Two formulations of epoprostenol sodium in the treatment of pulmonary arterial hypertension: EPITOME-1 (epoprostenol for injection in pulmonary arterial hypertension), a phase IV, open-label, randomized study

Am Heart J. 2014 Feb;167(2):218-225.e1. doi: 10.1016/j.ahj.2013.08.008. Epub 2013 Oct 16.

Abstract

Background: Epoprostenol sodium with arginine-mannitol excipients (epoprostenol AM; Veletri [Actelion Pharmaceuticals Ltd, Allschwil, Switzerland]) and epoprostenol sodium with glycine-mannitol excipients (epoprostenol GM; Flolan [GlaxoSmithKline, Triangle Park, NC]) are intravenous treatments for pulmonary arterial hypertension (PAH). Epoprostenol AM contains different inactive excipients, resulting in greater stability at room temperature compared with epoprostenol GM.

Methods: In this prospective, multicenter, open-label, randomized, phase IV exploratory study, epoprostenol-naïve patients in need of injectable prostanoid therapy were randomized 2:1 to open-label epoprostenol AM or epoprostenol GM. The study period was 28 days, followed by a 30-day safety follow-up. Study aims were to descriptively compare the safety, tolerability, drug metabolite levels, and treatment effects of epoprostenol AM and epoprostenol GM in PAH. Statistical analysis was descriptive only because of the exploratory nature of the study.

Results: Thirty patients with PAH (18-70 years, 24 women, 20 idiopathic PAH) were randomized to epoprostenol AM (n = 20) or epoprostenol GM (n = 10). Most frequently reported adverse events included jaw pain, headache, nausea, and flushing. Two deaths occurred during the study period, and 1 death occurred during the 30-day safety follow-up period, all in patients receiving epoprostenol AM. All deaths were classified by the treating physician as unrelated to epoprostenol AM. The median (range) change from baseline to day 28 in 6-minute walk distance was 36 m (-127 to 210 m) and 49 m (-44 to 110 m) for the epoprostenol AM and epoprostenol GM groups, respectively.

Conclusions: In this randomized clinical study of epoprostenol AM in PAH, use of this novel preparation with greater room temperature stability was well tolerated.

Publication types

  • Clinical Trial, Phase IV
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / pharmacokinetics
  • Dose-Response Relationship, Drug
  • Epoprostenol / administration & dosage*
  • Epoprostenol / pharmacokinetics
  • Exercise Tolerance / drug effects*
  • Familial Primary Pulmonary Hypertension
  • Female
  • Follow-Up Studies
  • Hemodynamics / drug effects*
  • Humans
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / metabolism
  • Hypertension, Pulmonary / physiopathology
  • Injections, Intravenous
  • Male
  • Middle Aged
  • Prospective Studies
  • Treatment Outcome
  • Young Adult

Substances

  • Antihypertensive Agents
  • Epoprostenol