Fernando Torres1, Harrison Farber2, Arsen Ristic3, Vallerie McLaughlin4, John Adams5, Jinkun Zhang5, Preston Klassen5, William Shanahan6, John Grundy5, Ines Hoffmann5, Christopher Cabell5, Pilar Escribano Subías7, Namita Sood8, Anne Keogh9, Gwyn D'Souza5, Lewis Rubin10. 1. Pulmonary/Critical Care, UT Southwestern Medical Center, William P. Clements Jr University Hospital, Dallas, TX, USA. 2. Pulmonary and Critical Care, Boston Medical Center, Boston University, Boston, MA, USA. 3. Dept of Cardiology, Clinical Center of Serbia and Belgrade University School of Medicine, Belgrade, Serbia. 4. Cardiovascular Medicine, University of Michigan, Ann Arbor, MI, USA. 5. Arena Pharmaceuticals, San Diego, CA, USA. 6. Hessian Pharmaceuticals, Hayward, CA, USA. 7. Dept of Cardiology, Hospital Universitario 12 de Octubre, Complutense University, Madrid, Spain. 8. University of Texas, Houston, TX, USA. 9. Heart Transplant, St Vincent's Hospital, Sydney, Australia. 10. Division of Pulmonary and Critical Care Medicine, University of California, San Diego, CA, USA ljrubin@ucsd.edu.
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.
RCT Entities:
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 ralinepagpatients and 29% of placebo patients. Study discontinuations occurred in 13% of ralinepagpatients and 10% of placebo patients. SUMMARY:Ralinepag reduced PVR compared with placebo in PAH patients on mono (41%) or dual combination (59%) background therapy.
Authors: Jennalyn D Mayeux; Irene Z Pan; John Dechand; Joshua A Jacobs; Tara L Jones; Stephen H McKellar; Emily Beck; Nathan D Hatton; John J Ryan Journal: Curr Cardiovasc Risk Rep Date: 2020-11-18
Authors: Irene Z Pan; Jessica R Carey; Joshua A Jacobs; John Dechand; Joshua J Sessions; Teshia Sorensen; Brittany A Penn; Jennalyn D Mayeux; Nathan D Hatton; John J Ryan Journal: Front Med (Lausanne) Date: 2020-03-31