A Phase III, Multicenter, Collaborative, Open-Label Clinical Trial of Sildenafil in Japanese Patients With Pulmonary Arterial Hypertension


Background: There is evidence that phosphodiesterase type-5 is effective for the treatment of pulmonary arterial hypertension (PAH). Methods and Results: A phase III, multicenter, open-label clinical trial of sildenafil 20mg t.i.d. was conducted in 21 Japanese patients with PAH to examine its efficacy, safety, and pharmacokinetics. The present trial consisted of a screening period and 12-week treatment. Patients who were enrolled in the present trial increased their 6-min walking distance of administration increased at week 12 by 84.2m from baseline. Hemodynamic parameters (eg, mean pulmonary artery pressure and pulmonary vascular resistance), Borg dyspnea scores, and plasma brain natriuretic peptide concentrations also improved compared to baseline. Most patients improved or sustained WHO functional class. Seven subjects, who were examined for the pharmacokinetics of sildefanil, showed relatively large interindividual variations in the Cmax, AUC0-8, Css,av, and Ctrough of the drug. Any serious adverse events, severe adverse events, and deaths were not observed. Most of events of undeniable causality were mild or moderate in severity. Sildefanil was well tolerated by the subjects. Conclusions: Sildenafil 20mg t.i.d. was effective and safe for Japanese patients with PAH. (Circ J 2011; 75: 677-682)


TAKEHARA Kazuhiko Department of Dermatology, Kanazawa University Hospital
YAMADA Norikazu Department of Cardiology, Mie University Graduate School of Medicine
NAKANISHI Norifumi Division of Cardiology, National Cardiovascular Center
Watanabe Hiroshi Department of Cardiology, Niigata City General Hospital
SATOH Tohru Department of Cardiology,Ashikaga Red Cross Hospital
Ogawa Satoshi Department Of Cardiology Keio University
Kuriyama Takayuki Department of Chest Medicine, School of Medicine, Chiba University
Tanabe Nobuhiro Department Of Respirology Chiba Graduate School Of Medicine
Miyaji Katsumasa Department Of Cardiology National Hospital Organization Okayama Medical Center
Yao Atsushi Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine
Saji Tsutomu First Department of Pediatrics, Toho University Omori Medical Center
Suzuki Yumiko Tokyo Laboratories, Pfizer Global R&D, Pfizer Japan Inc
Fujiwara Tadami Tokyo Laboratories, Pfizer Global R&D, Pfizer Japan Inc