Atazanavir (BMS-232632) in Combination With Ritonavir or Saquinavir, and Lopinavir/Ritonavir, Each With Tenofovir and a Nucleoside in Subjects With HIV

This study has been completed.
Sponsor:
Information provided by:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00035932
First received: May 6, 2002
Last updated: November 29, 2010
Last verified: November 2010
Results First Received: October 14, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: HIV Infections
Interventions: Drug: Atazanavir + ritonavir + tenofovir + nucleoside
Drug: Atazanavir + saquinavir + tenofovir + nucleoside
Drug: Lopinavir/ritonavir + tenofovir + nucleoside

  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
571 human immunodeficiency virus (HIV)-infected participants were enrolled; 358 (63%) were randomized to treatment. Of the 213 not randomized, 194 did not meet eligibility criteria; other reasons include duplicate enrollment (4), accrual closed (1), noncompliance (1), serious adverse event (2), patient request (11), missing information (4).

Reporting Groups
  Description
ATV 300 mg / RTV

atazanavir (ATV) 300 mg + ritonavir (RTV) 100 mg + tenofovir (TDF) 300 mg + nucleoside of choice

ATV , RTV, and TDF once daily, nucleoside per label 48 Weeks and then for as long as subject is in need of therapy through study

ATV 400 mg / SQV

ATV 400 mg + saquinavir (SQV) 1200 mg + TDF 300 mg + nucleoside of choice

ATV, SQV, and TDF once daily, nucleoside per label 48 Weeks and then for as long as subject is in need of therapy through study

LPV / RTV

lopinavir (LPV)/RTV 400/100 mg + TDF 300 mg + nucleoside of choice

LPV/RTV twice daily, TDF once daily, nucleoside per label 48 Weeks and then for as long as subject is in need of therapy through study


Participant Flow:   Overall Study
    ATV 300 mg / RTV     ATV 400 mg / SQV     LPV / RTV  
STARTED     119 [1]   110 [2]   118 [3]
Discontinued Prior to Week 48 Visit     26     29     13  
Discontinued Between Weeks 48 and 96     26     27     30  
Discontinued on or After Week 96     4     4     6  
COMPLETED     63 [4]   50 [5]   69 [6]
NOT COMPLETED     56     60     49  
Adverse Event                 10                 9                 9  
Death                 0                 0                 1  
Disease Progression / Relapse                 1                 1                 0  
Lost to Follow-up                 4                 4                 3  
Noncompliance                 6                 7                 6  
Protocol Violation While on Study                 0                 1                 2  
Withdrawal by Subject                 1                 5                 0  
Study Termination by Sponsor                 1                 0                 0  
Lack of Efficacy                 33                 33                 28  
[1] 120 randomized, 119 treated
[2] 115 randomized, 110 treated
[3] 123 randomized, 118 treated
[4] 63 remained on treatment, 0 completed at Week 96
[5] 50 remained on treatment, 0 completed at Week 96
[6] 59 remained on treatment, 10 completed at Week 96



  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 300 mg / RTV

ATV 300 mg + RTV 100 mg + TDF 300 mg + nucleoside of choice

ATV , RTV, and TDF once daily, nucleoside per label 48 Weeks and then for as long as subject is in need of therapy through study

ATV 400 mg / SQV

ATV 400 mg + SQV 1200 mg + TDF 300 mg + nucleoside of choice

ATV, SQV, and TDF once daily, nucleoside per label 48 Weeks and then for as long as subject is in need of therapy through study

LPV / RTV

LPV/RTV 400/100 mg + TDF 300 mg + nucleoside of choice

LPV/RTV twice daily, TDF once daily, nucleoside per label 48 Weeks and then for as long as subject is in need of therapy through study

Total Total of all reporting groups

Baseline Measures
    ATV 300 mg / RTV     ATV 400 mg / SQV     LPV / RTV     Total  
Number of Participants  
[units: participants]
  120     115     123     358  
Age  
[units: years]
Median ( Full Range )
  39  
  ( 24 to 71 )  
  41  
  ( 26 to 74 )  
  39  
  ( 25 to 72 )  
  40  
  ( 24 to 74 )  
Gender  
[units: participants]
       
Female     24     26     27     77  
Male     96     89     96     281  
Race/Ethnicity, Customized  
[units: participants]
       
White     75     70     71     216  
Hispanic/Latino     27     26     27     80  
Black     18     16     21     55  
Other     0     3     4     7  
Region of Enrollment  
[units: participants]
       
South America     56     55     54     165  
North America     39     38     47     124  
Europe     25     22     22     69  
Acquired Immunodeficiency Virus (AIDS)  
[units: participants]
       
Yes     33     33     36     102  
No     87     82     87     256  
Intravenous (IV) Drug Use  
[units: participants]
       
Yes     8     7     8     23  
No     112     108     115     335  
Cluster of Differentiation 4 (CD4) cell count  
[units: cells/mm^3]
Median ( Full Range )
  317  
  ( 40 to 1025 )  
  286  
  ( 42 to 1543 )  
  283  
  ( 14 to 1238 )  
  297  
  ( 14 to 1543 )  
Human Immunodeficiency Virus Ribonucleic Acid (HIV RNA)  
[units: log10 c/mL]
Median ( Full Range )
  4.44  
  ( 2.60 to 5.88 )  
  4.42  
  ( 2.60 to 5.88 )  
  4.47  
  ( 2.60 to 5.88 )  
  4.45  
  ( 2.60 to 5.88 )  



  Outcome Measures
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1.  Primary:   Mean Change From Baseline in HIV Ribonucleic Acid (RNA) at Week 24   [ Time Frame: Baseline, Week 24 ]

2.  Primary:   Mean Change From Baseline in HIV RNA at Week 48   [ Time Frame: Baseline, Week 48 ]

3.  Primary:   Mean Change From Baseline in HIV RNA at Week 96   [ Time Frame: Baseline, Week 96 ]

4.  Secondary:   Mean Change From Baseline in HIV RNA at Week 2   [ Time Frame: Baseline, Week 2 ]

5.  Secondary:   Participants Achieving Virologic Half Log Suppression (Limit of Quantification [LOQ] = 400 c/mL) at Week 24 (Overall and by Protease Inhibitor [PI] Sensitivity)   [ Time Frame: Baseline, Week 24 ]

6.  Secondary:   Participants Achieving Virologic Half Log Suppression (LOQ = 400 c/mL) at Week 48, (Overall and by PI Sensitivity)   [ Time Frame: Baseline, Week 48 ]

7.  Secondary:   Participants Achieving Virologic Half Log Suppression (LOQ = 400 c/mL) at Week 96   [ Time Frame: Baseline, Week 96 ]

8.  Secondary:   Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 24   [ Time Frame: Week 24 ]

9.  Secondary:   Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 24, by PI Sensitivity   [ Time Frame: Baseline, Week 24 ]

10.  Secondary:   Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 48   [ Time Frame: Week 48 ]

11.  Secondary:   Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 48, by PI Sensitivity   [ Time Frame: Baseline, Week 48 ]

12.  Secondary:   Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 96   [ Time Frame: Week 96 ]

13.  Secondary:   Participants Achieving Treatment Response (LOQ = 400 c/mL) Without Prior Failure at Week 24   [ Time Frame: Week 24 ]

14.  Secondary:   Participants Achieving Treatment Response (LOQ = 400 c/mL) Without Prior Failure at Week 48   [ Time Frame: Week 48 ]

15.  Secondary:   Participants Achieving Treatment Response (LOQ = 400 c/mL) Without Prior Failure at Week 96   [ Time Frame: Week 96 ]

16.  Secondary:   Participants Achieving Treatment Response (LOQ = 50 c/mL) Without Prior Failure at Week 24   [ Time Frame: Week 24 ]

17.  Secondary:   Participants Achieving Treatment Response (LOQ = 50 c/mL) Without Prior Failure at Week 48   [ Time Frame: Week 48 ]

18.  Secondary:   Participants Achieving Treatment Response (LOQ = 50 c/mL) Without Prior Failure at Week 96   [ Time Frame: Week 96 ]

19.  Secondary:   Change From Baseline in CD4 Cell Count at Week 24   [ Time Frame: Baseline, Week 24 ]

20.  Secondary:   Change From Baseline in CD4 Cell Count at Week 48   [ Time Frame: Baseline, Week 48 ]

21.  Secondary:   Change From Baseline in CD4 Cell Count at Week 96   [ Time Frame: Baseline, Week 96 ]

22.  Secondary:   Correlation of ATV Minimum Plasma Concentration (Cmin), Inhibitory Quotient (IQ), and Number of Protease Inhibitor (PI) Mutations at Baseline With HIV RNA Change From Baseline at Week 24   [ Time Frame: Baseline, Week 24 ]

23.  Secondary:   Correlation of ATV Minimum Plasma Concentration (Cmin), Inhibitory Quotient (IQ), and Number of Protease Inhibitor (PI) Mutations at Baseline With HIV RNA Change From Baseline at Week 48   [ Time Frame: Baseline, Week 48 ]

24.  Secondary:   Correlation of ATV Minimum Plasma Concentration (Cmin) Inhibitory Quotient (IQ), and Number of PI Mutations at Baseline and CD4 Cell Count Change From Baseline at Week 24   [ Time Frame: Baseline, Week 24 ]

25.  Secondary:   Correlation of ATV Minimum Plasma Concentration (Cmin) Inhibitory Quotient (IQ), and Number of PI Mutations at Baseline and CD4 Cell Count Change From Baseline at Week 48   [ Time Frame: Baseline, Week 48 ]

26.  Secondary:   Lipid Mean Percent Change From Baseline at Week 24   [ Time Frame: Baseline, Week 24 ]

27.  Secondary:   Lipid Mean Percent Change From Baseline at Week 48   [ Time Frame: Week 48 ]

28.  Secondary:   Lipid Mean Percent Change From Baseline at Week 96, Observed Values   [ Time Frame: Week 96 ]

29.  Secondary:   Deaths, Serious Adverse Events (SAEs), and Adverse Events (AEs) Through Week 48   [ Time Frame: From Enrollment through Week 48 ]

30.  Secondary:   Most Common AEs and AEs of Interest Through Week 48   [ Time Frame: From Enrollment to Week 48 ]

31.  Secondary:   Fasting Glucose Mean Change From Baseline at Week 24   [ Time Frame: Baseline, Week 24 ]

32.  Secondary:   Fasting Glucose Mean Change From Baseline at Week 48   [ Time Frame: Week 48 ]

33.  Secondary:   Grade 3/4 Laboratory Abnormalities Through Week 48   [ Time Frame: From Enrollment to Week 48 ]

34.  Secondary:   Fridericia-corrected QT (QTcF) Interval and Change From Baseline by Analysis Time Point   [ Time Frame: Baseline, Week 4 predose, 2-3 hours postdose, 6-12 hours postdose, Week 12, Week 24, Week 48 ]

35.  Secondary:   PR Interval and Change From Baseline by Analysis Time Point   [ Time Frame: Baseline, Week 4 predose, 2-3 hours postdose, 6-12 hours postdose, Week 12, Week 24, Week 48 ]

36.  Secondary:   Adherence to Regimen Though Week 48 Based on MACS the Multicenter AIDS Cohort Study (MACS) Adherence Questionnaire   [ Time Frame: Baseline, Week 24, Week 48 ]

37.  Secondary:   Mean Score of European Quality of Life-5 Dimensions (EQ-5D) Health Index Score at Baseline, Mid-Study (Week 24), and Final (Week 48)   [ Time Frame: Baseline, Week 24, Week 48 ]
  Hide Outcome Measure 37

Measure Type Secondary
Measure Title Mean Score of European Quality of Life-5 Dimensions (EQ-5D) Health Index Score at Baseline, Mid-Study (Week 24), and Final (Week 48)
Measure Description The EQ-5D is a 5-item questionnaire to assess health-related quality of life in 5 health dimensions (mobility, self-care, usual activity, pain/discomfort, anxiety/depression) are scored on a 3-level scale: no problems (1), some problems (2), extreme problems (3). Using a standard algorithm, responses are summarized into a single score, the EQ-5D Health Index Score (HIS), which ranges between 1 (representing perfect health) and 0 (representing the worst imaginable health state or death). The smallest coefficient of change is 0.03.
Time Frame Baseline, Week 24, Week 48  
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.
Treated participants; as-randomized population (refers to the treatment regimen assigned at randomization). n=number of participants evaluated with EQ-5D at given time point.

Reporting Groups
  Description
ATV 300 mg / RTV

ATV 300 mg + RTV 100 mg + TDF 300 mg + nucleoside of choice

ATV , RTV, and TDF once daily, nucleoside per label 48 Weeks and then for as long as subject is in need of therapy through study

ATV 400 mg / SQV

ATV 400 mg + SQV 1200 mg + TDF 300 mg + nucleoside of choice

ATV, SQV, and TDF once daily, nucleoside per label 48 Weeks and then for as long as subject is in need of therapy through study

LPV / RTV

LPV/RTV 400/100 mg + TDF 300 mg + nucleoside of choice

LPV/RTV twice daily, TDF once daily, nucleoside per label 48 Weeks and then for as long as subject is in need of therapy through study


Measured Values
    ATV 300 mg / RTV     ATV 400 mg / SQV     LPV / RTV  
Number of Participants Analyzed  
[units: participants]
  119     110     118  
Mean Score of European Quality of Life-5 Dimensions (EQ-5D) Health Index Score at Baseline, Mid-Study (Week 24), and Final (Week 48)  
[units: units on a scale]
Mean ± Standard Error
     
Baseline (n=99, 86, 100)     0.83  ± 0.02     0.85  ± 0.02     0.86  ± 0.02  
Mid-Study (n=103, 83, 95)     0.87  ± 0.02     0.86  ± 0.02     0.89  ± 0.01  
Final (n=93, 84, 96)     0.84  ± 0.02     0.85  ± 0.03     0.88  ± 0.02  

No statistical analysis provided for Mean Score of European Quality of Life-5 Dimensions (EQ-5D) Health Index Score at Baseline, Mid-Study (Week 24), and Final (Week 48)



38.  Secondary:   Mean Score of European Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) at Baseline, Mid-Study (Week 24), and Final (Week 48)   [ Time Frame: Baseline, Week 24, Week 48 ]

39.  Secondary:   Number of Participants Utilizing Resources for Managing Lipid Elevation   [ Time Frame: Baseline, Week 24, Week 48 ]

40.  Secondary:   Mean ATV, RTV and SQV Minimum Concentration (Cmin) Values   [ Time Frame: collected at the pre-dose time point after receiving atazanavir for at least four weeks ]

41.  Secondary:   HIV IC50 at Week 24   [ Time Frame: Week 24 ]

42.  Secondary:   Inhibitory Quotient at Week 24   [ Time Frame: Baseline, Week 24 ]

43.  Secondary:   Inhibitory Quotient at Week 48   [ Time Frame: Baseline, Week 48 ]

44.  Secondary:   HIV RNA Level - Treated Subjects With Evaluable Cmins at Week 24   [ Time Frame: Baseline, Week 24 ]

45.  Secondary:   HIV RNA Level - Treated Subjects With Evaluable Cmins at Week 48   [ Time Frame: Baseline, Week 48 ]


  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
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