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
Results First Received: December 15, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: HIV-Associated Lipodystrophy Syndrome
Interventions: 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)

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 219 participants were enrolled and 18 were never randomized (1 poor/noncompliance; 10 no longer met study criteria; 5 withdrew consent). 201 participants were randomized; however, 1 participant was never treated and is not included in the participant flow.

Reporting Groups
  Description
ATV/RTV Switch Arm Participants switching their current treatment with a ritonavir (RTV)-boosted protease inhibitor (PI)-containing highly active antiretroviral therapy (HAART) regimen to atazanavir (ATV)/RTV (ATV: 2 x 150 mg capsules once daily (QD) / RTV: 1 x 100 mg capsule QD) while continuing their background nucleoside reverse transcriptase inhibitors (NRTIs).
PI/RTV Control Arm Participants continued on their current treatment with an RTV-boosted, PI-containing HAART regimen while continuing their background NRTIs.

Participant Flow:   Overall Study
    ATV/RTV Switch Arm     PI/RTV Control Arm  
STARTED     131 [1]   69 [2]
Discontinued Prior to Week 96 Visit     16     9  
Discontinued on or After Week 96 Visit     1     0  
COMPLETED     114     60  
NOT COMPLETED     17     9  
Adverse Event                 6                 2  
Lack of Efficacy                 2                 0  
Lost to Follow-up                 3                 1  
Surgery for abdominal fat                 1                 0  
Change in antiviral regimen                 0                 1  
Poor/noncompliance                 1                 1  
No longer meets study criteria                 2                 0  
Withdrawal by Subject                 2                 4  
[1] Number randomized and treated
[2] Number randomized and treated(1 randomized and never treated subject not included in this number.)



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
ATV/RTV Switch Arm Participants switching their current treatment with a ritonavir (RTV)-boosted protease inhibitor (PI)-containing highly active antiretroviral therapy (HAART) regimen to atazanavir (ATV)/RTV (ATV: 2 x 150 mg capsules once daily (QD) / RTV: 1 x 100 mg capsule QD) while continuing their background nucleoside reverse transcriptase inhibitors (NRTIs).
PI/RTV Control Arm Participants continued on their current treatment with an RTV-boosted, PI-containing HAART regimen while continuing their background NRTIs.
Total Total of all reporting groups

Baseline Measures
    ATV/RTV Switch Arm     PI/RTV Control Arm     Total  
Number of Participants  
[units: participants]
  131     69     200  
Age  
[units: Years]
Median ( Full Range )
  43  
  ( 23 to 79 )  
  42  
  ( 26 to 65 )  
  43  
  ( 23 to 79 )  
Gender  
[units: participants]
     
Female     35     14     49  
Male     96     55     151  
Race/Ethnicity, Customized  
[units: Participants]
     
White     83     43     126  
Mestizo     31     15     46  
Black/African American     15     10     25  
American Indian/Alaska Native     1     0     1  
Latino/Hispanic     1     1     2  
Region of Enrollment  
[units: participants]
     
Europe     77     39     116  
North America     54     30     84  
Cluster of Differentiation 4 (CD4) Distribution [1]
[units: Participants]
     
50 to <100 cells/mm3     2     0     2  
100 to <200 cells/mm3     14     3     17  
200 to <350 cells/mm3     24     22     46  
350 to <500 cells/mm3     31     16     47  
≥500 cells/mm3     60     27     87  
Missing     0     1     1  
Fasting Glucose [2]
[units: participants]
     
<100 mg/dL     96     49     145  
100 mg/dL to <126 mg/dL     23     13     36  
>=126 mg/dL     5     4     9  
Fasting Lipids [3]
[units: participants]
     
Triglycerides <150 mg/dL     29     14     43  
Triglycerides 150 mg/dL to <200 mg/dL     28     9     37  
Triglycerides 200 mg/dL to <500 mg/dL     52     27     79  
Triglycerides >=500 mg/dL     14     12     26  
Non-HDL Cholesterol <130 mg/dL     22     16     38  
Non-HDL Cholesterol 130 mg/dL to <160 mg/dL     31     14     45  
Non-HDL Cholesterol 160 mg/dL to <190 mg/dL     32     15     47  
Non-HDL Cholesterol 190 mg/dL to <220 mg/dL     22     9     31  
Non-HDL Cholesterol >=220 mg/dL     16     8     24  
LDL Cholesterol <100 mg/dL     40     22     62  
LDL Cholesterol 100 mg/dL to <130 mg/dL     36     25     61  
LDL Cholesterol 130 mg/dL to <160 mg/dL     30     11     41  
LDL Cholesterol 160 mg/dL to <190 mg/dL     11     1     12  
LDL Cholesterol >=190 mg/dL     6     2     8  
Total Cholesterol <200 mg/dL     45     28     73  
Total Cholesterol 200 mg/dL to 240 mg/dL     42     19     61  
Total Cholesterol 240 mg/dL to 300 mg/dL     29     11     40  
Total Cholesterol >=300 mg/dL     7     4     11  
HDL Cholesterol <40 mg/dL     23     21     44  
HDL Cholesterol 40 mg/dL to <60 mg/dL     80     32     112  
HDL Cholesterol >=60 mg/dL     20     9     29  
Human Immunodeficiency Virus Ribonucleic Acid (HIV RNA) Distribution  
[units: Participants]
     
<50 c/mL     117     64     181  
50 to <400 c/mL     10     5     15  
400 to <1000 c/mL     2     0     2  
≥1000 c/mL     2     0     2  
Adipose Tissue at Baseline [4]
[units: cm2]
Median ( Inter-Quartile Range )
     
VAT     131.9  
  ( 93.8 to 185.8 )  
  128.1  
  ( 95.8 to 193.7 )  
  129.4  
  ( 94.3 to 186.1 )  
SAT     209.5  
  ( 123.6 to 300.7 )  
  183.9  
  ( 151.4 to 282.4 )  
  193.6  
  ( 140.3 to 289.2 )  
TAT     356.2  
  ( 263.9 to 446.3 )  
  328.6  
  ( 287.3 to 457.8 )  
  352.0  
  ( 268.5 to 453.1 )  
Body Mass Index (BMI) [5]
[units: kg/m2]
Median ( Inter-Quartile Range )
  25.9  
  ( 24.1 to 28.5 )  
  25.7  
  ( 24.2 to 28.8 )  
  25.9  
  ( 24.2 to 28.5 )  
Body Weight  
[units: kg]
Median ( Inter-Quartile Range )
  75  
  ( 69 to 83 )  
  77  
  ( 69 to 87 )  
  76  
  ( 69 to 84 )  
CD4 Cell Count [6]
[units: cells/mm3]
Median ( Full Range )
  470  
  ( 90 to 1919 )  
  437  
  ( 100 to 1078 )  
  459  
  ( 90 to 1919 )  
Trunk Fat, Limb Fat, Total Body Fat [7]
[units: kg]
Median ( Inter-Quartile Range )
     
Trunk Fat     11.8  
  ( 8.6 to 15.3 )  
  10.9  
  ( 8.8 to 13.8 )  
  11.4  
  ( 8.7 to 14.6 )  
Limb Fat     7.1  
  ( 4.6 to 10.4 )  
  6.7  
  ( 4.6 to 9.4 )  
  7.0  
  ( 4.6 to 10.0 )  
Total Body Fat     20.8  
  ( 14.1 to 26.0 )  
  18.7  
  ( 15.6 to 22.4 )  
  19.8  
  ( 14.8 to 25.7 )  
Trunk-to-Limb Fat Ratio [8]
[units: ratio]
Median ( Inter-Quartile Range )
  1.59  
  ( 1.27 to 2.04 )  
  1.73  
  ( 1.17 to 2.15 )  
  1.62  
  ( 1.23 to 2.10 )  
Waist Circumference  
[units: cm]
Median ( Inter-Quartile Range )
  94  
  ( 90 to 103 )  
  95  
  ( 91 to 100 )  
  94  
  ( 90 to 102 )  
Waist-to-Hip Ratio [9]
[units: ratio]
Median ( Inter-Quartile Range )
  0.99  
  ( 0.95 to 1.03 )  
  0.97  
  ( 0.94 to 1.02 )  
  0.99  
  ( 0.95 to 1.03 )  
[1] CD4=a protein marker on the surface of certain types of T lymphocytes and other cells; HIV binds to CD4 receptors to enter host cells.
[2] 7 participants in ATV/RTV arm and 3 participants in PI/RTV arm were missing this baseline measurement.
[3] Triglycerides, non-high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, total cholesterol, and HDL cholesterol. Values for all baseline fasting lipid measurements were missing for 8 participants in the ATV/RTV arm. Values for baseline fasting LDL cholesterol were missing for 8 participants in the PI/RTV arm; values for all other baseline lipid measurements were missing for 7 participants.
[4] Visceral, subcutaneous, and total adipose tissue (VAT, SAT, and TAT) as assessed by computed tomography (CT). Values for all 3 measurements were missing for 20 participants in the ATV/RTV arm (n=111). Values for all 3 measurements were missing for 10 participants in the PI/RTV arm (n=59).
[5] 131 participants in ATV/RTV arm and 67 participants in PI/RTV arm had this baseline measurement.
[6] CD4 cell=a type of white blood cell that bears the CD4 surface receptor and helps coordinate a range of immune system activities.
[7] Values for all 3 baseline fat measurements were missing for 14 participants in the ATV/RTV arm (n=117). Values for baseline trunk fat measurements were missing for 10 participants in the PI/RTV arm (n=59); values for baseline limb fat and total body fat measurements were missing for 13 participants in the PI/RTV arm (n=56).
[8] 117 participants in ATV/RTV arm and 56 participants in PI/RTV arm had this measure at baseline.
[9] 131 participants in ATV/RTV arm and 68 participants in PI/RTV arm had this baseline measurement.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   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 ]

2.  Secondary:   Change From Baseline in Trunk-to-limb Fat Ratio as Measured by DEXA at Week 96   [ Time Frame: Baseline, Week 96 ]
  Hide Outcome Measure 2

Measure Type Secondary
Measure Title Change From Baseline in Trunk-to-limb Fat Ratio as Measured by DEXA at Week 96
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Observed case (OC) analysis: n=participants with fat measurement at baseline and at the analysis timepoint. Last observation carried forward (LOCF): n=participants with fat measurement at baseline and at or before the analysis timepoint.

Reporting Groups
  Description
ATV/RTV Switch Arm Participants switching their current treatment with a ritonavir (RTV)-boosted protease inhibitor (PI)-containing highly active antiretroviral therapy (HAART) regimen to atazanavir (ATV)/RTV (ATV: 2 x 150 mg capsules once daily (QD) / RTV: 1 x 100 mg capsule QD) while continuing their background nucleoside reverse transcriptase inhibitors (NRTIs).
PI/RTV Control Arm Participants continued on their current treatment with an RTV-boosted, PI-containing HAART regimen while continuing their background NRTIs.

Measured Values
    ATV/RTV Switch Arm     PI/RTV Control Arm  
Number of Participants Analyzed  
[units: participants]
  131     69  
Change From Baseline in Trunk-to-limb Fat Ratio as Measured by DEXA at Week 96  
[units: ratio]
Mean ± Standard Error
   
LOCF Population (n=112; n=54)     0.04  ± 0.035     0.02  ± 0.046  
OC Population (n=94; n=45)     0.04  ± 0.041     0.05  ± 0.051  


Statistical Analysis 1 for Change From Baseline in Trunk-to-limb Fat Ratio as Measured by DEXA at Week 96
Groups [1] All groups
Method [2] t-test, 2 sided
P Value [3] 0.73
Difference in Means [4] 0.02
95% Confidence Interval ( -0.10 to 0.14 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  LOCF
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-value not adjusted for multiple testing, 2-sided 95% CI.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change From Baseline in Trunk-to-limb Fat Ratio as Measured by DEXA at Week 96
Groups [1] All groups
Method [2] t-test, 2 sided
P Value [3] 0.91
Difference in Means [4] -0.01
95% Confidence Interval ( -0.14 to 0.13 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  OC
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-value not adjusted for multiple testing, 2-sided 95% CI.
[4] Other relevant estimation information:
  No text entered.



3.  Secondary:   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 ]

4.  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   [ Time Frame: Baseline, Week 48, Week 96 ]

5.  Secondary:   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 ]

6.  Secondary:   Mean Percent Changes From Baseline in Fasting Lipids   [ Time Frame: Baseline, Week 48, Week 96 ]

7.  Secondary:   Mean Changes From Baseline in Fasting Glucose at Week 48 and Week 96   [ Time Frame: Baseline, Week 48, Week 96 ]

8.  Secondary:   Mean Changes From Baseline in Fasting Insulin at Week 48 and Week 96   [ Time Frame: Baseline, Week 48, Week 96 ]

9.  Secondary:   Mean Changes From Baseline in Fasting Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)   [ Time Frame: Baseline, Week 48, Week 96 ]

10.  Secondary:   Mean Changes From Baseline in Body Weight at Week 48 and Week 96   [ Time Frame: Baseline, Week 48, Week 96 ]

11.  Secondary:   Mean Changes From Baseline in Waist Circumference at Week 48 and Week 96   [ Time Frame: Baseline, Week 48, Week 96 ]

12.  Secondary:   Mean Changes From Baseline in Body Mass Index at Week 48 and Week 96   [ Time Frame: Baseline, Week 48, Week 96 ]

13.  Secondary:   Mean Changes From Baseline in Waist-to-Hip Ratio at Week 48 and Week 96   [ Time Frame: Baseline, Week 48, Week 96 ]

14.  Secondary:   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 ]

15.  Secondary:   Percentage of Participants With Abnormal Liver Function Tests   [ Time Frame: Week 48, Week 96 ]

16.  Secondary:   Percentage of Participants With Adverse Events (AEs) Leading to Discontinuation   [ Time Frame: Through Week 96 ]

17.  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   [ 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 ]

18.  Secondary:   Mean Change From Baseline in CD4 Count   [ Time Frame: Baseline, Week 48, Week 96 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: BMS Study Director
Organization: Bristol-Myers Squibb
e-mail: Clinical.Trials@bms.com


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