A Study of CK-1827452 Infusion in Stable Heart Failure

NCT ID: NCT00624442

Last Updated: 2021-05-14

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

45 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-04-30

Study Completion Date

2009-02-28

Brief Summary

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This study will assess the safety, tolerability, and pharmacodynamics of CK-1827452 infusion in patients with stable heart failure.

Detailed Description

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Conditions

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Heart Failure

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Cohort 1

4 treatment periods with a 2 hour infusion. The 4 treatment periods consist of 3 escalating dose levels of CK-1827452 and 1 placebo treatment randomized into the dose escalation sequence. Treatment periods occur at least 7 days apart.

Group Type EXPERIMENTAL

CK-1827452

Intervention Type DRUG

IV infusion for 1 hour at 0.125 mg/kg/h followed by 1 hour at 0.0625 mg/kg/h

CK-1827452

Intervention Type DRUG

IV infusion for 1 hour at 0.25 mg/kg/h followed by 1 hour at 0.125 mg/kg/h

CK-1827452

Intervention Type DRUG

IV infusion for 1 hour at 0.5 mg/kg/h followed by 1 hour at 0.25 mg/kg/h

Placebo

Intervention Type DRUG

IV infusion for 2 hours

Cohort 2

4 treatment periods with a 2 hour infusion. The 4 treatment periods consist of 3 escalating dose levels of CK-1827452 and 1 placebo treatment randomized into the dose escalation sequence. Treatment periods occur at least 7 days apart.

Group Type EXPERIMENTAL

CK-1827452

Intervention Type DRUG

IV infusion for 1 hour at 0.5 mg/kg/h followed by 1 hour at 0.25 mg/kg/h

CK-1827452

Intervention Type DRUG

IV infusion for 1 hour at 0.75 mg/kg/h followed by 1 hour at 0.375 mg/kg/h

CK-1827452

Intervention Type DRUG

IV infusion for 1 hour at 1.0 mg/kg/h followed by 1 hour at 0.5 mg/kg/h

Placebo

Intervention Type DRUG

IV infusion for 2 hours

Cohort 3

4 treatment periods with a 24 hour infusion. The 4 treatment periods consist of 3 escalating dose levels of CK-1827452 and 1 placebo treatment randomized into the dose escalation sequence. Treatment periods occur at least 7 days apart.

Group Type EXPERIMENTAL

Placebo

Intervention Type DRUG

IV infusion for 24 hours

CK-1827452

Intervention Type DRUG

IV infusion for 1 hour at 0.25 mg/kg/h followed by 23 hours at 0.025 mg/kg/h

CK-1827452

Intervention Type DRUG

IV infusion for 1 hour at 0.5 mg/kg/h followed by 23 hours at 0.05 mg/kg/h

CK-1827452

Intervention Type DRUG

IV infusion for 1 hour at 1.0 mg/kg/h followed by 23 hours at 0.1 mg/kg/h

Cohort 4

4 treatment periods with a 24 hour infusion. The 4 treatment periods consist of 3 escalating dose levels of CK-1827452 and 1 placebo treatment randomized into the dose escalation sequence. Treatment periods occur at least 7 days apart.

Group Type EXPERIMENTAL

CK-1827452

Intervention Type DRUG

IV infusion for 1 hour at 0.25 mg/kg/h followed by 1 hour at 0.125 mg/kg/h followed by 22 hours at 0.025 mg/kg/h

CK-1827452

Intervention Type DRUG

IV infusion for 1 hour at 0.5 mg/kg/h followed by 1 hour at 0.25 mg/kg/h followed by 22 hours at 0.05 mg/kg/h

CK-1827452

Intervention Type DRUG

IV infusion for 1 hour at 1.0 mg/kg/h followed by 1 hour at 0.5 mg/kg/h followed by 22 hours at 0.1 mg/kg/h

Placebo

Intervention Type DRUG

IV infusion for 24 hours

Cohort 5

2 treatment periods with a 72 hour infusion. The 2 treatment periods are randomly assigned and consist of 1 dose level of CK-1827452 (with dose de-escalation possible depending on tolerability) and 1 placebo treatment. Treatment period 2 occurs at least 7 days after the conclusion of period 1.

Group Type EXPERIMENTAL

CK-1827452

Intervention Type DRUG

IV infusion for 1 hour at 1.0 mg/kg/h followed 1 hour at 0.5 mg/kg/h followed by 70 hours at 0.1 mg/kg/h

Placebo

Intervention Type DRUG

IV infusion for 72 hours

CK-1827452

Intervention Type DRUG

IV infusion for 1 hour at 0.75 mg/kg/h followed 1 hour at 0.5 mg/kg/h followed by 70 hours at 0.1 mg/kg/h

Interventions

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CK-1827452

IV infusion for 1 hour at 0.125 mg/kg/h followed by 1 hour at 0.0625 mg/kg/h

Intervention Type DRUG

CK-1827452

IV infusion for 1 hour at 0.25 mg/kg/h followed by 1 hour at 0.125 mg/kg/h

Intervention Type DRUG

CK-1827452

IV infusion for 1 hour at 0.5 mg/kg/h followed by 1 hour at 0.25 mg/kg/h

Intervention Type DRUG

CK-1827452

IV infusion for 1 hour at 0.75 mg/kg/h followed by 1 hour at 0.375 mg/kg/h

Intervention Type DRUG

CK-1827452

IV infusion for 1 hour at 1.0 mg/kg/h followed by 1 hour at 0.5 mg/kg/h

Intervention Type DRUG

CK-1827452

IV infusion for 1 hour at 0.25 mg/kg/h followed by 1 hour at 0.125 mg/kg/h followed by 22 hours at 0.025 mg/kg/h

Intervention Type DRUG

CK-1827452

IV infusion for 1 hour at 0.5 mg/kg/h followed by 1 hour at 0.25 mg/kg/h followed by 22 hours at 0.05 mg/kg/h

Intervention Type DRUG

CK-1827452

IV infusion for 1 hour at 1.0 mg/kg/h followed by 1 hour at 0.5 mg/kg/h followed by 22 hours at 0.1 mg/kg/h

Intervention Type DRUG

Placebo

IV infusion for 2 hours

Intervention Type DRUG

Placebo

IV infusion for 24 hours

Intervention Type DRUG

CK-1827452

IV infusion for 1 hour at 1.0 mg/kg/h followed 1 hour at 0.5 mg/kg/h followed by 70 hours at 0.1 mg/kg/h

Intervention Type DRUG

Placebo

IV infusion for 72 hours

Intervention Type DRUG

CK-1827452

IV infusion for 1 hour at 0.75 mg/kg/h followed 1 hour at 0.5 mg/kg/h followed by 70 hours at 0.1 mg/kg/h

Intervention Type DRUG

CK-1827452

IV infusion for 1 hour at 0.25 mg/kg/h followed by 23 hours at 0.025 mg/kg/h

Intervention Type DRUG

CK-1827452

IV infusion for 1 hour at 0.5 mg/kg/h followed by 23 hours at 0.05 mg/kg/h

Intervention Type DRUG

CK-1827452

IV infusion for 1 hour at 1.0 mg/kg/h followed by 23 hours at 0.1 mg/kg/h

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Patient is male, or female of non-childbearing potential (two years post-menopausal or surgically sterilized)
2. Female patients must have a negative urine pregnancy test prior to entry into the study
3. Patient is 18 years old or greater
4. Patient has given signed informed consent
5. Patient is considered to be in suitable health in the opinion of the investigator, as determined by:

* A pre-study physical examination with no clinical abnormalities which in the opinion of the investigator would preclude participation in the study other than physical symptoms or signs consistent with stable heart failure
* An electrocardiogram (ECG) with no abnormalities in the opinion of the investigator that would impair assessment of stopping criteria

Exclusion Criteria

7. Patient has a documented diagnosis of heart failure with an ejection fraction of less than 40%
8. Patient has been on a stable dose of a beta blocker and an ACE (angiotensin-converting enzyme) inhibitor or an ARB (angiotensin II receptor blocker) for at least 4 weeks. If prescribed, diuretics must have been administered according to a consistent regimen for at least 4 weeks
9. Patient is currently in sinus rhythm
10. Patient has interpretable echocardiographic images on a screening echocardiogram


1. Patient has been hospitalized for heart failure, myocardial infarction, coronary revascularization, or another cardiac indication within the last 6 weeks
2. Patient has a current history of alcohol use which in the opinion of the investigator would preclude participation in the study
3. Patient has a current history of drug abuse
4. Patient has donated blood or blood products within 30 days prior to screening
5. Patient has Canadian Cardiovascular Society (CCS) Class III or IV angina
6. Patient has significant obstructive valvular disease or significant congenital heart disease
7. Patient has had a valve replacement
8. Patient is pacemaker dependent
9. Patient is on chronic anti-arrhythmic therapy, with the exception of amiodarone
10. Patient is currently taking, or has taken in the last 7 days, a CYP3A4 inhibitor or inducer medication
11. Patient has a history of hypertrophic obstructive cardiomyopathy
12. Patient weighs \> 120 kg
13. Patient has a supine resting systolic blood pressure \< 95 mmHg after 3 minutes rest
14. Patient has a supine resting heart rate ≥ 100 beats per minute after 3 minutes rest
15. Patient has an Modification of Diet in Renal Disease (MDRD) estimate of Glomerular Filtration Rate (GFR) ≤ 35 ml/min/1.73 m2
16. Patient has a potassium \< 3.5 mEq/L or \> 5.5 mEq/L
17. Patient has a sodium ≤ 133 mEq/L
18. Patient has a urea \> 15 mmole/L
19. Patient has a troponin I or T at screening that is detectable at the investigative site's clinical laboratory
20. Patient has a hemoglobin \< 11 gm/dL in males or \< 10 gm/dL in females
21. Patient has an alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALKP) or total bilirubin (TBILI) \> 3 times the upper limit of normal
22. Patient is, in the opinion of the investigator, not suitable to participate in the study
23. Patient has participated in any clinical study with an investigational drug within three months prior to the first day of dosing with the exception of coronary stent studies Patient has ever received CK-1827452
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Cytokinetics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of California, San Diego Medical Center

San Diego, California, United States

Site Status

Christiana Care Health Services, Inc.

Newark, Delaware, United States

Site Status

Diagnostic Services Clinic

Tbilisi, , Georgia

Site Status

Russian Cardiological Research and Production Complex

Moscow, , Russia

Site Status

Dzhanelidze Research Institute for Emergency Medical Care

Saint Petersburg, , Russia

Site Status

Almazov Federal Heart, Blood and Endocrinology Center

Saint Petersburg, , Russia

Site Status

St. Petersburg State Medical University

Saint Petersburg, , Russia

Site Status

Castle Hill Hospital, University of Hull

Hull, England, United Kingdom

Site Status

King's College Hospital

London, England, United Kingdom

Site Status

St. George's Hospital

London, England, United Kingdom

Site Status

St. Mary's Hospital & Imperial College

London, England, United Kingdom

Site Status

Manchester Heart Centre, Manchester Royal Infirmary

Manchester, England, United Kingdom

Site Status

ICON Development Solutions

Manchester, England, United Kingdom

Site Status

Wythenshawe Hospital

Manchester, England, United Kingdom

Site Status

Northwick Park Hospital

Middlesex, England, United Kingdom

Site Status

Ninewells Hospital and Medical School

Dundee, Scotland, United Kingdom

Site Status

BHF Cardiovascular Centre

Glasgow, Scotland, United Kingdom

Site Status

Countries

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United States Georgia Russia United Kingdom

References

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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)

Cleland JG, Teerlink JR, Senior R, Nifontov EM, Mc Murray JJ, Lang CC, Tsyrlin VA, Greenberg BH, Mayet J, Francis DP, Shaburishvili T, Monaghan M, Saltzberg M, Neyses L, Wasserman SM, Lee JH, Saikali KG, Clarke CP, Goldman JH, Wolff AA, Malik FI. The effects of the cardiac myosin activator, omecamtiv mecarbil, on cardiac function in systolic heart failure: a double-blind, placebo-controlled, crossover, dose-ranging phase 2 trial. Lancet. 2011 Aug 20;378(9792):676-83. doi: 10.1016/S0140-6736(11)61126-4.

Reference Type DERIVED
PMID: 21856481 (View on PubMed)

Other Identifiers

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CY 1121

Identifier Type: -

Identifier Source: org_study_id

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