OBJECTIVE: Selexipag is a novel, oral, selective prostacyclin (PGI2) receptor 
agonist in clinical development for the treatment of pulmonary arterial 
hypertension. Film-coated tablets with strength between 200 and 1,600 μg were 
used. Bioequivalence between 8 x 200 μg and a new 1,600 μg tablet was evaluated 
at steady state in healthy male subjects.
MATERIALS AND METHODS: This was an open-label, 2-treatment, 2-period, crossover, 
up-titration, phase 1 study. The treatments were selexipag at 1,600 μg b.i.d. 
for 4.5 days either as 8 x 200 μg tablets (reference: A) or 1 x 1,600 μg tablet 
(test: B), both preceded by an up-titration phase starting from 400 μg b.i.d. 
doses, in 200-μg steps every 4th day. Subjects were randomized 1 : 1 to the A-B 
or B-A sequence. The pharmacokinetics and tolerability of selexipag and its 
active metabolite, ACT-333679, were investigated.
RESULTS: 80 subjects were enrolled in the study: 65 subjects completed the study 
according to protocol, and 15 subjects withdrew from the study. The most 
frequent adverse events (AEs) were headache (86%), myalgia (73%), and jaw pain 
(73%). There was no difference in nature and overall frequency of AEs between 
the two treatments. Steady state was attained within 3 days of the selexipag 
1,600 Î¼g b.i.d.
TREATMENTS: The 90% confidence intervals (CIs) of the geometric mean ratio (B/A) 
at steady state for AUCÏ and Cmax,ss were within (0.80, 1.25) bioequivalence 
interval: (0.92, 1.06) and (0.95, 1.14), respectively, for selexipag and (0.95, 
1.06) and (0.94, 1.07), respectively, for the active metabolite, ACT-333679.
CONCLUSIONS: Bioequivalence was demonstrated between 8 x 200 μg and 1 x 1,600 μg 
selexipag at steady state.