A Study of the Effect of IW-1973 on the Exercise Capacity of Patients With Heart Failure With Preserved Ejection Fraction (HFpEF)
- Conditions
- Heart Failure With Preserved Ejection Fraction
- Interventions
- Drug: Placebo Oral Tablet
- Registration Number
- NCT03254485
- Lead Sponsor
- Akebia Therapeutics
- Brief Summary
The objective of the CAPACITY-HFpEF study is to evaluate the safety and efficacy of IW-1973 compared with placebo when administered daily for approximately 12 weeks to patients with HFpEF. The study will evaluate the effect of oral IW-1973 on peak exercise capacity in patients with HFpEF, with or without permanent or persistent atrial fibrillation.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 196
-
Patient is an ambulatory male or female ≥45 years old at the Screening Visit
-
Patient has heart failure with ejection fraction (EF) of ≥40%
-
Patient has a peak VO2 measuring <80% of age- and sex-adjusted normal values
-
Patient has evidence in medical history supporting clinical heart failure syndrome consisting of at least 1 of the following:
- Hospitalization or emergency department visit for heart failure within the past year
- Elevated B-type natriuretic peptide (BNP) or N-terminal pro b-type natriuretic peptide (NT-proBNP) within the past 6 months
- Echocardiographic evidence within the past 12 months of at least 2 of the following: left ventricular (LV) hypertrophy, left atrial (LA) enlargement, or diastolic dysfunction
- Hemodynamic evidence of elevated filling pressures
-
Patient meets at least 2 of the following criteria at the Screening Visit:
- Diagnosis of type 2 diabetes mellitus or prediabetes
- History of hypertension
- Body mass index (BMI) >30 kg/m2
- Age ≥70 years
- Patient has had acute coronary syndrome or percutaneous coronary intervention within 30 days before Randomization
- Patient has had cardiac transplantation or has cardiac transplantation planned during the study
- Patient has had cardiac artery bypass graft, cardiac mechanical support implantation, or other cardiac surgery in the 3 months before the Screening Visit or planned during the study
- Patient has severe chronic obstructive coronary disease as defined by chronic oxygen dependence
- Patient had had heart failure hospitalization with discharge within 30 days before the Screening Visit
- Patient has a history of clinically significant hypersensitivity or allergies to any of the inactive ingredients contained in the active or placebo drug products
- Patient has previously received IW-1973 in a study, or received an investigational drug during the 30 days or 5 half lives of that investigational drug (whichever is longer) before the Screening Visit, or is planning to receive another investigational drug at any time during the study
- Patient is taking specific inhibitors of phosphodiesterase 5 (PDE5), nonspecific inhibitors of PDE5, any supplements for the treatment of erectile dysfunction, riociguat, or nitrates or nitric oxide (NO) donors in any form
- Patient is taking strong cytochrome P450 3A (CYP3A) inhibitors
- Women of childbearing potential must have a negative pregnancy test prior to randomization and must agree to use protocol-specified contraception from the Screening Visit through 60 days after the final dose of study drug
- Male patients must be surgically sterile by vasectomy (conducted ≥60 days before the Screening Visit or confirmed via sperm analysis) or must agree to use protocol-specified contraception from the Screening Visit through 60 days after the final dose of study drug
- Other exclusion criteria per protocol
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description IW-1973 High Dose IW-1973 - Placebo Placebo Oral Tablet Placebo to match experimental drug
- Primary Outcome Measures
Name Time Method Change From Baseline in Peak Oxygen Consumption (VO2) at Week 12 Baseline and Week 12 Peak VO2 was obtained from Cardiopulmonary Exercise Test (CPET), which was used to evaluate the effect of praliciguat on peak exercise capacity. Baseline is defined as the last non-missing measurement prior to the first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the Week 12 value. Data were analyzed using an analysis of covariance (ANCOVA) model with treatment group and atrial fibrillation stratification factors as categorical variable terms and Baseline peak VO2 value as a covariate. Milliliter O2 per kilogram per minute = mL O2/kg/min
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Study Drug-related TEAEs Day 1 up to Day 113 An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. TEAEs are defined as those adverse events (AEs) that started or worsened in severity after the administration of study drug. Causality relationship to study drug was per Investigator assessment. Number of participants with TEAEs and study drug-related TEAEs is presented.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Ventilatory Efficiency at Week 12 Baseline and Week 12 Ventilatory efficiency was defined as minute ventilation/carbon dioxide (VE/VCO2) slope, production and was obtained from CPET. Baseline is defined as the last non-missing measurement prior to the first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the Week 12 value. Data were analyzed using an ANCOVA model with treatment group, atrial fibrillation stratification factor and peak VO2 stratification factor as categorical variable terms and baseline value as a covariate.
Change From Baseline in 6-minute Walk Test (6MWT) Distance at Week 12 Baseline and Week 12 6MWT was a simple assessment of everyday functional capacity and provided a global evaluation of the organ/physiologic systems involved in exercise. 6MWT assessed the distance travelled in 6 minutes, measured at approximately the same time of day. Baseline is defined as the last non-missing measurement prior to the first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the Week 12 value. Data were analyzed using an ANCOVA model with treatment group, atrial fibrillation stratification factor and peak VO2 stratification factor as categorical variable terms and Baseline value as a covariate.
CPET Responders at Week 12 At Week 12 CPET responders were defined as participants who improved by at least 1.5 mL O2/kg/min in peak VO2 from Baseline to Week 12. Baseline is defined as the last non-missing measurement prior to the first dose of study drug.
Trial Locations
- Locations (60)
University of Arizona
🇺🇸Tucson, Arizona, United States
Stanford University
🇺🇸Palo Alto, California, United States
Valley Clinical Trials
🇺🇸Northridge, California, United States
JEHM
🇺🇸National City, California, United States
Harbor UCLA Medical Center
🇺🇸Torrance, California, United States
Holy Cross Hospital
🇺🇸Fort Lauderdale, Florida, United States
South Denver Cardiology Associates
🇺🇸Littleton, Colorado, United States
East Coast Institute for Research
🇺🇸Jacksonville, Florida, United States
New Generation of Medical Research
🇺🇸Hialeah, Florida, United States
Progressive Medical Research
🇺🇸Port Orange, Florida, United States
Broward Research Center
🇺🇸Pembroke Pines, Florida, United States
Unity Point Health - Methodist Hospital
🇺🇸Peoria, Illinois, United States
Lousiana Heart Center
🇺🇸Bogalusa, Louisiana, United States
Michigan Heart
🇺🇸Ypsilanti, Michigan, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
VA Healthcare John Cochran Medical Center
🇺🇸Saint Louis, Missouri, United States
ProMedica Toledo Hospital
🇺🇸Toledo, Ohio, United States
Mount Sinai School of Medicine
🇺🇸New York, New York, United States
Oklahoma Heart Institute
🇺🇸Tulsa, Oklahoma, United States
Research Institute of Lancaster General Health
🇺🇸Lancaster, Pennsylvania, United States
PeaceHealth, Sacred Heart Physicians
🇺🇸Springfield, Oregon, United States
University of Vermont Medical Center
🇺🇸Burlington, Vermont, United States
Madigan Army Medical Center
🇺🇸Tacoma, Washington, United States
London Health Sciences Centre
🇨🇦London, Ontario, Canada
CIUSSS de l'Estrie - CHUS
🇨🇦Sherbrooke, Quebec, Canada
Institut Universitaire de Cardiologie et de Pneumologie De Quebec
🇨🇦Québec, Canada
Axis Clinical Trials
🇺🇸Los Angeles, California, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Boston University School of Medicine
🇺🇸Boston, Massachusetts, United States
Ohio State University Medical Center (OSUMC)
🇺🇸Columbus, Ohio, United States
North Dallas Research Associates
🇺🇸Dallas, Texas, United States
Texas Health Research and Education Insitute
🇺🇸Dallas, Texas, United States
Southwest Family Medicine Associates
🇺🇸Dallas, Texas, United States
Baylor University Medical Center
🇺🇸Dallas, Texas, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Mount Sinai Hospital
🇨🇦Toronto, Ontario, Canada
PCRS Network, LLC
🇺🇸Miami, Florida, United States
Franciscan Physician Network - Indiana Heart Physicians
🇺🇸Indianapolis, Indiana, United States
Drexel University College of Medicine
🇺🇸Philadelphia, Pennsylvania, United States
The Valley Hospital
🇺🇸Ridgewood, New Jersey, United States
Cardiology and Medicine Clinic
🇺🇸Little Rock, Arkansas, United States
St. Luke's Regional Medical Center
🇺🇸Boise, Idaho, United States
Lahey Clinic
🇺🇸Burlington, Massachusetts, United States
Ecogene-21
🇨🇦Chicoutimi, Quebec, Canada
Arizona Arrhythmia Research Center
🇺🇸Phoenix, Arizona, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Aurora Denver Cardiology
🇺🇸Denver, Colorado, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
South Oklahoma Heart Research
🇺🇸Oklahoma City, Oklahoma, United States
Newton Clinical Research
🇺🇸Oklahoma City, Oklahoma, United States
Oregon Health & Science University (OHSU)
🇺🇸Portland, Oregon, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Schnitzler Cardiovascular Consultants
🇺🇸San Antonio, Texas, United States
Virginia Commonwealth University Medical College of Virginia
🇺🇸Richmond, Virginia, United States
Unity Point Health
🇺🇸Madison, Wisconsin, United States
University of Wisconsin - Madison
🇺🇸Madison, Wisconsin, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States