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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01106014




Registration number
NCT01106014
Ethics application status
Date submitted
2/04/2010
Date registered
19/04/2010
Date last updated
4/02/2025

Titles & IDs
Public title
Selexipag (ACT-293987) in Pulmonary Arterial Hypertension
Scientific 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
Secondary ID [1] 0 0
AC-065A302
Universal Trial Number (UTN)
Trial acronym
GRIPHON
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pulmonary Arterial Hypertension 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Cardiovascular 0 0 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Selexipag
Treatment: Drugs - Placebo

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

Placebo comparator: 2 - Matching placebo is administered orally with a dosing interval of approximately12 h. A (mock) up-titration scheme is followed


Treatment: Drugs: Selexipag
Selexipag 200 µg tablets

Treatment: Drugs: Placebo
Placebo tablets matching selexipag
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Time From Randomization to the First Morbidity Event or Death (All Causes) up to 7 Days After the Last Study Drug Intake
Assessment method [1] 0 0
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
Timepoint [1] 0 0
Up to 7 days after end of double-blind treatment (maximum: 4.3 years)
Secondary outcome [1] 0 0
Change From Baseline to Week 26 in 6-minute Walk Distance (6MWD) at Trough
Assessment method [1] 0 0
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.
Timepoint [1] 0 0
Week 26
Secondary outcome [2] 0 0
Absence of Worsening From Baseline to Week 26 in Modified NYHA/WHO Functional Class (WHO FC)
Assessment method [2] 0 0
Timepoint [2] 0 0
Week 26

Eligibility
Key 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
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/12/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/10/2014
Sample size
Target
Accrual to date
Final
1156
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Actelion
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Aline Frey
Address 0 0
Actelion
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

TypeCitations or Other Details
Journal Sitbon O, Channick R, Chin KM, Frey A, Gaine S, Ga... [More Details]

Results are available at https://clinicaltrials.gov/study/NCT01106014