DORADO - Fixed Doses of Darusentan as Compared to Placebo in ResistantHypertensionA Phase 3 Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Parallel Group Study to Evaluate the Efficacy and Safety of Fixed Doses of Darusentan in Subjects with Resistant Systolic Hypertension Receiving Combination Therapy with Three or More Antihypertensive Drugs, Including a Diuretic (Protocol DAR-311) - DORADO

Conditions: Resistant hypertension
MedDRA version: 8.1Level: LLTClassification code 10038274Term: Refractory hypertension

Registration Number: EUCTR2006-001898-25-DE

Lead Sponsor: Gilead Sciences Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 352

Inclusion Criteria

- Subjects must be competent to provide written informed consent
- Aged 35 to 80 years
- Subjects must have resistant systolic hypertension consistent with current clinical guidelines for the treatment of hypertension. Subjects with diabetes and/or CKD must have an average sitting SBP of =130 mmHg and all other subjects must have an average sitting SBP =140 mmHg at Screening.
- Subjects must be receiving, and adhering to, full doses of appropriate guideline-recommended antihypertensive drugs from three classes of antihypertensive agents, including a diuretic.
- Subjects must have a BMI of 20 to 43 kg/m2, inclusive. If >43kg/m2, the subject must have an upper arm circumference <42 cm at Screening (Visit 1).
- Subjects must have an Egfr of = 30 MI/min/1.73m2 at Screening.
- Female subjects must be of non-childbearing potential, i.e. documented post-menopausal (cessation of regular menstrual periods) for at least 2 years or surgically sterile (i.e., hysterectomy and/or bilateral oophorectomy). Post-menopausal female subjects who are not surgically sterile will be required to use a double-barrier method of birth control throughout study participation.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

- Average sitting systolic blood pressure =180 mmHg or diastolic blood pressure =110 mmHg
- Serum ALT or AST =2X ULN
- Subjects who have experienced myocardial infarction, unstable angina pectoris, or a cerebrovascular accident (CVA) within 6 month; or sick sinus syndrome or second or third degree atrioventricular block, atrial fibrillation or recurrent atrial tachyarrhythmia, recurrent ventricular tachycardia, or symptomatic bradycardia
- Implanted pacemakers or implanted cardioverter defibrillator (ICD)
- Subjects with a historical or current diagnosis of symptomatic or asymptomatic CHF, treated or untreated.
- Hemodynamically significant valvular heart disease
- Type I diabetes mellitus
- Hemodialysis or peritoneal dialysis; or history of solid organ transplant (e.g., kidney, heart).
- Diagnosis or recurrence of malignancy within the past 3 years
- Subjects with sleep apnea are excluded, unless a post-treatment sleep study has confirmed treatment efficacy and there are no recordings of blood oxygen saturation (SpO2) <90% at any time during the testing period.
- Subjects who perform alternating shift or night work
- Subjects who have participated in a clinical study involving another investigational drug or device within 4 weeks prior to Screening
- Use of thiazolidinedione (i.e., glitazone) class of anti-diabetic medications (e.g., rosiglitazone, pioglitazone; alone or in combination pills) at or within 4 weeks of Screening (Visit 1). Subjects should not initiate treatment with thiazolidinediones at any time during the study.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of this study is to determine if darusentan is effective in reducing SBP in subjects with RHTN, despite treatment with full doses of three or more antihypertensive drugs, including a diuretic. ;Secondary Objective: Secondary objectives of this study are to examine the effect of darusentan on trough sitting DBP, mean 24-hour ambulatory blood pressure, percent of subjects meeting SBP goal, and eGFR, and to evaluate the safety and tolerability of the study drug in the subject population. ;Primary end point(s): The co-primary endpoints are the change from baseline to Week 14 in trough sitting SBP and trough sitting DBP, as measured by sphygmomanometry.

Secondary Outcome Measures