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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Actelion
ClinicalTrials.gov Identifier:
NCT01106014
First received: April 2, 2010
Last updated: March 16, 2016
Last verified: February 2016
Results First Received: February 2, 2016  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Pulmonary Arterial Hypertension
Interventions: Drug: Selexipag
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
A total of 1351 patients were screened from 181 sites in 39 countries worldwide. Of these, 1156 were randomized

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Screening assessments were performed up to a maximum of 28 days before baseline

Reporting Groups
  Description
SELEXIPAG During the 12-week titration phase, treatment was initiated at 200 μg twice daily (b.i.d.) and up-titrated weekly in 200 μg b.i.d. increments to the maximum tolerated dose (MTD) for each individual patient but not above 1600 μg b.i.d. At Week 12, patients continued the treatment at their individual MTD up to Week 26. Thereafter the dose could be up-titrated at scheduled visits if needed for patients receiving a dose < 1600 μg b.i.d. The dose could be decreased at any time in case of tolerability issues.
PLACEBO Matching placebo was administered orally following the same administration schedule as described for selexipag

Participant Flow:   Overall Study
    SELEXIPAG     PLACEBO  
STARTED     574     582  
COMPLETED     289     252  
NOT COMPLETED     285     330  
Morbidity or Mortality primary endpoint                 155                 242  
Adverse Event                 78                 42  
Withdrawal by Subject                 43                 37  
Administrative reason                 7                 6  
Lost to Follow-up                 2                 3  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Selexipag During the 12-week titration phase, treatment was initiated at 200 μg twice daily (b.i.d.) and up-titrated weekly in 200 μg b.i.d. increments to the maximum tolerated dose (MTD) for each individual patient but not above 1600 μg b.i.d. At Week 12, patients continued the treatment at their individual MTD up to Week 26. Thereafter the dose could be up-titrated at scheduled visits if needed for patients receiving a dose < 1600 μg b.i.d. The dose could be decreased at any time in case of tolerability issues.
Placebo Matching placebo was administered orally following the same administration schedule as described for selexipag
Total Total of all reporting groups

Baseline Measures
    Selexipag     Placebo     Total  
Number of Participants  
[units: participants]
  574     582     1156  
Age  
[units: Years]
Mean (Standard Deviation)
  48.2  (15.19)     47.9  (15.55)     48.1  (15.37)  
Gender  
[units: Participants]
     
Female     457     466     923  
Male     117     116     233  
Race/Ethnicity, Customized  
[units: Participants]
     
Caucasion / White     376     375     751  
Asian     125     120     245  
Hispanic     51     63     114  
Black     13     14     27  
Other     9     10     19  
Region of Enrollment  
[units: Participants]
     
Western Europe & Australia     161     160     321  
Eastern Europe     149     155     304  
Asia     115     113     228  
North America     95     98     193  
Latin America     54     56     110  
PAH etiology [1]
[units: Participants]
     
Idiopathic     312     337     649  
Heritable     13     13     26  
Associated with connective tissue disease     167     167     334  
Assoc. with corrected (>=12Mo) congenital shunts     60     50     110  
Associated with drug or toxin exposure     17     10     27  
Associated with HIV infection     5     5     10  
Modified NYHA/WHO Functional class (FC) [2]
[units: Participants]
     
FC I     4     5     9  
FC II     274     255     529  
FC III     293     314     607  
FC IV     3     8     11  
PAH medications at baseline [3]
[units: Participants]
     
None     112     124     236  
Endothelin Receptor Agonists (ERA)     94     76     170  
Phosphodiesterase type 5 inhibitors (PDE5-I)     189     185     374  
ERA and PDE5I in combination     179     197     376  
Time since PAH diagnosis  
[units: Years]
Median (Full Range)
  0.9  
  (0.0 to 37.3)  
  1.1  
  (0.0 to 38.9)  
  1.0  
  (0.0 to 38.9)  
6-minute walk distance (6MWD) at baseline  
[units: Meters]
Median (Full Range)
  376  
  (90 to 482)  
  369  
  (50 to 515)  
  372  
  (50 to 515)  
[1] Number of patients in each PAH etiology category
[2] Number of patients in each NYHA/WHO Functional class (FC) at screening. The WHO FC ranges from I to IV, with higher ranges indicating more severe functional restrictions
[3] Number of patients receiving PAH background medication at the time of study drug start



  Outcome Measures
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1.  Primary:   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) ]

2.  Secondary:   Change From Baseline to Week 26 in 6-minute Walk Distance (6MWD) at Trough   [ Time Frame: Week 26 ]

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


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Clinical trial disclosure desk
Organization: Actelion Pharmaceuticals Ltd
e-mail: clinical-trials-disclosure@actelion.com


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

Responsible Party: Actelion
ClinicalTrials.gov Identifier: NCT01106014     History of Changes
Other Study ID Numbers: AC-065A302
Study First Received: April 2, 2010
Results First Received: February 2, 2016
Last Updated: March 16, 2016
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