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

Actelion Pharmaceuticals

Status and phase: Completed; Phase 3

Conditions: Pulmonary Arterial Hypertension

Treatments: Drug: Selexipag; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01106014

AC-065A302

Details and patient eligibility

About

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.

Enrollment: 1,156 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,156 participants in 2 patient groups, including a placebo group

1

Experimental group

Description:

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

Treatment:

Drug: Selexipag

2

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo