A Phase II Double-Blind Study of Delavirdine Mesylate ( U-90152 ) in Combination With Zidovudine ( AZT ) and/or Didanosine ( ddI ) Versus AZT and ddI Combination Therapy

HIV Infections Clinical Trial

Official title:

A Phase II Double-Blind Study of Delavirdine Mesylate ( U-90152 ) in Combination With Zidovudine ( AZT ) and/or Didanosine ( ddI ) Versus AZT and ddI Combination Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000803
• Other study ID #: ACTG 261
• Secondary ID: 11238
• Status: Completed
• Phase: Phase 2
• Est. completion date: March 1997

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

To determine the safety and anti-HIV activity of delavirdine mesylate ( U-90152 ) in combination with zidovudine ( AZT ) and/or didanosine ( ddI ) versus AZT/ddI combination.

U-90152 has demonstrated anti-HIV activity. Since the combination of this drug with either AZT or ddI has synergistic inhibitory activity against HIV-1 in vitro, and triple therapy appears to have greater inhibitory activity against HIV-1 in vitro than dual therapy, the use of U-90152 in combination with AZT and/or ddI may improve the benefits of these drugs in persons with HIV disease.

Description:

U-90152 has demonstrated anti-HIV activity. Since the combination of this drug with either AZT or ddI has synergistic inhibitory activity against HIV-1 in vitro, and triple therapy appears to have greater inhibitory activity against HIV-1 in vitro than dual therapy, the use of U-90152 in combination with AZT and/or ddI may improve the benefits of these drugs in persons with HIV disease.

Patients are randomized to receive U-90152/AZT/ddI, U-90152/AZT, U-90152/ddI, or AZT/ddI for 48 weeks.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 471
• Est. completion date: March 1997
• Accepts healthy volunteers: No
• Gender: All
• Age group: 13 Years and older

Eligibility

Inclusion Criteria

Concurrent Medication:

Required:

• PCP prophylaxis for patients with CD4 count <= 200 cells/mm3.

Allowed:

• Topical antifungal agents.

• Oral ketoconazole, fluconazole, and itraconazole for candidiasis or disseminated fungal infections.

• Isoniazid, ethambutol, pyrazinamide, clofazimine, ciprofloxacin, and clarithromycin for acute or maintenance therapy for mycobacterial disease (also clarithromycin for MAC prophylaxis).

• Acute or maintenance therapy for toxoplasmosis.

• Acute or maintenance therapy with acyclovir (no more than 1000 mg/day) for herpes simplex virus infection.

• rEPO and rG-CSF.

• Antibiotics for bacterial infections (except rifampin and rifabutin).

• Antipyretics, analgesics, nonsteroidal anti-inflammatory agents, antiemetics, and methadone.

Concurrent Treatment:

Allowed for cutaneous Kaposi's sarcoma:

• Localized radiation therapy.

• Limited intralesional therapy.

Patients must have:

• HIV infection.

• CD4 count 100 - 500 cells/mm3.

• Prior cumulative monotherapy of <= 6 months (may have taken either AZT or ddI, but not both) OR no prior antiretroviral therapy.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Malignancy (other than basal or squamous cell carcinoma of the skin, Stage 1 or 2 cervical intraepithelial neoplasia, or minimal Kaposi's sarcoma).

• Considered to be unlikely to comply with study requirements.

Concurrent Medication:

Excluded:

• Antiretroviral therapies and biologic response modifiers (except for study medications, rEPO, and rG-CSF).

• Rifampin.

• Rifabutin.

• Terfenadine.

• Astemizole.

• Loratadine.

• Quinidine.

• Digitoxin.

• 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 intolerance to AZT at <= 600 mg/day or ddI at <= 400 mg/day or discontinuation of either drug for toxicity.

• History of intolerance to trifluoperazine or piperazine citrate (per amendment).

• History of pancreatitis.

• History of grade 2 or worse peripheral neuropathy.

• Unexplained temperature >= 38.5 C on any 7 days within the past 30 days.

• Chronic diarrhea on any 15 days during the past 30 days.

Prior Medication:

Excluded:

• Prior foscarnet as induction or maintenance therapy.

• Prior U-90152.

• Prior ddC or d4T.

• Prior AZT/ddI in combination or taken separately at different times.

• Prior non-nucleoside reverse transcriptase inhibitors (nevirapine, atevirdine, etc.).

• Prior protease inhibitors (although patients from ACTG 282 are eligible).

• HIV-1 vaccine within the past 21 days.

• Acute treatment for a serious infection or for any opportunistic infection within the past 14 days.

Excluded within the past 30 days:

• Interferon or interleukin.

• Rifampin.

• Rifabutin.

• Terfenadine.

• Astemizole.

• Loratadine.

• Recombinant EPO or G-CSF.

• Hydroxyurea.

• SPV-30.

• Any other investigational drug.

Active drug or alcohol use.

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Delavirdine mesylate

• Zidovudine

• Didanosine

Locations

Country	Name	City	State
Puerto Rico	Puerto Rico-AIDS CRS	San Juan
United States	University of Colorado Hospital CRS	Aurora	Colorado
United States	Johns Hopkins Adult AIDS CRS	Baltimore	Maryland
United States	Alabama Therapeutics CRS	Birmingham	Alabama
United States	Beth Israel Deaconess - East Campus A0102 CRS	Boston	Massachusetts
United States	Beth Israel Deaconess Med. Ctr., ACTG CRS	Boston	Massachusetts
United States	Bmc Actg Crs	Boston	Massachusetts
United States	Massachusetts General Hospital ACTG CRS	Boston	Massachusetts
United States	SUNY - Buffalo, Erie County Medical Ctr.	Buffalo	New York
United States	Univ. of Cincinnati CRS	Cincinnati	Ohio
United States	Case CRS	Cleveland	Ohio
United States	The Ohio State Univ. AIDS CRS	Columbus	Ohio
United States	Queens Med. Ctr.	Honolulu	Hawaii
United States	Univ. of Hawaii at Manoa, Leahi Hosp.	Honolulu	Hawaii
United States	Indiana Univ. School of Medicine, Infectious Disease Research Clinic	Indianapolis	Indiana
United States	Methodist Hosp. of Indiana	Indianapolis	Indiana
United States	USC CRS	Los Angeles	California
United States	Univ. of Miami AIDS CRS	Miami	Florida
United States	University of Minnesota, ACTU	Minneapolis	Minnesota
United States	Beth Israel Med. Ctr. (Mt. Sinai)	New York	New York
United States	Cornell University A2201	New York	New York
United States	Memorial Sloan-Kettering Cancer Ctr.	New York	New York
United States	NY Univ. HIV/AIDS CRS	New York	New York
United States	Stanford CRS	Palo Alto	California
United States	Hosp. of the Univ. of Pennsylvania CRS	Philadelphia	Pennsylvania
United States	Univ. of Rochester ACTG CRS	Rochester	New York
United States	St. Louis ConnectCare, Infectious Diseases Clinic	Saint Louis	Missouri
United States	Washington U CRS	Saint Louis	Missouri
United States	Ucsd, Avrc Crs	San Diego	California
United States	Ucsf Aids Crs	San Francisco	California
United States	University of Washington AIDS CRS	Seattle	Washington
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)

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (5)

Demeter LM, Meehan PM, Morse G, Gerondelis P, Dexter A, Berrios L, Cox S, Freimuth W, Reichman RC. HIV-1 drug susceptibilities and reverse transcriptase mutations in patients receiving combination therapy with didanosine and delavirdine. J Acquir Immune Defic Syndr Hum Retrovirol. 1997 Feb 1;14(2):136-44. — View Citation

Freimuth WW, Chuang-Stein CJ, Greenwald CA, Wathen LK, Edge-Padbury BA, Cox SR, Daenzer CL, Wang Y, Carberry PA. Delavirdine (DLV) combined with zidovudine (ZDV) or didanosine (ddI) produces sustained reduction in viral burden and increases in CD4 count in early and advanced HIV-1 infection. Int Conf AIDS. 1996 Jul 7-12;11(1):22 (abstract no MoB295)

Friedland GH, Pollard R, Griffith B, Hughes M, Morse G, Bassett R, Freimuth W, Demeter L, Connick E, Nevin T, Hirsch M, Fischl M. Efficacy and safety of delavirdine mesylate with zidovudine and didanosine compared with two-drug combinations of these agents in persons with HIV disease with CD4 counts of 100 to 500 cells/mm3 (ACTG 261). ACTG 261 Team. J Acquir Immune Defic Syndr. 1999 Aug 1;21(4):281-92. — View Citation

Griffit B, Morse G, Demeter L, Bassett R, Hughes M, Friedland G. Relationship between delavirdine (DLV) plasma levels, HIV RNA responses and DLV resistance during combination therapy with zidovudine (ZDV), and didanosine (ddI). Int Conf AIDS. 1998;12:52 (abstract no 12206)

Nokta M, Turk P. Partial restoration of HIV specific neutralizing activity (NA) of HIV infected patients receiving antiretrovial therapy: DDI/delaviridine (DLV), AZT/DLV, DDI/AZT or DDI/AZT/DLV. Int Conf AIDS. 1998;12:516 (abstract no 31108)