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Study of Reyataz in HIV-infected Patients With Lipodystrophy Syndrome

Primary Purpose

HIV-Associated Lipodystrophy Syndrome

Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Atazanavir (ATV) + ritonavir (RTV), continuation of backbone 2 nucleoside reverse transcriptase inhibitor (NRTIs)
continuation of current HAART (boosted protease inhibitor [PI] combination + 2 NRTIs)
Sponsored by
Bristol-Myers Squibb
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV-Associated Lipodystrophy Syndrome focused on measuring HIV infections

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Switch arm

Control Arm

Arm Description

Outcomes

Primary Outcome Measures

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.)

Secondary Outcome Measures

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.)
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.)
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.)
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.)
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
Mean Changes From Baseline in Fasting Glucose at Week 48 and Week 96
Mean Changes From Baseline in Fasting Insulin at Week 48 and 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.
Mean Changes From Baseline in Body Weight at Week 48 and Week 96
Mean Changes From Baseline in Waist Circumference at Week 48 and Week 96
Mean Changes From Baseline in Body Mass Index at Week 48 and 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.
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.
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.
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).
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.
Mean Change From Baseline in CD4 Count
Mean change from baseline in CD4 count among treated subjects

Full Information

First Posted
August 25, 2005
Last Updated
April 20, 2010
Sponsor
Bristol-Myers Squibb
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1. Study Identification

Unique Protocol Identification Number
NCT00135356
Brief Title
Study of Reyataz in HIV-infected Patients With Lipodystrophy Syndrome
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)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2010
Overall Recruitment Status
Completed
Study Start Date
July 2005 (undefined)
Primary Completion Date
July 2007 (Actual)
Study Completion Date
June 2008 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Bristol-Myers Squibb

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV-Associated Lipodystrophy Syndrome
Keywords
HIV infections

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
219 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Switch arm
Arm Type
Active Comparator
Arm Title
Control Arm
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Atazanavir (ATV) + ritonavir (RTV), continuation of backbone 2 nucleoside reverse transcriptase inhibitor (NRTIs)
Other Intervention Name(s)
Reyataz
Intervention Description
Capsules, Oral, ATV 300 mg + RTV 100 mg once daily up to 96 weeks
Intervention Type
Drug
Intervention Name(s)
continuation of current HAART (boosted protease inhibitor [PI] combination + 2 NRTIs)
Intervention Description
Protease inhibitor [PI] combination + 2 NRTIs
Primary Outcome Measure Information:
Title
Change From Baseline in Trunk-to-limb Fat Ratio as Measured by Dual Energy X-Ray Absortiometry (DEXA) at Week 48
Description
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.)
Time Frame
Baseline, Week 48
Secondary Outcome Measure Information:
Title
Change From Baseline in Trunk-to-limb Fat Ratio as Measured by DEXA at Week 96
Description
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.)
Time Frame
Baseline, Week 96
Title
Mean Percent Change From Baseline in Visceral Adipose Tissue (VAT) Area by Computed Tomography (CT) Scans and in Trunk Fat by DEXA.
Description
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.)
Time Frame
Baseline, Week 48, Week 96
Title
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
Description
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.)
Time Frame
Baseline, Week 48, Week 96
Title
Mean Percent Change From Baseline in Total Body Fat by DEXA and in Total Adipose Tissue (TAT) Area by CT Scans
Description
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.)
Time Frame
Baseline, Week 48, Week 96
Title
Mean Percent Changes From Baseline in Fasting Lipids
Description
Mean percent changes from baseline in fasting total, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and non-HDL cholesterol, triglycerides, and apolipoprotein B
Time Frame
Baseline, Week 48, Week 96
Title
Mean Changes From Baseline in Fasting Glucose at Week 48 and Week 96
Time Frame
Baseline, Week 48, Week 96
Title
Mean Changes From Baseline in Fasting Insulin at Week 48 and Week 96
Time Frame
Baseline, Week 48, Week 96
Title
Mean Changes From Baseline in Fasting Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)
Description
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.
Time Frame
Baseline, Week 48, Week 96
Title
Mean Changes From Baseline in Body Weight at Week 48 and Week 96
Time Frame
Baseline, Week 48, Week 96
Title
Mean Changes From Baseline in Waist Circumference at Week 48 and Week 96
Time Frame
Baseline, Week 48, Week 96
Title
Mean Changes From Baseline in Body Mass Index at Week 48 and Week 96
Time Frame
Baseline, Week 48, Week 96
Title
Mean Changes From Baseline in Waist-to-Hip Ratio at Week 48 and Week 96
Description
Mean changes from baseline in proportion of waist to hip measurements.
Time Frame
Baseline, Week 48, Week 96
Title
Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and AEs Leading to Discontinuation
Description
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.
Time Frame
Through Week 96 of study therapy
Title
Percentage of Participants With Abnormal Liver Function Tests
Description
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.
Time Frame
Week 48, Week 96
Title
Percentage of Participants With Adverse Events (AEs) Leading to Discontinuation
Description
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).
Time Frame
Through Week 96
Title
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
Description
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.
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
Title
Mean Change From Baseline in CD4 Count
Description
Mean change from baseline in CD4 count among treated subjects
Time Frame
Baseline, Week 48, Week 96

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol-Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
Facility Information:
Facility Name
Local Institution
City
Ft. Lauderdale
State/Province
Florida
Country
United States
Facility Name
Local Institution
City
Honolulu
State/Province
Hawaii
Country
United States
Facility Name
Local Institution
City
Huntersville
State/Province
North Carolina
Country
United States
Facility Name
Local Institution
City
Houston
State/Province
Texas
Country
United States
Facility Name
Local Institution
City
Ottawa
State/Province
Ontario
Country
Canada
Facility Name
Local Institution
City
Toronto
State/Province
Ontario
Country
Canada
Facility Name
Local Institution
City
Bondy Cedex
Country
France
Facility Name
Local Institution
City
Lagny-sur-Marne
Country
France
Facility Name
Local Institution
City
Lyon Cedex 02
Country
France
Facility Name
Local Institution
City
Lyon Cedex 03
Country
France
Facility Name
Local Institution
City
Nice Cedex
Country
France
Facility Name
Local Institution
City
Paris Cedex 12
Country
France
Facility Name
Local Institution
City
Frankfurt/ Main
Country
Germany
Facility Name
Local Institution
City
Muenchen
Country
Germany
Facility Name
Local Institution
City
Brescia
Country
Italy
Facility Name
Local Institution
City
Milano
Country
Italy
Facility Name
Local Institution
City
Modena
Country
Italy
Facility Name
Local Institution
City
Roma
Country
Italy
Facility Name
Local Institution
City
Guadalajara
State/Province
Jalisco
Country
Mexico
Facility Name
Local Institution
City
Zapopan
State/Province
Jalisco
Country
Mexico
Facility Name
Local Institution
City
Puebla
Country
Mexico
Facility Name
Local Institution
City
Szczecin
Country
Poland
Facility Name
Local Institution
City
Wroclaw
Country
Poland
Facility Name
Local Institution
City
Barcelona
Country
Spain
Facility Name
Local Institution
City
Elche (Alicante)
Country
Spain
Facility Name
Local Institution
City
Guipuzcoa
Country
Spain
Facility Name
Local Institution
City
Madrid
Country
Spain
Facility Name
Local Institution
City
Malaga
Country
Spain
Facility Name
Local Institution
City
Valencia
Country
Spain
Facility Name
Local Institution
City
Brighton
State/Province
East Sussex
Country
United Kingdom
Facility Name
Local Institution
City
London
State/Province
Greater London
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

Study of Reyataz in HIV-infected Patients With Lipodystrophy Syndrome

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