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

August 25, 2005
April 20, 2010
July 2005
July 2007   (final data collection date for primary outcome measure)
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.)
Not Provided
Complete list of historical versions of study NCT00135356 on ClinicalTrials.gov Archive Site
  • 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
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Study of Reyataz in HIV-infected Patients With Lipodystrophy Syndrome
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)

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.

Not Provided
Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
HIV-Associated Lipodystrophy Syndrome
  • 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
  • Drug: continuation of current HAART (boosted protease inhibitor [PI] combination + 2 NRTIs)
    Protease inhibitor [PI] combination + 2 NRTIs
  • Active Comparator: Switch arm
    Intervention: Drug: Atazanavir (ATV) + ritonavir (RTV), continuation of backbone 2 nucleoside reverse transcriptase inhibitor (NRTIs)
  • Active Comparator: Control Arm
    Intervention: Drug: continuation of current HAART (boosted protease inhibitor [PI] combination + 2 NRTIs)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
219
June 2008
July 2007   (final data collection date for primary outcome measure)

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)
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Italy,   United States,   Canada,   France,   Germany,   United Kingdom,   Mexico,   Poland,   Spain
 
NCT00135356
AI424-131
No
Study Director, Bristol-Myers Squibb
Bristol-Myers Squibb
Not Provided
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
Bristol-Myers Squibb
April 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP