TY - JOUR T1 - 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 JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.01030-2019 VL - 54 IS - 4 SP - 1901030 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 Y1 - 2019/10/01 UR - http://erj.ersjournals.com/content/54/4/1901030.abstract N2 - 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 ER -