Randomized, Phase I/II, Dose-Ranging, Open-Label Trial of the Anti-HIV Activity of Delavirdine Mesylate (DLV; U-90,152S)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000810
First received: November 2, 1999
Last updated: April 2, 2012
Last verified: April 2012
  Purpose

PRIMARY: To study the safety and tolerance of delavirdine mesylate ( U-90152 ) monotherapy. To compare the anti-HIV activity of three blood concentration levels of this agent with nucleoside analog monotherapy, either zidovudine ( AZT ) or didanosine ( ddI ), based on the reduction of HIV viral burden.

SECONDARY: To use pharmacokinetic parameters to assess the relationship between daily drug exposure and antiviral activity and toxicity of the U-90152, AZT, and ddI monotherapy. To assess anti-HIV activity using other disease markers.

Data suggest that bisheteroarylpiperazines (BHAPs) such as delavirdine mesylate are potent and safe anti-HIV agents and may have different biological behavior than other currently available non-nucleoside RT inhibitors.


Condition Intervention Phase
HIV Infections
Drug: Delavirdine mesylate
Drug: Zidovudine
Drug: Didanosine
Phase 1

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: Randomized, Phase I/II, Dose-Ranging, Open-Label Trial of the Anti-HIV Activity of Delavirdine Mesylate (DLV; U-90,152S)

Resource links provided by NLM:


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

Estimated Enrollment: 120
Study Completion Date: January 1996
Detailed Description:

Data suggest that bisheteroarylpiperazines (BHAPs) such as delavirdine mesylate are potent and safe anti-HIV agents and may have different biological behavior than other currently available non-nucleoside RT inhibitors.

Patients are randomized to receive U-90152 at one of three doses (treatment arms I through III) or either AZT or ddI (treatment arm IV). Patients on arm IV who are AZT-naive receive AZT; those who are AZT-experienced receive ddI. Treatment continues for 24 weeks.

PER 12/22/94 AMENDMENT: All patients receiving U-90152 have the same starting dose, to attain one of three target trough levels.

  Eligibility

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

Inclusion Criteria

Concurrent Medication:

Allowed:

  • PCP prophylaxis.
  • Topical antifungal agents, clotrimazole troches, nystatin oral suspension, topical ketoconazole, and oral fluconazole.
  • Acyclovir (<= 1000 mg/day) as maintenance therapy for herpes simplex virus.
  • Recombinant erythropoietin and G-CSF.
  • Antibiotics for bacterial infections, unless specifically excluded.
  • Symptomatic treatment such as antipyretics, analgesics, nonsteroidal anti-inflammatory agents, and antiemetics.
  • Antacids.

Patients must have:

  • HIV-1 infection.
  • CD4 count 200 - 500 cells/mm3.
  • Either no prior antiretroviral therapy or discontinued AZT monotherapy 3 or more weeks prior to study entry.

NOTE:

  • Half of patients should be antiretroviral naive.

Prior Medication:

Allowed:

  • Prior AZT.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

  • Malignancy other than minimal Kaposi's sarcoma.

Concurrent Medication:

Excluded:

  • Rifabutin.
  • Rifampin.
  • Terfenadine.
  • Astemizole.
  • Loratadine.
  • Trifluoperazine.
  • Piperazine citrate.
  • Any acute or chronic therapy for CMV, MAC, toxoplasmosis, or disseminated fungal infection.
  • Non-study antiretroviral therapies, interferons, biologic response modifiers, and HIV vaccines.
  • Systemic corticosteroids for more than 21 consecutive days.
  • Foscarnet.
  • Systemic cytotoxic chemotherapy for a malignancy.

Patients with the following prior conditions are excluded:

  • History of pancreatitis (in patients who received prior AZT).
  • History of grade 2 or worse peripheral neuropathy (in patients who received prior AZT).
  • History of hypersensitivity to BHAP compounds (e.g., trifluoperazine - Stelazine, piperazine citrate - Antepar).

Prior Medication:

Excluded within 30 days prior to study entry:

  • Any investigational medication.
  • Interferon.
  • Interleukin.
  • Rifabutin.
  • Rifampin.
  • Terfenadine.
  • Astemizole.
  • Loratadine.
  • Trifluoperazine.
  • Piperazine citrate.

Excluded at any time:

  • Prior ddI, ddC, d4T, or 3TC.
  • Prior foscarnet.
  • Prior BHAP compound or other non-nucleoside RT inhibitor.

Active substance abuse interfering with compliance.

  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: NCT00000810

Locations
United States, California
Stanford CRS
Stanford, California, United States, 943055107
United States, Colorado
University of Colorado Hospital CRS
Aurora, Colorado, United States, 80262
United States, District of Columbia
Howard University Hosp., Div. of Infectious Diseases, ACTU
Washington, District of Columbia, United States, 20059
United States, Florida
Univ. of Miami AIDS CRS
Miami, Florida, United States, 331361013
United States, Illinois
Northwestern University CRS
Chicago, Illinois, United States, 60611
United States, Indiana
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
Indianapolis, Indiana, United States
United States, New York
SUNY - Buffalo, Erie County Medical Ctr.
Buffalo, New York, United States
Univ. of Rochester ACTG CRS
Rochester, New York, United States, 14642
United States, North Carolina
Unc Aids Crs
Chapel Hill, North Carolina, United States
United States, Ohio
The Ohio State Univ. AIDS CRS
Columbus, Ohio, United States
Sponsors and Collaborators
Investigators
Study Chair: Para M
Study Chair: Fischl M
  More Information

Additional Information:
Publications:
Dereuddre-Bosquet N, Clayette P, Martin M, Fretier P, Jaccard P, Benveniste O, Lebeaut A, Dormont D. IL-10 and HIV-1 infection of human primary monocyte/macrophages. Int Conf AIDS. 1996 Jul 7-12;11(2):75 (abstract no WeA3107)
Para M, Weinstock M. Retrospective analysis of protease inhibitor efficacy among patients failing a delavirdine regimen. Int Conf AIDS. 1998;12:59 (abstract no 12236)
Morse G, Para M, Fischl M, Freimuth W. Concentration-targeted (CT) Delavirdine therapy in 82 patients in ACTG 260. Conf Retroviruses Opportunistic Infect. 1996 Jan 28-Feb 1;3rd:118
Para M, Morse G, Fischl M. Plasma protein binding of delavirdine in HIV-infected patients in ACTG 260. Int Conf AIDS. 1996 Jul 7-12;11(2):78 (abstract no WeB3131)
Demeter L, Shafer R, Para M, Morse G, Freimuth W, Merigan T, Reichman R. Delavirdine (DLV) susceptibility of HIV-1 isolates obtained from patients (pts) receiving DLV monotherapy (ACTG 260). Conf Retroviruses Opportunistic Infect. 1996 Jan 28-Feb 1;3rd:113
Para MF, Fischl M, Meehan P, Morse G, Wood K, Shafer R, Freimuth W, Demeter L, Holden-Wiltse J, Nevin T. ACTG 260: Randomized phase I/II concentration-controlled trial of the anti-HIV activity of delavirdine. Conf Retroviruses Opportunistic Infect. 1996 Jan 28-Feb 1;3rd:163

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000810     History of Changes
Other Study ID Numbers: ACTG 260, 11237
Study First Received: November 2, 1999
Last Updated: April 2, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Didanosine
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Antiviral Agents
Zidovudine

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
Didanosine
Zidovudine
Delavirdine
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 August 27, 2014