Nobuhiro Tanabe1, Satoshi Ikeda2, Nobuhiro Tahara3, Keiichi Fukuda4, Masaru Hatano5, Hiroshi Ito6, Tomotaka Nakayama7, Toshihisa Anzai8, Akiyoshi Hashimoto9, Teruo Inoue10, Kouji Kajinami11, Yasuki Kihara12, Hideyuki Kinoshita13, Koichiro Kuwahara14, Toyoaki Murohara15, Osamu Okazaki16, Satoshi Sakai17, Toru Satoh18, Yutaka Takeda19, Yasuchika Takeishi20, Mitsugu Taniguchi21, Hiroshi Watanabe22, Takeshi Yamamoto23, Keiko Yamauchi-Takihara24, Koichiro Yoshioka25, Shigetake Sasayama26. 1. Department of Advanced Medicine in Pulmonary Hypertension, Graduate School of Medicine, Chiba University. 2. Department of Cardiovascular Medicine, Nagasaki University Graduate School of Biomedical Sciences. 3. Department of Medicine, Division of Cardiovascular Medicine, Kurume University School of Medicine. 4. Department of Cardiology, Keio University School of Medicine. 5. Department of Therapeutic Strategy for Heart Failure, The University of Tokyo Hospital. 6. Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine. 7. Department of Pediatrics, Toho University Omori Medical Center. 8. Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center. 9. Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University Hospital. 10. Department of Cardiovascular Medicine, Dokkyo Medical University School of Medicine. 11. Department of Cardiology, Kanazawa Medical University. 12. Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical and Health Sciences. 13. Department of Community Medicine Supporting System, Kyoto University Graduate School of Medicine. 14. Department of Cardiovascular Medicine, Shinshu University School of Medicine. 15. Department of Cardiology, Nagoya University Graduate School of Medicine. 16. Department of Cardiology, National Center for Global Health and Medicine. 17. Cardiovascular Division, Department of Clinical Medicine, Faculty of Medicine, University of Tsukuba. 18. Division of Cardiology Department of Medicine, Kyorin University Hospital. 19. Department of Cardio-Renal Medicine and Hypertension, Nagoya City University Graduate School of Medical Sciences. 20. Department of Cardiovascular Medicine, Fukushima Medical University. 21. Department of Cardiology, Osaka Pref. Saiseikai Tondabayashi Hospital. 22. Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine. 23. Faculty of Health Science, Yamaguchi University Graduate School of Medicine. 24. Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine. 25. Graduate School of Medicine, Tokai University. 26. Uji Hospital.
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 PGI2formulations. 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].).
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 PGI2formulations. 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].).