DORADO-Fixed Doses of Darusentan as Compared to Placebo in Resistant Hypertension. A 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 Four of More Antihypertensive Drugs, Including a Diuretic - DORADO

Conditions: Resistant hypertension (RHTN)
MedDRA version: 9.1Level: LLTClassification code 10015488Term: Essential hypertension

Registration Number: EUCTR2006-001898-25-IT

Lead Sponsor: Gilead Colorado, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 352

Inclusion Criteria

1. Subjects must be competent to provide written informed consent. 2. Subjects must be 35-80 years of age. 3. Subjects must have resistant systolic hypertension consistent with current clinical guidelines for the treatment of hypertension 4. Subjects must be receiving, and adhering to, full doses of an appropriate guideline-recommended antihypertensive drug regimen for a minimum of 4 weeks prior to Screening (Visit 1), Documentation must be provided to demonstrate that each required antihypertensive medication meets one or more of the above criteria for full dosing in order for the subject to be considered eligible for study participation. 5. Subjects must have a BMI of 20 to 43 kg/m2, inclusive, or an upper arm circumference <42 cm at Screening (Visit 1). 6. Subjects must have an eGFR major of, or equal to 30 mL/min/1.73 m2 at Screening (Visit 1). 7. Female subjects must be of non-childbearing potential, i.e., documented post-menopausal for at least 2 years or surgically sterile. 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

1. Subjects with an average sitting SBP of 180 mmHg or more, or DBP of 110 mmHg or more 2. Subjects with left ventricular (LV) systolic dysfunction as evidenced by a LV ejection fraction <40% and/or a LV internal diastolic diameter (LVIDD) >3.2 cm/m2 or >6.0 cm, measured by echocardiogram at Screening (Visit 1) or within 3 months prior to Screening. 3. Subjects with a HbA1c >10% at Screening (Visit 1). 4. Subjects who have: a. A hemoglobin concentration <12 g/dL at Screening (Visit 1) or b. A hematocrit <36% at Screening (Visit 1) 5. Subjects with hypo- or hyperthyroidism, as evidenced by a serum thyroid stimulating hormone (TSH) concentration >1X ULN or less than the lower limit of normal (LLN) at Screening (Visit 1). 6. Subjects with a serum ALT or AST >2X ULN at Screening (Visit 1). 7. Subjects with other identifiable secondary causes of resistant hypertension (e.g., parathyroid disease, pheochromocytoma, aortic coarctation, Cushing's disease, hyperaldosteronism). 8. Subjects who have experienced a myocardial infarction, unstable angina pectoris, or a cerebrovascular accident within 6 months of the Screening Visit (Visit 1). 9. Subjects with sick sinus syndrome or second or third degree atrioventricular (AV) block, chronic atrial fibrillation or recurrent atrial tachyarrhythmia (including paroxysmal atrial tachycardia), a history of recurrent ventricular tachycardia, or symptomatic bradycardia. 10. Subjects with implanted pacemakers or an implanted cardioverter defibrillator (ICD). 11. Subjects with symptomatic CHF requiring treatment. 12. Subjects with hemodynamically significant valvular heart disease. 13. Subjects with Type 1 diabetes mellitus. 14. Subjects on hemodialysis or peritoneal dialysis at the time of Screening (Visit 1) and subjects with a history of renal transplant. 15. Subjects who have had a diagnosis or recurrence of malignancy within the past 3 years, with the exception of basal cell carcinoma of the skin or in situ carcinoma of the cervix. 16. Subjects with sleep apnea are excluded, unless a recent (within 30 days of Screening [Visit 1]) sleep study demonstrates no recordings of arterial oxygen saturation (SaO2) <90%, treated or untreated, at any time during the testing period. 17. Subjects who perform alternating shift or night work. 18. Women of childbearing potential or women who are pregnant or nursing. 19. Subjects not on stable doses of all concomitant medications for a minimum of 4 weeks prior to Screening, and subjects treated with any of the following prohibited medications:Oral Aspirin (beyond 325 mg/day), non-steroidal anti-inflammatory drugs (NSAIDS) Selective serotonin reuptake inhibitors Tricyclic antidepressants (TCAs), Another ERA (e.g., bosentan, sitaxsentan, atrasentan, TBC3711) 20. Subjects who have demonstrated non-compliance with previous medical regimens. 21. Subjects with a contraindication to treatment with an ERA. Contraindications include, but are not limited to, a history of elevated liver function tests (e.g., aminotransferases >2X ULN) or an event defined as a serious adverse event (SAE) attributed to previous treatment with an ERA. 22. Subjects who participated in a prior clinical study of darusentan and were randomized to, and received, active treatment. 23. Subjects who have participated in a clinical study involving another investigational drug or device within 4 weeks of the Screening Visit (Visit 1). 24. Subjects who have failed screeni

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 is to determinate if darusentan is effective in reducing SBF in subjects with RHTN, despite treatment with full doses of four or more anthypertertensive drug, including a diuretic;Secondary Objective: Secondary objectives 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 nd to evaluate the safety and tolerability of the study drug in the subject population;Primary end point(s): The primary endopint is change from baseline to week 14 in trough sitting SBP measured by sphygmomanometry

Secondary Outcome Measures