Conference: 2008 International PHA Conference and Scientific Sessions
Release Date: 06.20.2008
Presentation Type: Abstracts
Benza R.1, Rubin L.2, McLaughlin V.3, Channick R.2, Vosswinkel R.4, Tapson V.5, Robbins I.6, Olschewski H.7, Seeger W.6
1. UAB Birmingham, AL, USA
2. UCSD, La Jolla, CA, USA
3. University of Michigan, Ann Arbor, MI, USA
4. University of Giessen, Giessen, Germany
5. Duke University, Durham, NC, USA
6. Vanderbilt University, Nashville, TN, USA
7. Med. Univ, Graz, Austria
BACKGROUND: A Phase III study was conducted to determine the effects of chronically administered inhaled treprostinil (TRE), a prostacyclin analogue, on both exercise capacity and safety in patients with severe PAH.
METHODS: Double-blind, randomized (1:1), placebo-controlled, parallel-group study comparing inhaled TRE (up to 45 µg four times daily via ultrasonic nebulizer) to placebo (PBO) over 12 weeks in patients with NYHA functional class III-IV after at least 3 months of either bosentan 125 mg twice daily or sildenafil. Baseline entry criteria included six-minute walk distance (6MWD) of 200-450 meters. The primary endpoint was change in 6MWD (compared to PBO) from baseline to Week 12. Secondary efficacy included changes in NYHA functional class, Borg Dyspnea Score, signs and symptoms of PAH, and clinical worsening.
RESULTS: 235 patients (142 US, 93 Rest of World) were enrolled at 31 centers. Baseline characteristics included mean age of 53.7 years (18-75) with 56% idiopathic PAH, and 98% and 2% NYHA class III and IV, respectively. Baseline 6MWD (mean ± SD) was 348 ± 66 meters with 165 receiving bosentan and 70 receiving sildenafil. 212 patients completed 12-weeks of dosing. Median 6MWD (peak) at Week 12 improved 20 m (p<0.0006) compared to PBO, while 6MWD (trough) improved 14 meters (p<0.01). Clinical worsening, change in NYHA class and Borg Dyspnea Score were not significantly changed. TRE was well tolerated with the most frequent AEs reported as cough, headache and nausea.
CONCLUSIONS: Inhaled TRE provides incremental benefit to patients currently receiving oral medications for PAH, and offers several advantages including patient convenience, targeted drug delivery, peak and trough benefit, and an improved systemic safety profile.