DORADO-AC - Optimized Doses of Darusentan as Compared to an Active Control in Resistant Hypertension

Gilead Sciences

Status and phase: Completed; Phase 3

Conditions: Hypertension

Treatments: Drug: Darusentan; Drug: Guanfacine; Drug: Darusentan Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT00389779

Protocol DAR-312

Details and patient eligibility

About

This is a randomized, double-blind, placebo- and active-controlled study of a new experimental drug called darusentan. Darusentan is not currently approved by the United States Food and Drug Administration (FDA), which means that a doctor cannot prescribe this drug. The purpose of this study is to determine if darusentan is effective in reducing systolic and diastolic hypertension despite treatment with full doses of three or more antihypertensive drugs, including a diuretic. Subjects will be randomized to darusentan (optimized dose), an active comparator, or placebo, administered orally. The treatment period for this trial is 14 weeks.

Enrollment: 849 patients

Sex: All

Ages: 35 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

SELECTED INCLUSION CRITERIA:

1. Subjects who are competent to provide written consent;
2. Aged 35 to 80 years;
3. Subjects with diabetes and/or chronic kidney disease must have an average sitting systolic blood pressure greater than or equal to 130 mmHg;
4. All other subjects must have an average sitting systolic blood pressure greater than or equal to 140 mmHg;
5. Receiving and adhering to full doses of appropriate guideline-recommended antihypertensive drugs from three different classes of antihypertensive agents, including a diuretic;
6. Female subjects of non-childbearing potential (i.e., post-menopausal for at least 2 years or surgically sterile).

SELECTED EXCLUSION CRITERIA:

1. Average sitting systolic and diastolic blood pressure greater than or equal to 180 mmHg and 110 mmHg, respectively;
2. Subjects treated with a central alpha-2 agonist and/or imidazoline receptor agonist;
3. Left ventricular dysfunction;
4. Serum ALT or AST greater than 2 times the Upper Limit of Normal;
5. Subjects who have experienced myocardial infarction, unstable angina pectoris, or a cerebrovascular accident within 6 months; or sick sinus syndrome or second or third degree atrioventricular block, atrial fibrillation or recurrent atrial tachycardia, recurrent ventricular tachycardia, or symptomatic bradycardia;
6. Implanted pacemakers or cardioverter defibrillator;
7. Symptomatic congestive heart failure requiring treatment;
8. Hemodynamically significant valvular heart disease;
9. Hemodialysis or peritoneal dialysis, or history of renal transplant;
10. Type I diabetes mellitus;
11. Diagnosis or recurrence of malignancy within the past 3 years;
12. Sleep apnea, unless a recent sleep study demonstrated arterial oxygenation saturation greater than or equal to 90%, treated or untreated;
13. Subjects who perform alternating shift or night work;
14. Subjects who have participated in a clinical study involving another investigational drug or device within 4 weeks prior to Screening

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

849 participants in 3 patient groups, including a placebo group

Darusentan

Experimental group

Description:

Placebo to match darusentan for 2-week placebo run-in period, followed by darusentan capsules titrated to an optimal dose of 50 mg, 100 mg, or 300 mg administered orally once daily for 14 weeks

Treatment:

Drug: Darusentan

Drug: Darusentan Placebo

Guanfacine

Active Comparator group

Description:

Placebo to match darusentan for 2-week placebo run-in period, followed by guanfacine 1 mg capsules administered orally once daily for 14 weeks

Treatment:

Drug: Darusentan Placebo

Drug: Guanfacine

Darusentan Placebo

Placebo Comparator group

Description:

Placebo to match darusentan for 2-week placebo run-in period, followed by placebo to match darusentan administered orally once daily for 14 weeks

Treatment:

Drug: Darusentan Placebo