A Pharmacokinetic and Pharmacodynamic Study of Omecamtiv Mecarbil in Healthy Volunteers

NCT ID: NCT01380223

Last Updated: 2015-10-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-08-31
• Study Completion Date: 2006-04-30

Brief Summary

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

Conditions

Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Dose-escalation Cohort 1

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.

Group Type: EXPERIMENTAL

placebo

Intervention Type: DRUG

I.V. infusion of placebo for 8 hr

omecamtiv mecarbil

Intervention Type: DRUG

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

omecamtiv mecarbil

Intervention Type: DRUG

I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.015 mg/kg/hr

omecamtiv mecarbil

Intervention Type: DRUG

I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.025 mg/kg/hr

Dose-escalation Cohort 2

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.

Group Type: EXPERIMENTAL

placebo

Intervention Type: DRUG

I.V. infusion of placebo for 8 hr

omecamtiv mecarbil

Intervention Type: DRUG

I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.025 mg/kg/hr

omecamtiv mecarbil

Intervention Type: DRUG

I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.0625 mg/kg/hr

omecamtiv mecarbil

Intervention Type: DRUG

I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.125 mg/kg/hr

Dose-escalation Cohort 3

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.

Group Type: EXPERIMENTAL

placebo

Intervention Type: DRUG

I.V. infusion of placebo for 8 hr

omecamtiv mecarbil

Intervention Type: DRUG

I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.125 mg/kg/hr

omecamtiv mecarbil

Intervention Type: DRUG

I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.25 mg/kg/hr

omecamtiv mecarbil

Intervention Type: DRUG

I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.5 mg/kg/hr

Dose-escalation Cohort 4

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.

Group Type: EXPERIMENTAL

placebo

Intervention Type: DRUG

I.V. infusion of placebo for 8 hr

omecamtiv mecarbil

Intervention Type: DRUG

I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.5 mg/kg/hr

omecamtiv mecarbil

Intervention Type: DRUG

I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 1.0 mg/kg/hr

omecamtiv mecarbil

Intervention Type: DRUG

I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.75 mg/kg/hr (dose reduced)

omecamtiv mecarbil

Intervention Type: DRUG

I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.625 mg/kg/hr (dose reduced)

Interventions

placebo

I.V. infusion of placebo for 8 hr

Intervention Type: DRUG

omecamtiv mecarbil

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

Intervention Type: DRUG

omecamtiv mecarbil

I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.015 mg/kg/hr

Intervention Type: DRUG

omecamtiv mecarbil

I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.025 mg/kg/hr

Intervention Type: DRUG

omecamtiv mecarbil

I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.0625 mg/kg/hr

Intervention Type: DRUG

omecamtiv mecarbil

I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.125 mg/kg/hr

Intervention Type: DRUG

omecamtiv mecarbil

I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.25 mg/kg/hr

Intervention Type: DRUG

omecamtiv mecarbil

I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.5 mg/kg/hr

Intervention Type: DRUG

omecamtiv mecarbil

I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 1.0 mg/kg/hr

Intervention Type: DRUG

omecamtiv mecarbil

I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.75 mg/kg/hr (dose reduced)

Intervention Type: DRUG

omecamtiv mecarbil

I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.625 mg/kg/hr (dose reduced)

Intervention Type: DRUG

Other Intervention Names

CK-1827452, AMG 423; CK-1827452, AMG 423; CK-1827452, AMG 423; CK-1827452, AMG 423; CK-1827452, AMG 423; CK-1827452, AMG 423; CK-1827452, AMG 423; CK-1827452, AMG 423; CK-1827452, AMG 423; CK-1827452, AMG 423

Eligibility Criteria

Inclusion Criteria

1. Subject is male

2. Subject is aged between 18 and 50 years inclusive.

3. Subject has given signed informed consent.

4. Subject's Body Mass Index (BMI) is between 18 and 30 kg/m2 inclusive.

5. Subject weighs less than 100 kg.

6. Subject is considered to be in good health in the opinion of the investigator, as determined by:

1. A pre-study physical examination with no clinically significant abnormalities.

2. 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%)

3. An ECG with no clinically significant abnormalities.

7. 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.

8. Cardiac troponin I is less than the upper limit of the laboratory reference range.

9. 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.

Exclusion Criteria

1. Subject has had a clinically significant illness in the four weeks before screening.

2. 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.

3. Subject has a significant history of drug/solvent abuse or a positive drugs of abuse test at screening.

4. Subject with a history of alcohol abuse or currently drinks in excess of 28 units per week.

5. Subject smokes more than 5 cigarettes (or equivalent) per day.

6. 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.

7. Subject is in the opinion of the investigator not suitable to participate in the study.

8. Subject who has participated in any clinical study with an investigational drug/device within three months prior to the first day of dosing.

9. Subject who has a positive result of HIV screen, Hepatitis B screen or Hepatitis C screen.

10. Subject has had a serious adverse reaction or significant hypersensitivity to any drug.

11. Subject has donated 500 ml or more of blood within the month prior to screening.

12. Subject has a history of cardiovascular disease or family history of premature cardiovascular disease or death.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Cytokinetics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

ICON Development Solutions

Manchester, England, United Kingdom

Countries

United Kingdom

References

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.

Reference Type: DERIVED

PMID: 25951506 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 21856480 (View on PubMed)

Other Identifiers

2005-001886-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CY 1111

Identifier Type: -

Identifier Source: org_study_id