Investigation of safety and efficacy of the new more thermostable formulation of Flolan (epoprostenol) in Japanese patients with pulmonary arterial hypertension (PAH)—An open-label, single-arm study

Abstract

ObjectiveThis study was conducted to evaluate the safety and efficacy of a new more thermostable Flolan (epoprostenol) solution prepared with the reformulated pH 12.0 diluent in Japanese patients with pulmonary arterial hypertension (PAH) receiving higher doses of Flolan than those typically administered in Western countries.MethodsThis open-label, single-arm study was conducted in 10 Japanese PAH patients. During the run-in period, patients were intravenously infused with Flolan (45 ng/kg/min or higher doses) solution prepared with the existing pH 10.5 diluent. The patients were then switched to a new more thermostable Flolan solution prepared with the reformulated pH 12.0 diluent and observed for a 4-week treatment period. As a primary endpoint, safety after switching to the new Flolan solution was evaluated. Secondary endpoints included hemodynamics and the necessity for dose adjustment of Flolan in these patients.ResultsAll 10 patients completed the study period. Observed adverse events were nausea and hepatic function abnormal in 1 patient each, and both events were mild. No patients required dose adjustment due to the change from baseline in mean pulmonary artery pressure (mPAP) measured 3 hrs after switching to Flolan solution prepared with the reformulated diluent. No major changes from baseline in mPAP, pulmonary vascular resistance, or right atrial pressure were observed at 24 hrs and at 4 weeks after switching to the Flolan solution prepared with pH 12.0 diluent. Although some patients showed increases in cardiac output (CO) from baseline at 24 hrs and 4 weeks, no patients required dose reduction as a result of an increase in CO.ConclusionNeither safety/efficacy concerns nor any dose adjustments of Flolan after switching to a more thermostable Flolan solution prepared with the reformulated pH 12.0 diluent could be required in Japanese patients with PAH receiving higher doses of Flolan.Trial registrationClinicalTrials.gov Identifier: NCT02705807

Use of Epoprostenol in the Treatment of Pulmonary Arterial Hypertension

“…The pharmacological effects of epoprostenol are due to pulmonary and systemic arterial vasodilation. The effects on platelet aggregation are directly opposite to thromboxane A2 [ 25 ].…”

“…The Epoprostenol solution prepared with pH 12.0 diluent can be stored between 2°C to 8°C for a period of up to 8 days and administered up to 24 hours (temperature of up to 35°C) or up to 72 hours (up to 25°C). The change in the new Epoprostenol formulation is limited only to the diluent; the quantity and formulation of the active ingredient, epoprostenol, stands the same [ 25 ].…”