title: 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.affiliation: National Reference Center for Pulmonary Hypertension South Paris University, Hôpital Antoine Béclère, 157 rue de la Porte de Trivaux, 92141 Clamart Cedex, France. gerald.simonneau@abc.aphp.fr
authors.forename: Gérald
authors.initials: G
authors.lastname: Simonneau
authors.forename: Adam
authors.initials: A
authors.lastname: Torbicki
authors.forename: Marius M
authors.initials: MM
authors.lastname: Hoeper
authors.forename: Marion
authors.initials: M
authors.lastname: Delcroix
authors.forename: Kristóf
authors.initials: K
authors.lastname: Karlócai
authors.forename: Nazzareno
authors.initials: N
authors.lastname: Galiè
authors.forename: Bruno
authors.initials: B
authors.lastname: Degano
authors.forename: Diana
authors.initials: D
authors.lastname: Bonderman
authors.forename: Marcin
authors.initials: M
authors.lastname: Kurzyna
authors.forename: Michela
authors.initials: M
authors.lastname: Efficace
authors.forename: Ruben
authors.initials: R
authors.lastname: Giorgino
authors.forename: Irene M
authors.initials: IM
authors.lastname: Lang
mesh_terms: D000081:Acetamides / Q000627:therapeutic use*; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011719:Pyrazines / Q000627:therapeutic use*; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin / Q000819:agonists*; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000627:therapeutic use*
chemical_list: D000081:Acetamides; C113936:PTGIR protein, human; D011719:Pyrazines; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin; D014665:Vasodilator Agents; C523468:selexipag