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 PAH.
Forty-three adult patients with symptomatic PAH (receiving stable endothelin receptor antagonist and/or a phosphodiesterase type-5 inhibitor therapy) were randomised three to one: selexipag to placebo. Dosage was up-titrated in 200 μg increments from 200 μg twice daily on Day 1 to 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 endpoint; analysed on the per protocol set first and then on 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% CL: −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.
- ERS