A Pharmacokinetic and Pharmacodynamic Study of Omecamtiv Mecarbil in Healthy Volunteers

NCT01380223 | Completed Phase 1

• 2 other identifiers: CY 11112005-001886-32
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

This study will assess the safety, tolerability, and pharmacodynamics of omecamtiv mecarbil infusion in healthy male volunteers.

Conditions

Heart Failure

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of Omecamtiv Mecarbil in Healthy Volunteers

  The highest infusion rate tolerated by at least eight subjects. A dose was intolerable if: 1) the pattern of intolerance clearly distinguished active drug from placebo, or 2) the number of subjects intolerant of the dose level in question was at least 3 more than the number of subjects intolerant of placebo.

  2 days

Secondary Outcomes (2)

• Change From Baseline of Systolic Ejection Time at Various Omecamtiv Mecarbil Infusion Rates

  1 day

• Change From Baseline of Fractional Shortening at Various Omecamtiv Mecarbil Infusion Rates

  1 day

Study Arms (4)

Dose-escalation Cohort 1

EXPERIMENTAL

4 treatment periods consisting of a 2 hour placebo infusion (single blind) followed by a 6 hour infusion of study drug or placebo. Each subject will receive 3 active ascending doses of study drug and 1 dose of placebo randomized into the sequence of escalating doses in a double-blind manner. Treatment periods occur at least 7 days apart.

Drug: placebo; Drug: omecamtiv mecarbil

Dose-escalation Cohort 2

EXPERIMENTAL

4 treatment periods consisting of a 2 hour placebo infusion (single blind) followed by a 6 hour infusion of study drug or placebo. Each subject will receive 3 active ascending doses of study drug and 1 dose of placebo randomized into the sequence of escalating doses in a double-blind manner. Treatment periods occur at least 7 days apart.

Drug: placebo; Drug: omecamtiv mecarbil

Dose-escalation Cohort 3

EXPERIMENTAL

4 treatment periods consisting of a 2 hour placebo infusion (single blind) followed by a 6 hour infusion of study drug or placebo. Each subject will receive 3 active ascending doses of study drug and 1 dose of placebo randomized into the sequence of escalating doses in a double-blind manner. Treatment periods occur at least 7 days apart.

Drug: placebo; Drug: omecamtiv mecarbil

Dose-escalation Cohort 4

EXPERIMENTAL

4 treatment periods consisting of a 2 hour placebo infusion (single blind) followed by a 6 hour infusion of study drug or placebo. Each subject will receive 3 active ascending doses of study drug and 1 dose of placebo randomized into the sequence of escalating doses in a double-blind manner. Treatment periods occur at least 7 days apart.

Drug: placebo; Drug: omecamtiv mecarbil

Interventions

placebo DRUG

I.V. infusion of placebo for 8 hr

Dose-escalation Cohort 1; Dose-escalation Cohort 2; Dose-escalation Cohort 3; Dose-escalation Cohort 4

omecamtiv mecarbil DRUG

I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.005 mg/kg/hr

Also known as: CK-1827452, AMG 423

Dose-escalation Cohort 1

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subject is male
• Subject is aged between 18 and 50 years inclusive.
• Subject has given signed informed consent.
• Subject's Body Mass Index (BMI) is between 18 and 30 kg/m2 inclusive.
• Subject weighs less than 100 kg.
• Subject is considered to be in good health in the opinion of the investigator, as determined by:
• A pre-study physical examination with no clinically significant abnormalities.
• Vital signs within normal ranges (supine after 3 minutes rest - heart rate: 40 to 80 bpm; systolic BP: 100 to 140 mmHg; diastolic BP: 50-90 mmHg; respiration rate: 8 to 18 breaths per minute; oxygen saturation: 96-100%)
• An ECG with no clinically significant abnormalities.
• Subject's pre-study clinical laboratory findings are within normal range or if outside of the normal range not deemed clinically significant in the opinion of the investigator.
• Cardiac troponin I is less than the upper limit of the laboratory reference range.
• A screening echocardiogram demonstrates normal cardiac function, an ejection fraction of between 40% and 70% with no significant valvular regurgitation (grade 1) and/or stenosis and images are deemed to be of good quality by the sonographer.

You may not qualify if:

• Subject has had a clinically significant illness in the four weeks before screening.
• Use of prescribed mediations in the 3 weeks prior to dosing or over-the-counter preparations (including vitamin supplements and herbal remedies) for 7 days prior to dosing, except paracetamol which will be allowed up to 48 hours prior to dosing.
• Subject has a significant history of drug/solvent abuse or a positive drugs of abuse test at screening.
• Subject with a history of alcohol abuse or currently drinks in excess of 28 units per week.
• Subject smokes more than 5 cigarettes (or equivalent) per day.
• Subject is not willing to refrain from caffeine/xanthine containing products from 48 hours prior to the screening medical and admission on Day -1 until the post study medical.
• Subject is in the opinion of the investigator not suitable to participate in the study.
• Subject who has participated in any clinical study with an investigational drug/device within three months prior to the first day of dosing.
• Subject who has a positive result of HIV screen, Hepatitis B screen or Hepatitis C screen.
• Subject has had a serious adverse reaction or significant hypersensitivity to any drug.
• Subject has donated 500 ml or more of blood within the month prior to screening.
• Subject has a history of cardiovascular disease or family history of premature cardiovascular disease or death.

Sponsors & Collaborators

• Cytokinetics: lead

Study Sites (1)

ICON Development Solutions

Manchester, England, United Kingdom, United Kingdom

Location

Related Publications (2)

• Vu T, Ma P, Xiao JJ, Wang YM, Malik FI, Chow AT. Population pharmacokinetic-pharmacodynamic modeling of omecamtiv mecarbil, a cardiac myosin activator, in healthy volunteers and patients with stable heart failure. J Clin Pharmacol. 2015 Nov;55(11):1236-47. doi: 10.1002/jcph.538. Epub 2015 Jul 14.

  PMID: 25951506 DERIVED

• Teerlink JR, Clarke CP, Saikali KG, Lee JH, Chen MM, Escandon RD, Elliott L, Bee R, Habibzadeh MR, Goldman JH, Schiller NB, Malik FI, Wolff AA. Dose-dependent augmentation of cardiac systolic function with the selective cardiac myosin activator, omecamtiv mecarbil: a first-in-man study. Lancet. 2011 Aug 20;378(9792):667-75. doi: 10.1016/S0140-6736(11)61219-1.

  PMID: 21856480 DERIVED

MeSH Terms

Conditions

Heart Failure

Interventions

omecamtiv mecarbil

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2011
• First Posted: June 27, 2011
• Study Start: August 1, 2005
• Primary Completion: April 1, 2006
• Study Completion: April 1, 2006
• Last Updated: October 14, 2015

Record last verified: 2015-10

Locations

GB (1)