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

HIV Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000628
• Other study ID #: ACTG 184
• Secondary ID: Merck Protocol 0
• Status: Completed
• Phase: Phase 1
• First received: November 2, 1999
• Last updated: July 29, 2008

Study information

• Verified date: October 1994
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Unspecified
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• L-697,661

• Zidovudine

Locations

Country	Name	City	State
United States	Northwestern Univ Med School	Chicago	Illinois
United States	Rush Presbyterian - Saint Luke's Med Ctr	Chicago	Illinois
United States	Univ of Colorado Health Ctr / Denver Gen Hosp	Denver	Colorado
United States	San Francisco Gen Hosp	San Francisco	California
United States	Univ of Washington	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.	National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

References & Publications (3)

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)

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)

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. — View Citation

External Links

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