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
  Purpose
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.

Condition Intervention Phase
Pulmonary Arterial Hypertension
Drug: Selexipag
Drug: Placebo
Phase 3

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
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

Resource links provided by NLM:


Further study details as provided by Actelion:

Primary Outcome Measures:
  • 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



Secondary Outcome Measures:
  • 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 ]

Enrollment: 1156
Study Start Date: December 2009
Study Completion Date: October 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Drug: Selexipag
Selexipag 200 mcg 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
Selexipag matching placebo tablets

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Genders Eligible for Study:   Both
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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01106014

  Show 182 Study Locations
Sponsors and Collaborators
Actelion
Investigators
Study Director: Aline Frey Actelion
  More Information

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
Health Authority: Spain: Comité Ético de Investigación Clínica
United Kingdom: Research Ethics Committee
Poland: Ethics Committee
Switzerland: Swissmedic
China: Food and Drug Administration
Australia: National Health and Medical Research Council
United States: Food and Drug Administration
South Korea: Korea Food and Drug Administration (KFDA)
Russia: Pharmacological Committee, Ministry of Health
Czech Republic: State Institute for Drug Control
Germany: Ethics Commission
Slovakia: State Institute for Drug Control
Austria: Ethikkommission
Romania: Ethics Committee
Taiwan: Institutional Review Board
Germany: Federal Institute for Drugs and Medical Devices
Russia: Ethics Committee
Canada: Ethics Review Committee
Denmark: Danish Medicines Agency
Thailand: Food and Drug Administration
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Greece: National Organization of Medicines
Malaysia: Ministry of Health
Italy: Ethics Committee
Serbia: Ethics Committee
Australia: Human Research Ethics Committee
Ukraine: Ministry of Health
Singapore: Health Sciences Authority
Hungary: National Institute of Pharmacy
Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos
Slovak Republic: Ethics Committee
Sweden: Regional Ethical Review Board
Ukraine: State Pharmacological Center - Ministry of Health
Ireland: Research Ethics Committee
Serbia and Montenegro: Agency for Drugs and Medicinal Devices
Hungary: Research Ethics Medical Committee
Peru: Instituto Nacional de Salud
Australia: Department of Health and Ageing Therapeutic Goods Administration
Denmark: Ethics Committee
Mexico: Federal Commission for Protection Against Health Risks
Israel: Ministry of Health
Netherlands: Medical Ethics Review Committee (METC)
Turkey: Ethics Committee
Russia: Ministry of Health of the Russian Federation
Belgium: Federal Agency for Medicinal Products and Health Products
Italy: The Italian Medicines Agency
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Greece: Ethics Committee
Sweden: Medical Products Agency
Singapore: Domain Specific Review Boards
Russia: FSI Scientific Center of Expertise of Medical Application
Belarus: Ministry of Health
Israel: Ethics Commission
Romania: National Medicines Agency
United States: Institutional Review Board
Spain: Spanish Agency of Medicines
Taiwan: Department of Health
Austria: Federal Office for Safety in Health Care
India: Institutional Review Board
Czech Republic: Ethics Committee
Switzerland: Ethikkommission
South Korea: Institutional Review Board
Thailand: Ethical Committee
Ireland: Irish Medicines Board
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
France: Institutional Ethical Committee
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Chile: Comité de Ética Científico
United Kingdom: Medicines and Healthcare Products Regulatory Agency
India: Drugs Controller General of India
Canada: Health Canada
Turkey: Ministry of Health
Belgium: Institutional Review Board

Keywords provided by Actelion:
pulmonary arterial hypertension
PAH

Additional relevant MeSH terms:
Hypertension
Familial Primary Pulmonary Hypertension
Vascular Diseases
Cardiovascular Diseases
Hypertension, Pulmonary
Lung Diseases
Respiratory Tract Diseases
Selexipag
Antihypertensive Agents

ClinicalTrials.gov processed this record on July 21, 2016