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

NCT ID: NCT00000628

Last Updated: 2008-07-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL

Brief 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.

Detailed 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.

Conditions

HIV Infections

Keywords

Drug Evaluation; Drugs, Investigational; Drug Therapy, Combination; Acquired Immunodeficiency Syndrome; AIDS-Related Complex; Antiviral Agents

Study Design

• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT

Interventions

L-697,661

Intervention Type: DRUG

Zidovudine

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Principal Investigators

RT Schooley

Role: STUDY_CHAIR

Locations

San Francisco Gen Hosp

San Francisco, California, United States

Univ of Colorado Health Ctr / Denver Gen Hosp

Denver, Colorado, United States

Northwestern Univ Med School

Chicago, Illinois, United States

Rush Presbyterian - Saint Luke's Med Ctr

Chicago, Illinois, United States

Univ of Washington

Seattle, Washington, United States

Countries

United States

References

Kuritzkes DR, Curtis S, Rosandich M, Stein DS, Schooley RT. Delayed emergence of resistance to L-697,661 in patients receiving concomitant zidovudine. The ACTG 184 Study Team. Int Conf AIDS. 1993 Jun 6-11;9(1):467 (abstract no PO-B26-1994)

Reference Type: BACKGROUND

Schooley RT, Campbell TB, Kuritzkes DR, Blaschke T, Stein DS, Rosandich ME, Phair J, Pottage JC, Messari F, Collier A, Kahn J. Phase 1 study of combination therapy with L-697,661 and zidovudine. The ACTG 184 Protocol Team. J Acquir Immune Defic Syndr Hum Retrovirol. 1996 Aug 1;12(4):363-70. doi: 10.1097/00042560-199608010-00006.

Reference Type: BACKGROUND

PMID: 8673545 (View on PubMed)

Campbell TB, Routh JA, Bakhtiari M, Schooley RT, Kuritzkes DR. Detection of genotypic changes in reverse transcriptase during combination therapy with zidovudine and L-697,661. Detection of genotypic changes in reverse transcriptase during combination therapy with zidovudine and L-697,661. Int Conf AIDS. 1993 Jun 6-11;9(1):239 (abstract no PO-A26-0630)

Reference Type: BACKGROUND

Other Identifiers

Merck Protocol 020-00

Identifier Type: -

Identifier Source: secondary_id

ACTG 184

Identifier Type: -

Identifier Source: org_study_id