A Study of CK-1827452 Infusion in Stable Heart Failure
- Registration Number
- NCT00624442
- Lead Sponsor
- Cytokinetics
- Brief Summary
This study will assess the safety, tolerability, and pharmacodynamics of CK-1827452 infusion in patients with stable heart failure.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 45
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Cohort 1 Placebo 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. Cohort 2 Placebo 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. Cohort 3 CK-1827452 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. Cohort 5 Placebo 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. Cohort 1 CK-1827452 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. Cohort 3 Placebo 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. Cohort 4 Placebo 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. Cohort 5 CK-1827452 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. Cohort 2 CK-1827452 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. Cohort 4 CK-1827452 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.
- Primary Outcome Measures
Name Time Method Change From Baseline of Fractional Shortening at Various CK-1827452 Plasma Concentrations 4 days 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.
Change From Baseline of Systolic Ejection Time at Various CK-1827452 Plasma Concentrations 4 days 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.
- Secondary Outcome Measures
Name Time Method CK-1827452 Maximum Observed Plasma Concentration (Cmax) 2 days Determined by evaluation of plasma concentrations from blood samples collected prior to dosing and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 12, 24 and 48 hours after initiation of study drug infusion
CK-1827452 Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Plasma Concentration (AUClast) 2 days Determined by evaluation of plasma concentrations from blood samples collected prior to dosing and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 12, 24 and 48 hours after initiation of study drug infusion
Trial Locations
- Locations (17)
Wythenshawe Hospital
🇬🇧Manchester, England, United Kingdom
Manchester Heart Centre, Manchester Royal Infirmary
🇬🇧Manchester, England, United Kingdom
Diagnostic Services Clinic
🇬🇪Tbilisi, Georgia
St. Petersburg State Medical University
🇷🇺St. Petersburg, Russian Federation
ICON Development Solutions
🇬🇧Manchester, England, United Kingdom
Dzhanelidze Research Institute for Emergency Medical Care
🇷🇺St. Petersburg, Russian Federation
King's College Hospital
🇬🇧London, England, United Kingdom
University of California, San Diego Medical Center
🇺🇸San Diego, California, United States
Northwick Park Hospital
🇬🇧Middlesex, England, United Kingdom
Ninewells Hospital and Medical School
🇬🇧Dundee, Scotland, United Kingdom
BHF Cardiovascular Centre
🇬🇧Glasgow, Scotland, United Kingdom
Christiana Care Health Services, Inc.
🇺🇸Newark, Delaware, United States
Russian Cardiological Research and Production Complex
🇷🇺Moscow, Russian Federation
Almazov Federal Heart, Blood and Endocrinology Center
🇷🇺St. Petersburg, Russian Federation
Castle Hill Hospital, University of Hull
🇬🇧Hull, England, United Kingdom
St. George's Hospital
🇬🇧London, England, United Kingdom
St. Mary's Hospital & Imperial College
🇬🇧London, England, United Kingdom