A Comparison of Three Anti-HIV Drug Combinations Containing Saquinavir Soft Gelatin Capsules Used in HIV-1 Infected Patients

Roche

Status and phase: Completed; Phase 3

Conditions: HIV Infections

Treatments: Drug: Zidovudine; Drug: Nelfinavir mesylate; Drug: Delavirdine mesylate; Drug: Stavudine; Drug: Ritonavir; Drug: Lamivudine; Drug: Saquinavir

Study type: Interventional

Funder types: Industry

Identifiers

NCT00002378

M6101

NR15520

229H

Details and patient eligibility

About

To determine the proportion of patients whose plasma HIV-1 RNA level falls below the level of detection (< 400 copies/ml) at week 24 of study therapy. To determine the absolute change in plasma HIV-1 RNA during the 24 weeks of study treatment. To collect safety data on the treatment regimens.

AS PER AMENDMENT 12/12/97: To compare the virologic response of Fortovase (FTV) (Saquinavir) Soft Gel Capsule (SGC) tid plus nucleoside reverse transcriptase inhibitors (NRTIs) versus FTV bid plus NRTIs. Further, to compare the virologic response of FTV tid plus NRTIs versus FTV bid plus Nelfinavir bid plus a NRTI with respect to: the percentage of patients whose plasma HIV-1 RNA level falls below the Amplicor assay level of detection (< 400 copies/ml) at week 24 and week 48.

Full description

Patients will be randomized to receive 1 of 3 study regimens: Group A - Saquinavir (SQV) sgc plus 2 new reverse transcriptase inhibitors (RTIs), Group B - SQV sgc plus delavirdine plus new RTI, and Group C - SQV sgc plus nelfinavir plus new RTI, or SQV sgc plus ritonavir plus 2 new RTIs.

NOTE: "New RTI" is defined for this study as any reverse transcriptase inhibitor to which the patient has never been exposed.

AS PER AMENDMENT 12/12/97: In this open-label, multicenter, Phase IIIB, comparative study, 825 patients are randomized to treatment arms. (NOTE: 50% of the patients will be treatment naive and 50% will be NRTI experienced.) Further, patients are randomized with stratification based on HIV-1 RNA level (5,000-30,000 copies/ml vs. greater than 30,000 copies/ml) and prior antiretroviral therapy to one of the three study arms.

The drug regimens for the three treatment arms are as follows:

ARM A: Fortovase (FTV), plus 2 new NRTIs*. ARM B: FTV plus 2 new NRTIs*. ARM C: FTV plus nelfinavir plus new NRTI**.

Naive patients in Arm A and Arm B will take: d4T (or zidovudine) plus 3TC unless contraindicated.

** Naive patients in Arm C will take: d4T, unless contraindicated.

NRTI experienced patients in Arms A & B should be treated with 2 NRTIs to which he/she has not been previously exposed. If the patient has only 1 NRTI to which he/she has never been exposed, then the second NRTI can be one that the patient has been previously exposed to from the most distant past.

Therapy is administered for an initial 24 weeks and may be extended for an additional 24 weeks.

Sex: All

Ages: 16+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

Patients must have:

• HIV-1 infection.
• HIV RNA >= 5000 copies/ml by Amplicor assay.
• Signed, informed consent from parent or legal guardian for patients less than 18 years old.

Prior Medication:

Required:

(Note:

• 50% of the patients will be treatment naive).
• > 3 months cumulative therapy with antiretrovirals other than non-nucleoside reverse transcriptase inhibitors and/or protease inhibitors.
• Stable antiretroviral therapy for at least 4 weeks prior to enrollment.

Allowed:

• <= 2 weeks cumulative treatment with protease inhibitors.

AS PER AMENDMENT 12/12/97:

Required:

NRTI experienced patients:

• > 3 months cumulative therapy with antiretrovirals.
• <= 2 weeks cumulative previous treatment with non-nucleoside analogue reverse transcriptase inhibitors (NNRTIs).
• <= 2 weeks cumulative previous treatment with protease inhibitors.
• Must have at least one NRTI (preferably two) to which he/she has not been previously exposed.
• Stable antiretroviral therapy defined as within (+/-) 1 log HIV-1 RNA between the 2 most recent values greater than 8 weeks apart (may include screening visit) prior to study enrollment. (NOTE:
• If patient does not have a previous HIV-1 RNA value, screening will be accepted.)

Required:

• Note:
• 50% of the patients will be treatment naive and 50% will be NRTI experienced. AS PER AMENDMENT 12/12/97.