A Phase I Concentration-Targeted Multidose Study of Atevirdine Mesylate ( U-87201E ), AZT, and ddI or ddC

• Status: Completed
• Trial end date: 1995-02-01
• Target enrollment: 0
• Participant gender: All

Summary

To determine the safety, toxicity, pharmacokinetic profile, and antiretroviral activity of atevirdine mesylate ( U-87201E ) in HIV-infected patients. Per 06/04/93 amendment, to also evaluate the interactive effects of didanosine ( ddI ) or zalcitabine ( dideoxycytidine; ddC ) with zidovudine ( AZT ) on the pharmacokinetics of U-87201E and to assess the effects of the triple combination therapies on immunologic and virologic parameters.

Since the use of non-nucleoside reverse transcriptase inhibitors such as U-87201E has been associated with the rapid development of resistant HIV isolates, an initial evaluation of this drug in patients was made in combination with AZT. Because of the inability to detect resistance after 6 weeks of combined AZT/U-87201E therapy, this protocol will initially investigate U-87201E administered alone and then investigate the effect of this drug with AZT and ddI or ddC.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Glaxo Wellcome; Upjohn
• Treatments: Atevirdine; Didanosine; Zalcitabine; Zidovudine

Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

• PCP prophylaxis with pentamidine, TMP/SMX, or dapsone (if appropriate).

• Clotrimazole troches or nystatin oral suspension for oral candidiasis.

• Acyclovir (up to 1000 mg/day) for herpes lesions.

• Supportive care as deemed necessary for toxicities .

Patients must have:

• HIV infection.

• CD4 count <= 500 cells/mm3.

• No active opportunistic infections.

• Consent of parent, guardian, or person with power of attorney, if less than 18 years of age.

NOTE:

• Participation of women in the study is encouraged.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms and conditions are excluded:

• Acute medical problems, including opportunistic infections (e.g., active cryptococcosis, Pneumocystis carinii, herpes zoster, histoplasmosis, and CMV) or nonopportunistic diseases (e.g., liver or renal disease or lymphoma).

• Current diagnosis of malignancy for which systemic therapy would be required during the study.

• Active gastrointestinal disorders.

Concurrent Medication:

Excluded:

• Investigational drugs.

• Systemic therapy for malignancy.

• Phenobarbital, phenytoin, ketoconazole, rifampin, rifabutin, cimetidine, beta blockers, chronic antacids, antiarrhythmic agents, or other medications known to affect cardiac conduction or seizure threshold.

Patients with the following prior conditions are excluded:

• History of any cardiovascular disease, including conduction disturbances, arrhythmias or atherosclerotic heart disease.

• History of CNS disease such as seizure disorder, AIDS Dementia Complex, progressive multifocal leukoencephalopathy, or any other active neurological disorder.

• History of chronic gastrointestinal disorders such as chronic diarrhea (> 4 weeks duration).

Prior Medication:

Excluded:

• Antiretroviral or immunomodulator agents (such as AZT, ddI, ddC, interferon, etc.) within 15 days prior to study entry.

• Cytotoxic chemotherapy within 1 month prior to study entry.

• Prior U-87201E or other non-nucleoside reverse transcriptase inhibitors (i.e., nevirapine, TIBO, L697,661).

Present use of alcohol or illicit drugs.