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:
Epitome-1, a phase IV, open-label, randomized, multicenter study of the safety, tolerability,and pharmacokinetics of ACT- 385781A compared to Flolan® in injectable prostanoid treatment-naïve patients with PAH, was an open-label exploratory study of patients with PAH randomized 2:1 to epoprostenol AM or epoprostenol GM. The study was conducted at 7 centers in the United States, all experienced in the use of intravenous therapies for PAH. The trial was registered at www.clinicaltrials.gov (registration number: NCT01105091 ). This study was funded by Actelion Pharmaceuticals Ltd. Assistance in the final formatting of the manuscript and figures was provided by Lisa Thomas, Elements Communications Ltd.
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 -