A Randomized, Double-Blind Study of MKC-442 Combined With Viracept in Patients Who Are Epivir + Retrovir Experienced and Are Protease Inhibitor- and Non-Nucleoside Reverse Transcriptase Inhibitor-Naive

Concurrent Medication:

Required:

At least 1 different nucleoside analog, e.g., 3TC, d4T, or ddI (excluding zidovudine).

Allowed:

• Chemoprophylaxis for Pneumocystis carinii pneumonia.
• Short courses (less than 21 days) of acyclovir for acute treatment.
• Recombinant erythropoietin or G-CSF for Grade 3 or greater anemia and neutropenia, respectively.
• Allowed only with caution and close patient monitoring:
• Ketoconazole, fluconazole, itraconazole, and grapefruit juice.
• Medications metabolized by cytochrome P450.
• Oral contraceptives, contraceptive implants such as Norplant, or injection-type contraceptives such as Depo-Provera only if not sole method of contraception.

Patients may have:

• HIV-1 RNA greater than 10,000.
• No active AIDS-defining illnesses.
• Prior experience with 2 nucleoside analogues and able to switch to at least 1 different non-nucleoside analog, e.g., lamivudine (3TC), stavudine (d4T), or didanosine (ddI) with HIV-1 RNA 10,000 copies/ml or less. [AS PER:
• 8/4/98 AMENDMENT].
• [AS PER AMENDMENT 8/4/98:
• Nucleoside analog-naive patients must have HIV-1 RNA greater than 50,000 copies/ml.].

Prior Medication:

Allowed:

Treatment with 2 nucleoside analogs. Note:

• able to switch to at least 1 different nucleoside analog e.g., lamivudine (3TC), stavudine (d4T), or didanosine (ddI), while on study [AS PER AMENDMENT 8/4/98].

Exclusion Criteria

Co-existing Condition:

Patients with any of the following symptoms or conditions are excluded:

• Active AIDS-defining illnesses.
• Malabsorption syndrome or severe chronic diarrhea within 30 days of entry, or inability to consume adequate oral intake due to chronic nausea, emesis, or abdominal or esophageal discomfort. [AS PER AMENDMENT 8/4/98].
• Inadequately controlled seizure disorder [AS PER AMENDMENT 8/4/98].
• Any intercurrent illness that could affect viral load determination [AS PER AMENDMENT 8/4/98].

Concurrent Medication:

Excluded:

• Zidovudine.
• Immunomodulators (e.g., systemic corticosteroids, interleukin-2, or interferons). [AS PER AMENDMENT 8/4/98].
• Rifampin, rifabutin, phenobarbital, and hydantoin.
• Amiodarone, quinidine, astemizole, terfenadine, ergot derivatives, midazolam, triazolam, and cisapride.
• Neurotoxic agents (e.g., vincristine, thalidomide). [AS PER AMENDMENT 8/4/98].

Patients with the following prior conditions are excluded:

• History of acute or chronic pancreatitis.
• History of > grade 2 peripheral neuropathy.
• Patients with an acute and clinically significant medical event within 30 days of screening.

Prior Medication:

Excluded:

• Protease inhibitors.
• Non-nucleoside reverse transcriptase inhibitors.

Excluded within 30 days of study drug administration:

• Immunomodulators (e.g., systemic corticosteroids, interleukin-2, or interferons). [AS PER AMENDMENT 8/4/98].
• Rifampin, rifabutin, phenobarbital, and hydantoin.
• Amiodarone, quinidine, astemizole, terfenadine, ergot derivatives, midazolam, triazolam, and cisapride.
• Immunotherapeutic vaccines.
• Cytotoxic chemotherapeutic agents [AS PER AMENDMENT 8/4/98].

Prior Treatment:

Excluded within 30 days of study drug administration:

Radiation therapy [AS PER AMENDMENT 8/4/98].

Risk Behavior:

Excluded:

Current alcohol or illicit drug use that, in the opinion of the investigator, may interfere with ability of patient to comply with dosing schedule and protocol evaluations.