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

Fernando Torres, Harrison Farber, Arsen Ristic, Vallerie McLaughlin, John Adams, Jinkun Zhang, Preston Klassen, William Shanahan, John Grundy, Ines Hoffmann, Christopher Cabell, Pilar Escribano Subías, Namita Sood, Anne Keogh, Gwyn D'Souza, Lewis Rubin

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2 Scopus citations

Abstract

Purpose: This phase 2 study was designed to assess the efficacy, safety and tolerability of immediaterelease 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 dynscm-5 compared to an increase of 0.7 dynscm-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.

Original languageEnglish (US)
Article number1901030
JournalEuropean Respiratory Journal
Volume54
Issue number4
DOIs
StatePublished - Oct 1 2019

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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    Torres, F., Farber, H., Ristic, A., McLaughlin, V., Adams, J., Zhang, J., Klassen, P., Shanahan, W., Grundy, J., Hoffmann, I., Cabell, C., Subías, P. E., Sood, N., Keogh, A., D'Souza, G., & Rubin, L. (2019). 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. European Respiratory Journal, 54(4), [1901030]. https://doi.org/10.1183/13993003.01030-2019