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

NCT00000753 | Completed Phase 1

• 2 other identifiers: ACTG 18711162
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 6

Brief 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.

Conditions

HIV Infections

Keywords

Zalcitabine; Didanosine; Drug Therapy, Combination; Acquired Immunodeficiency Syndrome; AIDS-Related Complex; Antiviral Agents; Zidovudine

Interventions

Atevirdine mesylate DRUG

Zidovudine DRUG

Zalcitabine DRUG

Didanosine DRUG

Eligibility Criteria

• Age: 13 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Upjohn: collaborator
• Glaxo Wellcome: collaborator

Study Sites (6)

USC CRS

Los Angeles, California, 90033, United States

Location

Univ. of Miami AIDS CRS

Miami, Florida, 33136, United States

Location

St. Louis ConnectCare, Infectious Diseases Clinic

St Louis, Missouri, 63112, United States

Location

Washington U CRS

St Louis, Missouri, United States

Location

Univ. of Rochester ACTG CRS

Rochester, New York, 14642, United States

Location

The Ohio State Univ. AIDS CRS

Columbus, Ohio, 43210, United States

Location

Related Publications (2)

• Demeter LM, Meehan PM, Morse G, Fischl MA, Para M, Powderly W, Leedom J, Holden-Wiltse J, Greisberger C, Wood K, Timpone J Jr, Wathen LK, Nevin T, Resnick L, Batts DH, Reichman RC. Phase I study of atevirdine mesylate (U-87201E) monotherapy in HIV-1-infected patients. J Acquir Immune Defic Syndr Hum Retrovirol. 1998 Oct 1;19(2):135-44. doi: 10.1097/00042560-199810010-00006.

  PMID: 9768622 BACKGROUND

• Morse GD, Reichman RC, Fischl MA, Para M, Leedom J, Powderly W, Demeter LM, Resnick L, Bassiakos Y, Timpone J, Cox S, Batts D. Concentration-targeted phase I trials of atevirdine mesylate in patients with HIV infection: dosage requirements and pharmacokinetic studies. The ACTG 187 and 199 study teams. Antiviral Res. 2000 Jan;45(1):47-58. doi: 10.1016/s0166-3542(99)00073-x.

  PMID: 10774589 BACKGROUND

MeSH Terms

Conditions

HIV Infections; Acquired Immunodeficiency Syndrome; AIDS-Related Complex

Interventions

atevirdine; Zidovudine; Zalcitabine; Didanosine

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases

Intervention Hierarchy (Ancestors)

Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dideoxynucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Deoxycytidine; Cytidine; Inosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Ribonucleosides

Study Officials

• Reichman R

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 1999
• First Posted: August 31, 2001
• Study Completion: February 1, 1995
• Last Updated: November 4, 2021

Record last verified: 2021-10

Locations

US (6)