a pharmacokinetic study of l-697,661 alone and in combination with zidovudine

Conditions: HIV Infections

Summary: 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.

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.

Eligibility 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.

Keywords: drug evaluation drugs, investigational drug therapy, combination acquired immunodeficiency syndrome aids-related complex antiviral agents