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Study of Reyataz in HIV-infected Patients With Lipodystrophy Syndrome

This study has been completed.
Sponsor:
Information provided by:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00135356
First received: August 25, 2005
Last updated: April 20, 2010
Last verified: April 2010
History of Changes
  Purpose

The purpose of this clinical research study is to learn if human immunodeficiency virus (HIV)-infected subjects with abdominal fat accumulation on their highly active antiretroviral treatment (HAART) regimen have better changes in fat distribution after switching to atazanavir-ritonavir than those remaining on their current protease inhibitor boosted HAART regimen.


Condition Intervention Phase
HIV-Associated Lipodystrophy Syndrome
 Drug: Atazanavir (ATV) + ritonavir (RTV), continuation of backbone 2 nucleoside reverse transcriptase inhibitor (NRTIs)
Drug: continuation of current HAART (boosted protease inhibitor [PI] combination + 2 NRTIs)
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase IV, Open-Label, Randomized, Multicenter Trial Assessing a Reyataz-Based Substitution Approach in the Management of Lipodystrophy Syndrome. Research Into Atazanavir in Lipodystrophy (The REAL Study)

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Change From Baseline in Trunk-to-limb Fat Ratio as Measured by Dual Energy X-Ray Absortiometry (DEXA) at Week 48 [ Time Frame: Baseline, Week 48 ] [ Designated as safety issue: No ]
    Mean changes from Baseline in trunk-to-limb fat ratio as measured by DEXA, an x-ray scan used to measure bone mineral density. Clinical improvement is associated with a decrease in values. (Baseline trunk-to-limb fat ratio values can be found in the Baseline Characteristics section.)


Secondary Outcome Measures:
  • Change From Baseline in Trunk-to-limb Fat Ratio as Measured by DEXA at Week 96 [ Time Frame: Baseline, Week 96 ] [ Designated as safety issue: No ]
    Mean changes from baseline in trunk-to-limb fat ratio as measured by DEXA, an x-ray scan used to measure bone mineral density. Clinical improvement is associated with a decrease in values.(Baseline trunk-to-limb fat ratio values can be found in the Baseline Characteristics section.)

  • Mean Percent Change From Baseline in Visceral Adipose Tissue (VAT) Area by Computed Tomography (CT) Scans and in Trunk Fat by DEXA. [ Time Frame: Baseline, Week 48, Week 96 ] [ Designated as safety issue: No ]
    The mean percent change from baseline in physical signs of lipohypertrophy, as assessed objectively by changes in visceral adipose tissue (VAT) area (cm2) by computed tomography (CT) scans and by changes in trunk fat (kg) by DEXA. Clinical improvement is associated with a decrease in values. (Baseline values can be found in the Baseline Characteristics section.)

  • Mean Percent Change From Baseline in Peripheral Adipose Tissue (Limb Fat) by DEXA and by Changes in Subcutaneous Adipose Tissue (SAT) Area by CT Scans [ Time Frame: Baseline, Week 48, Week 96 ] [ Designated as safety issue: No ]
    The mean percent change from baseline in physical signs of lipoatrophy, as assessed objectively by changes in peripheral adipose tissue (ie, limb fat (kg) by DEXA and in subcutaneous adipose tissue (SAT) area by CT scans. Clinical improvement is associated with stable values, or an increase in values. (Baseline values can be found in the Baseline Characteristics section.)

  • Mean Percent Change From Baseline in Total Body Fat by DEXA and in Total Adipose Tissue (TAT) Area by CT Scans [ Time Frame: Baseline, Week 48, Week 96 ] [ Designated as safety issue: No ]
    The mean percent change from baseline in total body fat by DEXA and in total adipose tissue (TAT) area by CT scans. Total body fat and TAT are both associated many factors (trunk fat + limb fat + other [weight, etc]), and thus clinical improvement cannot be predicted based solely an increase or decrease of these values. (Baseline values can be found in the Baseline Characteristics section.)

  • Mean Percent Changes From Baseline in Fasting Lipids [ Time Frame: Baseline, Week 48, Week 96 ] [ Designated as safety issue: No ]
    Mean percent changes from baseline in fasting total, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and non-HDL cholesterol, triglycerides, and apolipoprotein B

  • Mean Changes From Baseline in Fasting Glucose at Week 48 and Week 96 [ Time Frame: Baseline, Week 48, Week 96 ] [ Designated as safety issue: No ]
  • Mean Changes From Baseline in Fasting Insulin at Week 48 and Week 96 [ Time Frame: Baseline, Week 48, Week 96 ] [ Designated as safety issue: No ]
  • Mean Changes From Baseline in Fasting Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) [ Time Frame: Baseline, Week 48, Week 96 ] [ Designated as safety issue: No ]
    HOMA-IR is an index used in evaluation of obese patients at risk for type 2 diabetes which requires fasting glucose and insulin concentrations. It is a mathematical model based on the theory of a negative feedback loop between the liver and β-cells that regulates both fasting glucose and insulin concentrations and can be used to estimate pancreatic β-cell function and degree of insulin resistance. HOMA-IR normal values are between 2 and 2.5. HOMA-IR ≥ 2.5 indicates insulin-resistance.

  • Mean Changes From Baseline in Body Weight at Week 48 and Week 96 [ Time Frame: Baseline, Week 48, Week 96 ] [ Designated as safety issue: No ]
  • Mean Changes From Baseline in Waist Circumference at Week 48 and Week 96 [ Time Frame: Baseline, Week 48, Week 96 ] [ Designated as safety issue: No ]
  • Mean Changes From Baseline in Body Mass Index at Week 48 and Week 96 [ Time Frame: Baseline, Week 48, Week 96 ] [ Designated as safety issue: No ]
  • Mean Changes From Baseline in Waist-to-Hip Ratio at Week 48 and Week 96 [ Time Frame: Baseline, Week 48, Week 96 ] [ Designated as safety issue: No ]
    Mean changes from baseline in proportion of waist to hip measurements.

  • Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and AEs Leading to Discontinuation [ Time Frame: Through Week 96 of study therapy ] [ Designated as safety issue: Yes ]
    Percentage of Participants with AEs, Serious AEs (SAEs), Deaths, and AEs leading to discontinuation. An AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. An SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a cancer, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event.

  • Percentage of Participants With Abnormal Liver Function Tests [ Time Frame: Week 48, Week 96 ] [ Designated as safety issue: Yes ]
    Percentage of participants with Abnormal Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Total Bilirubin (TBILI) measurements. Values for liver tests are graded using the modified World Health Organization (WHO) criteria. Grade 1 is mild, grade 2 is moderate, grade 3 is severe, grade 4 is life threatening or disabling.

  • Percentage of Participants With Adverse Events (AEs) Leading to Discontinuation [ Time Frame: Through Week 96 ] [ Designated as safety issue: Yes ]
    Percentage of Participants with AEs leading to discontinuation of study therapy. An AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. All events listed in this table were SAEs, except for renal impairment and hypertriglycerideamia, which were an AEs (and did not meet the 5 percent threshold reported in Adverse Event module of this record).

  • Kaplan-Meier Cumulative Proportion of Participants Without Virologic Rebound (HIV RNA ≥400 c/mL) at Timepoints up to Week 96 in Treated Participants With HIV RNA <400 c/mL at Baseline [ Time Frame: Weeks 8-12, Weeks 20-24, Weeks 32-36, Weeks 44-48, Weeks 56-60, Weeks 68-72, Weeks 80-84, Weeks 92-96 ] [ Designated as safety issue: No ]
    Virologic rebound was measured from the first dose of study therapy to the first of the 2 consecutive measurements ≥400 c/mL. Time to virologic rebound was analyzed using life tables. Measured Values show the Kaplan-Meier cumulative proportion of participants without virologic rebound up to the end of the respective interval.

  • Mean Change From Baseline in CD4 Count [ Time Frame: Baseline, Week 48, Week 96 ] [ Designated as safety issue: No ]
    Mean change from baseline in CD4 count among treated subjects


Enrollment: 219
Study Start Date: July 2005
Study Completion Date: June 2008
Primary Completion Date: July 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Switch arm Drug: Atazanavir (ATV) + ritonavir (RTV), continuation of backbone 2 nucleoside reverse transcriptase inhibitor (NRTIs)
Capsules, Oral, ATV 300 mg + RTV 100 mg once daily up to 96 weeks
Other Name: Reyataz
Active Comparator: Control Arm Drug: continuation of current HAART (boosted protease inhibitor [PI] combination + 2 NRTIs)
Protease inhibitor [PI] combination + 2 NRTIs

  Eligibility

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

Inclusion Criteria:

  • HIV-1 infected on HAART regimen containing 2 NRTI and boosted PI for at least 12 weeks prior to screening. Subjects may not have experienced virological failure to more than one prior PI-containing regimen. Must be able to swallow tablets
  • Viral load <400 c/mL at screening and stable for at least 6 months
  • Signs of fat redistribution and lipohypertrophy (abdominal) Waist to Hip Ratio >0.90 and Waist Circumference >88.2 cm for men and Waist Circumference >75.3 for women

Exclusion Criteria:

  • Pregnant or breastfeeding women
  • New HIV-related opportunistic infections
  • Active alcohol or substance use
  • Grade 4 lab toxicity
  • History of taking atazanavir (ATV)
  • Prohibited therapies, including non-nucleoside reverse transcriptase inhibitors (NNRTI)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00135356

  Show 31 Study Locations
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
BMS Clinical Trials Disclosure  This link exits the ClinicalTrials.gov site
For FDA Safety Alerts and Recalls refer to the following link www.fda.gov/MEDWATCH/safety.htm  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00135356     History of Changes
Other Study ID Numbers: AI424-131
Study First Received: August 25, 2005
Results First Received: December 15, 2009
Last Updated: April 20, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by Bristol-Myers Squibb:
HIV infections

Additional relevant MeSH terms:
Lipodystrophy
HIV-Associated Lipodystrophy Syndrome
Skin Diseases, Metabolic
Skin Diseases
Lipid Metabolism Disorders
Metabolic Diseases
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
 Protease Inhibitors
Ritonavir
Atazanavir
Reverse Transcriptase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Nucleic Acid Synthesis Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
HIV Protease Inhibitors
Anti-HIV Agents

ClinicalTrials.gov processed this record on March 07, 2013