Don't get left behind! The modernized ClinicalTrials.gov is coming. Check it out now.
Say goodbye to ClinicalTrials.gov!
The new site is coming soon - go to the modernized ClinicalTrials.gov
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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.

Condition or disease Intervention/treatment Phase
Pulmonary Arterial Hypertension Drug: Selexipag Drug: Placebo Phase 3

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1156 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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 Hypertension
Study Start Date : December 1, 2009
Actual Primary Completion Date : April 1, 2014
Actual Study Completion Date : October 1, 2014

Resource links provided by the National Library of Medicine

Drug Information available for: Selexipag

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
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
 Drug: Selexipag
Selexipag 200 µg tablets
Other Name: ACT-293987
Placebo Comparator: 2
Matching placebo is administered orally with a dosing interval of approximately12 h. A (mock) up-titration scheme is followed
 Drug: Placebo
Placebo tablets matching selexipag


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. 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



Secondary Outcome Measures :
  1. 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.

  2. Absence of Worsening From Baseline to Week 26 in Modified NYHA/WHO Functional Class (WHO FC) [ Time Frame: Week 26 ]

Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01106014


Locations
Show Show 182 study locations
Sponsors and Collaborators
Actelion
Investigators
Layout table for investigator information
Study Director: Aline Frey Actelion
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Publications of Results:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Layout table for additonal information
Responsible Party: Actelion
ClinicalTrials.gov Identifier: NCT01106014    
Other Study ID Numbers: AC-065A302
First Posted: April 19, 2010    Key Record Dates
Results First Posted: March 1, 2016
Last Update Posted: January 11, 2018
Last Verified: December 2017
Keywords provided by Actelion:
pulmonary arterial hypertension
PAH
Additional relevant MeSH terms:
Layout table for MeSH terms
Pulmonary Arterial Hypertension
Familial Primary Pulmonary Hypertension
Hypertension
Vascular Diseases
Cardiovascular Diseases
 Hypertension, Pulmonary
Lung Diseases
Respiratory Tract Diseases
Selexipag
Antihypertensive Agents