Efficacy and Safety of an Orally Administered Selective Prostacyclin Receptor Agonist, Selexipag, in Japanese Patients With Pulmonary Arterial Hypertension

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Author(s)

    • Tanabe Nobuhiro
    • Department of Advanced Medicine in Pulmonary Hypertension, Graduate School of Medicine, Chiba University
    • Inoue Teruo
    • Department of Cardiovascular Medicine, Dokkyo Medical University School of Medicine
    • Kihara Yasuki
    • Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical and Health Sciences
    • Kinoshita Hideyuki
    • Department of Community Medicine Supporting System, Kyoto University Graduate School of Medicine
    • Kuwahara Koichiro
    • Department of Cardiovascular Medicine, Shinshu University School of Medicine
    • Murohara Toyoaki
    • Department of Cardiology, Nagoya University Graduate School of Medicine
    • Okazaki Osamu
    • Department of Cardiology, National Center for Global Health and Medicine
    • Sakai Satoshi
    • Cardiovascular Division, Department of Clinical Medicine, Faculty of Medicine, University of Tsukuba
    • Satoh Toru
    • Division of Cardiology Department of Medicine, Kyorin University Hospital
    • Takeda Yutaka
    • Department of Cardio-Renal Medicine and Hypertension, Nagoya City University Graduate School of Medical Sciences
    • Ikeda Satoshi
    • Department of Cardiovascular Medicine, Nagasaki University Graduate School of Biomedical Sciences
    • Watanabe Hiroshi
    • Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine
    • Yamamoto Takeshi
    • Faculty of Health Science, Yamaguchi University Graduate School of Medicine
    • Tahara Nobuhiro
    • Department of Medicine, Division of Cardiovascular Medicine, Kurume University School of Medicine
    • Hatano Masaru
    • Department of Therapeutic Strategy for Heart Failure, The University of Tokyo Hospital
    • Ito Hiroshi
    • Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine
    • Anzai Toshihisa
    • Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center
    • Hashimoto Akiyoshi
    • Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University Hospital

Abstract

<p><b><i>Background:</i></b>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.</p><p><b><i>Methods and Results:</i></b>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/cm<sup>5</sup>(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 PGI<sub>2</sub>formulations. Thirty-four patients attained the individual maximum tolerated dose (maintenance dose).</p><p><b><i>Conclusions:</i></b>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].)</p>

Journal

  • Circulation Journal

    Circulation Journal 81(9), 1360-1367, 2017

    The Japanese Circulation Society

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