Trial Outcomes & Findings for GEMINI Study - A Study of Saquinavir/Ritonavir in Treatment-Naive Patients With HIV-1 Infection (NCT NCT00105079)

Last Updated: 2011-11-02

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

337 participants

Primary outcome timeframe

Week 48

Results posted on

2011-11-02

Participant Flow

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 .

Participant milestones

Participant milestones
Measure	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.
Overall Study STARTED	167	170
Overall Study Safety Population	163	168
Overall Study COMPLETED	128	135
Overall Study NOT COMPLETED	39	35

Reasons for withdrawal

Reasons for withdrawal
Measure	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.
Overall Study Adverse Event	5	12
Overall Study Death	3	1
Overall Study Lost to Follow-up	12	12
Overall Study Lack of Efficacy	9	3
Overall Study Refused treatment	6	4
Overall Study Violation of selection criteria at entry	0	2
Overall Study Protocol Violation	1	0
Overall Study Other	3	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Saquinavir/Ritonavir n=167 Participants 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 n=170 Participants lopinavir/ritonavir 400/100 mg BID + emtricitabine/tenofovir disoproxil fumarate 200/300 mg orally every day for 48 weeks.	Total n=337 Participants Total of all reporting groups
Age Continuous	38.3 years STANDARD_DEVIATION 9.31 • n=5 Participants	37.9 years STANDARD_DEVIATION 9.60 • n=7 Participants	38.1 years STANDARD_DEVIATION 9.45 • n=5 Participants
Sex: Female, Male Female	31 Participants n=5 Participants	39 Participants n=7 Participants	70 Participants n=5 Participants
Sex: Female, Male Male	136 Participants n=5 Participants	131 Participants n=7 Participants	267 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 48

Population: intent-to-treat (ITT) Population

Outcome measures

Outcome measures
Measure	Saquinavir/Ritonavir n=167 Participants 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 n=170 Participants lopinavir/ritonavir 400/100 mg BID + emtricitabine/tenofovir disoproxil fumarate 200/300 mg orally every day for 48 weeks.
Number of Patients With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Viral Load <50 Copies/mL Pts. with HIV-1 RNA Viral Load <50 copies/mL - YES	108 participants	108 participants
Number of Patients With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Viral Load <50 Copies/mL Pts. with HIV-1 RNA Viral Load <50 copies/mL - NO	59 participants	62 participants

SECONDARY outcome

Timeframe: Week 48

Population: Intent-to-Treat Population

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.

Outcome measures

Outcome measures
Measure	Saquinavir/Ritonavir n=167 Participants 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 n=170 Participants lopinavir/ritonavir 400/100 mg BID + emtricitabine/tenofovir disoproxil fumarate 200/300 mg orally every day for 48 weeks.
Number of Patients With HIV-1 RNA Viral Load <50 and <400 Copies/mL Patients with <50 Copies/mL	108 participants Interval 57.4 to 71.9	108 participants Interval 56.3 to 70.8
Number of Patients With HIV-1 RNA Viral Load <50 and <400 Copies/mL Patients with <400 Copies/mL	121 participants Interval 65.7 to 79.2	127 participants Interval 68.2 to 81.2

SECONDARY outcome

Timeframe: Baseline to Week 48

Population: 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.

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)

Outcome measures

Outcome measures
Measure	Saquinavir/Ritonavir n=167 Participants 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 n=170 Participants lopinavir/ritonavir 400/100 mg BID + emtricitabine/tenofovir disoproxil fumarate 200/300 mg orally every day for 48 weeks.
Change From Baseline in HIV-1 RNA Viral Load Baseline	5.20 copies/mL Interval 5.1 to 5.3	5.17 copies/mL Interval 5.1 to 5.3
Change From Baseline in HIV-1 RNA Viral Load Week 48 (n=126,133)	1.80 copies/mL Interval 1.8 to 1.9	1.83 copies/mL Interval 1.8 to 1.9
Change From Baseline in HIV-1 RNA Viral Load Change from Baseline to Week 48 (n=126,133)	-3.39 copies/mL Interval -3.5 to -3.3	-3.36 copies/mL Interval -3.5 to -3.2

SECONDARY outcome

Timeframe: Baseline to Week 48

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Saquinavir/Ritonavir n=167 Participants 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 n=170 Participants lopinavir/ritonavir 400/100 mg BID + emtricitabine/tenofovir disoproxil fumarate 200/300 mg orally every day for 48 weeks.
Change From Baseline in Cluster Differentiation Antigen 4 Positive (CD4+) Lymphocyte Count Baseline (n=166,169)	141.5 cells/mm^3 Interval 108.0 to 168.0	142.0 cells/mm^3 Interval 116.0 to 187.0
Change From Baseline in Cluster Differentiation Antigen 4 Positive (CD4+) Lymphocyte Count Week 48 (n=122,131)	319.0 cells/mm^3 Interval 277.0 to 370.0	348.0 cells/mm^3 Interval 317.0 to 401.0
Change From Baseline in Cluster Differentiation Antigen 4 Positive (CD4+) Lymphocyte Count Change from Baseline to Week 48 (n=121,130)	178.0 cells/mm^3 Interval 159.0 to 213.0	204.0 cells/mm^3 Interval 182.0 to 222.0

SECONDARY outcome

Timeframe: reported up to 28 days after the last dose of study treatment. (Up to 52 weeks)

Population: Safety population included all randomized patients who received at least one dose of study medication

Detailed information for Adverse Events and Serious Adverse Events will be represented in the SAE/AE section of PRS.

Outcome measures

Outcome measures
Measure	Saquinavir/Ritonavir n=163 Participants 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 n=168 Participants lopinavir/ritonavir 400/100 mg BID + emtricitabine/tenofovir disoproxil fumarate 200/300 mg orally every day for 48 weeks.
Number of Participants Assessed for Adverse Events (AEs)	163 participants	168 participants

SECONDARY outcome

Timeframe: baseline and all study visits (Up to Week 52)

Population: Safety population included all randomized patients who received at least one dose of study medication.

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.

Outcome measures

Outcome measures
Measure	Saquinavir/Ritonavir n=163 Participants 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 n=168 Participants lopinavir/ritonavir 400/100 mg BID + emtricitabine/tenofovir disoproxil fumarate 200/300 mg orally every day for 48 weeks.
Number of Patients Who Discontinued Treatment Due to Abnormal Laboratory Parameters	0 participants	0 participants

Adverse Events

Saquinavir/Ritonavir

Serious events: 24 serious events

Other events: 76 other events

Deaths: 0 deaths

Lopinavir/Ritonavir

Serious events: 19 serious events

Other events: 92 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Saquinavir/Ritonavir n=163 participants at risk 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 n=168 participants at risk lopinavir/ritonavir 400/100 mg BID + emtricitabine/tenofovir disoproxil fumarate 200/300 mg orally every day for 48 weeks.
Infections and infestations Upper respiratory tract infection	6.7% 11/163 • All new nonserious AEs and SAEs, irrespective of causal relationship, were reported up to 28 days after the last dose of study treatment. Serious AEs considered related to the test drug were to be reported indefinitely. (Up to 52 weeks) The safety population included all randomized patients who took at least 1 dose of the trial medication and had at least 1 post-baseline safety assessment.	13.7% 23/168 • All new nonserious AEs and SAEs, irrespective of causal relationship, were reported up to 28 days after the last dose of study treatment. Serious AEs considered related to the test drug were to be reported indefinitely. (Up to 52 weeks) The safety population included all randomized patients who took at least 1 dose of the trial medication and had at least 1 post-baseline safety assessment.
Infections and infestations Bronchitis	6.1% 10/163 • All new nonserious AEs and SAEs, irrespective of causal relationship, were reported up to 28 days after the last dose of study treatment. Serious AEs considered related to the test drug were to be reported indefinitely. (Up to 52 weeks) The safety population included all randomized patients who took at least 1 dose of the trial medication and had at least 1 post-baseline safety assessment.	3.0% 5/168 • All new nonserious AEs and SAEs, irrespective of causal relationship, were reported up to 28 days after the last dose of study treatment. Serious AEs considered related to the test drug were to be reported indefinitely. (Up to 52 weeks) The safety population included all randomized patients who took at least 1 dose of the trial medication and had at least 1 post-baseline safety assessment.
Gastrointestinal disorders Diarrhoea	28.2% 46/163 • All new nonserious AEs and SAEs, irrespective of causal relationship, were reported up to 28 days after the last dose of study treatment. Serious AEs considered related to the test drug were to be reported indefinitely. (Up to 52 weeks) The safety population included all randomized patients who took at least 1 dose of the trial medication and had at least 1 post-baseline safety assessment.	45.8% 77/168 • All new nonserious AEs and SAEs, irrespective of causal relationship, were reported up to 28 days after the last dose of study treatment. Serious AEs considered related to the test drug were to be reported indefinitely. (Up to 52 weeks) The safety population included all randomized patients who took at least 1 dose of the trial medication and had at least 1 post-baseline safety assessment.
Gastrointestinal disorders Nausea	24.5% 40/163 • All new nonserious AEs and SAEs, irrespective of causal relationship, were reported up to 28 days after the last dose of study treatment. Serious AEs considered related to the test drug were to be reported indefinitely. (Up to 52 weeks) The safety population included all randomized patients who took at least 1 dose of the trial medication and had at least 1 post-baseline safety assessment.	32.7% 55/168 • All new nonserious AEs and SAEs, irrespective of causal relationship, were reported up to 28 days after the last dose of study treatment. Serious AEs considered related to the test drug were to be reported indefinitely. (Up to 52 weeks) The safety population included all randomized patients who took at least 1 dose of the trial medication and had at least 1 post-baseline safety assessment.
Gastrointestinal disorders Vomiting	12.9% 21/163 • All new nonserious AEs and SAEs, irrespective of causal relationship, were reported up to 28 days after the last dose of study treatment. Serious AEs considered related to the test drug were to be reported indefinitely. (Up to 52 weeks) The safety population included all randomized patients who took at least 1 dose of the trial medication and had at least 1 post-baseline safety assessment.	16.7% 28/168 • All new nonserious AEs and SAEs, irrespective of causal relationship, were reported up to 28 days after the last dose of study treatment. Serious AEs considered related to the test drug were to be reported indefinitely. (Up to 52 weeks) The safety population included all randomized patients who took at least 1 dose of the trial medication and had at least 1 post-baseline safety assessment.
General disorders Fatigue	9.2% 15/163 • All new nonserious AEs and SAEs, irrespective of causal relationship, were reported up to 28 days after the last dose of study treatment. Serious AEs considered related to the test drug were to be reported indefinitely. (Up to 52 weeks) The safety population included all randomized patients who took at least 1 dose of the trial medication and had at least 1 post-baseline safety assessment.	7.1% 12/168 • All new nonserious AEs and SAEs, irrespective of causal relationship, were reported up to 28 days after the last dose of study treatment. Serious AEs considered related to the test drug were to be reported indefinitely. (Up to 52 weeks) The safety population included all randomized patients who took at least 1 dose of the trial medication and had at least 1 post-baseline safety assessment.
Nervous system disorders Headache	4.9% 8/163 • All new nonserious AEs and SAEs, irrespective of causal relationship, were reported up to 28 days after the last dose of study treatment. Serious AEs considered related to the test drug were to be reported indefinitely. (Up to 52 weeks) The safety population included all randomized patients who took at least 1 dose of the trial medication and had at least 1 post-baseline safety assessment.	8.3% 14/168 • All new nonserious AEs and SAEs, irrespective of causal relationship, were reported up to 28 days after the last dose of study treatment. Serious AEs considered related to the test drug were to be reported indefinitely. (Up to 52 weeks) The safety population included all randomized patients who took at least 1 dose of the trial medication and had at least 1 post-baseline safety assessment.
Nervous system disorders DIZZINESS	7.4% 12/163 • All new nonserious AEs and SAEs, irrespective of causal relationship, were reported up to 28 days after the last dose of study treatment. Serious AEs considered related to the test drug were to be reported indefinitely. (Up to 52 weeks) The safety population included all randomized patients who took at least 1 dose of the trial medication and had at least 1 post-baseline safety assessment.	8.3% 14/168 • All new nonserious AEs and SAEs, irrespective of causal relationship, were reported up to 28 days after the last dose of study treatment. Serious AEs considered related to the test drug were to be reported indefinitely. (Up to 52 weeks) The safety population included all randomized patients who took at least 1 dose of the trial medication and had at least 1 post-baseline safety assessment.
Metabolism and nutrition disorders DECREASED APPETITE	5.5% 9/163 • All new nonserious AEs and SAEs, irrespective of causal relationship, were reported up to 28 days after the last dose of study treatment. Serious AEs considered related to the test drug were to be reported indefinitely. (Up to 52 weeks) The safety population included all randomized patients who took at least 1 dose of the trial medication and had at least 1 post-baseline safety assessment.	4.8% 8/168 • All new nonserious AEs and SAEs, irrespective of causal relationship, were reported up to 28 days after the last dose of study treatment. Serious AEs considered related to the test drug were to be reported indefinitely. (Up to 52 weeks) The safety population included all randomized patients who took at least 1 dose of the trial medication and had at least 1 post-baseline safety assessment.
Psychiatric disorders INSOMNIA	3.7% 6/163 • All new nonserious AEs and SAEs, irrespective of causal relationship, were reported up to 28 days after the last dose of study treatment. Serious AEs considered related to the test drug were to be reported indefinitely. (Up to 52 weeks) The safety population included all randomized patients who took at least 1 dose of the trial medication and had at least 1 post-baseline safety assessment.	6.0% 10/168 • All new nonserious AEs and SAEs, irrespective of causal relationship, were reported up to 28 days after the last dose of study treatment. Serious AEs considered related to the test drug were to be reported indefinitely. (Up to 52 weeks) The safety population included all randomized patients who took at least 1 dose of the trial medication and had at least 1 post-baseline safety assessment.

Additional Information

Medical Communications

Hoffman-LaRoche

Phone: 800-821-8590

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER