Overview

This trial is active, not recruiting.

Condition pulmonary arterial hypertension
Treatments gs-4997, placebo to match gs-4997
Phase phase 2
Sponsor Gilead Sciences
Start date November 2014
End date April 2016
Trial size 151 participants
Trial identifier NCT02234141, 2014-002131-34, GS-US-357-1394

Summary

This study will compare the efficacy, safety, and tolerability of three doses of GS-4997 to placebo in adults with pulmonary arterial hypertension (PAH). The study will consist of a 24-week placebo-controlled treatment period and a long-term GS-4997 treatment period. Participants completing the 24-week placebo-controlled period will be eligible to receive active treatment with GS-4997 in the long-term treatment period.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
Participants will receive GS-4997 2 mg for 24 weeks and may continue on this dose during the long-term treatment phase.
gs-4997
GS-4997 tablet administered orally once daily
(Experimental)
Participants will receive GS-4997 6 mg for 24 weeks and may continue on this dose during the long-term treatment phase.
gs-4997
GS-4997 tablet administered orally once daily
(Experimental)
Participants will receive GS-4997 18 mg for 24 weeks and may continue on this dose during the long-term treatment phase.
gs-4997
GS-4997 tablet administered orally once daily
(Experimental)
Participants will receive placebo to match GS-4997 for 24 weeks, and may then be rerandomized 1:1:1 to GS-4997 2, 6, or 18 mg during the long-term treatment phase.
gs-4997
GS-4997 tablet administered orally once daily
placebo to match gs-4997
Placebo to match GS-4997 tablets administered orally once daily

Primary Outcomes

Measure
Change from baseline in pulmonary vascular resistance at Week 24, as measured by right heart catheterization
time frame: Baseline; Week 24

Secondary Outcomes

Measure
Change from baseline at Week 24 in other cardiopulmonary hemodynamic measures
time frame: Baseline; Week 24
Change from baseline at Week 24 in 6-minute walk distance (6MWD)
time frame: Baseline; Week 24
Change from baseline at Week 24 in Borg Dyspnea index (BDI) immediately following exercise
time frame: Baseline; Week 24
Change from baseline at Week 24 in World Health Organization (WHO) Functional Class
time frame: Baseline; Week 24
Change from baseline at Week 24 in N-terminal pro-brain natriuretic peptide (NT-proBNP)
time frame: Baseline; Week 24
Change from baseline at Week 24 in SF-36 Health Survey physical functioning scale
time frame: Baseline; Week 24
Change from baseline at Week 24 in emPHasis-10 questionnaire
time frame: Baseline; Week 24
Change from baseline at Week 24 in heart rate recovery after the 6-minute walk test (6MWT)
time frame: Baseline; Week 24
Time to clinical worsening (TTCW) evaluated in the 24-week placebo-controlled treatment period
time frame: Baseline; Week 24
Change from baseline in echocardiographic assessments of right ventricular function at Week 24
time frame: Baseline; Week 24

Eligibility Criteria

Male or female participants from 18 years up to 75 years old.

Inclusion Criteria: - Diagnosis of idiopathic pulmonary arterial hypertension (IPAH), heritable pulmonary arterial hypertension (HPAH), drug- and toxin-induced PAH, or PAH associated with connective tissue disease, HIV infection, or congenital heart defects (repaired greater than 1 year prior to Screening) - Meet all of the following hemodynamic criteria by means of a screening right heart catheterization (RHC) completed prior to randomization: - Mean pulmonary artery pressure (mPAP) of ≥ 25 mm Hg - Pulmonary vascular resistance (PVR) ≥ 400 dyne•sec/cm^5 - Pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic pressure (LVEDP) of ≤ 12 mm Hg if PVR ≥ 400 and < 500 dynes•sec/cm^5, or PCWP/LVEDP ≤ 15 mm Hg if PVR ≥ 500 dynes•sec/cm^5 - Be able to walk a distance of at least 100 m - Have World Health Organization (WHO) Functional Class II or III symptoms - Meet the following criteria determined by pulmonary function tests completed no more than 24 weeks prior to screening, performed with or without bronchodilation: - Forced expiratory volume in one second (FEV1) ≥ 55% of predicted normal - FEV1:forced vital capacity (FVC) ratio ≥ 0.60 - Receiving treatment with one or more drugs approved for PAH for ≥ 12 consecutive weeks and at stable dose for ≥ 8 consecutive weeks Exclusion Criteria: - Diagnosis of PAH associated with significant venous or capillary involvement (PCWP > 15 mm Hg), pulmonary capillary hemangiomatosis, portal hypertension, or unrepaired congenital heart defects - Pulmonary hypertension (PH) belonging to groups 2 to 5 of the 2013 NICE classification - Left ventricular ejection fraction (LVEF) ≤ 40% or clinically significant ischemic, valvular or constrictive heart disease - Uncontrolled hypertension (≥ 180/110 mm Hg) at Screening - End stage renal disease (receiving peritoneal dialysis, hemodialysis, or status after renal transplantation) - Severe liver disease (Child-Pugh Class C, with or without cirrhosis) Individuals may be rescreened one additional time with prior notification to and approval by the sponsor.

Additional Information

Official title A Phase 2, Dose-Ranging, Randomized, Double-Blind, Placebo-Controlled Study of GS-4997 in Subjects With Pulmonary Arterial Hypertension
Trial information was received from ClinicalTrials.gov and was last updated in May 2016.
Information provided to ClinicalTrials.gov by Gilead Sciences.