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Selexipag (ACT-293987) in Pulmonary Arterial Hypertension (GRIPHON)

This study has been completed.
Information provided by (Responsible Party):
Actelion Identifier:
First received: April 2, 2010
Last updated: March 16, 2016
Last verified: February 2016

April 2, 2010
March 16, 2016
December 2009
April 2014   (final data collection date for primary outcome measure)
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) ] [ Designated as safety issue: No ]

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

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 ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01106014 on Archive Site
  • Change From Baseline to Week 26 in 6-minute Walk Distance (6MWD) at Trough [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: Yes ]
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Selexipag (ACT-293987) in Pulmonary Arterial Hypertension
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 Hypertension
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.
Not Provided
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Pulmonary Arterial Hypertension
  • Drug: Selexipag
    Selexipag 200 mcg tablets
    Other Name: ACT-293987
  • Drug: Placebo
    Selexipag matching placebo tablets
  • Experimental: 1
    Selexipag is up-titrated from Day 1 to Week 12 to each patient's maximum tolerated dose in the range of 200-1600 mcg twice a day (b.i.d.) in 200 mcg steps starting with one 200 mcg oral tablet on Day 1. From Day 2 onwards, a b.i.d. dose regimen with an interval of approximately 12 hours is followed. If this dose (selexipag 200 μg b.i.d.) is well-tolerated, selexipag is up-titrated with weekly increments of 200 mcg. Up-titration is followed by a stable maintenance treatment period from Week 12 onwards, up to Week 26, at the maximum tolerated dose
    Intervention: Drug: Selexipag
  • Placebo Comparator: 2
    Matching placebo is administered orally with a dosing interval of approximately12 h. A (mock) up-titration scheme is followed
    Intervention: Drug: Placebo

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
October 2014
April 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Male and female patients 18-75 years old, with symptomatic PAH
  • PAH belonging to the following subgroups of the updated Dana Point Clinical Classification Group 1 (Idiopathic, or Heritable, or Drug or toxin induced, or Associated (APAH) with Connective tissue disease, Congenital heart disease with simple systemic-to-pulmonary shunt at least 1 year after surgical repair, or HIV infection)
  • Documented hemodynamic diagnosis of PAH by right heart catheterization, performed at any time prior to Screening
  • Six minute walk distance (6MWD) between 50 and 450 m at Screening within 2 weeks prior to the Baseline Visit
  • Signed informed consent

Exclusion Criteria:

  • Patients with pulmonary hypertension (PH) in the Updated Dana Point Classification Groups 2-5, and PAH Group 1 subgroups that are not covered by the inclusion criteria
  • Patients who have received prostacyclin or its analogs within 1 month before Baseline Visit, or are scheduled to receive any of these compounds during the trial
  • Patients with moderate or severe obstructive lung disease
  • Patients with moderate or severe restrictive lung disease
  • Patients with moderate or severe hepatic impairment (Child-Pugh B and C)
  • Patients with documented left ventricular dysfunction
  • Patients with severe renal insufficiency
  • Patients with BMI <18.5 Kg/m2
  • Patients who are receiving or have been receiving any investigational drugs within 1 month before the Baseline Visit
  • Acute or chronic impairment (other than dyspnea), limiting the ability to comply with study requirements, in particular with 6MWT
  • Recently conducted or planned cardio-pulmonary rehabilitation program based on exercise training
  • Psychotic, addictive or other disorder limiting the ability to provide informed consent or to comply with study requirements
  • Life expectancy less than 12 months
  • Females who are lactating or pregnant or plan to become pregnant during the study
  • Known hypersensitivity to any of the excipients of the drug formulations
18 Years to 75 Years   (Adult, Senior)
Contact information is only displayed when the study is recruiting subjects
United States,   Argentina,   Australia,   Austria,   Belarus,   Belgium,   Canada,   Chile,   China,   Colombia,   Czech Republic,   Denmark,   France,   Germany,   Greece,   Hungary,   India,   Ireland,   Israel,   Italy,   Korea, Republic of,   Malaysia,   Mexico,   Netherlands,   Peru,   Poland,   Romania,   Russian Federation,   Serbia,   Singapore,   Slovakia,   Spain,   Sweden,   Switzerland,   Taiwan,   Thailand,   Turkey,   Ukraine,   United Kingdom
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Study Director: Aline Frey Actelion
February 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP