Heart FailurePhase 1NCT01380223
A Pharmacokinetic and Pharmacodynamic Study of Omecamtiv Mecarbil in Healthy Volunteers
A Phase 1 study testing omecamtiv mecarbil in people with Heart Failure, run by Cytokinetics at 1 site in United Kingdom.
Trial summary
This study will assess the safety, tolerability, and pharmacodynamics of omecamtiv mecarbil infusion in healthy male volunteers. Read more about this study
- Who is it for?
- Ages 18 to 50 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Heart Failure
- What is being tested?
- omecamtiv mecarbil
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 35 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Aug 2005to Apr 2006
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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:
Show all 12Show fewer
- 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.
Who cannot join
- 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.
Show all 12Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
ICON Development Solutions
Manchester, England, United Kingdom
About this study
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
This study will assess the safety, tolerability, and pharmacodynamics of omecamtiv mecarbil infusion in healthy male volunteers.
- Conditions
- Heart Failure
- Being tested
- placebo, omecamtiv mecarbil
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
placeboDrug
I.V. infusion of placebo for 8 hr
omecamtiv mecarbilDrug
Also called CK-1827452, AMG 423
I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.005 mg/kg/hr
omecamtiv mecarbilDrug
Also called CK-1827452, AMG 423
I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.015 mg/kg/hr
omecamtiv mecarbilDrug
Also called CK-1827452, AMG 423
I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.025 mg/kg/hr
omecamtiv mecarbilDrug
Also called CK-1827452, AMG 423
I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.0625 mg/kg/hr
omecamtiv mecarbilDrug
Also called CK-1827452, AMG 423
I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.125 mg/kg/hr
omecamtiv mecarbilDrug
Also called CK-1827452, AMG 423
I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.25 mg/kg/hr
omecamtiv mecarbilDrug
Also called CK-1827452, AMG 423
I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.5 mg/kg/hr
omecamtiv mecarbilDrug
Also called CK-1827452, AMG 423
I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 1.0 mg/kg/hr
omecamtiv mecarbilDrug
Also called CK-1827452, AMG 423
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 mecarbilDrug
Also called CK-1827452, AMG 423
I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.625 mg/kg/hr (dose reduced)
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: placebo; Drug: omecamtiv mecarbil |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 days
Secondary outcomes (2)
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.
Measured: 1 day
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.
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2011 (estimated)
- Study startAug 2005
- Primary completionApr 2006
- Study completionApr 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cytokinetics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01380223
- Sponsor's protocol ID
- CY 1111
- Other IDs
- 2005-001886-32, 2005
- Status last verified
- Oct 2015
- First submitted
- 22 Jun 2011
- Last updated
- 14 Oct 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 25951506Teerlink 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.
PubMed 21856480
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01380223
- Acronym / sponsor ID
- CY 1111
- Conditions
- Heart Failure
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- CytokineticsIndustry (pharma, biotech, devices)
- Study start
- Aug 2005
- Primary completion
- Apr 2006 (actual)
- Study completion
- Apr 2006 (actual)
- First posted
- 27 Jun 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will assess the safety, tolerability, and pharmacodynamics of omecamtiv mecarbil infusion in healthy male volunteers.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Dose-escalation Cohort 1 | Experimental | Drug: placebo, Drug: omecamtiv mecarbil4 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. |
| Dose-escalation Cohort 2 | Experimental | Drug: placebo, Drug: omecamtiv mecarbil4 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. |
| Dose-escalation Cohort 3 | Experimental | Drug: placebo, Drug: omecamtiv mecarbil4 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. |
| Dose-escalation Cohort 4 | Experimental | Drug: placebo, Drug: omecamtiv mecarbil4 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. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| placeboI.V. infusion of placebo for 8 hr | Drug | Dose-escalation Cohort 1, Dose-escalation Cohort 2, Dose-escalation Cohort 3, Dose-escalation Cohort 4 |
| omecamtiv mecarbilAlso: CK-1827452, AMG 423I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.005 mg/kg/hr | Drug | Dose-escalation Cohort 1 |
| omecamtiv mecarbilAlso: CK-1827452, AMG 423I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.015 mg/kg/hr | Drug | Dose-escalation Cohort 1 |
| omecamtiv mecarbilAlso: CK-1827452, AMG 423I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.025 mg/kg/hr | Drug | Dose-escalation Cohort 1, Dose-escalation Cohort 2 |
| omecamtiv mecarbilAlso: CK-1827452, AMG 423I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.0625 mg/kg/hr | Drug | Dose-escalation Cohort 2 |
| omecamtiv mecarbilAlso: CK-1827452, AMG 423I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.125 mg/kg/hr | Drug | Dose-escalation Cohort 2, Dose-escalation Cohort 3 |
| omecamtiv mecarbilAlso: CK-1827452, AMG 423I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.25 mg/kg/hr | Drug | Dose-escalation Cohort 3 |
| omecamtiv mecarbilAlso: CK-1827452, AMG 423I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.5 mg/kg/hr | Drug | Dose-escalation Cohort 3, Dose-escalation Cohort 4 |
| omecamtiv mecarbilAlso: CK-1827452, AMG 423I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 1.0 mg/kg/hr | Drug | Dose-escalation Cohort 4 |
| omecamtiv mecarbilAlso: CK-1827452, AMG 423I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.75 mg/kg/hr (dose reduced) | Drug | Dose-escalation Cohort 4 |
| omecamtiv mecarbilAlso: CK-1827452, AMG 423I.V. infusion of placebo for 2 hr followed by 6 hr infusion of omecamtiv mecarbil at 0.625 mg/kg/hr (dose reduced) | Drug | Dose-escalation Cohort 4 |
Primary outcome
Maximum Tolerated Dose (MTD) of Omecamtiv Mecarbil in Healthy Volunteers
Time frame: 2 days
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 secondary outcomes
Change From Baseline of Systolic Ejection Time at Various Omecamtiv Mecarbil Infusion Rates
Time frame: 1 day
Change From Baseline of Fractional Shortening at Various Omecamtiv Mecarbil Infusion Rates
Time frame: 1 day
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2015.
- Derived from this study: PubMed 25951506Vu 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.
- Derived from this study: PubMed 21856480Teerlink 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.
Related trials for Heart Failure
RecruitingPhase 4
The Effects of Ferric Derisomaltose in Patients With Acute Heart Failure and Iron Deficiency on Exercise Capacity and Quality of Life(COREVIVE-HFrEF)
Heart Failure With Reduced Ejection Fraction, Iron Deficiency
Not yet recruitingPhase 2
A Study of Bimagrumab in Participants With HFpEF
Heart Failure, Diastolic, Diastolic Heart Failure
Recruiting
Evaluation of a French Hospital Discharge Therapeutic Education Program by Nurses for Heart Failure Patient (EduSor)
Heart Failure
Active, not recruiting
Assessment of Combined CCM and ICD Device in HFrEF
Heart Failure, Heart Failure With Reduced Ejection Fraction
Not yet recruiting
RELIEVE-HFrEF TRIAL: REducing Lung congestIon Symptoms Using the v-wavE Shunt in adVancEd Heart Failure With Reduced EF
Heart Failure and Reduced Ejection Fraction, Heart Failure Chronic
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing omecamtiv mecarbil in people with Heart Failure, run by Cytokinetics at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (MTD) of Omecamtiv Mecarbil in Healthy Volunteers (time frame: 2 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01380223, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2015.