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A Phase I Trial to Evaluate the Safety, Pharmacokinetics and Antiviral Activity of 141W94 After Multiple Dosing in Patients With HIV Infection

This study has been completed.

Sponsored by: Glaxo Wellcome
Information provided by: NIH AIDS Clinical Trials Information Service
ClinicalTrials.gov Identifier: NCT00002183
  Purpose

To assess the safety and tolerance of multiple oral doses of 141W94 alone, in combination with 1592U89, and in combination with Retrovir and Epivir, administered to patients with HIV infection as measured by the development of clinical adverse experiences and laboratory test abnormalities. To determine the steady-state pharmacokinetics of 141W94 alone and in combination with 1592U89 after multiple oral dosing. To obtain preliminary evidence of antiretroviral activity of 141W94 alone and in combination with 1592U89, the antiretroviral effect of combined Retrovir/Epivir and the antiretroviral effect of 141W94 when added to Retrovir/Epivir or to 1592U89/Retrovir/Epivir.


Condition Intervention Phase
HIV Infections
Drug: Abacavir sulfate
Drug: Amprenavir
Drug: Lamivudine
Drug: Zidovudine
Phase I

MedlinePlus related topics:   AIDS   

ChemIDplus related topics:   Zidovudine    Abacavir    Abacavir sulfate    Lamivudine    VX 478   

U.S. FDA Resources

Study Type:   Interventional
Study Design:   Treatment, Dose Comparison, Safety Study
Official Title:   A Phase I Trial to Evaluate the Safety, Pharmacokinetics and Antiviral Activity of 141W94 After Multiple Dosing in Patients With HIV Infection

Further study details as provided by NIH AIDS Clinical Trials Information Service:

Estimated Enrollment:   60

Detailed Description:

60 HIV-infected patients will be sequentially assigned to receive 1 of 5 doses of 141W94 alone or 141W94 plus 1592U89. After each patient has completed 4 weeks of the assigned regimen (Phase A), the patient will receive Epivir and Retrovir for up to 8 months (Phase B). Patients originally assigned, in Phase A, to receive 141W94 and 1592U89 continue to receive 1592U89 during this period. Upon termination of Phase B, 141W94 is added to existing regimens of Phase B (Phase C). Phase C will last for 12 weeks.

  Eligibility
Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

  • Localized therapy such as intralesional injections for Kaposi's sarcoma.

Patients must have:

  • HIV infection documented by a licensed HIV antibody ELISA confirmed by:
  • Western blot, or positive HIV blood culture, or positive HIV serum antigen and second antibody test positive by a method other than ELISA.
  • CD4+ counts >= 150 and <= 400 cells/mm3 within 2 weeks of study entry.

    1. Anticipated need for cytotoxic chemotherapeutic agents within 4 weeks prior to entry.

  • Alprazolam, carbamazepine, codeine, clarithromycin, dapsone, diazepam, diltiazem, erythromycin, estrogens, glucocorticoids, imipramine, itraconazole, ketoconazole, lidocaine, lovastatin, nifedipine, phenobarbital, phenytoin, quinidine, rifabutin, rifampin and warfarin.
  • The following medications should be used with caution in most instances or not at all:
  • terfenadine, astemizole, cisapride, triazolam and midazolam.

Anticipated need for treatment with radiation therapy within 4 weeks prior to entry.

1. Treatment with cytotoxic chemotherapeutic agents within 4 weeks prior to entry.

  • Patients who have previously received a protease inhibitor.
  • Antiretroviral therapy within 2 weeks prior to enrollment.

NOTE:

  • Patients with a known intolerance to either retrovir or epivir are not eligible for Phase B of this study.

NOTE:

  • Patients with previous epivir (3TC) experience will not be eligible for Regimen 6 of this study (combination therapy with 141W94 and 1592U89).
  • Treatment with immunomodulating agents, including but not limited to systemic corticosteroids, IL-2, alpha-IFN, beta-IFN, or gamma-IFN within 4 weeks prior to entry.
  • Treatment with HIV immunotherapeutic vaccine within 3 months prior to entry. Treatment with radiation therapy within 4 weeks prior to entry. Patients with current alcohol or illicit drug use which, in the opinion of the principal investigator, may interfere with the patients' ability to comply with the dosing schedule and protocol evaluations.
  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00002183

Locations
United States, California
UCSD    
      San Diego, California, United States, 92103
United States, Colorado
Univ of Colorado Health Sciences Ctr    
      Denver, Colorado, United States, 80262
United States, Georgia
AIDS Research Consortium of Atlanta    
      Atlanta, Georgia, United States, 30308

Sponsors and Collaborators
Glaxo Wellcome
  More Information


Publications:
Schooley R. Preliminary data from a phase I/II study on the safety and antiviral efficacy of the combination of 141W94 plus 1592U89 in HIV-infected patients with 150 to 400 CD4+ cells/mm(3). Conf Retroviruses Opportunistic Infect. 1997 Jan 22-26;4th:206 (abstract no LB3)
 
Sadler BM, Gillotin C, Lou Y, Stein DS. Pharmacokinetic and pharmacodynamic study of the human immunodeficiency virus protease inhibitor amprenavir after multiple oral dosing. Antimicrob Agents Chemother. 2001 Jan;45(1):30-7.
 

Study ID Numbers:   264B
First Received:   November 2, 1999
Last Updated:   June 23, 2005
ClinicalTrials.gov Identifier:   NCT00002183
Health Authority:   United States: Food and Drug Administration

Keywords provided by NIH AIDS Clinical Trials Information Service:
Drug Therapy, Combination  
Drug Administration Schedule  
HIV Protease Inhibitors  
VX 478  
Anti-HIV Agents  

Study placed in the following topic categories:
Virus Diseases
Amprenavir
Sexually Transmitted Diseases, Viral
HIV Infections
Sexually Transmitted Diseases
Acquired Immunodeficiency Syndrome
Lamivudine
Zidovudine
Abacavir
Retroviridae Infections
Immunologic Deficiency Syndromes

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
Communicable Diseases
HIV Protease Inhibitors
RNA Virus Infections
Anti-HIV Agents
Slow Virus Diseases
Immune System Diseases
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Infection
Antiviral Agents
Pharmacologic Actions
Protease Inhibitors
Antibiotics, Antitubercular
Reverse Transcriptase Inhibitors
Anti-Bacterial Agents
Anti-Retroviral Agents
Therapeutic Uses
Lentivirus Infections
Antitubercular Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on October 10, 2008




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