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

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.

• Authors: Gérald Simonneau, Adam Torbicki, Marius M Hoeper, Marion Delcroix, Kristóf Karlócai, Nazzareno Galiè, Bruno Degano, Diana Bonderman, Marcin Kurzyna, Michela Efficace, Ruben Giorgino, Irene M Lang
• Journal: The European respiratory journal (Eur Respir J) Vol. 40 Issue 4 Pg. 874-80 (Oct 2012) ISSN: 1399-3003 [Electronic] England
• PMID: 22362844 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

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

Topics

• 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)