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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT00389779
First received: October 17, 2006
Last updated: February 19, 2014
Last verified: February 2014
  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
Drug: Guanfacine
Drug: Darusentan 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:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Change from baseline in trough sitting systolic and diastolic blood pressure measured by sphygmomanometry [ Time Frame: Baseline to Week 14 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percentage of subjects reaching systolic blood pressure goal after 14 weeks of treatment [ Time Frame: Week 14 ] [ Designated as safety issue: No ]
  • Change from baseline in mean 24-hour systolic and diastolic blood pressure measured by ambulatory blood pressure monitoring (ABPM) [ Time Frame: Baseline to Week 14 ] [ Designated as safety issue: No ]
  • Change from baseline in estimated glomerular filtration rate (eGFR) [ Time Frame: Baseline to 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: Darusentan
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
Drug: Darusentan
Darusentan capsules administered orally once daily
Other Name: LU 135252
Drug: Darusentan Placebo
Placebo to match darusentan administered orally once daily
Active Comparator: Guanfacine
Placebo to match darusentan for 2-week placebo run-in period, followed by guanfacine 1 mg capsules administered orally once daily for 14 weeks
Drug: Guanfacine
Guanfacine capsules administered orally once daily
Drug: Darusentan Placebo
Placebo to match darusentan administered orally once daily
Placebo Comparator: Darusentan Placebo
Placebo to match darusentan for 2-week placebo run-in period, followed by placebo to match darusentan administered orally once daily for 14 weeks
Drug: Darusentan Placebo
Placebo to match darusentan administered orally once daily

  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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00389779

  Show 147 Study Locations
Sponsors and Collaborators
Gilead Sciences
  More Information

Additional Information:
No publications provided by Gilead Sciences

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT00389779     History of Changes
Other Study ID Numbers: Protocol DAR-312
Study First Received: October 17, 2006
Last Updated: February 19, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on October 23, 2014