Clinical Trial: Selexipag (ACT-293987) in Pulmonary Arterial Hypertension

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Multicenter, Double-blind, Placebo-controlled Phase 3 Study Assessing the Safety and Efficacy of Selexipag on Morbidity and Mortality in Patients With Pulmonary Arterial Hypert

Brief Summary: The AC-065A302 GRIPHON study is an event-driven Phase 3 study to demonstrate the effect of ACT-293987 on time to first morbidity or mortality event in patients with pulmonary arterial hypertension.

Detailed Summary:
Sponsor: Actelion

Current Primary Outcome: Time From Randomization to the First Morbidity Event or Death (All Causes) up to 7 Days After the Last Study Drug Intake [ Time Frame: Up to 7 days after end of double-blind treatment (maximum: 4.3 years) ]

Time from randomization to the first occurrence of a morbidity event or death (all causes) was analyzed with the Kaplan-Meier method (event-free KM estimates at different time points).

Morbidity event was defined as any of the following events confirmed by the Critical Event committee:

  • Hospitalization for worsening of pulmonary arterial hypertension (PAH),
  • Worsening of PAH resulting in need for lung transplantation or balloon atrial septostomy,
  • Initiation of parenteral prostanoid therapy or chronic oxygen therapy due to worsening of PAH,
  • Disease progression which was defined by a decrease in 6-minute walk distance from baseline (>=15%, confirmed by a 2nd test on a different day) combined with worsening of WHO FC for patients belonging to WHO FC II/III at baseline, or combined with the need for additional PAH-specific therapy for patients belonging to WHO FC III/IV at baseline.

Note: The number of patients at risk decreased over time but this cannot be captured below



Original Primary Outcome: Demonstrate the effect of ACT-293987 on time to first clinical worsening in pts. with PAH. Clinical worsening is delineated according to the definition of the Dana Point 4th World Symposium of PH McLaughlin VV. et al. JACC 2009; 54 (S1): S97-S107 [ Time Frame: Baseline (day 1) to over a period of up to 3.5 years ]

Current Secondary Outcome:

  • Change From Baseline to Week 26 in 6-minute Walk Distance (6MWD) at Trough [ Time Frame: Week 26 ]
    The 6-minute walk distance test (6MWD) is a non-encouraged test performed in a 30 m long flat corridor, where the patient is instructed to walk as far as possible, back and forth around two cones, with the permission to slow down, rest, or stop if needed. If the patient was used to taking bronchodilators before a walk, he/she was given them 5 to 30 min before the test. Also if the patient was on chronic oxygen therapy, oxygen was given at their standard rate during the test. Absolute change from baseline to Week 26 in 6MWD was measured at trough, i.e., either on the next day after the last study drug administration or at least 12 hours after study drug administration if on the same day.
  • Absence of Worsening From Baseline to Week 26 in Modified NYHA/WHO Functional Class (WHO FC) [ Time Frame: Week 26 ]


Original Secondary Outcome: Evaluate the effect of ACT-293987 on exercise capacity (6-minute walk distance & Borg dyspnea index) & other secondary & exploratory efficacy endpoints in patients with PAH [ Time Frame: Baseline (day 1) to over a period of up to 3.5 years ]

Information By: Actelion

Dates:
Date Received: April 2, 2010
Date Started: December 2009
Date Completion:
Last Updated: March 16, 2016
Last Verified: February 2016