TY - JOUR
T1 - Two formulations of epoprostenol sodium in the treatment of pulmonary arterial hypertension
T2 - EPITOME-1 (epoprostenol for injection in pulmonary arterial hypertension), a phase IV, open-label, randomized study
AU - Chin, Kelly M.
AU - Badesch, David B.
AU - Robbins, Ivan M.
AU - Tapson, Victor F.
AU - Palevsky, Harold I.
AU - Kim, Nick H.
AU - Kawut, Steven M.
AU - Frost, Adaani
AU - Benton, Wade W.
AU - Lemarie, Jean Christophe
AU - Bodin, Frederic
AU - Rubin, Lewis J.
AU - McLaughlin, Vallerie
N1 - Funding Information:
Kelly Chin has received research grants from Actelion, Bayer, Gilead, GlaxoSmithKline, Novartis, United Therapeutics, GeNO, and the National Institutes of Health and honoraria for service on Advisory Boards for Actelion, Bayer, and Gilead. David Badesch has received honoraria for service on Steering Committees and/or Advisory Boards for Actelion, Arena, Bayer, Gilead, Ikaria, Lung Rx, Pfizer, and United Therapeutics and received grant support from Actelion, Bayer, Gilead, Novartis, Pfizer, and United Therapeutics. Ivan Robbins has received research grants from Actelion, Gilead, Novartis, and United Therapeutics; honoraria for service on Advisory Boards for Actelion, Bayer, Gilead, and United Therapeutics; and honoraria for service on the REVEAL Steering Committee, which is supported by Actelion. Victor Tapson has received research grants and consulting fees from Actelion, Bayer, Gilead, Novartis, and United Therapeutics. Harold Palevsky has received research grants from Actelion and GeNO and honoraria for service on Advisory Boards from Actelion, Bayer, GeNO, Gilead, Pfizer, and United Therapeutics. Nick Kim has received research grants from Actelion, Gilead, and United Therapeutics and serves as a consultant for Bayer. Steven Kawut has received consulting fees, lecture fees, research grants, or funding to conduct CME conferences from Actelion, Gilead, Ikaria, Merck, Novartis, Pfizer, and United Therapeutics. Adaani Frost has received consulting fees and/or honoraria from Actelion, Aires, Ikaria, Gilead, and Pfizer; (through Baylor) funds for institutional review board–approved research from Actelion, Bayer, Eli Lilly, Gilead, Novartis, Pfizer, and United Therapeutics; and honoraria for her service on the REVEAL Steering Committee, which is supported by Actelion. Lewis Rubin has acted as a consultant for Actelion, AIRES, Bayer, GeNo, Gilead, GlaxoSmithKline, Liquidia, Pfizer, MondoBiotech, and United Therapeutics. Vallerie McLauglin has acted as a consultant and/or speaker for Actelion, Bayer, Gilead, and United Therapeutics and has received research grants from Actelion, Bayer, Novartis, and United Therapeutics. F. Bodin and W. Benton are full-time employees of Actelion Pharmaceuticals Ltd. J.C. Lemarié is a full-time employee of Effi-Stat and has provided statistical support funded by Actelion.
PY - 2014/2
Y1 - 2014/2
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ahj.2013.08.008
DO - 10.1016/j.ahj.2013.08.008
M3 - Article
C2 - 24439983
AN - SCOPUS:84892781340
SN - 0002-8703
VL - 167
SP - 218-225.e1
JO - American heart journal
JF - American heart journal
IS - 2
ER -