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.

Study Overview

• Status: Completed
• Conditions: HIV-Associated Lipodystrophy Syndrome
• Intervention / Treatment: 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)

• Study Type: Interventional
• Enrollment (Actual): 219
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada
      • Local Institution
    • Toronto, Ontario, Canada
      • Local Institution
• France
  • Bondy Cedex, France
    • Local Institution
  • Lagny-sur-Marne, France
    • Local Institution
  • Lyon Cedex 02, France
    • Local Institution
  • Lyon Cedex 03, France
    • Local Institution
  • Nice Cedex, France
    • Local Institution
  • Paris Cedex 12, France
    • Local Institution
• Germany
  • Frankfurt/ Main, Germany
    • Local Institution
  • Muenchen, Germany
    • Local Institution
• Italy
  • Brescia, Italy
    • Local Institution
  • Milano, Italy
    • Local Institution
  • Modena, Italy
    • Local Institution
  • Roma, Italy
    • Local Institution
• Mexico
  • Puebla, Mexico
    • Local Institution
  • Jalisco
    • Guadalajara, Jalisco, Mexico
      • Local Institution
    • Zapopan, Jalisco, Mexico
      • Local Institution
• Poland
  • Szczecin, Poland
    • Local Institution
  • Wroclaw, Poland
    • Local Institution
• Spain
  • Barcelona, Spain
    • Local Institution
  • Elche (Alicante), Spain
    • Local Institution
  • Guipuzcoa, Spain
    • Local Institution
  • Madrid, Spain
    • Local Institution
  • Malaga, Spain
    • Local Institution
  • Valencia, Spain
    • Local Institution
• United Kingdom
  • East Sussex
    • Brighton, East Sussex, United Kingdom
      • Local Institution
  • Greater London
    • London, Greater London, United Kingdom
      • Local Institution
• United States
  • Florida
    • Ft. Lauderdale, Florida, United States
      • Local Institution
  • Hawaii
    • Honolulu, Hawaii, United States
      • Local Institution
  • North Carolina
    • Huntersville, North Carolina, United States
      • Local Institution
  • Texas
    • Houston, Texas, United States
      • Local Institution

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Control Arm	Drug: continuation of current HAART (boosted protease inhibitor [PI] combination + 2 NRTIs); Protease inhibitor [PI] combination + 2 NRTIs
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 Names: Reyataz

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Trunk-to-limb Fat Ratio as Measured by Dual Energy X-Ray Absortiometry (DEXA) at Week 48	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.)	Baseline, Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Trunk-to-limb Fat Ratio as Measured by DEXA at Week 96	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.)	Baseline, Week 96
Mean Percent Change From Baseline in Visceral Adipose Tissue (VAT) Area by Computed Tomography (CT) Scans and in Trunk Fat by DEXA.	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.)	Baseline, Week 48, Week 96
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	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.)	Baseline, Week 48, Week 96
Mean Percent Change From Baseline in Total Body Fat by DEXA and in Total Adipose Tissue (TAT) Area by CT Scans	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.)	Baseline, Week 48, Week 96
Mean Percent Changes From Baseline in Fasting Lipids	Mean percent changes from baseline in fasting total, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and non-HDL cholesterol, triglycerides, and apolipoprotein B	Baseline, Week 48, Week 96
Mean Changes From Baseline in Fasting Glucose at Week 48 and Week 96		Baseline, Week 48, Week 96
Mean Changes From Baseline in Fasting Insulin at Week 48 and Week 96		Baseline, Week 48, Week 96
Mean Changes From Baseline in Fasting Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)	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.	Baseline, Week 48, Week 96
Mean Changes From Baseline in Body Weight at Week 48 and Week 96		Baseline, Week 48, Week 96
Mean Changes From Baseline in Waist Circumference at Week 48 and Week 96		Baseline, Week 48, Week 96
Mean Changes From Baseline in Body Mass Index at Week 48 and Week 96		Baseline, Week 48, Week 96
Mean Changes From Baseline in Waist-to-Hip Ratio at Week 48 and Week 96	Mean changes from baseline in proportion of waist to hip measurements.	Baseline, Week 48, Week 96
Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and AEs Leading to Discontinuation	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.	Through Week 96 of study therapy
Percentage of Participants With Abnormal Liver Function Tests	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.	Week 48, Week 96
Percentage of Participants With Adverse Events (AEs) Leading to Discontinuation	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).	Through Week 96
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	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.	Weeks 8-12, Weeks 20-24, Weeks 32-36, Weeks 44-48, Weeks 56-60, Weeks 68-72, Weeks 80-84, Weeks 92-96
Mean Change From Baseline in CD4 Count	Mean change from baseline in CD4 count among treated subjects	Baseline, Week 48, Week 96

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Study record dates

Study Major Dates

• Study Start: July 1, 2005
• Primary Completion (ACTUAL): July 1, 2007
• Study Completion (ACTUAL): June 1, 2008

Study Registration Dates

• First Submitted: August 25, 2005
• First Submitted That Met QC Criteria: August 25, 2005
• First Posted (ESTIMATE): August 26, 2005

Study Record Updates

• Last Update Posted (ESTIMATE): May 7, 2010
• Last Update Submitted That Met QC Criteria: April 20, 2010
• Last Verified: April 1, 2010

More Information

Terms related to this study

• Keywords: HIV infections
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Skin Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Disease; Lipid Metabolism Disorders; HIV Infections; Skin Diseases, Metabolic; Syndrome; Lipodystrophy; HIV-Associated Lipodystrophy Syndrome; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Viral Protease Inhibitors; Ritonavir; Protease Inhibitors; Reverse Transcriptase Inhibitors; Atazanavir Sulfate; HIV Protease Inhibitors
• Other Study ID Numbers: AI424-131