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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000628
First received: November 2, 1999
Last updated: July 29, 2008
Last verified: October 1994
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: L-697,661
Drug: Zidovudine
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Official Title: A Pharmacokinetic Study of L-697,661 Alone and in Combination With Zidovudine

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 27
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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000628

Locations
United States, California
San Francisco Gen Hosp
San Francisco, California, United States, 941102859
United States, Colorado
Univ of Colorado Health Ctr / Denver Gen Hosp
Denver, Colorado, United States, 80262
United States, Illinois
Northwestern Univ Med School
Chicago, Illinois, United States, 60611
Rush Presbyterian - Saint Luke's Med Ctr
Chicago, Illinois, United States, 60612
United States, Washington
Univ of Washington
Seattle, Washington, United States, 981224304
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Chair: RT Schooley
  More Information

Additional Information:
Publications:
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)
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)

ClinicalTrials.gov Identifier: NCT00000628     History of Changes
Other Study ID Numbers: ACTG 184, Merck Protocol 020-00
Study First Received: November 2, 1999
Last Updated: July 29, 2008
Health Authority: Unspecified

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Drug Evaluation
Drugs, Investigational
Drug Therapy, Combination
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Antiviral Agents

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Zidovudine
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on July 22, 2014