Multicenter, Randomized, Double-Blind, Double-Dummy, Phase 3 Study of the Safety and Efficacy of Ritonavir-Boosted Elvitegravir (EVG/r) Versus Raltegravir (RAL)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2012 by Gilead Sciences.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT00708162
First received: June 30, 2008
Last updated: February 10, 2012
Last verified: February 2012
  Purpose

The purpose of this study is to compare the safety, tolerability and efficacy of a regimen containing once-daily ritonavir-boosted elvitegravir or twice-daily raltegravir added to a background regimen in HIV-1 infected, antiretroviral treatment-experienced adults who have documented resistance, or at least six months experience prior to screening with two or more different classes of antiretroviral agents.


Condition Intervention Phase
HIV Infection
Drug: elvitegravir
Drug: Raltegravir
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-Blind, Double-Dummy, Phase 3 Study of the Safety and Efficacy of Ritonavir-Boosted Elvitegravir (EVG/r) Versus Raltegravir (RAL) Each Administered With a Background Regimen in HIV-1 Infected, Antiretroviral Treatment-Experienced Adults

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • The primary efficacy endpoint is the proportion of subjects achieving and maintaining confirmed HIV-1 RNA < 50 copies/mL through Week 48. [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To evaluate the efficacy, safety and tolerability of the two treatment arms through 96 weeks of treatment. [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]
  • To evaluate the long-term safety, tolerability, and efficacy of elvitegravir administered with a background regimen [ Time Frame: Open Label Extension ] [ Designated as safety issue: No ]

Enrollment: 712
Study Start Date: September 2008
Estimated Study Completion Date: March 2014
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Ritonavir-boosted elvitegravir 150 mg QD (ritonavir-boosted elvitegravir 85 mg QD for subjects taking atazanavir/r or lopinavir/r as part of their BR) + BR (N = 350)
Drug: elvitegravir
Elvitegravir 85 mg, 150 mg tablets or matching placebo administered orally QD (with ritonavir-boosted PI) to be taken with food.
Active Comparator: 2
Raltegravir 400 mg BID + BR (N = 350)
Drug: Raltegravir
Raltegravir 400 mg tablets or matching placebo administered orally BID and to be taken according to the prescribing information.
Other Name: Isentress

Detailed Description:

This is a double-blind, double-dummy, multicenter, randomized, active-controlled 96-week study to assess the safety and efficacy of a regimen containing ritonavir-boosted elvitegravir versus raltegravir, each administered with a background regimen (BR) containing a fully-active ritonavir-boosted protease inhibitor (PI) and a second single agent in HIV-1 infected, antiretroviral treatment-experienced adults. Subjects will be randomized in a 1:1 ratio to one of the following two treatment arms:

  • Treatment Arm 1: Ritonavir-boosted elvitegravir 150 mg QD (ritonavir-boosted elvitegravir 85 mg QD for subjects taking atazanavir/r or lopinavir/r as part of their BR) + BR (N = 350)
  • Treatment Arm 2: Raltegravir 400 mg BID + BR (N = 350)

Due to known pharmacokinetic interactions, subjects who are taking atazanavir/r (ATV/r) or lopinavir/r (LPV/r) as part of their BR will receive elvitegravir 85 mg if randomized to Treatment Arm 1.

The BR shall be constructed by the investigator based on viral resistance testing and shall be composed of a fully-active ritonavir-boosted PI and a second single agent.

The fully-active PI is defined by phenotypic resistance analysis. For phenotypic susceptibility, fully active is defined as being below the lower clinical or biological cutoff. The following ritonavir-boosted PIs are allowed to be prescribed by the investigator as part of the BR: atazanavir/r, darunavir/r, fosamprenavir/r, lopinavir/r, or tipranavir/r. Subjects must take their ritonavir dose based on the dosing schedule indicated in the prescribing information for the PI; no additional ritonavir is required to be taken with elvitegravir. No other marketed PIs will be allowed as part of the BR due to unknown pharmacokinetic interactions.

The second single agent may or may not be fully-active and can be one nucleoside or nucleotide reverse transcriptase inhibitor (NRTI), etravirine, maraviroc, or T-20. However, the second single agent must not include an integrase inhibitor; the non-nucleoside reverse transcriptase inhibitors (NNRTI) efavirenz, nevirapine, or delavirdine (due to unknown pharmacokinetic interactions); or fixed-dose combination antiretroviral therapies.

After Week 96, subjects will continue to take their blinded study drug and attend visits until treatment assignments have been unblinded, at which point they will all be given the option to participate in an open label elvitegravir extension phase of the study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Plasma HIV-1 RNA levels greater than or equal to 1,000 copies/mL at screening
  • Documented resistance or at least six months experience prior to screening with two or more different classes of antiretroviral agents
  • Stable antiretroviral regimen for at least 30 days prior to screening and must remain on screening regimen until the baseline visit
  • Eligible to receive one of the fully-active ritonavir-boosted-PIs, and an allowed second agent
  • Normal ECG
  • Adequate renal function
  • Hepatic transaminases less than or equal to 2.5 x upper limit of normal
  • Total bilirubin less than or equal to 1.5 mg/dL, or normal direct bilirubin
  • Adequate hematologic function
  • Prothrombin Time less than or equal to 1.25 x ULN
  • Serum amylase less than 1.5 x ULN
  • Negative serum pregnancy test (females of childbearing potential only)
  • Males and females of childbearing potential must agree to use highly effective contraception methods
  • Age greater than or equal to 18 years
  • Life expectancy greater than or equal to 1 year
  • Ability to understand and sign a written informed consent form

Exclusion Criteria:

  • New AIDS-defining condition diagnosed within the 30 days prior to screening
  • Prior treatment with any HIV-1 integrase inhibitor
  • Subjects experiencing ascites
  • Subjects experiencing encephalopathy
  • Females who are breastfeeding
  • Positive serum pregnancy test at any time during the study (female of childbearing potential)
  • Subjects receiving ongoing therapy with any disallowed medication
  • Current alcohol or substance use judged by the investigator to potentially interfere with study compliance
  • Malignancy other than cutaneous Kaposi's sarcoma or basal cell carcinoma
  • Active, serious infections (other than HIV-1 infection) requiring therapy
  • Participation in any other clinical trial (except for the etravirine expanded access program), without prior approval from sponsor
  • Any other clinical condition or prior therapy that would make subjects unsuitable for the study
  • Known hypersensitivity to study drug, metabolites or formulation excipients
  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: NCT00708162

  Hide Study Locations
Locations
United States, Arizona
Southwest Center for HIV/AIDS
Phoenix, Arizona, United States, 85006
United States, Arkansas
Health for Life Clinic, PLLC
Little Rock, Arkansas, United States, 72207
United States, California
AIDS Healthcare Foundation-Research Center
Beverly Hills, California, United States, 90804
Pacific Oaks Medical Group
Beverly Hills, California, United States, 90211
Center for Special Immunology
Fountain Valley, California, United States, 92708
The Living Hope Foundation
Long Beach, California, United States, 90813
Jeffrey Goodman Special Care Clinic
Los Angeles, California, United States, 90028
Tony Mills, MD Internal Medicine
Los Angeles, California, United States, 90069
Peter J. Ruane, MD, Inc.
Los Angeles, California, United States, 90036
University of Southern California, AIDS Clinical Trials Unit
Los Angeles, California, United States, 90033
Kaiser Permanente
Los Angeles, California, United States, 90027
Orange Coast Medical Group
Newport Beach, California, United States, 92663
East Bay AIDS Center
Oakland, California, United States, 94609
Alameda County Medical Center
Oakland, California, United States, 94602
Kaiser Permanente
Sacramento, California, United States, 95825
David J. Shamblaw, MD Inc.
San Diego, California, United States, 92103
Metropolis Medical
San Francisco, California, United States, 94115
San Francisco VA Medical Center/UCSF
San Francisco, California, United States, 94121
United States, Connecticut
Connecticut Health Care Group
Glastonbury, Connecticut, United States, 06033
Circle Medical LLC
Norwalk, Connecticut, United States, 06851
The Stamford Hospital - Stamford ID
Stamford, Connecticut, United States, 06902
United States, District of Columbia
Whitman-Walker Clinic
Washington, District of Columbia, United States, 20009
The George Washington University Medical Center
Washington, District of Columbia, United States, 20037
United States, Florida
South Florida Clinical Research
Atlantis, Florida, United States, 33462
NorthPoint Medical
Fort Lauderdale, Florida, United States, 33308
Therafirst Medical Centers
Fort Lauderdale, Florida, United States, 33308
Lifeway , Inc.
Fort Lauderdale, Florida, United States, 33308
Broward Health CCC
Fort Lauderdale, Florida, United States, 33311
Gary Richmond, MD, PA, Inc.
Fort Lauderdale, Florida, United States, 33316
Associates In Infectious Diseases
Fort Pierce, Florida, United States, 34952
University of Miami
Miami, Florida, United States, 33136
The Kinder Medical Group
Miami, Florida, United States, 33133
Wohlfeiler, Piperato and Associates, LLC
North Miami Beach, Florida, United States, 33169
Orlando Immunology Center
Orlando, Florida, United States, 32803
Infectious Disease of Central Florida
Orlando, Florida, United States, 32806
Barry M. Rodwick, M. D.
Safety Harbor, Florida, United States, 34695
St. Joseph's Comprehensive Research Institute
Tampa, Florida, United States, 33614
Treasure Coast Infectious Disease Consultants
Vero Beach, Florida, United States, 32960
United States, Georgia
AIDS Research Consortium of Atlanta
Atlanta, Georgia, United States, 30308
The Emory Clinic, Inc., Division of Infectious Diseases
Atlanta, Georgia, United States, 30308
Atlanta ID Group
Atlanta, Georgia, United States, 30309
Infectious Disease Specialists of Atlanta (IDSA)
Decatur, Georgia, United States, 30033
Mercer Univ. School of Medicine
Macon, Georgia, United States, 31201
Chatham County Health Department
Savannah, Georgia, United States, 31401
United States, Hawaii
Hawaii AIDS Clinical Research Program HACRP
Honolulu, Hawaii, United States, 96316
United States, Illinois
Howard Brown Health Center
Chicago, Illinois, United States, 60613
Northstar Medical Center
Chicago, Illinois, United States, 60657
The Ruth M. Rothstein CORE Center
Chicago, Illinois, United States, 60612
United States, Kentucky
University of Kentucky Healthcare/Bluegrass Care Clinic
Lexington, Kentucky, United States, 40536
United States, Maryland
University of Maryland, Institute of Human Virology
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Community Research Initiative of New England
Boston, Massachusetts, United States, 02215
United States, Michigan
Be Well Medical Center
Berkley, Michigan, United States, 48072
Henry Ford Hospital Div of Infectious Disease
Detroit, Michigan, United States, 48202
Wayne State University
Detroit, Michigan, United States, 48201
United States, Missouri
Southampton Healthcare, Inc.
St. Louis, Missouri, United States, 63139
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, New Jersey
ID Care
Hillsborough, New Jersey, United States, 08844
University of Medicine and Dentistry of New Jersey; University Hospital Infectious Disease Practice
Newark, New Jersey, United States, 07103
Saint Michael's Medical Center
Newark, New Jersey, United States, 07102
South Jersey Infectious Disease
Somer Point, New Jersey, United States, 08244
United States, New Mexico
Southwest C.A.R.E. Center
Santa Fe, New Mexico, United States, 87505
United States, New York
Albany Medical College
Albany, New York, United States, 12208
Montefiore Medical Center
Bronx, New York, United States, 10573
STAR Health Care Center
Brooklyn, New York, United States, 11203
Greiger Clinic
Mt. Vernon, New York, United States, 10550
Chelsea Village Medical, PC
New York, New York, United States, 10011
Ricky K. Hsu, MD, PC
New York, New York, United States, 10011
Mount Sinai School of Medicine
New York, New York, United States, 10029
Beth Israel Medical Center
New York, New York, United States, 10003
AIDS Community HealthCenter
Rochester, New York, United States, 14604
United States, North Carolina
University of North Carolina/ School of Medicine Division of Infectious Diseases/ AIDS Clinical Trials Unit
Chapel Hill, North Carolina, United States, 27514
Carolinas Medical Center
Charlotte, North Carolina, United States, 28207
Duke University
Durham, North Carolina, United States, 27710
Brody School of Medicine at East Carolina University
Greenville, North Carolina, United States, 27834
Rosedale Infectious Diseases
Huntersville, North Carolina, United States, 28078
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
Summa Health CARE Center
Akron, Ohio, United States, 44304
United States, Pennsylvania
Philadelphia FIGHT
Philadelphia, Pennsylvania, United States, 19107
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Thomas Jefferson University Jefferson Alumni Hall
Philadelphia, Pennsylvania, United States, 19107
United States, Texas
Central Texas Clinical Research
Austin, Texas, United States, 78705
Southwest Infectious Disease Clinical Research
Dallas, Texas, United States, 75219
AIDS Arms/ Peabody Health Center
Dallas, Texas, United States, 75215
North Texas Infectious Disease Consultants
Dallas, Texas, United States, 75246
Presbyterian Hospital of Dallas
Dallas, Texas, United States, 75231
Tarrant County Infectious Disease Associates
Fort Worth, Texas, United States, 76104
Garcia Family Health Group
Harlingen, Texas, United States, 78550
Gordon E. Crofoot, MD, PA
Houston, Texas, United States, 77098
Joseph C. Gathe, JR. MD, F.A.C.P.
Houston, Texas, United States, 77478
The Schrader Clinic
Houston, Texas, United States, 77098
University of Texas Health Science Center at Houston
Houston, Texas, United States, 77030
DCOL Center for Clinical Research
Longview, Texas, United States, 75605
United States, Virginia
Clinical Alliance for Research & Education - Infectious Diseases, LLC (CARE-ID)
Annandale, Virginia, United States, 22003
United States, Washington
EHS Pulmonary and Critical Care
Spokane, Washington, United States, 99204
Australia, New South Wales
Royal Prince Alfred Hospital
Camperdown, New South Wales, Australia, 2050
St. Vincent's Hospital, Sydney
Darlinghurst, New South Wales, Australia, 2010
Holdsworth House Medical Practice
Darlinghurst, New South Wales, Australia, 2010
Ground Zero Medical Centre
Darlinghurst, New South Wales, Australia, 2010
St George Hospital
Kogarah, New South Wales, Australia, 2217
East Sidney Doctors
Sidney, New South Wales, Australia, 2010
Albion Street Centre
Sydney, New South Wales, Australia, 2010
Westmead Hospital
Wentworthville, New South Wales, Australia, 2145
Belgium
Institute of Tropical Medicine
Antwerp, Belgium, 2000
C.H.U. St Pierre
Brussels, Belgium, 1000
Hôpital Erasme
Brussels, Belgium, 1070
CHU de Charleroi-Hopital civil
Charleroi, Belgium, 6000
Centre Hospitalier Universitaire de Liège
Liege, Belgium, 4000
Canada, British Columbia
Downtown Infectious Diseases Clinic
Vancouver, British Columbia, Canada, V35 4N9
Canada, Nova Scotia
Queen Elizabeth II Health Sciences Centre
Halifax, Nova Scotia, Canada, B3H 1V7
Canada, Ontario
University Health Network, Toronto General Hospital
Toronto, Ontario, Canada, M5G 2N2
Canadian Immunodeficiency Research Collaborative (CIRC) Inc.
Toronto, Ontario, Canada, M5B 1L6
CascAids Research
Toronto, Ontario, Canada, M4T 3A7
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada, M4N 3M5
Canada, Quebec
Immunodeficiency Service, McGill University Health Centre (MUHC)
Montreal, Quebec, Canada, H2X 2P4
Clinique medicale l'Actuel
Montreal, Quebec, Canada, H2L 4P9
Canada
University of Manitoba - Health Sciences Centre
Winnipeg, Canada, R3A 1R9
France
Hopital de Bicentre - Service de medecine Interne et Immunologie
Le Kremlin Bicetre, France, 94270
University Hospital of Montpellier - Gui de Chauliac
Montpellier, France, 34295
CHU Nantes
Nantes, France, 44093
C.H.U. de Nice - Hopital de l'Archet 1
Nice, France, 06202
APHP Hopital Bichat-Claude Bernard
Paris, France, 75018
Hopital Pitie Salpetriere - Infectious Deseases Department
Paris, France, 75013
Hopital Saint Louis
Paris, France, 75010
Hopital Tenon
Paris, France, 75020
Hopital Saint Antoine - Infectious Desease Department
Paris, France, 75012
CHU Bordeaux
Pessac, France, 33604
Hopital Purpan - Service of Infectious Diseases
Toulouse, France, 31059
Germany
Universitatsklinikum Bonn
Bonn, Germany, 53125
Universitatsklinikum Dusseldorf
Dusseldorf, Germany, 40225
Universitatklinikum Essen
Essen, Germany, 45122
Klinikum der J.W. Goethe-Universitat
Frankfurt, Germany, 60590
IFI-Institute
Hamburg, Germany, 20099
Ambulanzzentrum am Universitatsklinikum Hamburg Eppendorf
Hamburg, Germany, 20251
Medizinische Universitatsklinik Kiel
Kiel, Germany, 24116
Klinikum der Universitat zu Koln
Koln, Germany, 50937
MUC Research
Munich, Germany, 80335
Italy
Ospedali Riuniti Di Bergamo
Bergamo, Italy, 24128
Spedali Civili di Brescia
Brescia, Italy, 25137
Ospedale Luigi Sacco
Milan, Italy, 20157
Fondazione Centro San Raffaele del Monte Tabor
Milan, Italy, 20127
Ospedale L. Sacco
Milan, Italy, 20157
Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani I.R.C.C.S.
Rome, Italy, 00149
Universita' Cattolica Del Sacro Cuore
Rome, Italy, 00168
Universita La Sapienza Policlinico Umberto I
Rome, Italy, 00161
Mexico
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran (INCMYNSZ)
Mexico, D.f., Mexico, 14000
Hospital Regional de Leon Guanajuato
Leon, Guanajuato, Mexico, 31320
Hospital Civil de Guadalajara
Guadalajara, Jalisco, Mexico, 44280
Hospital Central Morones Prieto
San Luis Potosi, San Luis Potsi, Mexico, 78240
Netherlands
Erasmus Medisch Centrum
Rotterdam, Netherlands, 3000CA
Portugal
Hospital Fernando Fonseca
Amadora, Portugal, 2720-276
Hospital de Santa Maria
Lisbon, Portugal, 1649-035
Hospital Pulido Valente
Lisbon, Portugal, 1769-001
Hospital Santo Antonio dos Capuchos
Lisbon, Portugal, 1150-069
Hospital de Sao Joao
Porto, Portugal, 42020-451
Puerto Rico
Instituto de Investigacion Cientifica del Sur
Ponce, Puerto Rico, 00731
Clinical Research Puerto Rico, Inc.
San Juan, Puerto Rico, 00909
HOPE Clinical Research
San Juan, Puerto Rico, 00909
VA Caribbean healthcare System
San Juan, Puerto Rico, 00921
University of Puerto Rico, School of Medicine, Proyecto ACTU
San Juan, Puerto Rico, 00936
Spain
Hospital General Universitario de Alicante
Alicante, Spain, 03010
Hospital Universitario Germans Trias i Pujol
Barcelona, Spain, 08916
Hospital de la Santa Creu i Sant Pau
Barcelona, Spain, 08025
Hospital Clinic i Provincial de Barcelona
Barcelona, Spain, 08036
Hospital Reina Sofia
Cordoba, Spain, 14004
Hospital General Universitario del Elche
Elche, Spain, 03203
Hospital Clinico San Cecilio
Granada, Spain, 18014
Hospital Universitario La Paz
Madrid, Spain, 28046
Hospital General Universitario Gregorio Maranon
Madrid, Spain, 28007
Hospital Ramon y Cajal
Madrid, Spain, 28034
Hospital Doce De Octubre
Madrid, Spain, 28041
Hospital La Princesa
Madrid, Spain, 28006
Hospital Virgen de la Victoria
Malaga, Spain, 29010
Hospital Universitario de Canarias
Santa Cruz de Tenerife, Spain, 38320
Hospital Virgen del Rocio
Sevilla, Spain, 41013
Complexo Hospitalario Xeral-Cies (Chuvi) Vigo
Vigo, Spain, 36204
Switzerland
Universitatsspital Zurich
Zurich, Switzerland, CH-8091
United Kingdom
RIDU, Western General Hospital
Edinburgh, United Kingdom, EH4 2XU
Royal Free and University College Medical School
London, United Kingdom, WC1E 6JB
Imperial College Healthcare NHS Trust, St. Mary's Campus
London, United Kingdom, W2 1NY
North Manchester General Hospital
Manchester, United Kingdom, M8 6RB
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Javier Szwarcberg, MD, MPH Gilead Sciences
  More 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: NCT00708162     History of Changes
Other Study ID Numbers: GS-US-183-0145, EudraCT Number:2007-004225-26
Study First Received: June 30, 2008
Last Updated: February 10, 2012
Health Authority: United States: Food and Drug Administration
Australia: Human Research Ethics Committee
Belgium: Federal Agency for Medicinal Products and Health Products
Canada: Health Canada
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Ireland: Irish Medicines Board
Italy: Ministry of Health
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Portugal: National Pharmacy and Medicines Institute
Spain: Spanish Agency of Medicines
Switzerland: Swissmedic
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Gilead Sciences:
HIV
HIV I
Treatment Experienced

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Ritonavir
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 16, 2014