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

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 III

MedlinePlus related topics:

High Blood Pressure

ChemIDplus related topics:

Guanfacine Guanfacine hydrochloride

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study

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)

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 ]

Estimated Enrollment:	770
Study Start Date:	September 2006
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental 50, 100 or 300 mg	Drug: darusentan (LU 135252), guanfacine, and placebo 1 capsule QD, PO
2: Active Comparator 1 mg	Drug: darusentan (LU 135252), guanfacine, and placebo 1 capsule QD, PO
3: Placebo Comparator	Drug: darusentan (LU 135252), guanfacine, and placebo 1 capsule QD, PO

Eligibility

Ages Eligible for Study:	35 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

SELECTED INCLUSION CRITERIA:

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

SELECTED EXCLUSION CRITERIA:

Average sitting systolic and diastolic blood pressure greater than or equal to 180 mmHg and 110 mmHg, respectively;
Subjects treated with a central alpha-2 agonist and/or imidazoline receptor agonist;
Left ventricular dysfunction;
Serum ALT or AST greater than 2 times the Upper Limit of Normal;
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;
Implanted pacemakers or cardioverter defibrillator;
Symptomatic CHF requiring treatment;
Hemodynamically significant valvular heart disease;
Hemodialysis or peritoneal dialysis, or history of renal transplant;
Type I diabetes mellitus;
Diagnosis or recurrence of malignancy within the past 3 years;
Sleep apnea, unless a recent sleep study demonstrated arterial oxygenation saturation greater than or equal to 90%, treated or untreated;
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

Contacts and Locations

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

Contacts


Contact: Kathleen DeHaven	720-887-8500	kathleen.dehaven@gilead.com

Show 147 Study Locations

Sponsors and Collaborators

Gilead Sciences

More Information

Related Info This link exits the ClinicalTrials.gov site

Responsible Party:	Gilead Sciences, Inc. ( Kathleen DeHaven, Associate Director, Clinical Trial Management )
Study ID Numbers:	Protocol DAR-312
First Received:	October 17, 2006
Last Updated:	September 12, 2008
ClinicalTrials.gov Identifier:	NCT00389779
Health Authority:	United States: Food and Drug Administration

Study placed in the following topic categories:

Guanfacine

Vascular Diseases

Hypertension

Additional relevant MeSH terms:

Neurotransmitter Agents

Adrenergic alpha-Agonists

Molecular Mechanisms of Pharmacological Action

Adrenergic Agents

Therapeutic Uses

Physiological Effects of Drugs

Cardiovascular Diseases

Cardiovascular Agents

Antihypertensive Agents

Adrenergic Agonists

Pharmacologic Actions

ClinicalTrials.gov processed this record on September 19, 2008

Sponsored by:	Gilead Sciences
Information provided by:	Gilead Sciences
ClinicalTrials.gov Identifier:	NCT00389779