Gilead Sciences, a biopharmaceutical company, has reported encouraging data from DAR-311, a Phase III clinical trial evaluating the company’s once-daily oral endothelin receptor antagonist darusentan as an add-on treatment for resistant hypertension, defined as the failure to achieve goal blood pressure while adhering to full doses of an appropriate three-drug regimen that includes a diuretic.
DAR-311 (Dorado) is an international Phase III double-blind, placebo-controlled parallel group trial, in which 379 patients were randomized to receive once-daily doses of darusentan 50mg (n=81), 100mg (n=81), 300mg (n=85) or placebo (n=132) for up to 14 weeks as an add-on to existing antihypertensive regimens.
The co-primary efficacy endpoints were change from baseline to week 14 in trough sitting systolic blood pressure (SBP) and trough sitting diastolic blood pressure (DBP). Secondary endpoints included change from baseline in mean 24-hour SBP and DBP and percent of patients reaching SBP goal. Gilead announced topline results from the study in April 2009.
In DAR-311, mean reductions in trough sitting SBP from baseline of 16.5mmHg, 18.1mmHg, 18.1mmHg and 8.6 mmHg were observed for the darusentan 50mg, 100mg, 300mg and placebo groups, respectively, after 14 weeks of treatment. Mean reductions in trough sitting DBP from baseline of 10.1mmHg, 9.9mmHg, 10.7mmHg and 5.3mmHg were observed for the darusentan 50mg, 100mg, 300mg and placebo groups, respectively, after 14 weeks of treatment.
According to Gilead, ambulatory blood pressure monitoring (ABPM) performed at week 14 revealed highly significant (p<0.001) reductions from baseline in 24-hour SBP and DBP in patients treated with darusentan. Reductions in mean 24-hour SBP of 9mmHg, 9.8mmHg, 9.5mmHg and 1.1mmHg were observed for the darusentan 50mg, 100mg, 300mg and placebo groups, respectively.
For DBP, mean 24-hour reductions of 7.8mmHg, 7.7mmHg, 7.4mmHg and 0.7mmHg were observed for the darusentan 50mg, 100mg, 300mg and placebo groups, respectively. Reductions in ambulatory SBP were maintained throughout the 24-hour monitoring period and there were no significant changes in heart rate, the company said.