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.