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

Curr Med Res Opin. 2011 Sep;27(9):1827-34. doi: 10.1185/03007995.2011.605440. Epub 2011 Aug 4.

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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / adverse effects
  • Asian People
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Interactions
  • Epoprostenol / administration & dosage
  • Epoprostenol / adverse effects
  • Epoprostenol / analogs & derivatives
  • Familial Primary Pulmonary Hypertension
  • Female
  • Humans
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / ethnology
  • Hypertension, Pulmonary / metabolism
  • Male
  • Middle Aged
  • Phenylpropionates / administration & dosage*
  • Phenylpropionates / adverse effects
  • Phenylpropionates / pharmacokinetics*
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / adverse effects
  • Pyridazines / administration & dosage*
  • Pyridazines / adverse effects
  • Pyridazines / pharmacokinetics*
  • Treatment Outcome

Substances

  • Antihypertensive Agents
  • Phenylpropionates
  • Platelet Aggregation Inhibitors
  • Pyridazines
  • beraprost
  • Epoprostenol
  • ambrisentan

Associated data

  • ClinicalTrials.gov/NCT00540436