EPITOME-4, an open-label phase 3b study evaluating a new formulation of epoprostenol sodium in Japanese pulmonary arterial hypertension patients following switch from Flolan

Abstract

Rationale: Intravenous epoprostenol sodium with glycine and mannitol excipients (Flolan®) is an agent used for the treatment of pulmonary arterial hypertension (PAH). A new epoprostenol sodium formulation with arginine and sucrose excipients (epoprostenol AS), improving stability at room temperature, has been developed to improve quality of life for patients. The primary objective was to evaluate safety and tolerability of switching from Flolan® to epoprostenol AS. Methods: This was a two-site, open label, single-arm phase 3b study. Eight adult Japanese PAH patients treated with Flolan® on a stable dose were switched to epoprostenol AS, and followed for 12 weeks. Changes from baseline to 12 weeks were evaluated for hemodynamic parameters, measured at baseline, immediately after switching and after 12 weeks. Patient treatment satisfaction was assessed by the Treatment Satisfaction Questionnaire for Medication (TSQM-9). Results: The mean (range) age was 48 (25-69) years and 7 patients were female. The mean (range) time since PAH diagnosis was 6.2 (0.6-13.9) years. There were no unexpected safety or tolerability concerns after switching from Flolan® to epoprostenol AS up to Week 12. The dosage of the study treatment was maintained after switching (Table). In terms of pulmonary hemodynamics, the Wilcoxon signed rank sum test did not reveal any significant differences in change from baseline to immediately after switching or to Week 12 at the 5% level (Table). Treatment satisfaction as assessed by TSQM-9 showed a significant improvement in terms of convenience (51.40±10.19 at baseline versus 58.33±12.96 at week 12, p < 0.05). (Table presented) Conclusions: Switching from Flolan® to epoprostenol AS at the same dosage was well tolerated up to Week 12, and pulmonary hemodynamics were maintained. In addition, patient treatment satisfaction appeared to be improved with use of epoprostenol AS.