Efficacy and safety of an orally administered selective prostacyclin receptor agonist, selexipag, in Japanese patients with pulmonary arterial hypertension

Nobuhiro Tanabe, Satoshi Ikeda, Nobuhiro Tahara, Keiichi Fukuda, Masaru Hatano, Hiroshi Ito, Tomotaka Nakayama, Toshihisa Anzai, Akiyoshi Hashimoto, Teruo Inoue, Kouji Kajinami, Yasuki Kihara, Hideyuki Kinoshita, Koichiro Kuwahara, Toyoaki Murohara, Osamu Okazaki, Satoshi Sakai, Toru Satoh, Yutaka Takeda, Yasuchika TakeishiMitsugu Taniguchi, Hiroshi Watanabe, Takeshi Yamamoto, Keiko Yamauchi-Takihara, Koichiro Yoshioka, Shigetake Sasayama

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Abstract

Background: Selexipag is an orally available prostacyclin receptor (IP receptor) agonist with a non-prostanoid structure. In this open-label Phase II trial, the efficacy and safety of selexipag in Japanese patients with pulmonary arterial hypertension (PAH) is examined. Methods and Results: Selexipag was administered at 200 μg twice daily and titrated up to 1,600 μg by increments of 200 μg in 37 subjects to reach the individual maximum tolerated dose. At 16 weeks, in 33 patients comprising the per-protocol set, the pulmonary vascular resistance (PVR; primary endpoint) decreased from 683.2±237.3 to 560.3±238.7 dyn · s/cm5 (P<0.0001). For the secondary endpoint, the 6-min walk distance (6MWD) increased from 445.0±102.2 to 459.1±112.8 m (P=0.0324); World Health Organization functional class improved in 4 patients (12.1%), and was maintained in 29 patients (87.9%). A decrease in PVR was also shown in patients treated with selexipag, on top of a phosphodiesterase inhibitor and endothelin receptor antagonist. Most of the commonly reported adverse events were consistent with those reported for other PGI2 formulations. Thirty-four patients attained the individual maximum tolerated dose (maintenance dose). Conclusions: The efficacy and tolerability of selexipag in Japanese PAH patients was confirmed by improvement in pulmonary hemodynamics, exercise capacity, symptoms. Selexipag is an efficacious treatment option for Japanese PAH patients. (Trial registration: JAPIC Clinical Trials Information [JapicCTI-111532].)

Original languageEnglish
Pages (from-to)1360-1367
Number of pages8
JournalCirculation Journal
Volume81
Issue number9
DOIs
Publication statusPublished - 2017

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Keywords

  • Prostacyclin receptor agonist
  • Pulmonary arterial hypertension
  • Pulmonary hemodynamics
  • Safety
  • Selexipag

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Tanabe, N., Ikeda, S., Tahara, N., Fukuda, K., Hatano, M., Ito, H., Nakayama, T., Anzai, T., Hashimoto, A., Inoue, T., Kajinami, K., Kihara, Y., Kinoshita, H., Kuwahara, K., Murohara, T., Okazaki, O., Sakai, S., Satoh, T., Takeda, Y., ... Sasayama, S. (2017). Efficacy and safety of an orally administered selective prostacyclin receptor agonist, selexipag, in Japanese patients with pulmonary arterial hypertension. Circulation Journal, 81(9), 1360-1367. https://doi.org/10.1253/circj.CJ-16-1348