PT - JOURNAL ARTICLE AU - Fernando Torres AU - Harrison Farber AU - Arsen Ristic AU - Vallerie McLaughlin AU - John Adams AU - Jinkun Zhang AU - Preston Klassen AU - William Shanahan AU - John Grundy AU - Ines Hoffmann AU - Christopher Cabell AU - Pilar Escribano Subías AU - Namita Sood AU - Anne Keogh AU - Gwyn D'Souza AU - Lewis Rubin TI - Efficacy and safety of ralinepag, a novel oral IP agonist, in PAH patients on mono or dual background therapy Results from a Phase 2 randomized, parallel group, placebo-controlled trial AID - 10.1183/13993003.01030-2019 DP - 2019 Jan 01 TA - European Respiratory Journal PG - 1901030 4099 - http://erj.ersjournals.com/content/early/2019/07/08/13993003.01030-2019.short 4100 - http://erj.ersjournals.com/content/early/2019/07/08/13993003.01030-2019.full AB - Purpose This Phase 2 study was designed to assess the efficacy, safety and tolerability of immediate-release (IR) orally administered ralinepag, a selective, non-prostanoid prostacyclin receptor (IP) agonist with a 24-hour terminal half-life, compared to placebo in adult patients with symptomatic pulmonary arterial hypertension (PAH).Methods Sixty-one PAH patients who were receiving standard of 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 mcg twice daily (bid). 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 mcg (300 mcg bid). The primary efficacy endpoint was the absolute change in pulmonary vascular resistance (PVR) from baseline to Week 22. Additional endpoints included percentage change in PVR from baseline, other hemodynamic parameters, 6-minute walk distance (6MWD), and safety and tolerability.Results Ralinepag significantly decreased PVR by 163.9 dyn.sec/cm5 compared to an increase of 0.7 dyn.sec/cm5 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.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Torres reports grants from UT Southwestern Medical Center, during the conduct of the study.Conflict of interest: Dr. Farber has nothing to disclose.Conflict of interest: Dr. Ristic has nothing to disclose.Conflict of interest: Dr. McLaughlin has nothing to disclose.Conflict of interest: John AdamsConflict of interest: Dr. Zhang reports other from Arena Pharmaceuticals, outside the submitted work.Conflict of interest: Dr. Klassen reports other from Arena Pharmaceuticals, outside the submitted work.Conflict of interest: Dr. Shanahan reports other from Arena Pharmaceuticals, during the conduct of the study; other from Arena Pharmaceuticals, outside the submitted work.Conflict of interest: Dr. Grundy reports other from Arena Pharmaceuticals, outside the submitted work.Conflict of interest: Dr. Hoffmann reports other from Arena Pharmaceuticals, outside the submitted work.Conflict of interest: Dr. Cabell reports personal fees from Arena Pharmaceuticals, during the conduct of the study.Conflict of interest: Dr. ESCRIBANO-SUBIAS has nothing to disclose.Conflict of interest: Dr. Sood reports grants from The ohio State University, during the conduct of the study.Conflict of interest: Anne KeoghConflict of interest: Dr. D'Souza reports personal fees from Arena, outside the submitted work.Conflict of interest: Dr. Rubin has nothing to disclose.Conflict of interest: Dr. Cabell reports personal fees from Arena Pharmaceuticals, during the conduct of the study.Conflict of interest: Dr. masters has nothing to disclose.