Study of Reyataz in HIV-infected Patients With Lipodystrophy Syndrome

HIV-Associated Lipodystrophy Syndrome Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00135356
• Other study ID #: AI424-131
• Status: Completed
• Phase: Phase 4
• First received: August 25, 2005
• Last updated: April 20, 2010
• Start date: July 2005
• Est. completion date: June 2008

Study information

• Verified date: April 2010
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 219
• Est. completion date: June 2008
• Est. primary completion date: July 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV-Associated Lipodystrophy Syndrome
• Lipodystrophy
• Syndrome

Intervention

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
• continuation of current HAART (boosted protease inhibitor [PI] combination + 2 NRTIs)
Protease inhibitor [PI] combination + 2 NRTIs

Locations

Country	Name	City	State
Canada	Local Institution	Ottawa	Ontario
Canada	Local Institution	Toronto	Ontario
France	Local Institution	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
Germany	Local Institution	Frankfurt/ Main
Germany	Local Institution	Muenchen
Italy	Local Institution	Brescia
Italy	Local Institution	Milano
Italy	Local Institution	Modena
Italy	Local Institution	Roma
Mexico	Local Institution	Guadalajara	Jalisco
Mexico	Local Institution	Puebla
Mexico	Local Institution	Zapopan	Jalisco
Poland	Local Institution	Szczecin
Poland	Local Institution	Wroclaw
Spain	Local Institution	Barcelona
Spain	Local Institution	Elche (Alicante)
Spain	Local Institution	Guipuzcoa
Spain	Local Institution	Madrid
Spain	Local Institution	Malaga
Spain	Local Institution	Valencia
United Kingdom	Local Institution	Brighton	East Sussex
United Kingdom	Local Institution	London	Greater London
United States	Local Institution	Ft. Lauderdale	Florida
United States	Local Institution	Honolulu	Hawaii
United States	Local Institution	Houston	Texas
United States	Local Institution	Huntersville	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Canada,  France,  Germany,  Italy,  Mexico,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Mean Changes From Baseline in Fasting Glucose at Week 48 and Week 96		Baseline, Week 48, Week 96	No
Secondary	Mean Changes From Baseline in Fasting Insulin at Week 48 and Week 96		Baseline, Week 48, Week 96	No
Secondary	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 ß-cells that regulates both fasting glucose and insulin concentrations and can be used to estimate pancreatic ß-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	No
Secondary	Mean Changes From Baseline in Body Weight at Week 48 and Week 96		Baseline, Week 48, Week 96	No
Secondary	Mean Changes From Baseline in Waist Circumference at Week 48 and Week 96		Baseline, Week 48, Week 96	No
Secondary	Mean Changes From Baseline in Body Mass Index at Week 48 and Week 96		Baseline, Week 48, Week 96	No
Secondary	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	No
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	No
Secondary	Mean Change From Baseline in CD4 Count	Mean change from baseline in CD4 count among treated subjects	Baseline, Week 48, Week 96	No

External Links

•   BMS Clinical Trials Disclosure
•   For FDA Safety Alerts and Recalls refer to the following link www.fda.gov/MEDWATCH/safety.htm