Efficacy, safety, and pharmacokinetics of ambrisentan in Japanese adults with pulmonary arterial hypertension

Abstract

Objective:

To investigate the efficacy, safety, and pharmacokinetics of ambrisentan in Japanese adults with pulmonary arterial hypertension (PAH).

Research design and methods:

In this open-label, uncontrolled, dose-escalation study, 25 Japanese patients with PAH were scheduled to receive 5 mg of ambrisentan once daily for the first 12 weeks, and 10 mg once daily for an additional 12 weeks. The primary endpoint was improvement in exercise capacity from baseline which was indicated by 6-minute walk distance; the secondary endpoints included World Health Organization functional class, Borg dyspnea index, plasma brain natriuretic peptide level, and cardiopulmonary hemodynamics.

Clinical trial registration:

NCT00540436.

Results:

At week 24, improvements were noted in all endpoints, with no clinically significant elevation of serum aminotransferase level. Pharmacokinetics in these Japanese patients was similar to that of non-Japanese populations, suggesting that once-daily dosing is appropriate in Japanese patients. Ambrisentan was generally well tolerated. No new safety signals were identified.

Limitation:

This study lacked a control group and was insufficiently powered to reach definitive conclusions on the efficacy of ambrisentan.

Conclusion:

Ambrisentan is considered as safe and effective for Japanese adults with PAH.

Key words::

• 6-minute walk distance
• Dose-escalation study
• Endothelin receptor antagonist
• Hemodynamics
• Pulmonary arterial hypertension
• World Health Organization functional class

Transparency

Declaration of funding

Funding for this study was provided by GlaxoSmithKline (NCT00540436).

Declaration of financial/other relationships

S.Y. and K.S. have received consulting fees from GlaxoSmithKline. R.S., N.N., T.I., and H.N. are employees of the study sponsor.

Acknowledgements

All listed authors meet the criteria for authorship set forth by the International Committee for Medical Journal Editors. The authors wish to acknowledge the following individuals for their contributions as primary study investigators and critical review during the development of this manuscript: Norifumi Nakanishi, National Cardiovascular Center; Kazufumi Tsuchihashi, Sapporo Medical University Hospital; Sumiaki Tanaka, Kitasato University Hospital; Shusaku Fukaya, Fujita Health University Hospital; Hiromi Matsubara, Okayama Medical Center; Yoshiki Shiohira, Tomishiro Chuo Hospital; Ichizo Tsujino, Hokkaido University Hospital; Toshihisa Anzai, Keio University Hospital; Atsushi Yao, The University of Tokyo Hospital; Hiroshi Watanabe, Hamamatsu University School of Medicine; Kazuhiko Takehara, Kanazawa University Hospital; Takeshi Kimura, Kyoto University Hospital; Minori Mizoguchi, Kurume University Hospital; David Kiper, Supernatant Communications; and Chisato Mori, Chiba University, for his expert advice on male fertility.