Nevirapine or Atazanavir/Ritonavir Given With Emtricitabine/Tenofovir in Human Immunodeficiency Virus (HIV)-1-infected Treatment Naive Adults

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00389207
First received: October 17, 2006
Last updated: December 9, 2013
Last verified: December 2013
Results First Received: January 13, 2012  
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: nevirapine bid
Drug: nevirapine qd
Drug: atazanavir

  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
No text entered.

Reporting Groups
  Description
Nevirapine QD Nevirapine (NVP) 400mg QD on a background of the fixed combination Truvada® (emitricitabine 200mg QD and tenofovir 300mg QD)
Nevirapine BID NVP 200mg BID on a background of the fixed combination Truvada®
Atazanvir/Ritonavir Atazanvir 300mg QD boosted by ritonavir 100mg QD (ATZ/r) on a background of the fixed combination Truvada®

Participant Flow:   Overall Study
    Nevirapine QD     Nevirapine BID     Atazanvir/Ritonavir  
STARTED     188 [1]   188 [2]   193  
COMPLETED     125     116     152  
NOT COMPLETED     63     72     41  
Adverse Event                 26                 32                 10  
Protocol Violation                 3                 1                 4  
Lost to Follow-up                 12                 9                 7  
Withdrawal by Subject                 5                 7                 11  
Not specified                 17                 23                 9  
[1] 3 patients were randomized to NVP QD but not treated and so not part of the Full Analysis Set (FAS)
[2] 4 patients were randomized to NVP BID but not treated and so are not part of the FAS



  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
Nevirapine QD Nevirapine (NVP) 400mg QD on a background of the fixed combination Truvada® (emitricitabine 200mg QD and tenofovir 300mg QD)
Nevirapine BID NVP 200mg BID on a background of the fixed combination Truvada®
Atazanvir/Ritonavir ATZ/r on a background of the fixed combination Truvada®
Total Total of all reporting groups

Baseline Measures
    Nevirapine QD     Nevirapine BID     Atazanvir/Ritonavir     Total  
Number of Participants  
[units: participants]
  188     188     193     569  
Age  
[units: years]
Mean ± Standard Deviation
  38.4  ± 9.7     40.0  ± 10.5     37.6  ± 9.5     38.6  ± 9.9  
Gender  
[units: participants]
       
Female     36     25     31     92  
Male     152     163     162     477  
Baseline HIV viral load category  
[units: participants]
       
Baseline HIV viral load ≤ 100,000 copies/mL     71     71     65     207  
Baseline HIV viral load > 100,000 copies/mL     117     117     128     362  
Baseline log10 HIV viral load [1]
[units: log¬†10¬†Copies/mL]
Mean ± Standard Deviation
  5.1  ± 0.7     5.1  ± 0.6     5.1  ± 0.7     5.1  ± 0.7  
Baseline CD4+ cell count [1]
[units: Cells/mm^3]
Mean ± Standard Deviation
  183.3  ± 95.5     202.9  ± 93.6     193.2  ± 95.8     193.2  ± 95.1  
[1] 185 NVP QD patients, 188 NVP BID patients and 192 ATZ/R patients had data



  Outcome Measures
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1.  Primary:   Treatment Response at Week 48   [ Time Frame: From baseline to Week 48 ]

2.  Secondary:   Treatment Response at Week 48 (TLOVR Algorithm)   [ Time Frame: From baseline to Week 48 ]
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Measure Type Secondary
Measure Title Treatment Response at Week 48 (TLOVR Algorithm)
Measure Description Treatment response is defined as a VL <50 copies/mL measured at two consecutive visits up to Week 48 and without subsequent rebound or change of ARV therapy up to Week 48, based on time to loss of virologic response (TLOVR) algorithm, as a sensitivity analysis for the primary analysis.
Time Frame From baseline to 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.
FAS but numbers are reduced as indicated due to empty cells in analysis adjusting for baseline categories

Reporting Groups
  Description
Nevirapine QD+BID NVP 400mg QD or 200mg BID on a background of the fixed combination Truvada®
Atazanvir/Ritonavir ATZ/r on a background of the fixed combination Truvada®

Measured Values
    Nevirapine QD+BID     Atazanvir/Ritonavir  
Number of Participants Analyzed  
[units: participants]
  376     193  
Treatment Response at Week 48 (TLOVR Algorithm)  
[units: Patients]
   
Number of responders     261     142  
Number of non-responders     115     51  


Statistical Analysis 1 for Treatment Response at Week 48 (TLOVR Algorithm)
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] Yes
Method [3] Cochran-Mantel-Haenszel
P Value [4] 0.321
Risk Difference (RD) [5] -0.038
95% Confidence Interval ( -0.112 to 0.037 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  Non-inferiority margin 12% (or 0.12 as proportion)
[3] Other relevant method information, such as adjustments or degrees of freedom:
  Analysis controlling for screening viral load and CD4+ count categories. N=373 NVP QD patients and N=193 ATZ/r patients.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Test for superiority following confirmation of non-inferiority
[5] Other relevant estimation information:
  No text entered.



3.  Secondary:   Proportion of Patients With VL < 50 Copies/ml   [ Time Frame: From baseline to Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132 and 144/EOT ]

4.  Secondary:   Proportion of Patients With VL < 400 Copies/ml   [ Time Frame: From baseline to Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132 and 144/EOT ]

5.  Secondary:   Change in CD4+ Count From Baseline   [ Time Frame: From baseline to Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132 and 144/EOT ]

6.  Secondary:   Change in Framingham Score From Baseline   [ Time Frame: From baseline to Weeks 48, 96 and 144/EOT ]

7.  Secondary:   Change in Mental Health Summary (MHS) Score From Baseline   [ Time Frame: From baseline to Weeks 48, 96 and 144/EOT ]

8.  Secondary:   Change in Physical Health Summary (PHS) Score From Baseline   [ Time Frame: From baseline to Weeks 48, 96 and 144/EOT ]

9.  Secondary:   Number of Patients Hospitalized   [ Time Frame: From baseline to Week 24, Week 24 to 48, Week 48 to 96, and Week 96 to 144/EOT ]

10.  Secondary:   Non-scheduled Physician Visits   [ Time Frame: From baseline to Week 24, Week 24 to 48, Week 48 to 96, and Week 96 to 144/EOT ]

11.  Secondary:   Genotypic Resistance Associated With Virologic Failure   [ Time Frame: From baseline to Week 48 ]

12.  Secondary:   Treatment-emergent AIDS-defining Illness   [ Time Frame: From baseline to Week 144 ]

13.  Secondary:   Treatment-emergent AIDS-defining Illness Leading to Death   [ Time Frame: From baseline to Week 144 ]

14.  Secondary:   Lipodystrophy   [ Time Frame: From baseline to Week 144 ]

15.  Secondary:   Serum Lipid Abnormalities   [ Time Frame: From baseline to Week 144 ]

16.  Secondary:   Glycaemic Abnormalities   [ Time Frame: From baseline to Week 144 ]

17.  Secondary:   Treatment Response at Week 96   [ Time Frame: From baseline to Week 96 ]

18.  Secondary:   Treatment Response at Week 144   [ Time Frame: From baseline to Week 144 ]

19.  Secondary:   Proportion of Patients With Virological Rebound With VL >=50 Copies/mL After CVR (Confirmed Virological Response) at Week 24, 48, 96, 144   [ Time Frame: at Week 24, 48, 96, 144 ]

20.  Secondary:   Proportion of Patients With Virological Rebound With VL >=400 Copies/mL After CVR at Week 24, 48, 96, 144   [ Time Frame: at Week 24, 48, 96, 144 ]

21.  Secondary:   Proportion of Patients With Virologic Failure at Week 48, 96, 144   [ Time Frame: at Week 48, 96, 144 ]

22.  Secondary:   Time to Treatment Response (First Confirmed VL<50 Copies/mL)   [ Time Frame: baseline to week 144 ]

23.  Secondary:   Time to Loss of Virologic Response (Rebound)   [ Time Frame: Baseline to week 144 ]

24.  Secondary:   Time to Treatment Failure   [ Time Frame: baseline to week 144 ]

25.  Secondary:   Change in the Calculated Glomerular Filtration Rate (GFR) at Week 48, 96 and 144   [ Time Frame: From baseline to Week 48, 96, 144 ]

26.  Secondary:   Proportion of Patients With >= DAIDS Grade 2 Laboratory Abnormalities   [ Time Frame: week 148 ]

27.  Secondary:   Proportion of Patients Reporting Rash of Any Severity   [ Time Frame: week 148 ]

28.  Secondary:   Proportion of Patients Reporting Hepatic Events of Any Severity   [ Time Frame: week 148 ]

29.  Secondary:   Proportion of Patients Reporting CNS (Central Nervous System) Side Effects of Any Severity   [ Time Frame: week 148 ]

30.  Secondary:   Change of Cholesterol Values From Baseline to Week 48, 96, 144   [ Time Frame: baseline to week 48, 96, 144 ]

31.  Secondary:   Changes of Apolipoprotein Values From Baseline to Week 48, 96, 144   [ Time Frame: baseline to week 48, 96, 144 ]

32.  Secondary:   Change of hsCRP From Baseline to Week 48, 96, 144   [ Time Frame: baseline to week 48, 96, 144 ]

33.  Secondary:   Change of Total Triglycerides From Baseline to Week 48, 96, 144   [ Time Frame: baseline to week 48, 96, 144 ]

34.  Secondary:   Change of Total Cholesterol to HDL-cholesterol Ratio From Baseline to Week 48, 96, 144   [ Time Frame: baseline to week 48, 96, 144 ]


  Serious Adverse Events


  Other Adverse Events


  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.


Limitations and Caveats
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.  


Results Point of Contact:  
Name/Title: Boehringer Ingelheim Call Center
Organization: Boehringer Ingelheim Pharmaceuticals
phone: 1-800-243-0127
e-mail: clintriage.rdg@boehringer-ingelheim.com


No publications provided by Boehringer Ingelheim

Publications automatically indexed to this study:

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00389207     History of Changes
Other Study ID Numbers: 1100.1470, 2005-004330-40
Study First Received: October 17, 2006
Results First Received: January 13, 2012
Last Updated: December 9, 2013
Health Authority: Argentina: A.N.M.A.T. (Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica)
Germany: Federal Institute for Drugs and Medical Devices
Great Britain: MHRA
Italy: Comitato Etico dell'Azienda Osp. Riuniti di Bergamo - Bergamo
Mexico: Comision Federal para la Proteccion contra Riesgos Sanitarios (COFEPRIS)
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Portugal: National Pharmacy and Medicines Institute
Romania: National Medicines Agency, Bucharest
Spain: Agencia Espanola del Medicamento y Productos Sanitarios
Switzerland: Swissmedic Schweizerisches Heilmittelinstitut (Swiss Agency for Therapeutic Products)