PK and Tolerability of IV and Oral CK-1827452 in Patients With Ischemic Cardiomyopathy and Angina

NCT00682565 | Completed Phase 2 Results

• 1 other identifier: CY 1221
• Study Type: interventional
• Target: 94
• Locations: 2 countries
• Sites: 14

Brief Summary

This study investigates whether symptom-limited exercise capacity in ischemic cardiomyopathy patients with angina is deleteriously affected by treatment with CK-1827452.

Conditions

Heart Failure; Myocardial Ischemia; Angina Pectoris

Outcome Measures

Primary Outcomes (1)

• Participants Stopping Exercise Treadmill Test 3 (ETT-3) for Angina at Stage Earlier Than Baseline Exercise Treadmill Test (ETT-B)

  The Modified Naughton Exercise Treadmill Test was employed in this study. Exercise Treadmill Test 3 (ETT-3) was performed during the last 2 hours of the 20-hour infusion of study drug or placebo. Baseline Exercise Treadmill Test (ETT-B) was performed prior to dosing.

  1 day

Secondary Outcomes (4)

• Participants Stopping ETT-3 for Any Reason at Stage Earlier Than ETT-B

  1 day

• Increase in Exercise Duration During ETT-3 vs. ETT-B

  1 day

• Participants Stopping ETT-3 for Angina at Any Stage

  1 day

• Participants With 1 mm ST Segment Depression During ETT-3

  1 day

Study Arms (2)

Mid Dose CK-1827452 or Placebo

EXPERIMENTAL

CK-1827452 I.V. infusion for 2 hours at 24mg/hr followed by 18 hours at 6mg/hr or placebo, followed by 6 days three times a day oral dose and a final single oral dose

Drug: CK-1827452 24mg and 6 mg iv infusion; Drug: CK-1827452 12.5mg capsule; Drug: Placebo iv infusion; Drug: Placebo capsule

High Dose CK-1827452 or Placebo

EXPERIMENTAL

CK-1827452 I.V. infusion for 2 hours at 48mg/hr followed by 18 hours at 11mg/hr or placebo, followed by 6 days three times a day oral dose and a final single oral dose

Drug: CK-1827452 48 mg and 11 mg iv infusion; Drug: CK-1827452 25mg capsule; Drug: Placebo iv infusion; Drug: Placebo capsule

Interventions

CK-1827452 24mg and 6 mg iv infusion DRUG

I.V. infusion for 2 hours at 24mg/hr followed by 18 hours at 6mg/hr

Also known as: omecamtiv mecarbil

Mid Dose CK-1827452 or Placebo

CK-1827452 12.5mg capsule DRUG

12.5mg oral immediate release capsule

Also known as: omecamtiv mecarbil

Mid Dose CK-1827452 or Placebo

CK-1827452 48 mg and 11 mg iv infusion DRUG

I.V. infusion for 2 hours at 48mg/hr followed by 18 hours at 11mg/hr

Also known as: omecamtiv mecarbil

High Dose CK-1827452 or Placebo

CK-1827452 25mg capsule DRUG

25mg oral immediate release capsule

Also known as: omecamtiv mecarbil

High Dose CK-1827452 or Placebo

Placebo iv infusion DRUG

Matching placebo iv infusion

High Dose CK-1827452 or Placebo; Mid Dose CK-1827452 or Placebo

Placebo capsule DRUG

Matching placebo oral immediate release capsule

High Dose CK-1827452 or Placebo; Mid Dose CK-1827452 or Placebo

Eligibility Criteria

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

You may qualify if:

• 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.
• The patient has ischemic heart disease documented by any one or more of the following:
• A history of myocardial infarction documented by elevated CPK-MB, troponin I or T, or the presence of electrocardiographic Q waves consistent with myocardial infarction.
• Coronary angiography demonstrating at least 1 major epicardial coronary artery (i.e., left main, left anterior descending, left circumflex, or right coronary artery) with a stenosis of at least 60% diameter or greater but excluding stenosis of the left main coronary artery unless revascularized by coronary artery bypass grafting.
• The patient has a history of ≥ 1 episode of exercise induced angina within 2 months prior to the initial screening visit.
• The patient has been taking a beta blocker and an ACE inhibitor (and/or an ARB) for at least 4 weeks. If prescribed, diuretics must have been administered for at least 4 weeks prior to the initial screening visit.
• The patient is NYHA Class II-III at the time of enrollment and has been so for ≥ 3 months prior to the initial screening visit.
• The patient has a history of a left ventricular ejection fraction (LVEF) ≤ 35%.
• The patient has a history of EITHER a left ventricular end-diastolic diameter ≥ 55 mm, OR a left ventricular end-diastolic diameter index ≥ 32 mm/m2.
• The patient can be expected to complete at least 4 minutes of a Modified Naughton ETT (see Appendix B).
• 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.

You may not qualify if:

• The patient has acute myocarditis; clinically significant restrictive, constrictive, or hypertrophic obstructive cardiomyopathy; or clinically significant congenital heart disease.
• The patient has a SBP \> 160 mmHg, documented on at least 3 separate occasions, at least 10 minutes apart.
• The patient has a DBP \> 90 mmHg, documented on at least 3 separate occasions, at least 10 minutes apart.
• The patient has levels of troponin I or T, or CPK-MB \> the upper limit of normal at any time from 6 weeks prior to the Initial Screening Visit (Visit 1) and up to randomization.
• The patient has severe aortic or mitral stenosis.
• The patient has had an acute coronary syndrome, transient ischemic attack, or revascularization procedure within 6 weeks of the Initial Screening Visit (Visit 1).
• The patient has significant co-morbid conditions (i.e., lung disease, arthritis, peripheral vascular disease) that may limit his or her treadmill exercise capacity.
• The patient has renal impairment defined by a calculated creatinine clearance \< 30 cc/min or a need for renal replacement therapy.
• The patient has known hepatic impairment defined by a total bilirubin \> 3 mg/dL, or an ALT or AST \> 2 times the upper limit of normal.
• The patient has received an investigational drug or device within 30 days or 5 half-lives, whichever is greater, of randomization.
• The patient weighs \> 120 kg.
• The patient has a body temperature \> 38 ° C, confirmed by at least 2 successive measurements, at least 10 minutes apart.
• The patient has any laboratory abnormality which, in the opinion of the investigator, should preclude his or her participation in the study.
• The patient has had any prior treatment with CK-1827452.

Sponsors & Collaborators

• Cytokinetics: lead

Study Sites (14)

Tbilisi State Medical University Clinic #1

Tbilisi, 0102, Georgia

Location

Cardio-Reanimation Centre

Tbilisi, 0141, Georgia

Location

Cardiology Clinic

Tbilisi, 0144, Georgia

Location

National Center of Therapy

Tbilisi, 0159, Georgia

Location

Multiprofile Clinical Hospital of Tbilisi #2

Tbilisi, 0164, Georgia

Location

Diagnostic Services Clinic

Tbilisi, 0179, Georgia

Location

Altay Territory Cardiology Dispensary

Barnaul, Russia

Location

City Hospital #1

Barnaul, Russia

Location

City Clinical Hospital #59

Moscow, Russia

Location

City Clinical Hospital #64

Moscow, Russia

Location

Moscow Municipal Clinical Hospital #4

Moscow, Russia

Location

Federal Center of Heart, Blood and Endocrinology n.a. Almazov

Saint Petersburg, Russia

Location

Research Centre for Cardiology n.a. Almazov under Roszdrav

Saint Petersburg, Russia

Location

Volgograd Regional Cardiology Center

Volgograd, Russia

Location

Related Publications (1)

• Greenberg BH, Chou W, Saikali KG, Escandon R, Lee JH, Chen MM, Treshkur T, Megreladze I, Wasserman SM, Eisenberg P, Malik FI, Wolff AA, Shaburishvili T. Safety and tolerability of omecamtiv mecarbil during exercise in patients with ischemic cardiomyopathy and angina. JACC Heart Fail. 2015 Jan;3(1):22-29. doi: 10.1016/j.jchf.2014.07.009. Epub 2014 Nov 11.

  PMID: 25453536 DERIVED

MeSH Terms

Conditions

Heart Failure; Myocardial Ischemia; Angina Pectoris

Interventions

omecamtiv mecarbil; Infusions, Intravenous

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Administration, Intravenous; Drug Administration Routes; Drug Therapy; Therapeutics; Infusions, Parenteral

Results Point of Contact

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

650-624-3053

Study Officials

• Andrew A Wolff, MD, FACC

  Cytokinetics, Inc.

  STUDY CHAIR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: May 20, 2008
• First Posted: May 22, 2008
• Study Start: April 1, 2008
• Primary Completion: November 1, 2008
• Study Completion: March 1, 2009
• Last Updated: August 21, 2018
• Results First Posted: February 25, 2010

Record last verified: 2010-02

Locations

GE (6); RU (8)