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Induction/Simplification With Atazanavir + Ritonavir + Abacavir/Lamivudine Fixed-Dose Combination In HIV-1 Infection
This study is ongoing, but not recruiting participants.
First Received: February 23, 2007   Last Updated: December 11, 2008   History of Changes
Sponsor: GlaxoSmithKline
Information provided by: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00440947
  Purpose

This study was designed to test the efficacy, safety, tolerability and durability of the antiviral response between atazanavir (ATV) + ritonavir (RTV) + abacavir/lamivudine(ABC/3TC) each administered once daily (QD) for 36 weeks followed by randomization to either a simplification regimen of ATV or continuation of ATV+RTV for an additional 48 weeks, each in combination with ABC/3TC in antiretroviral (ART)-naive, HIV-1 infected, HLA-B*5701 negative subjects.


Condition Intervention Phase
HIV Infection
Drug: ABC/3TC + ATV/r x 36wks followed by ABC/3TC + ATV x 48wks
Drug: ABC/3TC + ATV/r x 36wks followed by ABC/3TC + ATV/r x 48wks
Phase III

Study Type: Interventional
Study Design: Treatment, Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study
Official Title: See Detailed Description

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Compare the efficacy and safety between Abacavir/Lamivudine(ABC/3TC)+ Atazanavir(ATV)+ Ritonavir(RTV) vs ABC/3TC + ATV for 48 wks in subjects who achieve initial virologic suppression on ABC/3TC + ATV + RTV, based on proportion with HIV-1 RNA <50 c/mL [ Time Frame: 48 Weeks ]

Secondary Outcome Measures:
  • Compare HIV-1 RNA <50 and <400c/mL (proportions), immunologic response, adverse events over 36 and 84 wks. Incidence of clinically suspected ABC HSR after excluding subjects who are HLA-B*5701 positive [ Time Frame: 84 Weeks ]

Enrollment: 500
Study Start Date: March 2007
Estimated Study Completion Date: April 2009
Estimated Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Detailed Description:

Safety and Efficacy of an Initial Regimen of Atazanavir + Ritonavir + the Abacavir/Lamivudine Fixed-Dose Combination Tablet (ABC/3TC FDC) for 36 weeks followed by Simplification to Atazanavir with ABC/3TC FDC or Maintenance of the Initial Regimen for an Additional 48 weeks in Antiretroviral-Naive HIV-1 Infected HLA-B*5701 Negative Subjects

  Eligibility

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

Inclusion criteria:

  • Subject is ≥ 18 years of age and has documented evidence of HIV-1 infection. (A female is eligible to enter and participate in this study if she is of: non child-bearing potential, child bearing potential with a negative pregnancy test and agrees to approved contraception methods, or agreement for complete abstinence.)
  • Subject is antiretroviral-naïve (defined as having ≤14 days of prior therapy with any NRTI and no prior therapy with either a PI or NNRTI).
  • Subject has plasma HIV-1 RNA ≥ 1,000 copies/mL by Roche COBAS AMPLICOR™ (Version 1.5) method at screening (if no other documentation of HIV infection is available, a positive result here may serve as documentation of HIV infection for this study).
  • Subject is willing and able to understand and provide written informed consent prior to participation in this study.

Exclusion criteria:

  • Subject is HLA-B*5701 positive.
  • Subject testing positive for Hepatitis B or both Hepatitis B and Hepatitis C at screening (+ HbsAg)
  • Genotyping results performed at the screening indicate that the subject has any of the following mutations at the reverse transcriptase (RT) enzyme: K65R, L74V, or Y115F, or a combination of two or more thymidine analog mutations (M41L, D67N, K70R, K219Q or E) that include changes at either L210 or T215, or ≥ 3 of the following protease mutations associated with atazanavir resistance: D30, V32, M36, M46, I47, G48, I50, I54, A71, G73, V77, V82, I84, N88, and L90.
  • Women who are pregnant or breastfeeding.
  • Subject has an active or acute CDC Clinical Category C event at screening. Treatment for the acute event must have been completed at least 30 days prior to screening.
  • Subject is, in the opinion of the investigator, unable to complete the 84-week dosing period and protocol evaluations and assessments.
  • Subject has ongoing clinically relevant pancreatitis or clinically relevant hepatitis at screening.
  • Presence of a newly diagnosed HIV-related opportunistic infection or any medical condition requiring acute therapy at the time of enrollment.
  • Subject suffers from a serious medical condition, such as diabetes, congestive heart failure, cardiomyopathy or other cardiac dysfunction (including known, clinically significant cardiac conduction system disease, severe first degree atrioventricular block [PR interval > 0.26 seconds], second or third-degree atrioventricular block), which in the opinion of the investigator would compromise the safety of the subject.
  • Subject has pre-existing mental, physical, or substance abuse disorder, which in the opinion of the investigator would interfere with the subject's ability to comply with the dosing schedule and protocol evaluations and assessments.
  • Subject has a history of inflammatory bowel disease or malignancy, intestinal ischemia, malabsorption, or other gastrointestinal dysfunction, which may interfere with drug absorption or render the subject unable to take oral medication.
  • Subject requires treatment with foscarnet, hydroxyurea or other agents with documented activity against HIV-1 in vitro within 28 days of study administration.
  • Subject requires treatment with immunomodulating agents (such as systemic corticosteroids, interleukins, vaccines, or interferons) within 28 days prior to screening, or subject had received an HIV-1 immunotherapeutic vaccine within 90 days prior to screening. Subjects using inhaled corticosteroids are eligible for enrollment.
  • Creatinine clearance <50 mL/min via the Cockroft-Gault method [Cockroft, 1976].
  • Active alcohol or substance use sufficient, in the investigator's opinion, to prevent adequate compliance with study therapy or to increase the risk of developing pancreatitis or chemical hepatitis.
  • Hypersensitivity to any component of the study drugs.
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >5 times the upper limit of normal (ULN).
  • Total bilirubin > 1.5 times the upper limit of normal (ULN).
  • Subject has any acute laboratory abnormality at screening, which, in the opinion of the investigator, would preclude the subject's participation in the study of an investigational compound. Any grade 4 laboratory abnormality would exclude a subject from study participation.
  • Subject requires treatment with radiation therapy or cytotoxic chemotherapeutic agents within 28 days prior to screening, or has an anticipated need for these agents within the study period.
  • Enrolled in one or more investigational drug protocols, which may have impacted HIV-1 RNA suppression.
  • Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study.
  • Subjects requiring concomitant administration of proton pump inhibitors.
  • Subjects who require treatment with the prohibited medications within 28 days of commencement of investigational product, or an anticipated need during the study.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00440947

  Hide Study Locations
Locations
United States, Arizona
GSK Investigational Site
Phoenix, Arizona, United States, 85012
United States, California
GSK Investigational Site
Long Beach, California, United States, 90813
GSK Investigational Site
Los Angeles, California, United States, 90033
GSK Investigational Site
Garden Grove, California, United States, 92845
GSK Investigational Site
Los Angeles, California, United States, 90022
GSK Investigational Site
Oakland, California, United States, 94609
GSK Investigational Site
Newport Beach, California, United States, 92663
United States, Colorado
GSK Investigational Site
Denver, Colorado, United States, 80220
United States, Connecticut
GSK Investigational Site
Glastonbury, Connecticut, United States, 06033
United States, District of Columbia
GSK Investigational Site
Washington, District of Columbia, United States, 20009
GSK Investigational Site
Washington, District of Columbia, United States, 20036
GSK Investigational Site
Washington, District of Columbia, United States, 20037
GSK Investigational Site
Washington, District of Columbia, United States, 20007
United States, Florida
GSK Investigational Site
Hollywood, Florida, United States, 33020
GSK Investigational Site
Sarasota, Florida, United States, 34243
GSK Investigational Site
Tampa, Florida, United States, 33607
GSK Investigational Site
Fort Lauderdale, Florida, United States, 33316
GSK Investigational Site
Port St. Lucie, Florida, United States, 34952
GSK Investigational Site
Plantation, Florida, United States, 33317
GSK Investigational Site
Fort Lauderdale, Florida, United States, 33308
GSK Investigational Site
Tampa, Florida, United States, 33602
GSK Investigational Site
Orlando, Florida, United States, 32803
GSK Investigational Site
Miami, Florida, United States, 33101
United States, Georgia
GSK Investigational Site
Atlanta, Georgia, United States, 30308
GSK Investigational Site
Atlanta, Georgia, United States, 30339
GSK Investigational Site
Atlanta, Georgia, United States, 30309
GSK Investigational Site
Augusta, Georgia, United States, 30912
GSK Investigational Site
Decatur, Georgia, United States, 30033
United States, Illinois
GSK Investigational Site
Chicago, Illinois, United States, 60657
GSK Investigational Site
Chicago, Illinois, United States, 60637
GSK Investigational Site
Maywood, Illinois, United States, 60153
United States, Kentucky
GSK Investigational Site
Lexington, Kentucky, United States, 40536
United States, Maryland
GSK Investigational Site
Baltimore, Maryland, United States, 21201
United States, Massachusetts
GSK Investigational Site
Boston, Massachusetts, United States, 02215
GSK Investigational Site
Springfield, Massachusetts, United States, 01107
GSK Investigational Site
Boston, Massachusetts, United States, 02115
United States, Michigan
GSK Investigational Site
Detroit, Michigan, United States, 48202
United States, Minnesota
GSK Investigational Site
Minneapolis, Minnesota, United States, 55404
GSK Investigational Site
Minneapolis, Minnesota, United States, 55415
United States, Missouri
GSK Investigational Site
St. Louis, Missouri, United States, 63110
United States, New Jersey
GSK Investigational Site
Somers Point, New Jersey, United States, 08244
GSK Investigational Site
Hillsborough, New Jersey, United States, 08844
GSK Investigational Site
Newark, New Jersey, United States, 07102
United States, New York
GSK Investigational Site
New York, New York, United States, 10011
GSK Investigational Site
Valhalla, New York, United States, 10595
United States, North Carolina
GSK Investigational Site
Charlotte, North Carolina, United States, 28209
GSK Investigational Site
Greenville, North Carolina, United States, 27834
United States, Ohio
GSK Investigational Site
Toledo, Ohio, United States, 43614
GSK Investigational Site
Akron, Ohio, United States, 44304
United States, Oregon
GSK Investigational Site
Portland, Oregon, United States, 97219
United States, Pennsylvania
GSK Investigational Site
Philadelphia, Pennsylvania, United States, 19107
GSK Investigational Site
Philadelphia, Pennsylvania, United States, 19104
United States, Rhode Island
GSK Investigational Site
Providence, Rhode Island, United States, 2906
United States, Texas
GSK Investigational Site
Houston, Texas, United States, 77027
GSK Investigational Site
Austin, Texas, United States, 78705
GSK Investigational Site
Houston, Texas, United States, 77004
GSK Investigational Site
Fort Worth, Texas, United States, 76104
GSK Investigational Site
Dallas, Texas, United States, 75204
GSK Investigational Site
Dallas, Texas, United States, 75246
GSK Investigational Site
Houston, Texas, United States, 77030
GSK Investigational Site
Galveston, Texas, United States, 77555
GSK Investigational Site
El Paso, Texas, United States, 79925
GSK Investigational Site
Longview, Texas, United States, 75605
United States, Virginia
GSK Investigational Site
Lynchburg, Virginia, United States, 24501
GSK Investigational Site
Annandale, Virginia, United States, 22003
GSK Investigational Site
Norfolk, Virginia, United States, 23507
GSK Investigational Site
Hampton, Virginia, United States, 23666
Canada, Ontario
GSK Investigational Site
Toronto, Ontario, Canada, M5G 2N2
GSK Investigational Site
Toronto, Ontario, Canada, M4N 3M5
GSK Investigational Site
Toronto, Ontario, Canada, M5B 1L6
Canada, Quebec
GSK Investigational Site
Montreal, Quebec, Canada, H2L 4P9
GSK Investigational Site
Montreal, Quebec, Canada, H2L 5B1
GSK Investigational Site
Montreal, Quebec, Canada, H2X 2P4
Puerto Rico
GSK Investigational Site
Ponce, Puerto Rico, 00717
GSK Investigational Site
Ponce, Puerto Rico, 00731
GSK Investigational Site
San Juan, Puerto Rico, 00910
GSK Investigational Site
San Juan, Puerto Rico, 00909-1711
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials, MD GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GSK ( Study Director )
Study ID Numbers: EPZ108859, ARIES study
Study First Received: February 23, 2007
Last Updated: December 11, 2008
ClinicalTrials.gov Identifier: NCT00440947     History of Changes
Health Authority: United States: Food and Drug Administration;   Canada: Health Canada

Keywords provided by GlaxoSmithKline:
ARIES
Antiretroviral-naive
HIV
EPZICOM
REYATAZ
NORVIR
simplification

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

ClinicalTrials.gov processed this record on November 25, 2009