GEMINI Study - A Study of Saquinavir/Ritonavir in Treatment-Naive Patients With HIV-1 Infection

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00105079
First received: March 4, 2005
Last updated: September 23, 2011
Last verified: September 2011
Results First Received: March 29, 2011  
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: saquinavir [Invirase]
Drug: Lopinavir/ritonavir
Drug: Emtricitabine/tenofovir disoproxil fumarate
Drug: Ritonavir

  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
This study was conducted between 28 April 2005 and 24 August 2007 at 38 study centers in the United States, Canada, France and Thailand. Patients were randomized to receive saquinavir/ritonavir 1000/100 mg PO BID plus emtricitabine/tenofovir 200/300 mg PO QD or lopinavir/ritonavir 400/100 mg PO BID plus emtricitabine/tenofovir 200/300 mg PO QD .

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
Saquinavir/Ritonavir saquinavir mesylate 1000 mg twice daily (BID) + ritonavir 100 mg BID + emtricitabine/tenofovir disoproxil fumarate 200/300 mg orally every day for 48 weeks.
Lopinavir/Ritonavir lopinavir/ritonavir 400/100 mg BID + emtricitabine/tenofovir disoproxil fumarate 200/300 mg orally every day for 48 weeks.

Participant Flow:   Overall Study
    Saquinavir/Ritonavir     Lopinavir/Ritonavir  
STARTED     167     170  
Safety Population     163     168  
COMPLETED     128     135  
NOT COMPLETED     39     35  
Adverse Event                 5                 12  
Death                 3                 1  
Lost to Follow-up                 12                 12  
Lack of Efficacy                 9                 3  
Refused treatment                 6                 4  
Violation of selection criteria at entry                 0                 2  
Protocol Violation                 1                 0  
not specified                 3                 1  



  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
Saquinavir/Ritonavir saquinavir mesylate 1000 mg twice daily (BID) + ritonavir 100 mg BID + emtricitabine/tenofovir disoproxil fumarate 200/300 mg orally every day for 48 weeks.
Lopinavir/Ritonavir lopinavir/ritonavir 400/100 mg BID + emtricitabine/tenofovir disoproxil fumarate 200/300 mg orally every day for 48 weeks.
Total Total of all reporting groups

Baseline Measures
    Saquinavir/Ritonavir     Lopinavir/Ritonavir     Total  
Number of Participants  
[units: participants]
  167     170     337  
Age  
[units: years]
Mean ± Standard Deviation
  38.3  ± 9.31     37.9  ± 9.60     38.1  ± 9.45  
Gender  
[units: participants]
     
Female     31     39     70  
Male     136     131     267  



  Outcome Measures
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1.  Primary:   Number of Patients With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Viral Load <50 Copies/mL   [ Time Frame: Week 48 ]

Measure Type Primary
Measure Title Number of Patients With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Viral Load <50 Copies/mL
Measure Description

The primary objective of this study was to evaluate the efficacy of saquinavir/ritonavir BID plus emtricitabine/tenofovir QD versus lopinavir/ritonavir BID plus emtricitabine/tenofovir QD in treatment-naïve HIV-1 infected adults.

Blood samples for HIV-1 RNA viral load measurement were collected at the Week 48 clinic visit. The number of participants with HIV-1 RNA results <50 copies/mL is reported.

Time Frame 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.
intent-to-treat (ITT) Population

Reporting Groups
  Description
Saquinavir/Ritonavir saquinavir mesylate 1000 mg twice daily (BID) + ritonavir 100 mg BID + emtricitabine/tenofovir disoproxil fumarate 200/300 mg orally every day for 48 weeks.
Lopinavir/Ritonavir lopinavir/ritonavir 400/100 mg BID + emtricitabine/tenofovir disoproxil fumarate 200/300 mg orally every day for 48 weeks.

Measured Values
    Saquinavir/Ritonavir     Lopinavir/Ritonavir  
Number of Participants Analyzed  
[units: participants]
  167     170  
Number of Patients With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Viral Load <50 Copies/mL  
[units: participants]
   
Pts. with HIV-1 RNA Viral Load <50 copies/mL - YES     108     108  
Pts. with HIV-1 RNA Viral Load <50 copies/mL - NO     59     62  

No statistical analysis provided for Number of Patients With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Viral Load <50 Copies/mL



2.  Secondary:   Number of Patients With HIV-1 RNA Viral Load <50 and <400 Copies/mL   [ Time Frame: Week 48 ]

Measure Type Secondary
Measure Title Number of Patients With HIV-1 RNA Viral Load <50 and <400 Copies/mL
Measure Description

The secondary objectives of the study were to evaluate the safety, adherence, and tolerability of saquinavir/ritonavir BID plus emtricitabine/tenofovir QD versus lopinavir/ritonavir BID plus emtricitabine/tenofovir QD in treatment-naïve HIV-1 infected adults.

Blood samples for HIV-1 RNA viral load measurement were collected at the Week 48 clinic visit. The number of participants with HIV-1 RNA results <50 copies/mL and the number of participants with HIV-1 RNA results <400 copies/mL are reported.

Time Frame 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.
Intent-to-Treat Population

Reporting Groups
  Description
Saquinavir/Ritonavir saquinavir mesylate 1000 mg twice daily (BID) + ritonavir 100 mg BID + emtricitabine/tenofovir disoproxil fumarate 200/300 mg orally every day for 48 weeks.
Lopinavir/Ritonavir lopinavir/ritonavir 400/100 mg BID + emtricitabine/tenofovir disoproxil fumarate 200/300 mg orally every day for 48 weeks.

Measured Values
    Saquinavir/Ritonavir     Lopinavir/Ritonavir  
Number of Participants Analyzed  
[units: participants]
  167     170  
Number of Patients With HIV-1 RNA Viral Load <50 and <400 Copies/mL  
[units: participants]
   
Patients with <50 Copies/mL     108     108  
Patients with <400 Copies/mL     121     127  

No statistical analysis provided for Number of Patients With HIV-1 RNA Viral Load <50 and <400 Copies/mL



3.  Secondary:   Change From Baseline in HIV-1 RNA Viral Load   [ Time Frame: Baseline to Week 48 ]

Measure Type Secondary
Measure Title Change From Baseline in HIV-1 RNA Viral Load
Measure Description Descriptive statistics for change from baseline in log10 transformed plasma HIV-1 RNA load (copies/mL) were presented by treatment arm. Logarithmic transformation (base 10) was applied to HIV-1 RNA viral load at baseline and at each study visit. Change from baseline in plasma HIV-1 RNA was derived as follows: Change from baseline = Log10 (HIV-1 RNA at week x) – Log10 (HIV-1 RNA at baseline)
Time Frame 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.
ITT Population. (n) in each of the categories is the number of participants from the ITT population who had data available at that time point.

Reporting Groups
  Description
Saquinavir/Ritonavir saquinavir mesylate 1000 mg twice daily (BID) + ritonavir 100 mg BID + emtricitabine/tenofovir disoproxil fumarate 200/300 mg orally every day for 48 weeks.
Lopinavir/Ritonavir lopinavir/ritonavir 400/100 mg BID + emtricitabine/tenofovir disoproxil fumarate 200/300 mg orally every day for 48 weeks.

Measured Values
    Saquinavir/Ritonavir     Lopinavir/Ritonavir  
Number of Participants Analyzed  
[units: participants]
  167     170  
Change From Baseline in HIV-1 RNA Viral Load  
[units: copies/mL]
Mean ( 95% Confidence Interval )
   
Baseline     5.20  
  ( 5.1 to 5.3 )  
  5.17  
  ( 5.1 to 5.3 )  
Week 48 (n=126,133)     1.80  
  ( 1.8 to 1.9 )  
  1.83  
  ( 1.8 to 1.9 )  
Change from Baseline to Week 48 (n=126,133)     -3.39  
  ( -3.5 to -3.3 )  
  -3.36  
  ( -3.5 to -3.2 )  

No statistical analysis provided for Change From Baseline in HIV-1 RNA Viral Load



4.  Secondary:   Change From Baseline in Cluster Differentiation Antigen 4 Positive (CD4+) Lymphocyte Count   [ Time Frame: Baseline to Week 48 ]

Measure Type Secondary
Measure Title Change From Baseline in Cluster Differentiation Antigen 4 Positive (CD4+) Lymphocyte Count
Measure Description Summary statistics for change from baseline in CD4+ lymphocyte count were presented by treatment arm. Change from baseline in CD4+ lymphocyte count was derived as follows: Change from baseline = (CD4+ count at week x) – (CD4+ count at baseline).
Time Frame 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.
ITT Population. (n) in each of the categories is the number of participants from the ITT population who had data available at that time point.

Reporting Groups
  Description
Saquinavir/Ritonavir saquinavir mesylate 1000 mg twice daily (BID) + ritonavir 100 mg BID + emtricitabine/tenofovir disoproxil fumarate 200/300 mg orally every day for 48 weeks.
Lopinavir/Ritonavir lopinavir/ritonavir 400/100 mg BID + emtricitabine/tenofovir disoproxil fumarate 200/300 mg orally every day for 48 weeks.

Measured Values
    Saquinavir/Ritonavir     Lopinavir/Ritonavir  
Number of Participants Analyzed  
[units: participants]
  167     170  
Change From Baseline in Cluster Differentiation Antigen 4 Positive (CD4+) Lymphocyte Count  
[units: cells/mm^3]
Median ( 95% Confidence Interval )
   
Baseline (n=166,169)     141.5  
  ( 108.0 to 168.0 )  
  142.0  
  ( 116.0 to 187.0 )  
Week 48 (n=122,131)     319.0  
  ( 277.0 to 370.0 )  
  348.0  
  ( 317.0 to 401.0 )  
Change from Baseline to Week 48 (n=121,130)     178.0  
  ( 159.0 to 213.0 )  
  204.0  
  ( 182.0 to 222.0 )  

No statistical analysis provided for Change From Baseline in Cluster Differentiation Antigen 4 Positive (CD4+) Lymphocyte Count



5.  Secondary:   Number of Participants Assessed for Adverse Events (AEs)   [ Time Frame: reported up to 28 days after the last dose of study treatment. (Up to 52 weeks) ]

Measure Type Secondary
Measure Title Number of Participants Assessed for Adverse Events (AEs)
Measure Description Detailed information for Adverse Events and Serious Adverse Events will be represented in the SAE/AE section of PRS.
Time Frame reported up to 28 days after the last dose of study treatment. (Up to 52 weeks)  
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.
Safety population included all randomized patients who received at least one dose of study medication

Reporting Groups
  Description
Saquinavir/Ritonavir saquinavir mesylate 1000 mg twice daily (BID) + ritonavir 100 mg BID + emtricitabine/tenofovir disoproxil fumarate 200/300 mg orally every day for 48 weeks.
Lopinavir/Ritonavir lopinavir/ritonavir 400/100 mg BID + emtricitabine/tenofovir disoproxil fumarate 200/300 mg orally every day for 48 weeks.

Measured Values
    Saquinavir/Ritonavir     Lopinavir/Ritonavir  
Number of Participants Analyzed  
[units: participants]
  163     168  
Number of Participants Assessed for Adverse Events (AEs)  
[units: participants]
  163     168  

No statistical analysis provided for Number of Participants Assessed for Adverse Events (AEs)



6.  Secondary:   Number of Patients Who Discontinued Treatment Due to Abnormal Laboratory Parameters   [ Time Frame: baseline and all study visits (Up to Week 52) ]

Measure Type Secondary
Measure Title Number of Patients Who Discontinued Treatment Due to Abnormal Laboratory Parameters
Measure Description Routine clinical testing, including hematology and standard chemistry panel was performed at all study visits. Laboratory tests for a fasting lipid profile and fasting insulin determination were obtained at baseline, weeks 24 and 48, and the 4-week follow-up visit. The number of participants who discontinued treatment due to an abnormal laboratory result at any visit is reported.
Time Frame baseline and all study visits (Up to Week 52)  
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.
Safety population included all randomized patients who received at least one dose of study medication.

Reporting Groups
  Description
Saquinavir/Ritonavir saquinavir mesylate 1000 mg twice daily (BID) + ritonavir 100 mg BID + emtricitabine/tenofovir disoproxil fumarate 200/300 mg orally every day for 48 weeks.
Lopinavir/Ritonavir lopinavir/ritonavir 400/100 mg BID + emtricitabine/tenofovir disoproxil fumarate 200/300 mg orally every day for 48 weeks.

Measured Values
    Saquinavir/Ritonavir     Lopinavir/Ritonavir  
Number of Participants Analyzed  
[units: participants]
  163     168  
Number of Patients Who Discontinued Treatment Due to Abnormal Laboratory Parameters  
[units: participants]
  0     0  

No statistical analysis provided for Number of Patients Who Discontinued Treatment Due to Abnormal Laboratory Parameters




  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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