Clinical trial NCT00000628: A Pharmacokinetic Study of L-697,661 Alone and in Combination With Zidovudine
Official title: A Pharmacokinetic Study of L-697,661 Alone and in Combination With Zidovudine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Keywords: Drug Evaluation
Drugs, Investigational
Drug Therapy, Combination
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Antiviral Agents
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2001-08-31
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: San Francisco Gen Hosp
state: California
city: Denver
country: United States
facility: Univ of Colorado Health Ctr / Denver Gen Hosp
state: Colorado
city: Chicago
country: United States
facility: Northwestern Univ Med School
state: Illinois
city: Chicago
country: United States
facility: Rush Presbyterian - Saint Luke's Med Ctr
state: Illinois
city: Seattle
country: United States
facility: Univ of Washington
state: Washington
Study officials:
name: RT Schooley
role: STUDY_CHAIR
References:
citation: 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)
citation: 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.
citation: 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)