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.
Acetates
/ therapeutic use
Adult
Aged
Carbamates
/ therapeutic use
Double-Blind Method
Drug Therapy, Combination
Endothelin Receptor Antagonists
/ therapeutic use
Enzyme Activators
/ therapeutic use
Female
Humans
Male
Middle Aged
Phosphodiesterase 5 Inhibitors
/ therapeutic use
Pulmonary Arterial Hypertension
/ drug therapy
Receptors, Epoprostenol
/ agonists
Soluble Guanylyl Cyclase
Vascular Resistance
Walk Test
Young Adult
Journal
The European respiratory journal
ISSN: 1399-3003
Titre abrégé: Eur Respir J
Pays: England
ID NLM: 8803460
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
24
01
2019
accepted:
18
06
2019
pubmed:
9
8
2019
medline:
8
10
2020
entrez:
9
8
2019
Statut:
epublish
Résumé
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). 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. Ralinepag significantly decreased PVR by 163.9 dyn·s·cm Ralinepag reduced PVR compared with placebo in PAH patients on mono (41%) or dual combination (59%) background therapy.
Identifiants
pubmed: 31391223
pii: 13993003.01030-2019
doi: 10.1183/13993003.01030-2019
pii:
doi:
Substances chimiques
Acetates
0
Carbamates
0
Endothelin Receptor Antagonists
0
Enzyme Activators
0
Phosphodiesterase 5 Inhibitors
0
Receptors, Epoprostenol
0
ralinepag
0
Soluble Guanylyl Cyclase
EC 4.6.1.2
Banques de données
ClinicalTrials.gov
['NCT02279160']
Types de publication
Clinical Trial, Phase II
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright ©ERS 2019.
Déclaration de conflit d'intérêts
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.