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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03759392
Other study ID # CY 1031
Secondary ID 2018-001233-40
Status Completed
Phase Phase 3
First received
Last updated
Start date April 9, 2019
Est. completion date January 6, 2022

Study information

Verified date February 2023
Source Cytokinetics
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the effect of treatment with omecamtiv mecarbil compared with placebo on exercise capacity as determined by cardiopulmonary exercise testing following 20 weeks of treatment with omecamtiv mecarbil or placebo


Description:

Oversight Authorities: United States: Food and Drug Administration Canada: Health Canada France: National Agency for the Safety of Medicine and Health Products Germany: Federal Institute for Drugs and Medical Devices Hungary: National Institute of Pharmacy and Nutrition Italy: Italian Medicines Agency Netherlands: Medicines Evaluation Board Poland: Chief Pharmaceutical Inspectorate Sweden: Medical Products Agency


Recruitment information / eligibility

Status Completed
Enrollment 276
Est. completion date January 6, 2022
Est. primary completion date November 8, 2021
Accepts healthy volunteers No
Gender All
Age group 18 Years to 85 Years
Eligibility Inclusion Criteria - Male or female, greater than or equal to 18 to lesser than or equal to 85 years of age - History of chronic HF, defined as requiring continuous treatment with medications for HF for a minimum of 3 months before screening - New York Heart Association (NYHA) class II or III at screening - Left ventricular ejection fraction less than or equal to 35% - On maximally tolerated HF standard of care (SoC) therapies consistent with regional clinical practice guidelines, if not contraindicated and according to investigator judgment of the subject's clinical status. Beta blocker dose must be stable for 30 days prior to randomization. - N-terminal (NT)-proBNP level greater than or equal to 200 pg/mL - Peak VO2 less than or equal to 75% of the predicted normal value with respiratory exchange ratio (RER) greater than or equal to 1.05 on a screening CPET, confirmed by a CPET core laboratory Exclusion Criteria - Severe uncorrected valvular heart disease - Paroxysmal atrial fibrillation or flutter documented within the previous 6 months, direct-current (DC) cardioversion or ablation procedure for atrial fibrillation within 6 months, or plan to attempt to restore sinus rhythm within 6 months of randomization. Subjects with persistent atrial fibrillation and no sinus rhythm documented in the prior 6 months are permitted. - Symptomatic bradycardia, second-degree Mobitz type II, or third-degree heart block without a pacemaker. - History of gastrointestinal bleeding requiring hospitalization, urgent procedure or transfusion in the prior year, or received intravenous (IV) iron, blood transfusion, or an erythropoiesis-stimulating agent (ESA) within 3 months prior to screening, or planned blood transfusion or ESA use during the study screening or treatment period. Chronic, stable use of oral iron is permitted. - Ongoing or planned enrollment in cardiac rehabilitation. - Requires assistance to walk or use of mobility assistive devices such as motorized devices, wheelchairs, or walkers. The use of canes for stability while ambulating is acceptable if the subject is deemed capable of performing CPET. - Major medical event or procedure within 3 months prior to randomization, including: hospitalization, surgery, renal replacement therapy or cardiac procedure. This includes episodes of decompensated HF that require IV HF treatment. - At screening: Resting systolic BP greater than 140 mmHg or less than 85 mmHg, or diastolic BP greater than 90 mmHg (mean of triplicate readings); Resting heart rate greater than 90 beats per minute, or less than 50 beats per minute (mean of triplicate readings); Estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73m2 (by the modified Modification of Diet in Renal Disease equation); Hepatic impairment defined by a total bilirubin (TBL) greater than or equal to 2 times the upper limit of normal (ULN), or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than or equal to 3 times ULN. Patients with documented Gilbert syndrome and TBL greater than or equal to 2 times ULN due to unconjugated hyperbilirubinemia, without other hepatic impairment, are permitted. - Room air oxygen saturation under 90% at screening - Hemoglobin less than 10.0 g/dL at screening - Significant adverse finding (e.g., exercise-induced early ischemic changes, abnormal decrease in BP [systolic BP falls by more than 10 mmHg], unexpected arrhythmia or other serious finding) during CPET at screening that precludes safe participation in the study, per investigator - Chronotropic incompetence (including inadequate pacemaker rate response) during CPET at screening, defined as a maximum heart rate <60% of the maximum predicted heart rate

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Omecamtiv Mecarbil
Oral omecamtiv mecarbil twice daily for up to 20 weeks with dose level determined by periodic blood testing
Placebo
Oral placebo twice daily for up to 20 weeks

Locations

Country Name City State
Canada Foothills Medical Centre Calgary Alberta
Canada Ecogene-21 Chicoutimi Quebec
Canada London Health Sciences Centre - University Hospital London Ontario
Canada Mcgill University Health Centre (MUHC)-The Montreal General Hospital (MGH) Montreal Quebec
Canada Universite de Montreal Institut de Cardiologie de Montreal ICM Montreal Heart Institute MHI Montreal Quebec
France Centre Hospitalier De La Cote Basque Bayonne cedex
France Groupe Hospitalier Mutualiste de Grenoble Grenoble
France Centre Hospitalier Universitaire de Grenoble-Hopital Albert Michallon La Tronche
France Universite De Nantes - L'Institut Du Thorax Nantes CEDEX 1
France Assistance Publique - Hopitaux de Paris (AP-HP) - Hopital Lariboisiere Paris
France Chu de Rouen Hopital Charles Nicolle Rouen Cedex
France Centre Hospitalier Universitaire (CHU) de Toulouse - Hopital Rangueil Toulouse Cedex 9
Germany Kerckhoff-Klinik- Bad Nauheim Bad Nauheim
Germany Praxisklinik Dresden Dresden
Germany Universitaetsklinik Heidelberg Heidelberg Baden-wurttemberg
Germany Universitaetsklinikum Des Saarlandes Und Medizinische Fakultaet Der Universitaet Des Saarlandes Homburg
Germany Universitaetsklinikum Jena Jena Thueringen
Germany Universitatsklinikum Magdeburg Magdeburg Saxony-Anhalt
Hungary Balatonfuredi Allami Szivkorhaz Balatonfured
Hungary Semmelweis University Heart and Vascular Center Budapest
Hungary Pecsi Tudomanyegyetem (PTE) Altalanos Orvostudomanyi Kar (AOK) (University of Pecs Medical School) Pecs
Italy Azienda Ospedaliera S.Orsola Malpighi Bologna Province Of Bologna
Italy Azienda Ospedaliera Spedali Civili di Brescia-Universita degli Studi Di Brescia Brescia Province Of Brescia
Italy Ospedali Riuniti Foggia Foggia Apulia
Italy Centro Cardiologico Monzino IRCCS Milano Lombardia
Italy Divisione di Cardiologia con Utic ed Emodinamica Napoli
Italy Ospedale Monaldi Napoli
Italy Insituto Di Ricovero E Cura A Carattere Scientifico San Raffaele Pisana Roma Rome
Netherlands Jeroen Bosch Ziekenhuis 'S-Hertogenbosch
Netherlands Onze Lieve Vrouwe Gasthuis (OLVG) Locatie West Amsterdam
Netherlands University Medical Center Groningen Groningen
Netherlands Leids Universitair Medisch Centrum (LUMC) Leiden
Netherlands Radboud Universiteit - Radboud Universitair Medisch Centrum (Radboudumc) Nijmegen
Netherlands Erasmus MC - Universitair Medisch Centrum Rotterdam Rotterdam South Holland
Netherlands Universitair Medisch Centrum Utrecht - Wilhelmina Kinderziekenhuis Utrecht
Netherlands Maxima Medisch Centrum Veldhoven Veldhoven
Poland Uniwersytecki Szpital Kliniczny w Bialymstoku Bialystok
Poland Uniwersyteckie Centrum Kliniczne Kliniczne Centrum Kardiologii Gdansk
Poland Oddzial Kliniczny Choroby Wiencowej i Niewydolnosci Serca z Pododdzialem Intensywnego Nadzoru Kardiologicznego Krakow
Poland Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika, Oddzial Kardiologiczny Lodz
Poland Centrum Medyczne Medyk Sp z o.o. Sp. k. Rzeszow Podkarpackie
Poland Instytut Kardiologii Heart Failure Clinic Warsaw
Poland Centrum Chorob Serca, Uniwersytecki Szpital Kllniczny im. Jana Mikulicza Radeckiego we Wrociawiu Wroclaw
Sweden Sahlgrenska Universitetssjukhuset Göteborg
Sweden Enhet Klinisk forskning, hjartmedicin, Skanes Universitet Sjukhus Lund
United States Alaska Heart and Vascular Institute Anchorage Alaska
United States University of Michigan Ann Arbor Michigan
United States Emory University Atlanta Georgia
United States University of Maryland Baltimore Maryland
United States Massachusetts General Hospital (MGH) - Cardiac Unit Associates Boston Massachusetts
United States Capital Area Research, LLC Camp Hill Pennsylvania
United States The Ohio State University Columbus Ohio
United States Baylor Scott and White Heart and Vascular Hospital Dallas Texas
United States University of Texas - Southwestern Medical Center Dallas Texas
United States Henry Ford Heart & Vascular Institute Detroit Michigan
United States Duke University Medical Center Durham North Carolina
United States Cardiovascular Associates Of The Delaware Valley (Cadv), P.A. - Elmer Physicians Care Center - Elmer Elmer New Jersey
United States Inova Heart and Vascular Institute Falls Church Virginia
United States Holy Cross Hospital - Fort Lauderdale Fort Lauderdale Florida
United States Greenville Health System Greenville South Carolina
United States Hartford Hospital-University of Connecticut School of Medicine Hartford Connecticut
United States Penn State Hershey Children's Hospital Hershey Pennsylvania
United States Community Hospital South, Inc. Indianapolis Indiana
United States Saint Vincent Medical Group Inc. Indianapolis Indiana
United States Glacier View Research Institute, Cardiology Kalispell Montana
United States Saint Luke's Health System Kansas City Missouri
United States Lancaster Heart And Stroke Foundation Lancaster Pennsylvania
United States Arkansas Cardiology Clinic Little Rock Arkansas
United States South Denver Cardiology Associates, PC Littleton Colorado
United States NYU Langone Medical Center New York New York
United States Newark Beth Israel Medical Center Newark New Jersey
United States University of Nebraska Medical Center Omaha Nebraska
United States Broward Research Center - Pembroke Pines Pembroke Pines Florida
United States McLaren Health Care Corporation Petoskey Michigan
United States Oregon Health Portland Oregon
United States Wake Med Health and Hospital Raleigh North Carolina
United States Queens Heart Institute Rosedale New York
United States Harbor-UCLA Medical Center Torrance California
United States St. John Clinical Research Institute Tulsa Oklahoma
United States Wake Forest University School of Medicine Winston-Salem North Carolina
United States Michigan Heart Ypsilanti Michigan

Sponsors (1)

Lead Sponsor Collaborator
Cytokinetics

Countries where clinical trial is conducted

United States,  Canada,  France,  Germany,  Hungary,  Italy,  Netherlands,  Poland,  Sweden, 

Outcome

Type Measure Description Time frame Safety issue
Primary Change in Peak Oxygen Uptake on Cardiopulmonary Exercise Testing From Baseline to Week 20 The effect of treatment on exercise capacity, as assessed by peak oxygen uptake, was assessed during cardiopulmonary exercise testing (CPET) with gas-exchange analysis. Cycle ergometry was the preferred modality for exercise testing; treadmill exercise testing was an acceptable alternative. Participants were to use the same testing modality for all exercise tests during the study. Whenever possible, CPET was administered by the same study personnel using the same equipment throughout the study. Baseline and Week 20
Secondary Change in Total Workload During Cardiopulmonary Exercise Testing From Baseline to Week 20 Total workload was measured during CPET (cycle ergometry [preferred] or treadmill exercise testing) and represents the maximum load to which a participant was subjected during CPET in order to produce work. Baseline and Week 20
Secondary Change in Ventilatory Efficiency During Cardiopulmonary Exercise Testing From Baseline to Week 20 Ventilatory efficiency (ventilation [VE]/volume of exhaled carbon dioxide [VCO2]) was measured through CPET with gas exchange analysis. Baseline and Week 20
Secondary Change in the Average Daily Activity Units Measured Over a 2-week Period From Baseline (Week -2 to Day 1) to Weeks 18-20 The effect of treatment on daily activity, as assessed by average daily activity units, was evaluated by actigraphy. Actigraphy was collected during 4 sessions throughout the study for 2 week intervals. Baseline (Week -2 to Day 1) to Weeks 18-20
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