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

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ClinicalTrials.gov Identifier: NCT01106014
Recruitment Status : Completed
First Posted : April 19, 2010
Results First Posted : March 1, 2016
Last Update Posted : January 11, 2018
Sponsor:
Information provided by (Responsible Party):
Actelion

Tracking Information
First Submitted Date  ICMJE April 2, 2010
First Posted Date  ICMJE April 19, 2010
Results First Submitted Date  ICMJE February 2, 2016
Results First Posted Date  ICMJE March 1, 2016
Last Update Posted Date January 11, 2018
Study Start Date  ICMJE December 1, 2009
Actual Primary Completion Date April 1, 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 2, 2016)
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 Measures  ICMJE
 (submitted: April 16, 2010)
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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 2, 2016)
  • 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 Measures  ICMJE
 (submitted: April 16, 2010)
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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Selexipag (ACT-293987) in Pulmonary Arterial Hypertension
Official Title  ICMJE 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
Brief Summary The AC-065A302 (GRIPHON) study is an event-driven Phase 3 study to demonstrate the effect of selexipag on time to first morbidity or mortality event in patients with pulmonary arterial hypertension.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Pulmonary Arterial Hypertension
Intervention  ICMJE
  • Drug: Selexipag
    Selexipag 200 µg tablets
    Other Name: ACT-293987
  • Drug: Placebo
    Placebo tablets matching selexipag
Study Arms  ICMJE
  • 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 µg twice a day (b.i.d.) in 200 µg steps starting with one 200 µg 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 µg. 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
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 28, 2013)
1156
Original Estimated Enrollment  ICMJE
 (submitted: April 16, 2010)
670
Actual Study Completion Date  ICMJE October 1, 2014
Actual Primary Completion Date April 1, 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Austria,   Belarus,   Belgium,   Canada,   Chile,   China,   Colombia,   Czechia,   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,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT01106014
Other Study ID Numbers  ICMJE AC-065A302
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Actelion
Study Sponsor  ICMJE Actelion
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Aline Frey Actelion
PRS Account Actelion
Verification Date December 2017

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