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 Takeishi & 6 others Mitsugu 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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Epoprostenol Receptors
Pulmonary Hypertension
Safety
Maximum Tolerated Dose
Phosphodiesterase Inhibitors
selexipag
Epoprostenol
Vascular Resistance
Hemodynamics
Clinical Trials
Exercise
Lung

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Efficacy and safety of an orally administered selective prostacyclin receptor agonist, selexipag, in Japanese patients with pulmonary arterial hypertension. / Tanabe, Nobuhiro; Ikeda, Satoshi; Tahara, Nobuhiro; Fukuda, Keiichi; Hatano, Masaru; Ito, Hiroshi; Nakayama, Tomotaka; Anzai, Toshihisa; Hashimoto, Akiyoshi; Inoue, Teruo; Kajinami, Kouji; Kihara, Yasuki; Kinoshita, Hideyuki; Kuwahara, Koichiro; Murohara, Toyoaki; Okazaki, Osamu; Sakai, Satoshi; Satoh, Toru; Takeda, Yutaka; Takeishi, Yasuchika; Taniguchi, Mitsugu; Watanabe, Hiroshi; Yamamoto, Takeshi; Yamauchi-Takihara, Keiko; Yoshioka, Koichiro; Sasayama, Shigetake.

In: Circulation Journal, Vol. 81, No. 9, 2017, p. 1360-1367.

Research output: Contribution to journalArticle

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, Takeishi, Y, Taniguchi, M, Watanabe, H, Yamamoto, T, Yamauchi-Takihara, K, Yoshioka, K & Sasayama, S 2017, 'Efficacy and safety of an orally administered selective prostacyclin receptor agonist, selexipag, in Japanese patients with pulmonary arterial hypertension', Circulation Journal, vol. 81, no. 9, pp. 1360-1367. https://doi.org/10.1253/circj.CJ-16-1348
Tanabe, Nobuhiro ; Ikeda, Satoshi ; Tahara, Nobuhiro ; Fukuda, Keiichi ; Hatano, Masaru ; Ito, Hiroshi ; Nakayama, Tomotaka ; Anzai, Toshihisa ; Hashimoto, Akiyoshi ; Inoue, Teruo ; Kajinami, Kouji ; Kihara, Yasuki ; Kinoshita, Hideyuki ; Kuwahara, Koichiro ; Murohara, Toyoaki ; Okazaki, Osamu ; Sakai, Satoshi ; Satoh, Toru ; Takeda, Yutaka ; Takeishi, Yasuchika ; Taniguchi, Mitsugu ; Watanabe, Hiroshi ; Yamamoto, Takeshi ; Yamauchi-Takihara, Keiko ; Yoshioka, Koichiro ; Sasayama, Shigetake. / Efficacy and safety of an orally administered selective prostacyclin receptor agonist, selexipag, in Japanese patients with pulmonary arterial hypertension. In: Circulation Journal. 2017 ; Vol. 81, No. 9. pp. 1360-1367.
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T1 - Efficacy and safety of an orally administered selective prostacyclin receptor agonist, selexipag, in Japanese patients with pulmonary arterial hypertension

AU - Tanabe, Nobuhiro

AU - Ikeda, Satoshi

AU - Tahara, Nobuhiro

AU - Fukuda, Keiichi

AU - Hatano, Masaru

AU - Ito, Hiroshi

AU - Nakayama, Tomotaka

AU - Anzai, Toshihisa

AU - Hashimoto, Akiyoshi

AU - Inoue, Teruo

AU - Kajinami, Kouji

AU - Kihara, Yasuki

AU - Kinoshita, Hideyuki

AU - Kuwahara, Koichiro

AU - Murohara, Toyoaki

AU - Okazaki, Osamu

AU - Sakai, Satoshi

AU - Satoh, Toru

AU - Takeda, Yutaka

AU - Takeishi, Yasuchika

AU - Taniguchi, Mitsugu

AU - Watanabe, Hiroshi

AU - Yamamoto, Takeshi

AU - Yamauchi-Takihara, Keiko

AU - Yoshioka, Koichiro

AU - Sasayama, Shigetake

PY - 2017

Y1 - 2017

N2 - 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].)

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KW - Prostacyclin receptor agonist

KW - Pulmonary arterial hypertension

KW - Pulmonary hemodynamics

KW - Safety

KW - Selexipag

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