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

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)

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: saquinavir [Invirase]; Drug: Emtricitabine/tenofovir disoproxil fumarate; Drug: Ritonavir; Drug: Lopinavir/ritonavir

• Study Type: Interventional
• Enrollment (Actual): 337
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
    • Ottawa, Ontario, Canada, K1H 8L6
    • Toronto, Ontario, Canada, M4N 3M5
    • Toronto, Ontario, Canada, M5G 2C4
    • Toronto, Ontario, Canada, M5B 1L6
  • Quebec
    • Montreal, Quebec, Canada, H2l 4P9
    • Montreal, Quebec, Canada, H2L 5B1
    • Montreal, Quebec, Canada, H2X 2P4
• France
  • Avignon, France, 84902
  • Lyon, France, 69437
  • Lyon, France, 69288
  • Marseille, France, 13009
  • Marseille, France, 13385
  • Nantes, France, 44035
  • Nice, France, 06202
  • Paris, France, 75014
  • Paris, France, 75651
  • Paris, France, 75010
  • Rouen, France, 73031
  • Strasbourg, France, 67091
  • Suresnes, France, 92150
  • Toulouse, France, 31052
  • Tourcoing, France, 59208
• Puerto Rico
  • Ponce, Puerto Rico, 00717-1563
• Thailand
  • Bangkok, Thailand, 10330
• United States
  • Alabama
    • Hobson City, Alabama, United States, 36201
  • Arizona
    • Tucson, Arizona, United States, 85745
  • California
    • Berkeley, California, United States, 94705
    • Los Angeles, California, United States, 90028
  • District of Columbia
    • Washington, District of Columbia, United States, 20009
  • Florida
    • Jacksonville, Florida, United States, 32204
    • Miami, Florida, United States, 33136
    • Orlando, Florida, United States, 32803
    • Vero Beach, Florida, United States, 32960
  • Georgia
    • Atlanta, Georgia, United States, 30309
    • Macon, Georgia, United States, 31201
  • Illinois
    • Chicago, Illinois, United States, 60613
  • Michigan
    • Ypsilanti, Michigan, United States, 48197
  • Missouri
    • St Louis, Missouri, United States, 63139
  • New Jersey
    • Newark, New Jersey, United States, 07102
  • New York
    • New York, New York, United States, 10011
  • North Carolina
    • Huntersville, North Carolina, United States, 28078
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
  • Texas
    • Houston, Texas, United States, 77004

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: April 1, 2005
• Primary Completion (Actual): August 1, 2007
• Study Completion (Actual): July 1, 2008

Study Registration Dates

• First Submitted: March 4, 2005
• First Submitted That Met QC Criteria: March 4, 2005
• First Posted (Estimate): March 7, 2005

Study Record Updates

• Last Update Posted (Estimate): November 2, 2011
• Last Update Submitted That Met QC Criteria: September 23, 2011
• Last Verified: September 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Tenofovir; Emtricitabine; Ritonavir; Lopinavir; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Saquinavir
• Other Study ID Numbers: ML18413

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No