Status:

COMPLETED

A Phase I Concentration-Controlled Trial to Assess the Safety, Tolerance, Pharmacokinetics and Development of Decreased HIV-1 Susceptibility to the Combination of Atevirdine Mesylate (U-87201E), Zidovudine (AZT), and Didanosine (ddI)

Lead Sponsor:

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborating Sponsors:

Upjohn

Glaxo Wellcome

Conditions:

HIV Infections

Eligibility:

MALE

13+ years

Phase:

PHASE1

Brief Summary

Part I: To determine the pharmacokinetic dose for atevirdine mesylate ( U-87201E ) when used in combination with zidovudine ( AZT ). To determine the pharmacokinetic profiles of U-87201E and AZT over ...

Detailed Description

Interest exists in the development of antiretroviral agents that possess different mechanisms of action from nucleoside analogs such as AZT. U-87201E is a non-nucleoside reverse transcriptase (RT) inh...

Eligibility Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

  • PCP prophylaxis with aerosolized pentamidine, trimethoprim / sulfamethoxazole or dapsone.
  • Clotrimazole troches or nystatin oral suspension for oral candidiasis.
  • Acyclovir (up to 1000 mg/day) for herpes lesions.

Patients must have:

  • HIV infection documented by serologic tests or HIV culture OR prior diagnosis of AIDS by established CDC criteria.
  • CD4 counts = or < 500 cells/mm3 on two evaluations.

Part II only:

  • No prior therapy with antiretroviral or immunomodulating agents (e.g., AZT, ddI, ddC, interferon).

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms and conditions are excluded:

  • Acute medical problems at time of study entry (including active opportunistic infections such as active cryptococcosis, Pneumocystis carinii, herpes zoster, histoplasmosis, or CMV, or nonopportunistic diseases including liver disease, renal disease, orthostatic hypotension, hypertension, lymphoma).
  • Current diagnosis of malignancy for which systemic therapy would be required during the study.

Concurrent Medication:

Excluded:

  • Any other investigational drugs.
  • Phenobarbital, phenytoin, ketoconazole, rifampin, cimetidine, beta blockers, chronic anti-acid therapy, antiarrhythmic agents or other medications known to affect cardiac conduction or seizure threshold.
  • Cytotoxic chemotherapy.

Patients with the following prior conditions are excluded:

  • History of cardiovascular disease including conduction disturbances, arrhythmias, atherosclerotic heart disease, or valvular heart disease.
  • History of CNS disease such as seizure disorder, AIDS Dementia Complex, Progressive Multifocal Leukoencephalopathy, or any other active neurological disorder.
  • History of active or chronic gastrointestinal disorders such as chronic diarrhea (> 4 weeks duration), constipation, unexplained abdominal pain (such as irritable bowel syndrome), or other GI motility disorders.
  • History of hypercholesterolemia requiring medication or serum cholesterol = or > 300.

Part I patients only:

  • History of inability to tolerate zidovudine (200 mg q 8 hours).

Part III patients only:

  • History of pancreatitis or > grade 2 peripheral neuropathy.

Prior Medication:

Excluded:

  • Cytotoxic chemotherapy within 1 month prior to study entry.

Part II only:

  • prior therapy with antiretroviral or immunomodulatory agents (including but not limited to AZT, ddI, ddC, and interferon).

Current use of alcohol or illicit drugs.

Key Trial Info

Start Date :

Trial Type :

INTERVENTIONAL

End Date :

October 1 1993

Estimated Enrollment :

15 Patients enrolled

Trial Details

Trial ID

NCT00000742

End Date

October 1 1993

Last Update

November 4 2021

Active Locations (5)

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Page 1 of 2 (5 locations)

1

USC CRS

Los Angeles, California, United States, 90033

2

Univ. of Miami AIDS CRS

Miami, Florida, United States

3

Washington U CRS

St Louis, Missouri, United States

4

Univ. of Rochester ACTG CRS

Rochester, New York, United States, 14642