Long-term safety and efficacy of ambrisentan in Japanese adults with pulmonary arterial hypertension

Abstract

Objective:

To investigate the safety and efficacy of long-term administration of ambrisentan in Japanese adults with pulmonary arterial hypertension (PAH).

Research design and methods:

In this open-label extension of a preceding multicenter dose-escalation study, 21 Japanese patients with PAH received treatment with 5 or 10 mg of ambrisentan once daily and were comprehensively evaluated every 12 weeks. The primary endpoint was the safety of long-term ambrisentan administration, as defined by the incidence and severity of adverse events. The secondary (efficacy) endpoints were change in exercise capacity (as indicated by 6-minute walk distance), World Health Organization functional class, Borg dyspnea index, plasma brain natriuretic peptide level, cardiopulmonary hemodynamics, and time to clinical worsening of PAH.

Clinical trial registration:

NCT00554619.

Results:

The mean total duration of treatment (i.e., including the preceding dose-escalation study) was approximately 139 weeks. There were fewer adverse events related to ambrisentan in this study than in the preceding study, and we identified no new safety signals that might preclude the long-term use of ambrisentan among Japanese adults with PAH. Improvements observed in efficacy endpoints in the preceding study were maintained in the present study.

Limitations:

This study did not include a control group and lacked the statistical power to reach definite conclusions regarding the efficacy of ambrisentan.

Conclusion:

Our results suggest that long-term administration of ambrisentan is well tolerated and efficacious for Japanese adults with PAH.

Keywords::

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

Transparency

Declaration of funding

This study was funded by GlaxoSmithKline (NCT00554619).

Declaration of financial/other relationships

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

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgments

All listed authors meet the criteria for authorship set forth by the International Committee for Medical Journal Editors. We wish to acknowledge the following individuals for their contributions as primary study investigators: Norifumi Nakanishi, National Cerebral and 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 Central 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. GlaxoSmithKline sponsored David Kipler, Supernatant Communications, for writing and editorial services and Chisato Mori, Chiba University, for his expert advice on male fertility.