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

NCT ID: NCT00000810

Last Updated: 2021-11-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

120 participants

Study Classification

INTERVENTIONAL

Study Completion Date

1996-01-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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HIV Infections

Keywords

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Didanosine Acquired Immunodeficiency Syndrome AIDS-Related Complex Antiviral Agents Zidovudine

Study Design

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Primary Study Purpose

TREATMENT

Interventions

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Delavirdine mesylate

Intervention Type DRUG

Zidovudine

Intervention Type DRUG

Didanosine

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Para M

Role: STUDY_CHAIR

Fischl M

Role: STUDY_CHAIR

Locations

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Stanford CRS

Stanford, California, United States

Site Status

University of Colorado Hospital CRS

Aurora, Colorado, United States

Site Status

Howard University Hosp., Div. of Infectious Diseases, ACTU

Washington D.C., District of Columbia, United States

Site Status

Univ. of Miami AIDS CRS

Miami, Florida, United States

Site Status

Northwestern University CRS

Chicago, Illinois, United States

Site Status

Indiana Univ. School of Medicine, Infectious Disease Research Clinic

Indianapolis, Indiana, United States

Site Status

SUNY - Buffalo, Erie County Medical Ctr.

Buffalo, New York, United States

Site Status

Univ. of Rochester ACTG CRS

Rochester, New York, United States

Site Status

Unc Aids Crs

Chapel Hill, North Carolina, United States

Site Status

The Ohio State Univ. AIDS CRS

Columbus, Ohio, United States

Site Status

Countries

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United States

References

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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)

Reference Type BACKGROUND

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)

Reference Type BACKGROUND

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

Reference Type BACKGROUND

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)

Reference Type BACKGROUND

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

Reference Type BACKGROUND

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

Reference Type BACKGROUND

Demeter LM, Shafer RW, Meehan PM, Holden-Wiltse J, Fischl MA, Freimuth WW, Para MF, Reichman RC. Delavirdine susceptibilities and associated reverse transcriptase mutations in human immunodeficiency virus type 1 isolates from patients in a phase I/II trial of delavirdine monotherapy (ACTG 260). Antimicrob Agents Chemother. 2000 Mar;44(3):794-7. doi: 10.1128/AAC.44.3.794-797.2000.

Reference Type BACKGROUND
PMID: 10681363 (View on PubMed)

Para MF, Meehan P, Holden-Wiltse J, Fischl M, Morse G, Shafer R, Demeter LM, Wood K, Nevin T, Virani-Ketter N, Freimuth WW. ACTG 260: a randomized, phase I-II, dose-ranging trial of the anti-human immunodeficiency virus activity of delavirdine monotherapy. The AIDS Clinical Trials Group Protocol 260 Team. Antimicrob Agents Chemother. 1999 Jun;43(6):1373-8. doi: 10.1128/AAC.43.6.1373.

Reference Type BACKGROUND
PMID: 10348755 (View on PubMed)

Other Identifiers

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11237

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG 260

Identifier Type: -

Identifier Source: org_study_id