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

HIV Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000810
• Other study ID #: ACTG 260
• Secondary ID: 11237
• Status: Completed
• Phase: Phase 1
• Est. completion date: January 1996

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: January 1996
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Delavirdine mesylate

• Zidovudine

• Didanosine

Locations

Country	Name	City	State
United States	University of Colorado Hospital CRS	Aurora	Colorado
United States	SUNY - Buffalo, Erie County Medical Ctr.	Buffalo	New York
United States	Unc Aids Crs	Chapel Hill	North Carolina
United States	Northwestern University CRS	Chicago	Illinois
United States	The Ohio State Univ. AIDS CRS	Columbus	Ohio
United States	Indiana Univ. School of Medicine, Infectious Disease Research Clinic	Indianapolis	Indiana
United States	Univ. of Miami AIDS CRS	Miami	Florida
United States	Univ. of Rochester ACTG CRS	Rochester	New York
United States	Stanford CRS	Stanford	California
United States	Howard University Hosp., Div. of Infectious Diseases, ACTU	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

References & Publications (8)

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

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. — View Citation

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)

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)

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)

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

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. — View Citation