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┬ác/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
  Show All Outcome Measures

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 ]

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
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Time Frame The AE data below represents data from start of study in November 2001 through the last locked database of the study, 18 November 2009.
Additional Description No text entered.

Frequency Threshold
Threshold above which other adverse events are reported   5%  

Reporting Groups
  Description
ATV300/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
ATV400/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

Other Adverse Events
    ATV300/RTV     ATV400/SQV     LPV/RTV  
Total, other (not including serious) adverse events        
# participants affected / at risk     101/119     95/110     104/118  
Eye disorders        
OCULAR ICTERUS † 1      
# participants affected / at risk     13/119 (10.92%)     4/110 (3.64%)     0/118 (0.00%)  
Gastrointestinal disorders        
NAUSEA † 1      
# participants affected / at risk     23/119 (19.33%)     30/110 (27.27%)     18/118 (15.25%)  
VOMITING † 1      
# participants affected / at risk     16/119 (13.45%)     17/110 (15.45%)     12/118 (10.17%)  
DIARRHOEA † 1      
# participants affected / at risk     30/119 (25.21%)     34/110 (30.91%)     63/118 (53.39%)  
DYSPEPSIA † 1      
# participants affected / at risk     7/119 (5.88%)     10/110 (9.09%)     6/118 (5.08%)  
GASTRITIS † 1      
# participants affected / at risk     1/119 (0.84%)     6/110 (5.45%)     1/118 (0.85%)  
FLATULENCE † 1      
# participants affected / at risk     6/119 (5.04%)     8/110 (7.27%)     6/118 (5.08%)  
ABDOMINAL PAIN † 1      
# participants affected / at risk     7/119 (5.88%)     12/110 (10.91%)     10/118 (8.47%)  
ABDOMINAL DISTENSION † 1      
# participants affected / at risk     6/119 (5.04%)     8/110 (7.27%)     8/118 (6.78%)  
ABDOMINAL PAIN UPPER † 1      
# participants affected / at risk     5/119 (4.20%)     16/110 (14.55%)     7/118 (5.93%)  
General disorders        
FATIGUE † 1      
# participants affected / at risk     9/119 (7.56%)     10/110 (9.09%)     10/118 (8.47%)  
PYREXIA † 1      
# participants affected / at risk     19/119 (15.97%)     9/110 (8.18%)     10/118 (8.47%)  
ASTHENIA † 1      
# participants affected / at risk     7/119 (5.88%)     7/110 (6.36%)     9/118 (7.63%)  
OEDEMA PERIPHERAL † 1      
# participants affected / at risk     2/119 (1.68%)     2/110 (1.82%)     6/118 (5.08%)  
INFLUENZA LIKE ILLNESS † 1      
# participants affected / at risk     8/119 (6.72%)     4/110 (3.64%)     4/118 (3.39%)  
Hepatobiliary disorders        
JAUNDICE † 1      
# participants affected / at risk     19/119 (15.97%)     7/110 (6.36%)     0/118 (0.00%)  
HYPERBILIRUBINAEMIA † 1      
# participants affected / at risk     23/119 (19.33%)     8/110 (7.27%)     1/118 (0.85%)  
Immune system disorders        
HYPERSENSITIVITY † 1      
# participants affected / at risk     0/119 (0.00%)     6/110 (5.45%)     2/118 (1.69%)  
Infections and infestations        
INFLUENZA † 1      
# participants affected / at risk     20/119 (16.81%)     17/110 (15.45%)     14/118 (11.86%)  
PNEUMONIA † 1      
# participants affected / at risk     6/119 (5.04%)     5/110 (4.55%)     3/118 (2.54%)  
SINUSITIS † 1      
# participants affected / at risk     15/119 (12.61%)     14/110 (12.73%)     19/118 (16.10%)  
BRONCHITIS † 1      
# participants affected / at risk     13/119 (10.92%)     12/110 (10.91%)     17/118 (14.41%)  
PHARYNGITIS † 1      
# participants affected / at risk     8/119 (6.72%)     7/110 (6.36%)     7/118 (5.93%)  
GASTROENTERITIS † 1      
# participants affected / at risk     2/119 (1.68%)     4/110 (3.64%)     7/118 (5.93%)  
NASOPHARYNGITIS † 1      
# participants affected / at risk     17/119 (14.29%)     13/110 (11.82%)     19/118 (16.10%)  
URINARY TRACT INFECTION † 1      
# participants affected / at risk     10/119 (8.40%)     9/110 (8.18%)     9/118 (7.63%)  
UPPER RESPIRATORY TRACT INFECTION † 1      
# participants affected / at risk     7/119 (5.88%)     5/110 (4.55%)     14/118 (11.86%)  
Investigations        
LIPASE INCREASED † 1      
# participants affected / at risk     8/119 (6.72%)     2/110 (1.82%)     8/118 (6.78%)  
WEIGHT DECREASED † 1      
# participants affected / at risk     10/119 (8.40%)     9/110 (8.18%)     13/118 (11.02%)  
BLOOD BILIRUBIN INCREASED † 1      
# participants affected / at risk     11/119 (9.24%)     4/110 (3.64%)     1/118 (0.85%)  
BLOOD TRIGLYCERIDES INCREASED † 1      
# participants affected / at risk     7/119 (5.88%)     2/110 (1.82%)     9/118 (7.63%)  
ASPARTATE AMINOTRANSFERASE INCREASED † 1      
# participants affected / at risk     2/119 (1.68%)     2/110 (1.82%)     6/118 (5.08%)  
Metabolism and nutrition disorders        
DECREASED APPETITE † 1      
# participants affected / at risk     7/119 (5.88%)     12/110 (10.91%)     12/118 (10.17%)  
HYPERTRIGLYCERIDAEMIA † 1      
# participants affected / at risk     8/119 (6.72%)     6/110 (5.45%)     8/118 (6.78%)  
Musculoskeletal and connective tissue disorders        
MYALGIA † 1      
# participants affected / at risk     12/119 (10.08%)     6/110 (5.45%)     9/118 (7.63%)  
BACK PAIN † 1      
# participants affected / at risk     15/119 (12.61%)     13/110 (11.82%)     13/118 (11.02%)  
ARTHRALGIA † 1      
# participants affected / at risk     10/119 (8.40%)     10/110 (9.09%)     7/118 (5.93%)  
PAIN IN EXTREMITY † 1      
# participants affected / at risk     5/119 (4.20%)     7/110 (6.36%)     4/118 (3.39%)  
Nervous system disorders        
HEADACHE † 1      
# participants affected / at risk     23/119 (19.33%)     28/110 (25.45%)     22/118 (18.64%)  
DIZZINESS † 1      
# participants affected / at risk     7/119 (5.88%)     9/110 (8.18%)     7/118 (5.93%)  
PARAESTHESIA † 1      
# participants affected / at risk     5/119 (4.20%)     5/110 (4.55%)     10/118 (8.47%)  
HYPOAESTHESIA † 1      
# participants affected / at risk     2/119 (1.68%)     2/110 (1.82%)     8/118 (6.78%)  
NEUROPATHY PERIPHERAL † 1      
# participants affected / at risk     5/119 (4.20%)     4/110 (3.64%)     7/118 (5.93%)  
Psychiatric disorders        
ANXIETY † 1      
# participants affected / at risk     8/119 (6.72%)     9/110 (8.18%)     4/118 (3.39%)  
INSOMNIA † 1      
# participants affected / at risk     12/119 (10.08%)     6/110 (5.45%)     10/118 (8.47%)  
DEPRESSION † 1      
# participants affected / at risk     12/119 (10.08%)     11/110 (10.00%)     14/118 (11.86%)  
Respiratory, thoracic and mediastinal disorders        
COUGH † 1      
# participants affected / at risk     14/119 (11.76%)     9/110 (8.18%)     17/118 (14.41%)  
OROPHARYNGEAL PAIN † 1      
# participants affected / at risk     9/119 (7.56%)     5/110 (4.55%)     11/118 (9.32%)  
Skin and subcutaneous tissue disorders        
RASH † 1      
# participants affected / at risk     7/119 (5.88%)     10/110 (9.09%)     12/118 (10.17%)  
PRURITUS † 1      
# participants affected / at risk     4/119 (3.36%)     7/110 (6.36%)     6/118 (5.08%)  
LIPOATROPHY † 1      
# participants affected / at risk     2/119 (1.68%)     6/110 (5.45%)     5/118 (4.24%)  
LIPODYSTROPHY ACQUIRED † 1      
# participants affected / at risk     9/119 (7.56%)     10/110 (9.09%)     11/118 (9.32%)  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA 12.1



  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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