Back to resultsA Pharmacokinetic and Pharmacodynamic Study of Omecamtiv Mecarbil in Healthy Volunteers
Primary Purpose
Heart Failure
Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
placebo
omecamtiv mecarbil
omecamtiv mecarbil
omecamtiv mecarbil
omecamtiv mecarbil
omecamtiv mecarbil
omecamtiv mecarbil
omecamtiv mecarbil
omecamtiv mecarbil
omecamtiv mecarbil
omecamtiv mecarbil
Sponsored by
About this trial
This is an interventional treatment trial for Heart Failure
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Sites / Locations
- ICON Development Solutions
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Dose-escalation Cohort 1
Dose-escalation Cohort 2
Dose-escalation Cohort 3
Dose-escalation Cohort 4
Arm Description
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.
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.
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.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Change From Baseline of Systolic Ejection Time at Various Omecamtiv Mecarbil Infusion Rates
Pooled analysis of the echocardiographic measure systolic ejection time. The systolic ejection time is the period during which the aortic valve is open and blood is flowing across the valve. Echocardiograms from cohorts 1,2,3,4 were binned into either placebo group or groups based on infusion rate of omecamtiv mecarbil.
Change From Baseline of Fractional Shortening at Various Omecamtiv Mecarbil Infusion Rates
Pooled analysis of the echocardiographic measure fractional shortening. Fractional shortening is the percentage of change from baseline in the left ventricular cavity dimension with systole. Echocardiograms from cohorts 1,2,3,4 were binned into either placebo group or groups based on infusion rate of omecamtiv mecarbil.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01380223
Brief Title
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
2. Study Status
Record Verification Date
October 2015
Overall Recruitment Status
Completed
Study Start Date
August 2005 (undefined)
Primary Completion Date
April 2006 (Actual)
Study Completion Date
April 2006 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cytokinetics
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study will assess the safety, tolerability, and pharmacodynamics of omecamtiv mecarbil infusion in healthy male volunteers.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
35 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Dose-escalation Cohort 1
Arm Type
Experimental
Arm Description
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.
Arm Title
Dose-escalation Cohort 2
Arm Type
Experimental
Arm Description
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.
Arm Title
Dose-escalation Cohort 3
Arm Type
Experimental
Arm Description
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.
Arm Title
Dose-escalation Cohort 4
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
I.V. infusion of placebo for 8 hr
Intervention Type
Drug
Intervention Name(s)
omecamtiv mecarbil
Other Intervention Name(s)
CK-1827452, AMG 423
Intervention Description
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
Intervention Name(s)
omecamtiv mecarbil
Other Intervention Name(s)
CK-1827452, AMG 423
Intervention Description
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
Intervention Name(s)
omecamtiv mecarbil
Other Intervention Name(s)
CK-1827452, AMG 423
Intervention Description
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
Intervention Name(s)
omecamtiv mecarbil
Other Intervention Name(s)
CK-1827452, AMG 423
Intervention Description
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
Intervention Name(s)
omecamtiv mecarbil
Other Intervention Name(s)
CK-1827452, AMG 423
Intervention Description
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
Intervention Name(s)
omecamtiv mecarbil
Other Intervention Name(s)
CK-1827452, AMG 423
Intervention Description
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
Intervention Name(s)
omecamtiv mecarbil
Other Intervention Name(s)
CK-1827452, AMG 423
Intervention Description
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
Intervention Name(s)
omecamtiv mecarbil
Other Intervention Name(s)
CK-1827452, AMG 423
Intervention Description
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
Intervention Name(s)
omecamtiv mecarbil
Other Intervention Name(s)
CK-1827452, AMG 423
Intervention Description
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
Intervention Name(s)
omecamtiv mecarbil
Other Intervention Name(s)
CK-1827452, AMG 423
Intervention Description
I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.625 mg/kg/hr (dose reduced)
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose (MTD) of Omecamtiv Mecarbil in Healthy Volunteers
Description
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.
Time Frame
2 days
Secondary Outcome Measure Information:
Title
Change From Baseline of Systolic Ejection Time at Various Omecamtiv Mecarbil Infusion Rates
Description
Pooled analysis of the echocardiographic measure systolic ejection time. The systolic ejection time is the period during which the aortic valve is open and blood is flowing across the valve. Echocardiograms from cohorts 1,2,3,4 were binned into either placebo group or groups based on infusion rate of omecamtiv mecarbil.
Time Frame
1 day
Title
Change From Baseline of Fractional Shortening at Various Omecamtiv Mecarbil Infusion Rates
Description
Pooled analysis of the echocardiographic measure fractional shortening. Fractional shortening is the percentage of change from baseline in the left ventricular cavity dimension with systole. Echocardiograms from cohorts 1,2,3,4 were binned into either placebo group or groups based on infusion rate of omecamtiv mecarbil.
Time Frame
1 day
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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.
Facility Information:
Facility Name
ICON Development Solutions
City
Manchester
State/Province
England
ZIP/Postal Code
United Kingdom
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
25951506
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.
Results Reference
derived
PubMed Identifier
21856480
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.
Results Reference
derived
Learn more about this trial
A Pharmacokinetic and Pharmacodynamic Study of Omecamtiv Mecarbil in Healthy Volunteers
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