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

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)

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.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: Darusentan; Drug: Darusentan Placebo; Drug: Guanfacine

• Study Type: Interventional
• Enrollment (Actual): 849
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • Consultorios Medicos Privados S.A.
  • Buenos Aires, Argentina
    • Hospital General de Agudos "Dr. Abel Zubizarreta"
  • Buenos Aires, Argentina
    • Policlinica Bancaria "9 de Julio"
  • Ciudad de, Argentina
    • Centro Médico Privado
  • Ciudad de Buenos Aires, Argentina
    • Diabaid (Instituto de Asistencia Integral en Diabetes)
  • Ciudad de Buenos Aires, Argentina
    • MD Investigaciones
  • Cordoba, Argentina
    • Fundación Rusculleda
  • Corrientes, Argentina
    • Instituto de Cardiologia de Corrientes
  • La Plata, Argentina
    • Framingham Centro Médico
  • Quilmes, Argentina
    • Instituto de Investigaciones Clinicas de Quilmes
  • Rosario, Argentina
    • Instituto de Investigaciones Clinicas
  • Santa Fe, Argentina
    • Centro de Investigaciones Clinicas del Litoral
  • Buenos Aires
    • Bahia Blanca, Buenos Aires, Argentina
      • Hospital Italiano Regional Del Sur
    • Bahia Blanca, Buenos Aires, Argentina
      • Instituto de Investigaciones Clínicas Bahia Blanca
    • Mar del Plata, Buenos Aires, Argentina
      • Instituto de Investigaciones Clínicas Mar del Plata
• Australia
  • Bedford Park, Australia
    • Flinders Medical Centre
  • Herston, Australia
    • Royal Brisbane & Women's Hospital
  • Melbourne, Australia
    • Alfred Hospital
  • Perth, Australia
    • Royal Perth Hospital
• Belgium
  • Brussel, Belgium
    • U.Z. Brussel
  • De Pinte, Belgium
    • Private Practice of Dr. Geert Hollanders
  • Genk, Belgium
    • Private Practice of Dr. Francis Vrancken
  • Genk, Belgium
    • Private Practice of Dr. Herwig Van Aerde
  • Genk, Belgium
    • Private Practice of Dr. Willy Denier
  • Hoeilaart, Belgium
    • Private Practice of Dr. Herman Docx
  • Natoye, Belgium
    • Private Practice of Dr. Yohan Balthazar
  • Pulle, Belgium
    • Private Practice of Dr. Sophie Baeyens
  • Riemst, Belgium
    • Private Practice of Dr. Jean Gilissen
  • Tielt, Belgium
    • Private Practice of Dr. Guido Mehuys
  • Wetteren, Belgium
    • Private Practice of Dr. Luc Capiau
• Brazil
  • Rio de Janeiro, Brazil
    • Hospital Universitário Pedro Ernesto
• Denmark
  • Aalborg, Denmark
    • Aalborg University Hospital
  • Naestved, Denmark
    • Region Sjaelland, Storstrommens Sygenhus, Naestved
• France
  • Blois, France
    • George Delamare
  • Dommartin les Toul, France
    • Centre d'Investigation Clinique
  • La Jubaudiere, France
    • Private Practice of Dr. Brune Charrier
  • Le Mesnil en vallee, France
    • Private Practice of Dr. Jean Boulet-Gercourt
  • Le Temple-de-Bretagne, France
    • Private Practice of Dr. Gildas Ganuchaud
  • Martigues, France
    • Private Practice of Dr. Jacques Samat
  • Murs-Erigne, France
    • Private Practice of dr. Marty Jacques
  • Nantes, France
    • Private Practice of Dr. Alain Boye
  • Nantes, France
    • Private Practice of Dr. Francois Volny
  • Vihiers, France
    • Private Practice of Dr. Thierry Schaupp
• Germany
  • Bad Worishofen, Germany
    • Private Practice of Dr. Josef Junggeburth
  • Berlin, Germany
    • Charité Campus Mitte, Universitätsmedizin Berlin
  • Berlin, Germany
    • Klinische Forschung Berlin-Buch GmbH
  • Berlin, Germany
    • Private Practice of Dr. Isabelle Schenkenberger
  • Frankfurt, Germany
    • PD Dr. med. Bernhard Winkelmann
  • Hamburg, Germany
    • Clinical Research Hamburg
  • Hamburg, Germany
    • Dr. Med. Susanne Mindt-Prufert
  • Heidelberg, Germany
    • Private Practice for Internal Medicine & Cardiology
  • Koeln, Germany
    • Private Practice of Dr. Tobias Marsen
  • Ruedersdorf, Germany
    • IFG-Institut fur Gesundheitsforderung GmbH
• New Zealand
  • Auckland, New Zealand
    • Centre for Clinical Research and Effective Practice (CCRep)
  • Christchurch, New Zealand
    • Christchurch Hospital
  • Greenlane, New Zealand
    • Greenlane Clinical Centre
  • Hamilton, New Zealand
    • Cardiology Clinical Trial Unit
  • Tauranga, New Zealand
    • Tauranga Hospital
• Spain
  • Barcelona, Spain
    • Hospital Universitario de Bellvitge
  • Elche, Spain
    • Hospital General Universitario de Elche
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35235
      • Alabama Internal Medicine, PC
    • Birmingham, Alabama, United States, 35242
      • Greystone Medical Research, LLC
    • Huntsville, Alabama, United States, 35801
      • The Heart Center, PC
    • Montgomery, Alabama, United States, 36106
      • Mulberry Medical Associates, PC
  • Arizona
    • Glendale, Arizona, United States, 85306
      • Arizona Center For Clinical Research
    • Glendale, Arizona, United States, 85306
      • Cardiovascular Consultants, Ltd.
    • Phoenix, Arizona, United States, 85016
      • Lovelace Scientific Resources, Inc
    • Sierra Vista, Arizona, United States, 85635
      • Cochise Clinical Research
    • Tucson, Arizona, United States, 85715
      • Southwest Heart
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • HealthFirst Physician of AR, PA dba Convenient Care Clinic
    • Jonesboro, Arkansas, United States, 72401
      • NEA Clinic
    • Little Rock, Arkansas, United States, 72204
      • Arkansas Primary Care Clinic, PA
    • Little Rock, Arkansas, United States, 72205
      • Medical Investigations Inc.
  • California
    • Bakersfield, California, United States, 93301
      • Highgrove Medical Center
    • Bakersfield, California, United States, 93308
      • Central Cardiology Medical Clinic
    • Beverly Hills, California, United States, 90211
      • Impact Clinical Trials
    • Los Angeles, California, United States, 90073
      • VA Greater Los Angeles Healthcare System
    • Rancho Cucamonga, California, United States, 91730
      • Rancho Cucamonga Clinical Trials
    • Santa Monica, California, United States, 90404
      • Pacific Heart Institute
    • Torrance, California, United States, 90502
      • Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80012
      • Aurora Denver Cardiology Associates
    • Aurora, Colorado, United States, 80218
      • Aurora Denver Cardiology Associates
  • Florida
    • Coral Gables, Florida, United States, 33134
      • Clinical Research of South Florida
    • Defuniak Springs, Florida, United States, 32435
      • Doctors Medical center of Walton County
    • Fort Lauderdale, Florida, United States, 33316
      • Broward General Medical Center
    • Ft. Lauderdale, Florida, United States, 33316
      • Maxine Hamilton, MD, PA
    • Jacksonville, Florida, United States, 32259
      • St. John's Center for Clinical Research
    • Largo, Florida, United States, 33773
      • Private Practice of Dr. Bridget Bellingar
    • Miami, Florida, United States, 33144
      • A+ Research Inc.
    • Miami, Florida, United States, 33155
      • AppleMed Research, Inc.
    • N. Miami Beach, Florida, United States, 33179
      • Internal Medicine Associates of South Florida
    • Ormond Beach, Florida, United States, 32174
      • Ormond Medical Arts Pharmaceutical Research Center
    • Pensacola, Florida, United States, 32514
      • Northwest Florida Heart Group, PA - Research Dept
    • Sarasota, Florida, United States, 34231
      • Cardiovascular Center of Sarasota
    • St. Petersburg, Florida, United States, 33701
      • Suncoast Cardiovascular Research, Inc.
    • Tampa, Florida, United States, 33603
      • Tampa Bay Nephrology Associates, PL
    • Tampa, Florida, United States, 33607
      • Orlando Rangel, MD, PA
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Medical College of Georgia
    • Bogart, Georgia, United States, 30622
      • AMR Research Associates, LLC
    • Tucker, Georgia, United States, 30084
      • Atlanta Vascular Research Foundation
  • Illinois
    • Bannockburn, Illinois, United States, 60015
      • North Shore Cardiologist
    • Melrose Park, Illinois, United States, 60160
      • Consultants in Cardiovascular Med (CIS)
    • Normal, Illinois, United States, 61761
      • Illinois Heart & Lunch Research
    • Peoria, Illinois, United States, 61606
      • Methodist Medical Center-Heart, Lung & Vascular Institute
  • Indiana
    • Muncie, Indiana, United States, 47303
      • Medical Consultants, Pc
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University Medical Associates
  • Louisiana
    • Lafayette, Louisiana, United States, 70503
      • Dr. Jeffrey Chen
    • New Orleans, Louisiana, United States, 70114
      • Louisiana Research Associates, Inc
  • Maine
    • Auburn, Maine, United States, 04210
      • Maine Research Associate
    • Biddeford, Maine, United States, 04005
      • PrimeCare Internal Medicine
  • Michigan
    • Alpena, Michigan, United States, 49707
      • Great Lakes Heart Center Of Alpena
    • Petoskey, Michigan, United States, 49770
      • Internal Medicine of Nothern Michigan
  • Minnesota
    • Minneapolis, Minnesota, United States, 55417
      • Minneapolis VAMC
    • St. Cloud, Minnesota, United States, 56303
      • Central Minnesota Heart Center at St. Cloud Hospital
    • St. Paul, Minnesota, United States, 55102
      • St. Paul Cardiology
  • Montana
    • Kalispell, Montana, United States, 59901
      • Glacier View Cardiology, PC
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Impact Clinical Trials
  • New Jersey
    • Linden, New Jersey, United States, 07036
      • NJ Heart
    • Passaic, New Jersey, United States, 07055
      • New Jersey Physicians
  • New York
    • Brooklyn, New York, United States, 11214
      • Lifeline Research Institute
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Metrolina Internal Medicine, PA
    • Charlotte, North Carolina, United States, 28211
      • Heart Care Center of Charlotte
    • Winterville, North Carolina, United States, 27858
      • Physicians East, PA
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Plaza Medical Group, Pc
    • Tulsa, Oklahoma, United States, 74136
      • Castlerock Clinical Research Counsultants, LLC
  • Oregon
    • Ashland, Oregon, United States, 97520
      • Integrated Medical Research PC
  • Rhode Island
    • Pawtucket, Rhode Island, United States, 02860
      • Blackstone Cardiology Associates
  • South Carolina
    • Charleston, South Carolina, United States, 29403
      • Charleston Cardiology
    • Greenville, South Carolina, United States, 29601
      • Paris View Family Practice
    • Greer, South Carolina, United States, 29651
      • Internal Medicine Of Greer
  • Tennessee
    • Cleveland, Tennessee, United States, 37311
      • Scenic City Research
  • Texas
    • Beaumont, Texas, United States, 77702
      • Southeast Texas Clinical Research Center
    • Dallas, Texas, United States, 75231
      • Cardiovascular Research Inst. of Dallas
    • Dallas, Texas, United States, 75251
      • Galenos Research
    • El Paso, Texas, United States, 79935
      • Sergio F Rovner, MD
    • Houston, Texas, United States, 77008
      • Salim Gopalani, MD, PA
    • Houston, Texas, United States, 77055
      • Humayun Mirza, MD, PA
    • Houston, Texas, United States, 77074
      • Clinical Trial Network
    • Houston, Texas, United States, 77090
      • Houston Clinical Research Assoc.
    • Hurst, Texas, United States, 76054
      • Innovative Research of West Florida
    • Plano, Texas, United States, 75093
      • North Texas Medical Research
    • Temple, Texas, United States, 76508
      • Scott & White Memorial Hospital
  • Vermont
    • Burlington, Vermont, United States, 05401
      • Fletcher Allen Health Care/University of Vermont
  • Virginia
    • Hopewell, Virginia, United States, 23860
      • Kamlesh N. Dave Cardiology
  • West Virginia
    • Charleston, West Virginia, United States, 25304
      • WVU Physicians of Charleston
  • Wisconsin
    • Madison, Wisconsin, United States, 43717
      • Alpha Medical Research, Llc
    • Madison, Wisconsin, United States, 53717
      • Executive Health and Research Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: 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: Darusentan Placebo; Placebo to match darusentan administered orally once daily; Drug: Guanfacine; Guanfacine capsules 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in trough sitting systolic and diastolic blood pressure measured by sphygmomanometry	Baseline to Week 14

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of subjects reaching systolic blood pressure goal after 14 weeks of treatment	Week 14
Change from baseline in mean 24-hour systolic and diastolic blood pressure measured by ambulatory blood pressure monitoring (ABPM)	Baseline to Week 14
Change from baseline in estimated glomerular filtration rate (eGFR)	Baseline to Week 14

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• Bakris GL, Lindholm LH, Black HR, Krum H, Linas S, Linseman JV, Arterburn S, Sager P, Weber M. Divergent results using clinic and ambulatory blood pressures: report of a darusentan-resistant hypertension trial. Hypertension. 2010 Nov;56(5):824-30. doi: 10.1161/HYPERTENSIONAHA.110.156976. Epub 2010 Oct 4.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: September 1, 2006
• Primary Completion (Actual): August 1, 2009
• Study Completion (Actual): August 1, 2009

Study Registration Dates

• First Submitted: October 17, 2006
• First Submitted That Met QC Criteria: October 18, 2006
• First Posted (Estimate): October 19, 2006

Study Record Updates

• Last Update Posted (Estimate): March 18, 2014
• Last Update Submitted That Met QC Criteria: February 19, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Endothelin Receptor Antagonists; Guanfacine; Darusentan
• Other Study ID Numbers: Protocol DAR-312

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No