Hyuk-Jae Chang1, Shinjeong Song1, Sung-A Chang2, Hyung-Kwan Kim3, Hae-Ok Jung4, Jung-Hyun Choi5, Jae Seung Lee6, Kye-Hun Kim7, Jin-Ok Jeong8, Ju Hee Lee9, Duk-Kyung Kim10. 1. Division of Cardiology, Department of Internal Medicine, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, South Korea. 2. Division of Cardiology, Department of Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. 3. Division of Cardiology, Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea. 4. Cardiovascular Center, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea. 5. Division of Cardiology, Pusan National University Hospital, Pusan, South Korea. 6. Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. 7. The Heart Center of Chonnam National University Hospital, Chonnam National University Research Institute of Medical Sciences, Gwangju, South Korea. 8. Department of Internal Medicine, Cardiovascular Center, Chungnam National University Hospital, Chungnam National University School of Medicine, Daejeon, South Korea. 9. Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, South Korea. 10. Division of Cardiology, Department of Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. Electronic address: dukkyung.kim@gmail.com.
Abstract
PURPOSE:Udenafil is an oral phosphodiesterase-5 inhibitor approved for the treatment of erectile dysfunction. In a multicenter, placebo-controlled, randomized Phase IIa study, the reduction of pulmonary vascular resistance index was greater with a 50-mg baseline dose of udenafil than with the 100-mg dose, the cardiac index did not decrease at most points, and the safety was excellent, suggesting that 50-mg udenafil could be used in a Phase IIb trial. METHODS: In this 16-week, double-blind, placebo-controlled study, 63 patients with pulmonary arterial hypertension were randomized to receive 50-mg udenafil or a placebo BID. The primary efficacy end point was the 6-min walking distance. The secondary efficacy end points were the Borg dyspnea score and time to clinical worsening. Patients who completed the 16-week study could participate in a long-term extension study. FINDINGS: In terms of the difference between the baseline and 16-week 6-min walking distance in both groups, the mean placebo-corrected treatment effect was 25 (58) m (P = 0.0873). Among the patients with a history of endothelin receptor antagonist therapy, the treatment effect at week 16 between the udenafil and placebo groups was 34 (60) m (P = 0.0460). However, there were no significant differences in the Borg dyspnea score and time to clinical worsening between groups. The safety profile and adverse effects of udenafil were similar to those of typical phosphodiesterase-5 inhibitors seen in previous studies. IMPLICATIONS: Udenafil has a favorable safety profile and improves exercise capacity in patients with pulmonary arterial hypertension. ClinicalTrials.gov identifier: NCT01553721.
RCT Entities:
PURPOSE:Udenafil is an oral phosphodiesterase-5 inhibitor approved for the treatment of erectile dysfunction. In a multicenter, placebo-controlled, randomized Phase IIa study, the reduction of pulmonary vascular resistance index was greater with a 50-mg baseline dose of udenafil than with the 100-mg dose, the cardiac index did not decrease at most points, and the safety was excellent, suggesting that 50-mg udenafil could be used in a Phase IIb trial. METHODS: In this 16-week, double-blind, placebo-controlled study, 63 patients with pulmonary arterial hypertension were randomized to receive 50-mg udenafil or a placebo BID. The primary efficacy end point was the 6-min walking distance. The secondary efficacy end points were the Borg dyspnea score and time to clinical worsening. Patients who completed the 16-week study could participate in a long-term extension study. FINDINGS: In terms of the difference between the baseline and 16-week 6-min walking distance in both groups, the mean placebo-corrected treatment effect was 25 (58) m (P = 0.0873). Among the patients with a history of endothelin receptor antagonist therapy, the treatment effect at week 16 between the udenafil and placebo groups was 34 (60) m (P = 0.0460). However, there were no significant differences in the Borg dyspnea score and time to clinical worsening between groups. The safety profile and adverse effects of udenafil were similar to those of typical phosphodiesterase-5 inhibitors seen in previous studies. IMPLICATIONS: Udenafil has a favorable safety profile and improves exercise capacity in patients with pulmonary arterial hypertension. ClinicalTrials.gov identifier: NCT01553721.
Authors: David J Goldberg; Victor Zak; Bryan H Goldstein; Kurt R Schumacher; Jonathan Rhodes; Daniel J Penny; Christopher J Petit; Salil Ginde; Shaji C Menon; Seong-Ho Kim; Gi Beom Kim; Todd T Nowlen; Michael V DiMaria; Benjamin P Frischhertz; Jonathan B Wagner; Kimberly E McHugh; Brian W McCrindle; Amanda J Shillingford; Arash A Sabati; Anji T Yetman; Anitha S John; Marc E Richmond; Matthew D Files; R Mark Payne; Andrew S Mackie; Christopher K Davis; Shabana Shahanavaz; Kevin D Hill; Ruchira Garg; Jeffrey P Jacobs; Michelle S Hamstra; Stacy Woyciechowski; Kathleen A Rathge; Michael G McBride; Peter C Frommelt; Mark W Russell; Elaine M Urbina; James L Yeager; Victoria L Pemberton; Mario P Stylianou; Gail D Pearson; Stephen M Paridon Journal: Circulation Date: 2019-11-17 Impact factor: 29.690