Efficacy and safety of ralinepag, a novel oral IP agonist, in PAH patients on mono or dual background therapy: results from a phase 2 randomised, parallel group, placebo-controlled trial. Issue 4 (10th October 2019)

• Record Type: Journal Article
• Authors: Torres, Fernando; Farber, Harrison; Ristic, Arsen; McLaughlin, Vallerie; Adams, John; Zhang, Jinkun; Klassen, Preston; Shanahan, William; Grundy, John; Hoffmann, Ines; Cabell, Christopher; Escribano Subías, Pilar; Sood, Namita; Keogh, Anne; D'Souza, Gwyn; Rubin, Lewis
• Is Part Of: European respiratory journal. Volume 54:Issue 4(2019)
• Publication Date: 2019-10-10
• Subjects: Respiratory organs -- Diseases -- Periodicals; Respiration -- Periodicals; 616.2
• DOI: 10.1183/13993003.01030-2019
• Languages: English
• ISSNs: 0903-1936

Abstract

Purpose: This phase 2 study was designed to assess the efficacy, safety and tolerability of immediate-release orally administered ralinepag, a selective, non-prostanoid prostacyclin receptor agonist with a 24-h terminal half-life, compared to placebo in adult patients with symptomatic pulmonary arterial hypertension (PAH). Methods: 61 PAH patients who were receiving standard care, including mono or dual PAH-targeted background therapy were randomised 2:1 to ralinepag (n=40) or placebo (n=21). The starting dose of ralinepag was 10 μg twice daily. Dosage was then up-titrated as tolerated over the course of the 9-week dose-titration period, to a maximum total daily dose of 600 μg (300 μg twice daily). The primary efficacy end-point was the absolute change in pulmonary vascular resistance (PVR) from baseline to week 22. Additional end-points included percentage change in PVR from baseline, other haemodynamic parameters, 6-min walk distance (6MWD) and safety and tolerability. Results: Ralinepag significantly decreased PVR by 163.9 dyn·s·cm −5 compared to an increase of 0.7 dyn·s·cm −5 with placebo (p=0.02); the least-squares mean change from baseline PVR was −29.8% compared with placebo (p=0.03). 6MWD increased from baseline by 36.2 m with ralinepag and 29.4 m with placebo (p=0.90). Serious adverse events occurred in 10% of ralinepag patients and 29% of placebo patients. Study discontinuations occurred in 13% of ralinepag patients and 10% of placebo patients. Summary: Ralinepag reduced PVR compared with placebo in PAH patients on mono (41%) or dual combination (59%) background therapy. In this 22-week randomised, placebo-controlled phase 2 study of PAH patients on single or dual oral background therapy, ralinepag, an oral IP receptor agonist, significantly reduced PVR. http://bit.ly/2XHSccO