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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: L-697,661
* Drug: Zidovudine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Parallel Assignment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: L-697,661|nan|
|Drug: Zidovudine|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug Evaluation, Drugs, Investigational, Drug Therapy, Combination, Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Antiviral Agents