Clinical trial NCT01380223: A Pharmacokinetic and Pharmacodynamic Study of Omecamtiv Mecarbil in Healthy Volunteers
Official title: A First-in-Man, Phase I, Double-Blind, Randomized, Four-Way Crossover, Placebo-Controlled, Dose-Escalation, Pharmacokinetic and Pharmacodynamic Study of CK-1827452 (Omecamtiv Mecarbil) in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Heart Failure
Lead sponsor: Cytokinetics
Sponsor class: INDUSTRY
First posted: 2011-06-27
Enrollment: 35
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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


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.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of Omecamtiv Mecarbil in Healthy Volunteers
timeFrame: 2 days
Secondary outcomes:
measure: Change From Baseline of Systolic Ejection Time at Various Omecamtiv Mecarbil Infusion Rates
timeFrame: 1 day
measure: Change From Baseline of Fractional Shortening at Various Omecamtiv Mecarbil Infusion Rates
timeFrame: 1 day
Other outcomes:
Locations:
city: Manchester
country: United Kingdom
facility: ICON Development Solutions
state: England
Study officials:
References:
citation: 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.
citation: 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.