Selexipag: an oral, selective prostacyclin receptor agonist for the treatment of pulmonary arterial hypertension

Eur Respir J. 2012 Oct;40(4):874-80. doi: 10.1183/09031936.00137511. Epub 2012 Feb 23.

Abstract

In this phase 2 proof-of-concept study we examined the safety and efficacy of selexipag, an orally available, selective prostacyclin receptor (IP receptor) agonist, as a treatment for pulmonary arterial hypertension (PAH). 43 adult patients with symptomatic PAH (receiving stable endothelin receptor antagonist and/or a phosphodiesterase type-5 inhibitor therapy) were randomised three to one to receive either selexipag or placebo. Dosage was up-titrated in 200-μg increments from 200 μg twice daily on day 1 to the maximum tolerated dose by day 35 (maximum allowed dose of 800 μg twice daily). Change in pulmonary vascular resistance at week 17 expressed as a percentage of the baseline value was the primary efficacy end-point, and was analysed in the per protocol set first and then in the all-treated set to assess robustness of results. A statistically significant 30.3% reduction in geometric mean pulmonary vascular resistance was observed after 17 weeks' treatment with selexipag compared with placebo (95% confidence limits -44.7- -12.2; p=0.0045, Wilcoxon rank sum test). This was supported by a similar result from the all-treated set. Selexipag was well tolerated with a safety profile in line with the expected pharmacological effect. Our results encourage the further investigation of selexipag for the treatment of PAH.

Trial registration: ClinicalTrials.gov NCT00993408.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Acetamides / therapeutic use*
  • Administration, Oral
  • Adult
  • Aged
  • Familial Primary Pulmonary Hypertension
  • Female
  • Humans
  • Hypertension, Pulmonary / drug therapy*
  • Male
  • Middle Aged
  • Pyrazines / therapeutic use*
  • Receptors, Epoprostenol
  • Receptors, Prostaglandin / agonists*
  • Treatment Outcome
  • Vascular Resistance / drug effects
  • Vasodilator Agents / therapeutic use*

Substances

  • Acetamides
  • PTGIR protein, human
  • Pyrazines
  • Receptors, Epoprostenol
  • Receptors, Prostaglandin
  • Vasodilator Agents
  • selexipag

Associated data

  • ClinicalTrials.gov/NCT00993408