Sitaxsentan (SITAX), an oral, once-daily, highly selective (>6500:1) ETA endothelin receptor antagonist has been studied in 2 previously reported, pivotal, randomized, PBO-controlled PAH studies (STRIDE-1, 12 week duration, Barst AJRCCM, 2004; and STRIDE-2, 18 week duration, Barst, ATS, 2005). Here, we report a prospectively defined combined analysis of clinical worsening events from both studies. This combined analysis has been submitted to the November, 2005 American College of Rheumatology meeting.
STRIDE-1 (n=178) and STRIDE-2 (n=246) included PAH pts with WHO Class II, III, and IV: idiopathic PAH (56%) or associated with connective tissue disease (28%) or congenital heart defects (16%). While the 2 pivotal studies evaluated 100mg and 300mg in STRIDE 1 and 50mg and 100mg in STRIDE 2, the 100 mg dose was evaluated in both trials and has been shown to be the optimal dose based on overall risk-benefit considerations. Clinical events were defined as hospitalization for worsening PAH, death, transplantation, addition of new chronic PAH treatment, or a combined deterioration in WHO functional class and ≥ 15% decrease from baseline in 6MW. Time to clinical worsening events was assessed from the date of the first dose of study drug through the first clinical event. Subjects were censored at study completion.
115 pts were treated with SITAX 100mg and 119 with PBO. Time to clinical worsening was better in the SITAX 100mg vs PBO group (p=0.0464) with no events in 96% of the SITAX 100mg pts vs no events in 89% of the PBO pts.
Sitaxsentan 100 mg once daily improves time to clinical worsening in patients with PAH.
Sitaxsentan 100mg once daily has been shown to be effective and safe in the treatment of PAH.
David Badesch, Grant monies (from sources other than industry) American Lung Association, American Heart Association, National Institutes of Health, and the Scleroderma Foundation; Grant monies (from industry related sources) Glaxo Wellcome/GlaxoSmithKline, UnitedTherapeutics, Boehringer Ingelheim, Actelion, ICOS/Texas Biotechnologies, Encysive, Pfizer, Myogen, CoTherix.; Consultant fee, speaker bureau, advisory committee, etc. Glaxo Wellcome/GlaxoSmithKline, Actelion, Berlex, Astra-Merck, Astra-Zeneca, Myogen, Intermune, Forest Labs, Encysive, Exhale Ther; Product/procedure echnique that is considered research and is NOT yet approved for any purpose. Sitaxsentan.