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Abstract: Slide Presentations |

SITAXSENTAN THERAPY IN PULMONARY ARTERIAL HYPERTENSION RESULTS IN SIGNIFICANTLY FEWER LIVER FUNCTION ABNORMALITIES THAN BOSENTAN FREE TO VIEW

Terrance Coyne, MD*; Richard Dixon, PhD
Author and Funding Information

Encysive Pharmaceuticals, Houston, TX


Chest


Chest. 2005;128(4_MeetingAbstracts):174S. doi:10.1378/chest.128.4_MeetingAbstracts.174S
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Abstract

PURPOSE:  The first approved endothelin receptor antagonist (ETRA) for the treatment of pulmonary arterial hypertension (PAH) is bosentan (BOS), an oral, twice-daily, non-selective ETA/ETB ETRA. While a significant advance for PAH, BOS therapy has been complicated by abnormal liver function tests [>3X upper limit of normal (abLFT)] in a controlled trial setting (12% at the labeled dose) and in clinical practice, a finding that has been subsequently seen at varying rates with all ETRAs studied in PAH. Sitaxsentan (SITAX), is an oral, once-daily, highly selective (>6500:1) ETA ETRA in development for PAH which demonstrated lower abLFT rates with 100mg QD in STRIDE-1. These lower abLFT rates were confirmed in STRIDE-2: 6.5% of patients randomized to placebo, 3.2% for SITAX 100mg, 4.9% for SITAX 50mg, and 11.5% for BOS. Here, we report on the long-term LFT rates observed for patients (pts) treated for up to one year with BOS, in accordance with the product label, or SITAX.

METHODS:  STRIDE-2 was an 18 week, multi-center, placebo-controlled study that randomized 246 patients (pts) 1:1:1:1 to PBO, SITAX 100 mg, SITAX 50 mg or open label, efficacy-rater blinded, BOS followed by an extension with pts receiving either BOS or SITAX 100 mg. During the extension, pts on PBO in STRIDE-2 were randomized to SITAX 100mg or BOS; pts on SITAX 50mg received SITAX 100mg and pts on SITAX 100mg or BOS were continued on those treatments.

RESULTS:  Kaplan-Meier estimates of time to abLFT at 1 year of exposure are 4.0% for SITAX 100mg and 18.7% for BOS (p = 0.0086).

CONCLUSION:  Long-term treatment with SITAX 100mg QD results in significantly fewer liver function abnormalities than bosentan.

CLINICAL IMPLICATIONS:  Sitaxsentan 100mg QD has been shown to be safe and effective in the treatment of PAH, with a lower rate of liver function abnormalities than bosentan.

DISCLOSURE:  Terrance Coyne, Shareholder Encysive Pharmaceuticals; Employee Encysive Pharmaceuticals; Product/procedure echnique that is considered research and is NOT yet approved for any purpose. Sitaxsentan.

Tuesday, November 1, 2005

10:30 AM - 12:00 PM


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