants who received at least one dose of omecamtiv mecarbil and had at least one evaluable omecamtiv mecarbil PK concentration at given time point.

Outcome measures

Outcome measures
Measure	Omecamtiv Mecarbil 25 mg BID n=20 Participants Omecamtiv mecarbil 25 mg BID	Omecamtiv Mecarbil 25 mg to 37.5 mg BID Target Dose n=18 Participants Omecamtiv mecarbil 25 mg BID up to Week 4 or Week 8 and 25 mg or 37.5 mg BID after Week 4 or Week 8, based on Week 2 PK	Omecamtiv Mecarbil 25 mg to 50 mg BID Target Dose n=20 Participants Omecamtiv Mecarbil 25 mg BID up to Week 4 or Week 8 and 25 mg or 50 mg BID after Week 4 or Week 8, based on Week 2 PK	Omecamtiv Mecarbil 25 mg to 50 mg BID Target Dose Omecamtiv Mecarbil 25 mg BID up to Week 4 or Week 8 and 25 mg or 50 mg BID after Week 4 or Week 8, based on Week 2 PK
Pharmacokinetics (PK): Concentration Before Morning Dose (Cpredose) Over Time Week 4	222 ng/mL Standard Deviation 63.5	196 ng/mL Standard Deviation 44	209 ng/mL Standard Deviation 61.9	—
Pharmacokinetics (PK): Concentration Before Morning Dose (Cpredose) Over Time Week 2	239 ng/mL Standard Deviation 106	179 ng/mL Standard Deviation 77.1	208 ng/mL Standard Deviation 61.6	—
Pharmacokinetics (PK): Concentration Before Morning Dose (Cpredose) Over Time Week 12	217 ng/mL Standard Deviation 66.1	228 ng/mL Standard Deviation 56.9	282 ng/mL Standard Deviation 120	—
Pharmacokinetics (PK): Concentration Before Morning Dose (Cpredose) Over Time Week 16	206 ng/mL Standard Deviation 84.5	244 ng/mL Standard Deviation 67.7	292 ng/mL Standard Deviation 118	—

PRIMARY outcome

Timeframe: Week 8 (Day 56) at predose, at 2 hours ±30 minutes; 4 hours ±30 minutes; 6 hours ±30 minutes; 8 hours ±30 minutes after morning dose

Population: PK Analysis Set: all randomized participants who received at least one dose of omecamtiv mecarbil and had at least one evaluable omecamtiv mecarbil PK concentration.

Outcome measures

Outcome measures
Measure	Omecamtiv Mecarbil 25 mg BID n=9 Participants Omecamtiv mecarbil 25 mg BID	Omecamtiv Mecarbil 25 mg to 37.5 mg BID Target Dose n=8 Participants Omecamtiv mecarbil 25 mg BID up to Week 4 or Week 8 and 25 mg or 37.5 mg BID after Week 4 or Week 8, based on Week 2 PK	Omecamtiv Mecarbil 25 mg to 50 mg BID Target Dose n=1 Participants Omecamtiv Mecarbil 25 mg BID up to Week 4 or Week 8 and 25 mg or 50 mg BID after Week 4 or Week 8, based on Week 2 PK	Omecamtiv Mecarbil 25 mg to 50 mg BID Target Dose Omecamtiv Mecarbil 25 mg BID up to Week 4 or Week 8 and 25 mg or 50 mg BID after Week 4 or Week 8, based on Week 2 PK
PK: Area Under the Curve Until 8 Hours After Morning Dose at Week 8 (AUC0-8)	1850 hr*ng/mL Standard Deviation 563	1850 hr*ng/mL Standard Deviation 383	2360 hr*ng/mL Standard Deviation 465	—

SECONDARY outcome

Timeframe: Baseline, Week 16 (Day 112)

Population: All participants who received at least one dose of study drug with observed data. The 4 active treatment arms include only those participants who had a minimum investigational product exposure period of 25 days.

LS mean was from the repeated measures model, which included treatment group, stratification factor (from IVRS), scheduled visit, baseline value, and the interaction of treatment group with scheduled visit as covariates.

Outcome measures

Outcome measures
Measure	Omecamtiv Mecarbil 25 mg BID n=20 Participants Omecamtiv mecarbil 25 mg BID	Omecamtiv Mecarbil 25 mg to 37.5 mg BID Target Dose n=19 Participants Omecamtiv mecarbil 25 mg BID up to Week 4 or Week 8 and 25 mg or 37.5 mg BID after Week 4 or Week 8, based on Week 2 PK	Omecamtiv Mecarbil 25 mg to 50 mg BID Target Dose n=17 Participants Omecamtiv Mecarbil 25 mg BID up to Week 4 or Week 8 and 25 mg or 50 mg BID after Week 4 or Week 8, based on Week 2 PK	Omecamtiv Mecarbil 25 mg to 50 mg BID Target Dose n=17 Participants Omecamtiv Mecarbil 25 mg BID up to Week 4 or Week 8 and 25 mg or 50 mg BID after Week 4 or Week 8, based on Week 2 PK
Change From Baseline at Week 16 in Systolic Ejection Time (SET)	-1.7 msec Standard Error 4.7	20.5 msec Standard Error 4.9	27.6 msec Standard Error 5.4	23.8 msec Standard Error 5.2

OTHER_PRE_SPECIFIED outcome

Timeframe: From first dose of study drug up to Week 20 (Day 140 + 3 days)

Population: Safety Analysis Set: all participants who received at least one dose of study drug.

An adverse event (AE) is defined as any untoward medical occurrence. Serious AEs are defined as AEs that meets at least 1 of the following serious criteria: fatal, life threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, congenital anomaly/birth defect, other medically important serious event. AEs are graded as: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death. TEAEs are defined as events occurring after the first dose of study drug.

Outcome measures

Outcome measures
Measure	Omecamtiv Mecarbil 25 mg BID n=21 Participants Omecamtiv mecarbil 25 mg BID	Omecamtiv Mecarbil 25 mg to 37.5 mg BID Target Dose n=21 Participants Omecamtiv mecarbil 25 mg BID up to Week 4 or Week 8 and 25 mg or 37.5 mg BID after Week 4 or Week 8, based on Week 2 PK	Omecamtiv Mecarbil 25 mg to 50 mg BID Target Dose n=19 Participants Omecamtiv Mecarbil 25 mg BID up to Week 4 or Week 8 and 25 mg or 50 mg BID after Week 4 or Week 8, based on Week 2 PK	Omecamtiv Mecarbil 25 mg to 50 mg BID Target Dose n=20 Participants Omecamtiv Mecarbil 25 mg BID up to Week 4 or Week 8 and 25 mg or 50 mg BID after Week 4 or Week 8, based on Week 2 PK
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) All TEAEs	14 Participants	10 Participants	10 Participants	12 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Grade >= 2 TEAEs	10 Participants	6 Participants	6 Participants	7 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Grade >= 3 TEAEs	3 Participants	4 Participants	1 Participants	2 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Grade >= 4 TEAEs	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Serious AEs	3 Participants	4 Participants	1 Participants	3 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) TEAEs Leading to Withdrawal of Study Drug	0 Participants	2 Participants	1 Participants	0 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Fata Adverse Events	0 Participants	1 Participants	0 Participants	0 Participants

Adverse Events

Placebo BID

Serious events: 3 serious events

Other events: 10 other events

Deaths: 0 deaths

Omecamtiv Mecarbil 25 mg BID

Serious events: 4 serious events

Other events: 8 other events

Deaths: 1 deaths

Omecamtiv Mecarbil 25 mg to 37.5 mg BID Target Dose

Serious events: 1 serious events

Other events: 10 other events

Deaths: 0 deaths

Omecamtiv Mecarbil 25 mg to 50 mg BID Target Dose

Serious events: 3 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo BID n=21 participants at risk Placebo for omecamtiv mecarbil BID	Omecamtiv Mecarbil 25 mg BID n=21 participants at risk Omecamtiv mecarbil 25 mg BID	Omecamtiv Mecarbil 25 mg to 37.5 mg BID Target Dose n=19 participants at risk Omecamtiv mecarbil 25 mg BID up to Week 4 or Week 8 and 25 mg or 37.5 mg BID after Week 4 or Week 8, based on Week 2 PK	Omecamtiv Mecarbil 25 mg to 50 mg BID Target Dose n=20 participants at risk Omecamtiv Mecarbil 25 mg BID up to Week 4 or Week 8 and 25 mg or 50 mg BID after Week 4 or Week 8, based on Week 2 PK
Cardiac disorders Angina pectoris	0.00% 0/21 • From first dose of study drug up to Week 20 (Day 140 + 3 days) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/21 • From first dose of study drug up to Week 20 (Day 140 + 3 days) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/19 • From first dose of study drug up to Week 20 (Day 140 + 3 days) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.0% 1/20 • From first dose of study drug up to Week 20 (Day 140 + 3 days) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Cardiac disorders Cardiac failure	4.8% 1/21 • From first dose of study drug up to Week 20 (Day 140 + 3 days) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	4.8% 1/21 • From first dose of study drug up to Week 20 (Day 140 + 3 days) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/19 • From first dose of study drug up to Week 20 (Day 140 + 3 days) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.0% 1/20 • From first dose of study drug up to Week 20 (Day 140 + 3 days) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Cardiac disorders Cardiac failure chronic	0.00% 0/21 • From first dose of study drug up to Week 20 (Day 140 + 3 days) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	4.8% 1/21 • From first dose of study drug up to Week 20 (Day 140 + 3 days) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/19 • From first dose of study drug up to Week 20 (Day 140 + 3 days) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.0% 1/20 • From first dose of study drug up to Week 20 (Day 140 + 3 days) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Cardiac disorders Cardiac failure congestive	0.00% 0/21 • From first dose of study drug up to Week 20 (Day 140 + 3 days) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	4.8% 1/21 • From first dose of study drug up to Week 20 (Day 140 + 3 days) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/19 • From first dose of study drug up to Week 20 (Day 140 + 3 days) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/20 • From first dose of study drug up to Week 20 (Day 140 + 3 days) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Cardiac disorders Cardiac ventricular thrombosis	4.8% 1/21 • From first dose of study drug up to Week 20 (Day 140 + 3 days) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/21 • From first dose of study drug up to Week 20 (Day 140 + 3 days) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/19 • From first dose of study drug up to Week 20 (Day 140 + 3 days) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/20 • From first dose of study drug up to Week 20 (Day 140 + 3 days) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Cardiac disorders Cardio-respiratory arrest	0.00% 0/21 • From first dose of study drug up to Week 20 (Day 140 + 3 days) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	4.8% 1/21 • From first dose of study drug up to Week 20 (Day 140 + 3 days) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/19 • From first dose of study drug up to Week 20 (Day 140 + 3 days) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/20 • From first dose of study drug up to Week 20 (Day 140 + 3 days) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Cardiac disorders Ventricular fibrillation	0.00% 0/21 • From first dose of study drug up to Week 20 (Day 140 + 3 days) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	4.8% 1/21 • From first dose of study drug up to Week 20 (Day 140 + 3 days) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/19 • From first dose of study drug up to Week 20 (Day 140 + 3 days) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/20 • From first dose of study drug up to Week 20 (Day 140 + 3 days) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Vascular stent restenosis	0.00% 0/21 • From first dose of study drug up to Week 20 (Day 140 + 3 days) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/21 • From first dose of study drug up to Week 20 (Day 140 + 3 days) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/19 • From first dose of study drug up to Week 20 (Day 140 + 3 days) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.0% 1/20 • From first dose of study drug up to Week 20 (Day 140 + 3 days) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Hepatobiliary disorders Hepatic function abnormal	0.00% 0/21 • From first dose of study drug up to Week 20 (Day 140 + 3 days) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	4.8% 1/21 • From first dose of study drug up to Week 20 (Day 140 + 3 days) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/19 • From first dose of study drug up to Week 20 (Day 140 + 3 days) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/20 • From first dose of study drug up to Week 20 (Day 140 + 3 days) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Pneumonia	4.8% 1/21 • From first dose of study drug up to Week 20 (Day 140 + 3 days) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/21 • From first dose of study drug up to Week 20 (Day 140 + 3 days) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.3% 1/19 • From first dose of study drug up to Week 20 (Day 140 + 3 days) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/20 • From first dose of study drug up to Week 20 (Day 140 + 3 days) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Sepsis	0.00% 0/21 • From first dose of study drug up to Week 20 (Day 140 + 3 days) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	4.8% 1/21 • From first dose of study drug up to Week 20 (Day 140 + 3 days) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/19 • From first dose of study drug up to Week 20 (Day 140 + 3 days) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/20 • From first dose of study drug up to Week 20 (Day 140 + 3 days) Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.

Other adverse events

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Email: [email protected]

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