Efficacy and Safety of Selexipag in Adults With Raynaud's Phenomenon Secondary to Systemic Sclerosis: A Randomized, Placebo-Controlled, Phase II Study.

Objective. To determine the effect of selexipag, an oral, selective IP prostacyclin receptor agonist, on the frequency of attacks of Raynaud's phenomenon (RP) in patients with systemic sclerosis (SSc). Methods. Patients with SSc-related RP were randomized 1:1 to placebo (n = 38) or selexipag (n = 36) in individualized doses (maximum of 1,600 mu g twice dally) during a 3-week titration period. The primary end point was the weekly average number of RP attacks during the study maintenance period, analyzed using a Bayesian approach with a negative binomial model adjusted for baseline number of RP attacks. Other outcome measures included Raynaud's Condition Score (RCS), RP attack duration, and treatment-emergent adverse events (AEs). Results. Baseline characteristics were comparable between treatment groups. For 833% of patients, the individualized maintenance dosage of selexipag was <= 800 mu g twice dally. No significant difference was observed between placebo and selexipag in weekly average number of electronic diary (eDiary)-recorded RP attacks during the maintenance period (1.4.2 attacks during the maintenance period and 21.5 attacks during the baseline week in the placebo group [n = 32] versus 1.8.0 attacks during the maintenance period and 22.4 attacks during the baseline week in the selexipag group [n = 27]; adjusted mean treatment difference of 3.4 in favor of placebo). No significant treatment effect was observed on RCS or RP attack duration. In the double-blind period, 86.8% of placebo-treated patients and 100% of selexipag-treated patients reported >= 1 AE; 553% and 91.7%, respectively, reported >= 1 prostacyclin-associated AE. Conclusion. Treatment with selexipag did not reduce the number of RP attacks compared with placebo. The safety profile of selexipag was similar to that previously reported. This study provides important information about the feasibility of eDiary reporting of RP attacks in clinical trials.