title: Evaluation of a new formulation of epoprostenol sodium in Japanese patients with pulmonary arterial hypertension (EPITOME4).
abstract: BACKGROUND
  Pulmonary arterial hypertension (PAH) is associated with poor prognosis despite significant recent advances in its treatment. An intravenous formulation of epoprostenol sodium containing glycine and mannitol (epoprostenol GM; GlaxoSmithKline, London, UK) is widely used to treat PAH. A new formulation of epoprostenol sodium containing arginine and sucrose excipients (epoprostenol AS; Actelion Pharmaceuticals Japan Ltd., Tokyo, Japan) shows better stability at room temperature after preparing diluted solutions. The primary objective of this study was to evaluate the safety and tolerability of switching from epoprostenol GM to epoprostenol AS in Japanese patients with PAH. The authors also evaluated the efficacy and treatment satisfaction after switching formulations.
  
  
  METHODS
  This was a two-site, open-label, single-arm, Phase 3b study. Eight adult Japanese PAH patients (seven females) treated with a stable dose of epoprostenol GM for ≥30 days were switched to epoprostenol AS and followed for 12 weeks. Outcomes included safety, changes from baseline to 12 weeks in pulmonary hemodynamic factors (pulmonary vascular resistance, mean pulmonary arterial pressure, and cardiac output), and treatment satisfaction, assessed using the Treatment Satisfaction Questionnaire for Medication (TSQM-9).
  
  
  RESULTS
  The mean (range) age and time since diagnosis of PAH were 48 (25-69) years and 6.2 (0.6-13.9) years, respectively. There were no unexpected safety or tolerability concerns after switching formulations. The epoprostenol dose was maintained after switching formulations. There were no significant changes in pulmonary hemodynamic factors from baseline to week 12. Regarding treatment satisfaction, there was a significant improvement in convenience, which is demonstrated in the score of the domain increased from 51.40 ± 10.19 at baseline to 58.33 ± 12.96 at week 12 (P < 0.05).
  
  
  CONCLUSIONS
  Switching from epoprostenol GM to the same dose of epoprostenol AS was well tolerated over 12 weeks of treatment, and pulmonary hemodynamics were maintained. Switching to epoprostenol AS was also associated with improvements in treatment satisfaction (convenience). Clinical Trials: JapicCTI-122017.
authors: Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo, Japan. u1@ta-mu.net
authors: Yuichi
authors: Y
authors: Tamura
authors: Tomohiko
authors: T
authors: Ono
authors: Keiichi
authors: K
authors: Fukuda
authors: Toru
authors: T
authors: Satoh
authors: Shigetake
authors: S
authors: Sasayama
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001120:Arginine; D002626:Chemistry, Pharmaceutical; D004355:Drug Stability; D004356:Drug Storage / Q000379:methods; D011464:Epoprostenol / Q000627:therapeutic use*; D005079:Excipients; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D007564:Japan; D008297:Male; D008875:Middle Aged; D017060:Patient Satisfaction; D013395:Sucrose; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D005079:Excipients; D013395:Sucrose; D001120:Arginine; D011464:Epoprostenol
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