Trial Outcomes & Findings for Study to Assess the Effect of Omecamtiv Mecarbil on Exercise Capacity in Subjects With Heart Failure (NCT NCT03759392)

Last Updated: 2023-03-07

Results Overview

The effect of treatment on exercise capacity, as assessed by peak oxygen uptake, was assessed during cardiopulmonary exercise testing (CPET) with gas-exchange analysis. Cycle ergometry was the preferred modality for exercise testing; treadmill exercise testing was an acceptable alternative. Participants were to use the same testing modality for all exercise tests during the study. Whenever possible, CPET was administered by the same study personnel using the same equipment throughout the study.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

276 participants

Primary outcome timeframe

Baseline and Week 20

Results posted on

2023-03-07

Participant Flow

Participants with heart failure with reduced ejection fraction (HFrEF) were enrolled at 63 sites in Canada, France, Germany, Hungary, Italy, Netherlands, Poland, Sweden, and the United States. The first participant enrolled on 09 April 2019, and the last participant completed follow-up on 06 January 2022.

A total of 276 participants were randomized in a 2:1 ratio to treatment: 185 to omecamtiv mecarbil and 91 to placebo.

Participant milestones

Participant milestones
Measure	Omecamtiv Mecarbil Omecamtiv mecarbil was administered as an oral modified release tablet twice daily for up to 20 weeks. Participants randomized to this arm started at an omecamtiv mecarbil dose of 25 mg twice daily. The dose could be increased based on plasma concentrations at Weeks 2 and 6.	Placebo Participants randomized to this arm received placebo tablets (matching the appearance of the omecamtiv mecarbil tablets) twice daily for up to 20 weeks.
Overall Study STARTED	185	91
Overall Study COMPLETED	164	85
Overall Study NOT COMPLETED	21	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Omecamtiv Mecarbil Omecamtiv mecarbil was administered as an oral modified release tablet twice daily for up to 20 weeks. Participants randomized to this arm started at an omecamtiv mecarbil dose of 25 mg twice daily. The dose could be increased based on plasma concentrations at Weeks 2 and 6.	Placebo Participants randomized to this arm received placebo tablets (matching the appearance of the omecamtiv mecarbil tablets) twice daily for up to 20 weeks.
Overall Study Adverse Event	12	4
Overall Study Death	2	1
Overall Study Withdrawal by Subject	2	0
Overall Study Protocol Violation	2	0
Overall Study Physician Decision	0	1
Overall Study Consistently forgot to bring study drug kits to site visits (for compliance check)	1	0
Overall Study No longer able to take medicines	1	0
Overall Study Stopped taking study drug	1	0

Baseline Characteristics

The time since HFrEF diagnosis was missing for 1 participant in the omecamtiv mecarbil arm.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Omecamtiv Mecarbil n=185 Participants Omecamtiv mecarbil was administered as an oral modified-release tablet twice daily for up to 20 weeks. Participants randomized to this arm started at an omecamtiv mecarbil dose of 25 mg twice daily. The dose could be increased based on plasma concentrations at Weeks 2 and 6.	Placebo n=91 Participants Participants randomized this arm received placebo tablets (matching the appearance of the omecamtiv mecarbil tablets) twice daily for up to 20 weeks.	Total n=276 Participants Total of all reporting groups
Age, Continuous	63.3 years STANDARD_DEVIATION 9.64 • n=185 Participants	64.4 years STANDARD_DEVIATION 11.41 • n=91 Participants	63.6 years STANDARD_DEVIATION 10.25 • n=276 Participants
Sex: Female, Male Female	27 Participants n=185 Participants	15 Participants n=91 Participants	42 Participants n=276 Participants
Sex: Female, Male Male	158 Participants n=185 Participants	76 Participants n=91 Participants	234 Participants n=276 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=185 Participants	0 Participants n=91 Participants	1 Participants n=276 Participants
Race (NIH/OMB) Asian	3 Participants n=185 Participants	2 Participants n=91 Participants	5 Participants n=276 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=185 Participants	0 Participants n=91 Participants	0 Participants n=276 Participants
Race (NIH/OMB) Black or African American	16 Participants n=185 Participants	6 Participants n=91 Participants	22 Participants n=276 Participants
Race (NIH/OMB) White	163 Participants n=185 Participants	82 Participants n=91 Participants	245 Participants n=276 Participants
Race (NIH/OMB) More than one race	0 Participants n=185 Participants	0 Participants n=91 Participants	0 Participants n=276 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=185 Participants	1 Participants n=91 Participants	3 Participants n=276 Participants
Time since HFrEF diagnosis	7.6 years STANDARD_DEVIATION 6.14 • n=184 Participants • The time since HFrEF diagnosis was missing for 1 participant in the omecamtiv mecarbil arm.	7.8 years STANDARD_DEVIATION 6.88 • n=91 Participants • The time since HFrEF diagnosis was missing for 1 participant in the omecamtiv mecarbil arm.	7.7 years STANDARD_DEVIATION 6.38 • n=275 Participants • The time since HFrEF diagnosis was missing for 1 participant in the omecamtiv mecarbil arm.
Primary cause of heart failure: ischemic heart disease	117 Participants n=185 Participants	48 Participants n=91 Participants	165 Participants n=276 Participants

PRIMARY outcome

Timeframe: Baseline and Week 20

Population: Full Analysis Set (all randomized participants who received at least 1 dose of randomized study drug)

Outcome measures

Outcome measures
Measure	Omecamtiv Mecarbil n=162 Participants Omecamtiv mecarbil was administered as an oral modified-release tablet twice daily for up to 20 weeks. Participants randomized to this arm started at an omecamtiv mecarbil dose of 25 mg twice daily. The dose could be increased based on plasma concentrations at Weeks 2 and 6.	Placebo n=81 Participants Participants randomized this arm received placebo tablets (matching the appearance of the omecamtiv mecarbil tablets) twice daily for up to 20 weeks.
Change in Peak Oxygen Uptake on Cardiopulmonary Exercise Testing From Baseline to Week 20	-0.239 mL/min/kg Standard Error 0.1718	0.207 mL/min/kg Standard Error 0.2412

SECONDARY outcome

Timeframe: Baseline and Week 20

Population: Full Analysis Set

Total workload was measured during CPET (cycle ergometry \[preferred\] or treadmill exercise testing) and represents the maximum load to which a participant was subjected during CPET in order to produce work.

Outcome measures

Outcome measures
Measure	Omecamtiv Mecarbil n=162 Participants Omecamtiv mecarbil was administered as an oral modified-release tablet twice daily for up to 20 weeks. Participants randomized to this arm started at an omecamtiv mecarbil dose of 25 mg twice daily. The dose could be increased based on plasma concentrations at Weeks 2 and 6.	Placebo n=81 Participants Participants randomized this arm received placebo tablets (matching the appearance of the omecamtiv mecarbil tablets) twice daily for up to 20 weeks.
Change in Total Workload During Cardiopulmonary Exercise Testing From Baseline to Week 20	-3.798 Watt Standard Error 1.3352	1.590 Watt Standard Error 1.9477

SECONDARY outcome

Timeframe: Baseline and Week 20

Population: Full Analysis Set

Ventilatory efficiency (ventilation \[VE\]/volume of exhaled carbon dioxide \[VCO2\]) was measured through CPET with gas exchange analysis.

Outcome measures

Outcome measures
Measure	Omecamtiv Mecarbil n=162 Participants Omecamtiv mecarbil was administered as an oral modified-release tablet twice daily for up to 20 weeks. Participants randomized to this arm started at an omecamtiv mecarbil dose of 25 mg twice daily. The dose could be increased based on plasma concentrations at Weeks 2 and 6.	Placebo n=81 Participants Participants randomized this arm received placebo tablets (matching the appearance of the omecamtiv mecarbil tablets) twice daily for up to 20 weeks.
Change in Ventilatory Efficiency During Cardiopulmonary Exercise Testing From Baseline to Week 20	0.277 slope Standard Error 0.3616	-0.138 slope Standard Error 0.5065

SECONDARY outcome

Timeframe: Baseline (Week -2 to Day 1) to Weeks 18-20

Population: The analysis population included participants in the Full Analysis Set with available data at both assessment time frames (ie, baseline \[Week -2 to Day 1\] and Weeks 18-20).

The effect of treatment on daily activity, as assessed by average daily activity units, was evaluated by actigraphy. Actigraphy was collected during 4 sessions throughout the study for 2 week intervals.

Outcome measures

Outcome measures
Measure	Omecamtiv Mecarbil n=147 Participants Omecamtiv mecarbil was administered as an oral modified-release tablet twice daily for up to 20 weeks. Participants randomized to this arm started at an omecamtiv mecarbil dose of 25 mg twice daily. The dose could be increased based on plasma concentrations at Weeks 2 and 6.	Placebo n=77 Participants Participants randomized this arm received placebo tablets (matching the appearance of the omecamtiv mecarbil tablets) twice daily for up to 20 weeks.
Change in the Average Daily Activity Units Measured Over a 2-week Period From Baseline (Week -2 to Day 1) to Weeks 18-20	-0.2 10^5 activity units Standard Error 0.30	-0.5 10^5 activity units Standard Error 0.38

Adverse Events

Omecamtiv Mecarbil

Serious events: 30 serious events

Other events: 126 other events

Deaths: 3 deaths

Placebo

Serious events: 13 serious events

Other events: 58 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Cytokinetics MD

Cytokinetics, Inc.

Phone: 650-624-2929

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Omecamtiv Mecarbil n=185 participants at risk Omecamtiv mecarbil was administered as an oral modified-release tablet twice daily for up to 20 weeks. Participants randomized to this arm started at an omecamtiv mecarbil dose of 25 mg twice daily. The dose could be increased based on plasma concentrations at Weeks 2 and 6.	Placebo n=91 participants at risk Participants randomized this arm received placebo tablets (matching the appearance of the omecamtiv mecarbil tablets) twice daily for up to 20 weeks.
Cardiac disorders Cardiac failure	2.7% 5/185 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.	2.2% 2/91 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.
Cardiac disorders Angina pectoris	2.2% 4/185 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.	3.3% 3/91 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.
Cardiac disorders Atrial fibrillation	2.2% 4/185 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.	3.3% 3/91 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.
Cardiac disorders Palpitations	0.00% 0/185 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.	2.2% 2/91 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.
General disorders Fatigue	4.9% 9/185 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.	4.4% 4/91 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.
General disorders Non-cardiac chest pain	2.2% 4/185 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.	3.3% 3/91 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.
General disorders Asthenia	2.2% 4/185 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.	0.00% 0/91 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.
General disorders Chest discomfort	2.2% 4/185 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.	0.00% 0/91 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.
General disorders Oedema peripheral	2.2% 4/185 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.	0.00% 0/91 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.
Respiratory, thoracic and mediastinal disorders Cough	2.7% 5/185 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.	1.1% 1/91 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.7% 5/185 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.	8.8% 8/91 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	2.2% 4/185 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.	0.00% 0/91 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.
Musculoskeletal and connective tissue disorders Arthralgia	3.2% 6/185 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.	0.00% 0/91 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.
Musculoskeletal and connective tissue disorders Back pain	2.7% 5/185 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.	4.4% 4/91 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.
Musculoskeletal and connective tissue disorders Myalgia	2.7% 5/185 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.	1.1% 1/91 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.
Gastrointestinal disorders Diarrhoea	3.8% 7/185 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.	4.4% 4/91 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.
Gastrointestinal disorders Nausea	1.6% 3/185 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.	3.3% 3/91 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.
Injury, poisoning and procedural complications Fall	3.8% 7/185 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.	1.1% 1/91 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.
Nervous system disorders Dizziness	4.9% 9/185 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.	5.5% 5/91 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.
Nervous system disorders Headache	2.2% 4/185 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.	3.3% 3/91 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.
Metabolism and nutrition disorders Gout	2.2% 4/185 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.	3.3% 3/91 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.
Vascular disorders Hypotension	2.2% 4/185 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.	1.1% 1/91 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.
Skin and subcutaneous tissue disorders Pruritus	2.2% 4/185 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.	1.1% 1/91 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.
Skin and subcutaneous tissue disorders Rash	0.00% 0/185 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.	4.4% 4/91 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.
Psychiatric disorders Insomnia	2.7% 5/185 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.	1.1% 1/91 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.
Renal and urinary disorders Acute kidney injury	2.2% 4/185 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.	1.1% 1/91 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.
Infections and infestations Bronchitis	1.1% 2/185 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.	2.2% 2/91 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.
Infections and infestations Urinary tract infection	0.54% 1/185 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.	2.2% 2/91 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.
Vascular disorders Hypertension	1.6% 3/185 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.	3.3% 3/91 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.
Metabolism and nutrition disorders Hyperkalaemia	1.6% 3/185 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.	1.1% 1/91 • Adverse events were collected from randomization through the end of study/safety follow-up visit (scheduled to occur 4 weeks after the last dose of study drug) or 30 days after the last dose of study drug, whichever was later.