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.
Abstract
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
Footnotes
This study is registered at clinicaltrials.gov with identifier NCT02279160. The study protocol and statistical analysis plan are available on the clinicaltrials.gov website. The database for this clinical trial is the sole property of the sponsor, which has sole authority for the provision of access.
Support statement: This study was sponsored by Arena Pharmaceuticals, Inc. Funding information for this article has been deposited with the Crossref Funder Registry.
Conflict of interest: F. Torres reports grants from UT Southwestern Medical Center, during the conduct of the study.
Conflict of interest: H. Farber has nothing to disclose.
Conflict of interest: A. Ristic has nothing to disclose.
Conflict of interest: V. McLaughlin has nothing to disclose.
Conflict of interest: J. Adams
Conflict of interest: J. Zhang is an employee of Arena Pharmaceuticals.
Conflict of interest: P. Klassen is an employee of Arena Pharmaceuticals.
Conflict of interest: W. Shanahan is a former employee of Arena Pharmaceuticals and hold shares.
Conflict of interest: J. Grundy is an employee of Arena Pharmaceuticals.
Conflict of interest: I. Hoffmann is an employee of Arena Pharmaceuticals.
Conflict of interest: C. Cabell is an employee of Arena Pharmaceuticals
Conflict of interest: P. Escribano-Subias has nothing to disclose.
Conflict of interest: N. Sood reports grants for research from The Ohio State University, during the conduct of the study.
Conflict of interest: A. Keogh has nothing to disclose.
Conflict of interest: G. D'Souza reports personal fees (consulting and travel) from Arena, outside the submitted work.
Conflict of interest: L. Rubin has nothing to disclose.
- Received January 24, 2019.
- Accepted June 18, 2019.
- Copyright ©ERS 2019