EPITOME-2: An open-label study assessing the transition to a new formulation of intravenous epoprostenol in patients with pulmonary arterial hypertension.

Sitbon O, Delcroix M, Bergot E, Boonstra AB, Granton J, Langleben D, Subías PE, Galiè N, Pfister T, Lemarié JC, Simonneau G

Université Paris-Sud, INSERM U999, Centre de Référence de l'Hypertension Pulmonaire Sévère, Service Pneumologie, Hôpital Bicêtre, Le Kremlin-Bicêtre, Paris, France.
Department of Pneumology, University Hospital of Leuven, Leuven, Belgium.
Centre de Compétence de l'Hypertension Pulmonaire Sévère, Service de Pneumologie, CHU Caen, Université Caen UMR 1086, Caen, France.
Department of Pulmonology, VU University Medical Center, Amsterdam, The Netherlands.
Pulmonary Hypertension Programme at UHN, University of Toronto, Toronto, Canada.
Center for Pulmonary Vascular Disease, Division of Cardiology, Jewish General Hospital, McGill University, Montreal, Canada.
Unidad de Hipertensión Pulmonar, Servicio de Cardiología, Madrid, Spain.
Institute of Cardiology, University of Bologna, Bologna, Italy.
Department of Clinical Science, Actelion Pharmaceuticals Ltd, Allschwil, Switzerland.
Effi-stat, Paris, France.

Abstract

BACKGROUND: Continuous infusion of epoprostenol is the treatment of choice in patients with pulmonary arterial hypertension in functional classes III to IV. However, this treatment's limitations include instability at room temperature. A new epoprostenol formulation offers improved storage conditions and patient convenience.
METHODS: The EPITOME-2 trial was an open-label, prospective, multicenter, single-arm, phase IIIb study. Patients with pulmonary arterial hypertension on long-term, stable epoprostenol therapy were transitioned from epoprostenol with glycine and mannitol excipients (Flolan; GlaxoSmithKline, Durham, NC) to epoprostenol with arginine and sucrose excipients (Veletri; Actelion Pharmaceuticals Ltd, Allschwil, Switzerland). Patients were followed up for 3 months, and dose adjustments were recorded. Efficacy measures included the 6-minute walk distance, hemodynamics assessed by right heart catheterization, and New York Heart Association functional class. Safety and tolerability of the transition were also evaluated. Quality of life was assessed using the Treatment Satisfaction Questionnaire for Medication.
RESULTS: Forty-two patients enrolled in the study, and 1 patient withdrew consent before treatment; thus, 41 patients received treatment and completed the study. Six patients required dose adjustments. There were no clinically relevant changes from baseline to month 3 in any of the efficacy end points. Adverse events were those previously described with intravenous prostacyclin therapy. Treatment Satisfaction Questionnaire for Medication scores showed an improvement from baseline to month 3 in the domain of treatment convenience.
CONCLUSIONS: Transition from epoprostenol with glycine and mannitol excipients to epoprostenol with arginine and sucrose excipients did not affect treatment efficacy, raised no new safety or tolerability concerns, and provided patients with an increased sense of treatment convenience.

PMID:24439982