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

Study Overview
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Brief Summary
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This 2 arm study will evaluate the efficacy, safety and tolerability of saquinavir/ritonavir or lopinavir/ritonavir in combination with emtricitabine/tenofovir in patients with human immunodeficiency virus type 1 (HIV-1) infection who have received no prior HIV treatment. Patients will be randomized to receive either saquinavir/ritonavir 1000/100mg oral (po) twice daily (bid) + emtricitabine/tenofovir 200/300mg po once daily (qd), or lopinavir/ritonavir 400/100mg po bid + emtricitabine/tenofovir 200/300mg po qd. The anticipated time on study treatment is 3-12 months, and the target sample size is 100-500 individuals.

Official Title
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A 48-week, Randomized, Open-label, 2-arm Study to Compare the Efficacy of Saquinavir/Ritonavir Twice Daily (BID) Plus Emtricitabine/Tenofovir Once Daily (QD) Versus Lopinavir/Ritonavir BID Plus Emtricitabine/Tenofovir QD in Treatment-naïve Human Immunodeficiency Virus Type 1 (HIV-1) Infected Patients (GEMINI Study)

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: saquinavir [Invirase]
* Drug: Lopinavir/ritonavir
* Drug: Emtricitabine/tenofovir disoproxil fumarate
* Drug: Ritonavir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients >=18 years of age; chronic HIV-1 infection; treatment-naive; HIV-1 RNA viral load >=10,000copies/mL; women of childbearing potential must have a negative pregnancy test, and must use reliable contraception for the duration of the study and for 90 days after the last dose of study medication. Exclusion Criteria: females who are pregnant or breastfeeding; active hepatitis B infection; previous treatment with antiretroviral medication; patients who have received an investigational drug within the last 4 weeks.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: saquinavir/ritonavir<br>saquinavir mesylate 1000 mg twice daily (BID) + ritonavir 100 mg BID + emtricitabine/tenofovir disoproxil fumarate 200/300 mg orally every day for 48 weeks. | Drug: saquinavir [Invirase]<br>* 1000 milligram (mg) Oral (po) twice daily (bid)<br>* Other names: Invirase;Drug: Emtricitabine/tenofovir disoproxil fumarate<br>* Emtricitabine/tenofovir disoproxil fumarate 200/300 mg po qd<br>* Other names: Truvada;Drug: Ritonavir<br>* 100 mg po bid<br>* Other names: Norvir;|
| Active Comparator: lopinavir/ritonavir<br>lopinavir/ritonavir 400/100 mg BID + emtricitabine/tenofovir disoproxil fumarate 200/300 mg orally every day for 48 weeks. | Drug: Lopinavir/ritonavir<br>* Lopinavir/ritonavir 400/100 mg po bid<br>* Other names: Kaletra;Drug: Emtricitabine/tenofovir disoproxil fumarate<br>* Emtricitabine/tenofovir disoproxil fumarate 200/300 mg po qd<br>* Other names: Truvada;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Viral Load <50 Copies/mL | 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. | Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With HIV-1 RNA Viral Load <50 and <400 Copies/mL | 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. | Week 48 | 
| Change From Baseline in HIV-1 RNA Viral Load | 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) | Baseline to Week 48 | 
| Change From Baseline in Cluster Differentiation Antigen 4 Positive (CD4+) Lymphocyte Count | 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). | Baseline to Week 48 | 
| Number of Participants Assessed for Adverse Events (AEs) | Detailed information for Adverse Events and Serious Adverse Events will be represented in the SAE/AE section of PRS. | reported up to 28 days after the last dose of study treatment. (Up to 52 weeks) | 
| Number of Patients Who Discontinued Treatment Due to Abnormal Laboratory Parameters | 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. | baseline and all study visits (Up to Week 52) |