A Study of CK-1827452 Infusion in Stable Heart Failure

NCT00624442 | Completed Phase 2 Results

• 1 other identifier: CY 1121
• Study Type: interventional
• Target: 45
• Locations: 4 countries
• Sites: 17

Brief Summary

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

Conditions

Heart Failure

Outcome Measures

Primary Outcomes (2)

• Change From Baseline of Systolic Ejection Time at Various CK-1827452 Plasma Concentrations

  Pooled analysis of the echocardiographic measure systolic ejection time from echocardiograms taken at all timepoints. 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 and 5 (564 echocardiograms) were binned into either placebo group or 1 of 6 groups based on plasma concentration of CK-1827452.

  4 days

• Change From Baseline of Fractional Shortening at Various CK-1827452 Plasma Concentrations

  Pooled analysis of the echocardiographic measure fractional shortening from echocardiograms taken at all timepoints. Fractional shortening is the percentage of change from baseline in the left ventricular cavity dimension with systole. Echocardiograms from cohorts 1,2,3,4 and 5 (564 echocardiograms) were binned into either placebo group or 1 of 6 groups based on plasma concentration of CK-1827452.

  4 days

Secondary Outcomes (2)

• CK-1827452 Maximum Observed Plasma Concentration (Cmax)

  2 days

• CK-1827452 Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Plasma Concentration (AUClast)

  2 days

Study Arms (5)

Cohort 1

EXPERIMENTAL

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.

Drug: CK-1827452; Drug: Placebo

Cohort 2

EXPERIMENTAL

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.

Drug: CK-1827452; Drug: Placebo

Cohort 3

EXPERIMENTAL

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.

Drug: Placebo; Drug: CK-1827452

Cohort 4

EXPERIMENTAL

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.

Drug: CK-1827452; Drug: Placebo

Cohort 5

EXPERIMENTAL

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.

Drug: CK-1827452; Drug: Placebo

Interventions

CK-1827452 DRUG

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

Cohort 1

Placebo DRUG

IV infusion for 2 hours

Cohort 1; Cohort 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient is male, or female of non-childbearing potential (two years post-menopausal or surgically sterilized)
• Female patients must have a negative urine pregnancy test prior to entry into the study
• Patient is 18 years old or greater
• Patient has given signed informed consent
• 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

You may not qualify if:

• Patient has a documented diagnosis of heart failure with an ejection fraction of less than 40%
• 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
• Patient is currently in sinus rhythm
• Patient has interpretable echocardiographic images on a screening echocardiogram
• Patient has been hospitalized for heart failure, myocardial infarction, coronary revascularization, or another cardiac indication within the last 6 weeks
• Patient has a current history of alcohol use which in the opinion of the investigator would preclude participation in the study
• Patient has a current history of drug abuse
• Patient has donated blood or blood products within 30 days prior to screening
• Patient has Canadian Cardiovascular Society (CCS) Class III or IV angina
• Patient has significant obstructive valvular disease or significant congenital heart disease
• Patient has had a valve replacement
• Patient is pacemaker dependent
• Patient is on chronic anti-arrhythmic therapy, with the exception of amiodarone
• Patient is currently taking, or has taken in the last 7 days, a CYP3A4 inhibitor or inducer medication
• Patient has a history of hypertrophic obstructive cardiomyopathy

Sponsors & Collaborators

• Cytokinetics: lead

Study Sites (17)

University of California, San Diego Medical Center

San Diego, California, 92103, United States

Location

Christiana Care Health Services, Inc.

Newark, Delaware, 19713, United States

Location

Diagnostic Services Clinic

Tbilisi, Georgia

Location

Russian Cardiological Research and Production Complex

Moscow, 121552, Russia

Location

Dzhanelidze Research Institute for Emergency Medical Care

Saint Petersburg, 192242, Russia

Location

Almazov Federal Heart, Blood and Endocrinology Center

Saint Petersburg, 194156, Russia

Location

St. Petersburg State Medical University

Saint Petersburg, 197089, Russia

Location

Castle Hill Hospital, University of Hull

Hull, England, HU16 5JQ, United Kingdom

Location

King's College Hospital

London, England, SE5 9RS, United Kingdom

Location

St. George's Hospital

London, England, SW17 ORE, United Kingdom

Location

St. Mary's Hospital & Imperial College

London, England, W2 1LA, United Kingdom

Location

Manchester Heart Centre, Manchester Royal Infirmary

Manchester, England, M13 9WL, United Kingdom

Location

ICON Development Solutions

Manchester, England, M15 6SH, United Kingdom

Location

Wythenshawe Hospital

Manchester, England, M23 9LT, United Kingdom

Location

Northwick Park Hospital

Middlesex, England, HA1 3UJ, United Kingdom

Location

Ninewells Hospital and Medical School

Dundee, Scotland, DD1 9SY, United Kingdom

Location

BHF Cardiovascular Centre

Glasgow, Scotland, G12 8TA, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 25951506 DERIVED

• 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.

  PMID: 21856481 DERIVED

MeSH Terms

Conditions

Heart Failure

Interventions

omecamtiv mecarbil

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Limitations and Caveats

Other Adverse Event table shows treatment emergent adverse events that occurred in two or more patients. Total for Other Adverse Events is the number of patients affected by an adverse event where an adverse event occurred in two or more patients.

Results Point of Contact

• Title: Medical Director
• Organization: Cytokinetics, Inc.

(650) 624-3011

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2007
• First Posted: February 27, 2008
• Study Start: April 1, 2007
• Primary Completion: February 1, 2009
• Study Completion: February 1, 2009
• Last Updated: May 14, 2021
• Results First Posted: August 16, 2010

Record last verified: 2021-04

Locations

GB (10); RU (4); US (2); GE (1)