Pharmacokinetics of Oral CK-1827452 in Patients With Stable Heart Failure

A Phase 2 study testing CK-1827452 in people with Heart Failure, run by Cytokinetics at 3 sites in Georgia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

This study is designed to understand the pharmacokinetics of different oral formulations of CK-1827452 being considered for future studies in patients with heart failure. This study will compare the pharmacokinetics and safety and tolerability of both modified-release (MR) and immediate-release (IR) oral formulations… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Heart Failure
What is being tested?: CK-1827452
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 35 participants
Where: 3 sitesGeorgia
Study dates: Apr 2009to Oct 2009
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

The patient has signed an Informed Consent Form/Patient Information Sheet for this study approved by the governing Institutional Review Board (IRB) or Independent Ethics Committee (IEC)
The patient is at least 18 years old at the time of consent
Left ventricular ejection fraction (LVEF) ≤ 35% as determined by the Investigator within 3 weeks prior to enrollment
Treated for at least 4 weeks with a beta blocker and an ACE inhibitor (and/or an ARB) unless not tolerated. If prescribed, diuretics must have been administered according to a consistent regimen for at least 4 weeks.
Diagnosed with heart failure for ≥ 3 months prior to enrollment
Patient is considered to be an appropriate candidate for study enrollment as determined by the patient's clinical laboratory findings, vital signs and ECGs within normal range, or if outside of the normal range not deemed clinically significant in the opinion of the Investigator
For female patients only: The patient is post-menopausal (≥ 1 year) or sterilized, or if she is of childbearing potential, she is not breastfeeding, her pregnancy test is negative, she has no intention to become pregnant during the course of the study, and she is using contraceptive drugs or devices. For male patients only: Male patients agree for the duration of the study and 10 weeks after the end of the study to use a condom during sexual intercourse with female partners who are of reproductive potential and to have female partners use an additional effective means of contraception (eg, diaphragm plus spermicide, or oral contraceptives) or the male subject must agree to abstain from sexual intercourse for 10 weeks after the end of the study.

Who cannot join

Patient has been hospitalised for heart failure, acute coronary syndrome, myocardial infarction, coronary revascularisation, transient ischemic attack or stroke, cardiac arrhythmia, or major surgery within 6 weeks prior to enrollment
Poorly controlled hypertension defined as blood pressure > 150/95 mmHg, documented on at least 2 separate occasions prior to enrollment
The patient has a supine heart rate ≥ 100 beats per minute after 10 minutes of rest
Patient has a troponin I at screening that is above the upper limit of normal
The patient has severe aortic or mitral stenosis
The patient has active myocarditis; clinically significant restrictive, constrictive, or hypertrophic obstructive cardiomyopathy; clinically significant congenital heart disease; history of major organ transplantation

Show all 15Show fewer

The patient has Canadian Cardiovascular Society Class IV angina
Patient is on chronic anti-arrhythmic therapy, with the exception of amiodarone
Patient has impaired renal function defined as an estimated GFR ≤ 30 ml/min/1.73 m2 calculated by the Modification of Diet in Renal Disease (MDRD) equation
Patient is currently taking, or has taken within 14 days prior to enrollment, a potent CYP3A4 inhibitor (medication or food). Patient is currently taking, or has taken within 28 days prior to enrollment, a potent CYP3A4 inducer (medication or food).
The patient has hepatic impairment defined as a total bilirubin > 3 mg/dL, or an ALT or AST > 2 times the upper limit of normal
Concomitant non-cardiovascular disease that is expected to reduce life expectancy to less than 1 year
The patient has received an investigational drug or device within 30 days or 5 half-lives, whichever is greater, of enrollment
Patient has, in the opinion of the Investigator, a condition that compromises the ability of the subject to give written informed consent or to comply with study procedures, including scheduled self-administration of oral CK-1827452
The patient has had any prior treatment with CK-1827452

Trial locations and contacts

3 sites in 1 country.

Georgia3 sites

Cardio-Reanimation Centre
Tbilisi
Diagnostic Services Clinic
Tbilisi
Tbilisi State Medical University Clinic #1
Tbilisi

Other trials in Georgia

About this study

Official title: An Open Label Study to Investigate the Pharmacokinetics of CK-1827452 Administered Orally to Patients With Stable Heart Failure

Conditions: Heart Failure
Being tested: CK-1827452
Keywords: 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.

CK-1827452Drug
50 mg MR CK-1827452 BID for 10 days
CK-1827452Drug
37.5 mg IR CK-1827452 TID for 10 days
CK-1827452Drug
100 mg MR CK-1827452 BID for 10 days

Study groups in NCT00941681
Study group	Role	What they receive
Cohort 1: MR 50 mg BID	Experimental	Modified-release (MR) 50 mg dose of CK-1827452 twice a day (BID) for 10 days. Receives: Drug: CK-1827452
Cohort 2: IR 37.5 mg TID	Experimental	Immediate-release (IR) 37.5 mg dose of CK-1827452 three times a day (TID) for 10 days. Receives: Drug: CK-1827452
Cohort 3: MR 100 mg BID	Experimental	Modified-release (MR) 100 mg dose of CK-1827452 twice a day (BID) for 10 days Receives: Drug: CK-1827452

What is being measured

The primary outcome is the main question the study is designed to answer.

C Max (Day 1, Dose 1)
Maximum plasma concentration (C max) measured in nanograms per milliliter (ng/mL) post first dose and pre second dose on day 1. Doses are approximately 12 hours apart in cohort 1 and 3 and 8 hours apart in cohort 2.
Measured: 1 day
T Max (Day 1, Dose 1)
Time of observed maximum plasma concentration (T max) measured in hours (hr) post first dose and pre second dose on day 1. Doses are approximately 12 hours apart in cohort 1 and 3 and 8 hours apart in cohort 2.
Measured: 1 day
AUC (Day 1, Dose 1)
Area under the curve (AUC) measured in hours * nanograms per milliliter (hr*ng/mL) post first dose and pre second dose on day 1. Doses are approximately 12 hours apart in cohort 1 and 3 and 8 hours apart in cohort 2.
Measured: 1 day
C Max (Day 10)
Maximum plasma concentration (C max) measured in nanograms per milliliter (ng/mL) post dose on day 10. Only one dose was administered on day 10 (final dose of study).
Measured: 1 day
T Max (Day 10)
Time of observed maximum plasma concentration (T max) measured in hours (hr) post dose on day 10. Only one dose was administered on day 10 (final dose of study).
Measured: 1 day
AUC (Day 10)
Area under the curve (AUC) measured in hours * nanograms per milliliter (hr*ng/mL) post dose on day 10. Only one dose was administered on day 10 (final dose of study).
Measured: 1 day

Secondary outcomes (1)

Evaluate the Safety and Tolerability of Oral Formulations of CK-1827452 When Dosed to Steady-state in Patients With Stable Heart Failure.
Measured: 1 week

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Apr 2009Oct 2009

First posted17 Jul 2009 (estimated)
Study startApr 2009
Primary completionOct 2009
Study completionOct 2009

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
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 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 35 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00941681
Sponsor's protocol ID: CY 1021
Status last verified: Feb 2013
First submitted: 15 Jul 2009
Last updated: 12 Feb 2013
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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

All Heart Failure trials

Study at a glance

From the registry record, last updated by the sponsor on 12 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open Label Study to Investigate the Pharmacokinetics of CK-1827452 Administered Orally to Patients With Stable Heart Failure
ClinicalTrials.gov ID: NCT00941681
Acronym / sponsor ID: CY 1021
Conditions: Heart Failure
Keywords: omecamtiv mecarbil
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 35 participants (actual)
Lead sponsor: CytokineticsIndustry (pharma, biotech, devices)
Study start: Apr 2009
Primary completion: Oct 2009 (actual)
Study completion: Oct 2009 (actual)
First posted: 17 Jul 2009 (estimated)
Results: Posted 21 Dec 2010

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Cohort 1: MR 50 mg BID	Experimental	Drug: CK-1827452Modified-release (MR) 50 mg dose of CK-1827452 twice a day (BID) for 10 days.
Cohort 2: IR 37.5 mg TID	Experimental	Drug: CK-1827452Immediate-release (IR) 37.5 mg dose of CK-1827452 three times a day (TID) for 10 days.
Cohort 3: MR 100 mg BID	Experimental	Drug: CK-1827452Modified-release (MR) 100 mg dose of CK-1827452 twice a day (BID) for 10 days

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

The patient has signed an Informed Consent Form/Patient Information Sheet for this study approved by the governing Institutional Review Board (IRB) or Independent Ethics Committee (IEC)
The patient is at least 18 years old at the time of consent
Left ventricular ejection fraction (LVEF) ≤ 35% as determined by the Investigator within 3 weeks prior to enrollment
Treated for at least 4 weeks with a beta blocker and an ACE inhibitor (and/or an ARB) unless not tolerated. If prescribed, diuretics must have been administered according to a consistent regimen for at least 4 weeks.
Diagnosed with heart failure for ≥ 3 months prior to enrollment

Key exclusion criteria (15 listed)

Patient has been hospitalised for heart failure, acute coronary syndrome, myocardial infarction, coronary revascularisation, transient ischemic attack or stroke, cardiac arrhythmia, or major surgery within 6 weeks prior to enrollment
Poorly controlled hypertension defined as blood pressure > 150/95 mmHg, documented on at least 2 separate occasions prior to enrollment
The patient has a supine heart rate ≥ 100 beats per minute after 10 minutes of rest
Patient has a troponin I at screening that is above the upper limit of normal
The patient has severe aortic or mitral stenosis

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
CK-182745250 mg MR CK-1827452 BID for 10 days	Drug	Cohort 1: MR 50 mg BID
CK-182745237.5 mg IR CK-1827452 TID for 10 days	Drug	Cohort 2: IR 37.5 mg TID
CK-1827452100 mg MR CK-1827452 BID for 10 days	Drug	Cohort 3: MR 100 mg BID

Primary outcome

C Max (Day 1, Dose 1)
Time frame: 1 day
Maximum plasma concentration (C max) measured in nanograms per milliliter (ng/mL) post first dose and pre second dose on day 1. Doses are approximately 12 hours apart in cohort 1 and 3 and 8 hours apart in cohort 2.
T Max (Day 1, Dose 1)
Time frame: 1 day
Time of observed maximum plasma concentration (T max) measured in hours (hr) post first dose and pre second dose on day 1. Doses are approximately 12 hours apart in cohort 1 and 3 and 8 hours apart in cohort 2.
AUC (Day 1, Dose 1)
Time frame: 1 day
Area under the curve (AUC) measured in hours * nanograms per milliliter (hr*ng/mL) post first dose and pre second dose on day 1. Doses are approximately 12 hours apart in cohort 1 and 3 and 8 hours apart in cohort 2.
C Max (Day 10)
Time frame: 1 day
Maximum plasma concentration (C max) measured in nanograms per milliliter (ng/mL) post dose on day 10. Only one dose was administered on day 10 (final dose of study).
T Max (Day 10)
Time frame: 1 day
Time of observed maximum plasma concentration (T max) measured in hours (hr) post dose on day 10. Only one dose was administered on day 10 (final dose of study).
AUC (Day 10)
Time frame: 1 day
Area under the curve (AUC) measured in hours * nanograms per milliliter (hr*ng/mL) post dose on day 10. Only one dose was administered on day 10 (final dose of study).

1 secondary outcome

Evaluate the Safety and Tolerability of Oral Formulations of CK-1827452 When Dosed to Steady-state in Patients With Stable Heart Failure.
Time frame: 1 week

Results and safety

Results posted to the registry on 21 Dec 2010, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cohort 1: MR 50 mg BID	12	12
Cohort 2: IR 37.5 mg TID	11	10
Cohort 3: MR 100 mg BID	12	12

Primary outcome: C Max (Day 1, Dose 1)

Time frame: 1 day. Mean (Standard Deviation). Unit: ng/mL

Measure	Cohort 1: MR 50 mg BID n = 12	Cohort 2: IR 37.5 mg TID n = 11	Cohort 3: MR 100 mg BID n = 8
Value	58 (27)	243 (148)	209 (164)

Population analysed: PK population (4 patients excluded from cohort 3 analysis due to improper dosing).

Primary outcome: T Max (Day 1, Dose 1)

Time frame: 1 day. Mean (Standard Deviation). Unit: hr

Measure	Cohort 1: MR 50 mg BID n = 12	Cohort 2: IR 37.5 mg TID n = 11	Cohort 3: MR 100 mg BID n = 8
Value	3.5 (2.9)	3.7 (3.7)	3.5 (3.9)

Population analysed: PK population (4 patients excluded from cohort 3 analysis due to improper dosing).

Primary outcome: AUC (Day 1, Dose 1)

Time frame: 1 day. Mean (Standard Deviation). Unit: hr*ng/mL

Measure	Cohort 1: MR 50 mg BID n = 12	Cohort 2: IR 37.5 mg TID n = 11	Cohort 3: MR 100 mg BID n = 8
Value	446 (206)	1003 (387)	1650 (1354)

Population analysed: PK population (4 patients excluded from cohort 3 analysis due to improper dosing).

Primary outcome: C Max (Day 10)

Time frame: 1 day. Mean (Standard Deviation). Unit: ng/mL

Measure	Cohort 1: MR 50 mg BID n = 12	Cohort 2: IR 37.5 mg TID n = 10	Cohort 3: MR 100 mg BID n = 8
Value	205 (111)	420 (158)	704 (494)

Population analysed: PK population (4 patients excluded from cohort 3 analysis due to improper dosing and 1 patient excluded from cohort 2 due to sudden death).

1 secondary outcome is reported in the full results.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cohort 1: MR 50 mg BID	0 of 12 (0%)	0 of 12 (0%)	Not reported
Cohort 2: IR 37.5 mg TID	1 of 11 (9.1%)	0 of 11 (0%)	Not reported
Cohort 3: MR 100 mg BID	0 of 12 (0%)	2 of 12 (16.7%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2013.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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.

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing CK-1827452 in people with Heart Failure, run by Cytokinetics at 3 sites in Georgia.

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 7 inclusion and 15 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 12 Feb 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Georgia. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Dec 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

C Max (Day 1, Dose 1) (time frame: 1 day). The study lists 6 primary outcomes in all. 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 NCT00941681.

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 12 Feb 2013.