Journal
CHEST
Volume 142, Issue 6, Pages 1383-1390Publisher
ELSEVIER SCIENCE BV
DOI: 10.1378/chest.11-2212
Keywords
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Categories
Funding
- United Therapeutics Corporation
- Actelion Pharmaceuticals Ltd
- Bayer
- Cotherix
- Gilead
- Lung LLC
- Novartis AG
- Actelion Pharmaceuticals Ltd/CoTherix, Inc
- Gilead/Myogen, Inc
- GlaxoSmithKline
- Eli Lilly
- Company/Icos Corporation
- Pfizer
- Inc/Encysive Pharmaceuticals
- United Therapeutics Corporation/Lung LLC
- Medtronic Inc
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Background: Infused and inhaled treprostinil are effective for treatment of pulmonary arterial hypertension (PAH), although their administration routes have limitations. This study assessed the efficacy and safety of bid oral sustained-release treprostinil in the treatment of PAH with a concomitant endothelin receptor antagonist (ERA) and/or phosphodiesterase type 5 inhibitor. Methods: A 16-week, multicenter, double-blind, placebo-controlled study was conducted in 350 patients with PAH randomized to placebo or oral treprostinil. All patients were stable on background ERA, PDE-5 inhibitor, or both. Primary end point was Hodges-Lehmann placebo-corrected median difference in change from baseline 6-min walk distance (6MWD) at week 16. Secondary end points included time to clinical worsening, change in World Health Organization functional class, Borg dyspnea score, and dyspnea fatigue index score. Results: Thirty-nine patients (22%) receiving oral treprostinil and 24 patients (14%) receiving placebo discontinued the study. Placebo-corrected median difference in change from baseline 6MWD at week 16 was 11 in (P = .07). Improvements in dyspnea fatigue index score (P = .01) and combined 6MWD and Borg dyspnea score (P = .01) were observed with oral treprostinil vs placebo treatment. Patients who achieved a week-16 bid oral treprostinil dose of 1.25 to 3.25 mg and 3.5 to 16 mg experienced a greater change in 6MWD (18 m and 34 m, respectively) than patients who achieved a bid close of < 1 mg or discontinued because of adverse events (4 m). Conclusions: The primary end point of improvement in 6MWD at week 16 did not achieve significance. This study enhanced understanding of oral treprostinil titration and dosing, which has set the stage for additional studies. Trial registry: ClinicalTrials.gov; No.: NCT00325442; URL: www.clinicaltrials.gov CHEST 2012; 142(6):1383-1390
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