A Study of the Effect of IW-1973 on the Exercise Capacity of Patients With Heart Failure With Preserved Ejection Fraction (HFpEF)

Phase 2

Completed

Conditions: Heart Failure With Preserved Ejection Fraction

Interventions: Drug: IW-1973
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

Inclusion Criteria

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:
1. Hospitalization or emergency department visit for heart failure within the past year
2. Elevated B-type natriuretic peptide (BNP) or N-terminal pro b-type natriuretic peptide (NT-proBNP) within the past 6 months
3. 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
4. Hemodynamic evidence of elevated filling pressures
Patient meets at least 2 of the following criteria at the Screening Visit:
1. Diagnosis of type 2 diabetes mellitus or prediabetes
2. History of hypertension
3. Body mass index (BMI) >30 kg/m2
4. Age ≥70 years

Exclusion Criteria

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): Arizona Arrhythmia Research Center
🇺🇸
Phoenix, Arizona, United States
Mayo Clinic
🇺🇸
Rochester, Minnesota, United States
University of Arizona
🇺🇸
Tucson, Arizona, United States
Cardiology and Medicine Clinic
🇺🇸
Little Rock, Arkansas, United States
JEHM
🇺🇸
National City, California, United States
Axis Clinical Trials
🇺🇸
Los Angeles, California, United States
Valley Clinical Trials
🇺🇸
Northridge, California, United States
Stanford University
🇺🇸
Palo Alto, California, United States
Harbor UCLA Medical Center
🇺🇸
Torrance, California, United States
Aurora Denver Cardiology
🇺🇸
Denver, Colorado, United States
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Arizona Arrhythmia Research Center
🇺🇸Phoenix, Arizona, United States