A Study of MKC-442 in Combination With Other Anti-HIV Drugs

A Randomized, Double-Blind Study of MKC-442 Combined With Stavudine, Didanosine, and Hydroxyurea in HIV-Infected Patients Who Are Protease Inhibitor Experienced and Non-Nucleoside Reverse Transcriptase Inhibitor Naive

The purpose of this study is to see if it is safe and effective to give MKC-442 plus stavudine (d4T) plus didanosine (ddI) plus hydroxyurea.

Patients are randomized to receive either MKC-442 or placebo, along with stavudine(d4T), didanosine(ddI), and hydroxyurea. Patients will be treated and followed for 48 weeks.

Inclusion Criteria

Concurrent Medication:

Allowed:

- Based on medical history, medical condition, prior use of antiretroviral drugs, and genotypic analysis of the predominant strain of HIV-1 isolated from the plasma, administration of a combination of two or more available antiretroviral agents by prescription may be given with MKC-442.

Patient must have:

• HIV infection with HIV-1 RNA greater than or equal to 5,000 by Roche Amplicor method within 30 days of entry.
• A failed protease inhibitor-containing regimen.
• Negative serum beta human chorionic gonadotropin test within 30 days of entry.

Prior Medication:

Allowed:

• Prior nucleoside reverse transcriptase and protease inhibitors.
• Cytotoxic chemotherapy more than 30 days prior to entry.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Malabsorption or severe chronic diarrhea within 30 days prior to entry, or inability to consume adequate oral intake because of chronic nausea, emesis, or abdominal or esophageal discomfort.
• Inadequately controlled seizure disorder.
• Known intolerance to stavudine, didanosine, and/or hydroxyurea.
• Acute and clinically significant medical event within 30 days of screening.
• Any clinical or laboratory abnormality greater than Grade 3 toxicity, with the exception of laboratory values given.

Concurrent Treatment:

Excluded:

- Any experimental antiretroviral therapy or immunomodulators directed against HIV-1, e.g., IL-4, cyclosporine steroids at doses greater than 40 mg/day.

Prior Medication:

Excluded:

- Non-nucleoside reverse transcriptase inhibitor therapy.

Prior Treatment:

Excluded:

• Radiation therapy within 30 days of entry except to a local lesion.
• Transfusion of blood or blood products within 21 days of screening.
• Cytotoxic therapy within 3 months of study entry.

Risk Behavior:

Excluded:

Active substance abuse that may interfere with compliance or protocol evaluations.