A Pharmacokinetic Study of L-697,661 Alone and in Combination With Zidovudine

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: HIV Infections

Treatments: Drug: Zidovudine; Drug: L-697,661

Study type: Interventional

Funder types: Industry; NIH

Identifiers

NCT00000628

ACTG 184

Merck Protocol 020-00

Details and patient eligibility

About

Part 1: To study the potential safety and pharmacokinetic (blood level) effects of zidovudine (AZT) on L-697,661; to obtain additional pharmacokinetic information in humans with L-697,661; to study the effect of L-697,661 on hepatic enzyme induction. Part 2: To begin a study of the antiviral activity of L-697,661.

L-697,661 is a newly identified compound that inhibits HIV replication (reproduction and growth) in cell culture. It works together with AZT against HIV.

Full description

L-697,661 is a newly identified compound that inhibits HIV replication (reproduction and growth) in cell culture. It works together with AZT against HIV.

Part 1: Twelve patients are randomly assigned to one of two groups. Group 1 patients receive AZT for 7 days, followed by AZT plus L-697,661 with food for 56 days. Group 2 patients receive no drug for 7 days, followed by L-697,661 with food for 56 days. Antipyrine is administered 1 hour prior to study drug on days 8, 22, and 35.

Part 2: Fifteen patients receive L-697,661 with food, for 8 weeks. Therapy with L-697,661 may be extended beyond 8 weeks for up to 24 weeks.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

Patients must have:

• HIV infection.

Prior Medication: Included:

• Patients in Part 1 must have received no previous zidovudine (AZT) or a stable dose of at least 500 mg/day without evidence of toxicity.
• Patients in Part 2 must have received no previous AZT or = or > 300 mg/day for < 6 consecutive weeks within 1 year prior to study entry.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

• Acute HIV-related opportunistic infection requiring ongoing treatment.
• Diarrhea defined as 3 or more liquid stools/day for one week.
• Wilson's or Gilbert's disease, porphyria, or other chronic or acute hepatic disease.
• Potentially life-threatening allergic reactions to any of the components of zidovudine.
• Acute or chronic medical conditions that in the opinion of the investigator would place patient at risk by participation in this study.

Concurrent Medication:

Excluded:

• Systemic bronchodilators, acetaminophen, aspirin.

Prior Medication:

Excluded:

• Didanosine (ddI) or dideoxycytidine (ddC) within 14 days prior to entry.
• Immune modulators or investigational drugs within 30 days prior to entry.
• Drugs known to induce hepatocellular enzymes, such as phenobarbital, phenytoin, warfarin, ketoconazole, and oral contraceptives, within 30 days prior to entry.

Patients in Part 2 only:

Excluded:

• Zidovudine within 4 weeks prior to receiving first dose of study drug.

Risk Behavior:

Excluded:

• Patients who the investigator feels would not comply with study requirements.

Patients may not have the following prior conditions:

• Acute or chronic medical conditions that in the opinion of the investigator would place patient at risk by participation in this study.
• Potentially life-threatening allergic reactions to any of the components of zidovudine.