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

This study has been completed.
Sponsor:
Information provided by:
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT00389779
First received: October 17, 2006
Last updated: October 2, 2009
Last verified: October 2009
History of Changes
  Purpose

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.


Condition Intervention Phase
Hypertension
 Drug: darusentan (LU 135252), guanfacine, and placebo
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3 Randomized, Double-Blind, Placebo- and Active-Controlled, Multi-center, Parallel Group Study to Evaluate the Safety and Efficacy of Darusentan in Subjects With Resistant Hypertension Receiving Combination Therapy With Three or More Antihypertensive Drugs, Including a Diuretic, as Compared to Guanfacine or Placebo (Protocol DAR-312)

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Co-primary efficacy measures: changes from baseline in trough sitting systolic and diastolic blood pressure measured by sphygmomanometry [ Time Frame: Week 14 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Secondary efficacy measures: 1) change from baseline in mean 24-hour systolic and diastolic blood pressure measured by ABPM; 2) percent of subjects reaching systolic blood pressure goal after 14 weeks of treatment; 3) change from baseline in eGFR. [ Time Frame: Week 14 ] [ Designated as safety issue: No ]

Enrollment: 849
Study Start Date: September 2006
Study Completion Date: August 2009
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
50, 100 or 300 mg
 Drug: darusentan (LU 135252), guanfacine, and placebo
1 capsule QD, PO
Other Name: guanfacine
Active Comparator: 2
1 mg
 Drug: darusentan (LU 135252), guanfacine, and placebo
1 capsule QD, PO
Other Name: guanfacine
Placebo Comparator: 3 Drug: darusentan (LU 135252), guanfacine, and placebo
1 capsule QD, PO
Other Name: guanfacine

  Eligibility

Ages Eligible for Study:   35 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 CHF 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00389779

  Show 147 Study Locations
Sponsors and Collaborators
Gilead Sciences
  More Information

Additional Information:
Related Info  This link exits the ClinicalTrials.gov site

No publications provided by Gilead Sciences

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Kathleen DeHaven, Associate Director, Clinical Trial Management, Gilead Sciences, Inc.
ClinicalTrials.gov Identifier: NCT00389779     History of Changes
Other Study ID Numbers: Protocol DAR-312
Study First Received: October 17, 2006
Last Updated: October 2, 2009
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hypertension
Vascular Diseases
Cardiovascular Diseases
Antihypertensive Agents
Guanfacine
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
 Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on June 17, 2013