A Randomized, Double-Blind Active-Controlled, Dose-Ranging Study of the Safety and Efficacy of Chronically Administered MDL 28,574A in the Treatment of HIV-Infected Patients

A Randomized, Double-Blind Active-Controlled, Dose-Ranging Study of the Safety and Efficacy of Chronically Administered MDL 28,574A in the Treatment of HIV-Infected Patients

To characterize the safety and efficacy of fixed doses of MDL 28,574A administered alone and in combination with zidovudine ( AZT ) in patients with asymptomatic or mildly symptomatic HIV infection. To examine the demographic effects on population pharmacokinetics and pharmacodynamics of MDL 28,574A alone and in combination with AZT.

Inclusion Criteria

Concurrent Medication:

Allowed:

• Prior antiretroviral agents for up to 6 months per agent.

Patients must have:

• HIV infection.
• Asymptomatic or mildly symptomatic.
• CD4 count 301 - 500 cells/mm3.

Exclusion Criteria

Co-existing Condition:

Patients with the following condition are excluded:

Unable or unwilling to comply with study procedures.

Concurrent Medication:

Excluded:

• Chemoprophylactic therapy for mycobacterial infection.
• Any nonstudy prescription medications without approval of investigator.

Patients with the following prior conditions are excluded:

• History of grade 3 or 4 toxicity to <= 600 mg/day AZT.
• History of intolerance to lactose.
• Chronic diarrhea within 6 months prior to study entry.
• Unexplained intermittent or chronic fever, defined as temperature >= 38.5 C for any 7 days within the 30 days prior to study entry.

Prior Medication:

Excluded:

• Antiretroviral therapy within 2 weeks prior to study entry.
• Prior HIV vaccines.
• Biological response modifiers within 30 days prior to study entry.
• Prior foscarnet.
• Any investigational drug with a washout < 5 half-lives prior to study entry.
• Any medications known to alter renal, hepatic, or hematologic / immunologic function (such as barbiturates, phenothiazines, cimetidine, immunomodulators, etc.) within 14 days prior to study entry.

Recent history of alcohol and/or drug abuse.