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

• Status: Completed
• Trial end date: 1969-12-31
• Target enrollment: 0
• Participant gender: All

Summary

To compare the proportion of patients whose plasma HIV-1 RNA level falls and remains below the limit of quantification by the Roche Amplicor Monitor (400 copies/ml)[AS PER AMENDMENT 8/4/98: 50 copies/ml] between weeks 0 and 24. To determine the short-term safety and tolerability of MKC-442 plus nelfinavir (Viracept) plus dual nucleoside analogs. To determine the time to viral failure and time to tolerability failure through Week 48 of therapy.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Triangle Pharmaceuticals
• Treatments: Emivirine; HIV Protease Inhibitors; Nelfinavir; Protease Inhibitors; Reverse Transcriptase Inhibitors; Zidovudine

Criteria

Inclusion Criteria

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.