Comparison of Ro 31-8959 Plus Zidovudine (AZT) Versus AZT Plus Zalcitabine (ddC) Versus Ro 31-8959 Plus AZT Plus ddC

• ClinicalTrials.gov Identifier: NCT00001040
• Recruitment Status: Completed
• First Posted: August 31, 2001
• Last Update Posted: March 1, 2011
• Sponsor: Hoffmann-La Roche
• Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)

Study Description

Brief Summary:

PRIMARY: To determine the efficacy and toxicity of three treatment regimens: saquinavir mesylate (Ro 31-8959) plus zidovudine (AZT) vs. AZT plus zalcitabine (dideoxycytidine; ddC) vs. Ro 31-8959 plus AZT plus ddC.

SECONDARY: To investigate the pharmacokinetics and effects on various clinical parameters of the three regimens.

Condition or disease	Intervention/treatment	Phase
HIV Infections	Drug: Saquinavir; Drug: Zidovudine; Drug: Zalcitabine	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Enrollment: 300 participants
• Primary Purpose: Treatment
• Official Title: Double-Blind, Randomized, Phase II Study of Ro 31-8959 Plus Zidovudine (AZT) Versus AZT Plus Zalcitabine (Dideoxycytidine; ddC) Versus Ro 31-8959 Plus AZT Plus ddC
• Actual Primary Completion Date: May 1994

Arms and Interventions

Outcome Measures

Eligibility Criteria

• Ages Eligible for Study: 13 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria

Prior Medication: Required:

• At least 4 months total of AZT at some point in the past, alone or in combination with other antiretroviral therapy.

Patients must have:

• HIV seropositivity.
• Diagnosis of AIDS, ARC, PGL, or asymptomatic infection.
• CD4 count > 50 to <= 300 cells/mm3.
• Life expectancy of at least 6 months.
• Prior AZT therapy.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Acute serious opportunistic infections requiring immediate treatment, including (but not limited to) tuberculosis, CMV, cryptococcal meningitis, disseminated MAC, cerebral toxoplasmosis, and Pneumocystis carinii pneumonia.
• Known intolerance to Ro 31-8959, AZT, or ddC.
• Symptoms suggestive of pancreatitis.
• Moderate or severe peripheral neuropathy as evidenced by discomfort from numbness, tingling, burning or pain of the extremities or any related symptoms that are accompanied by an objective finding.
• Visceral Kaposi's sarcoma.
• Lymphoma that will require therapy within the next 6 months.
• Transfusion dependence.

Concurrent Medication:

Excluded:

• Investigational or antineoplastic agents.

Concurrent Treatment:

Excluded:

• Radiotherapy (other than local skin radiotherapy).
• Transfusions.

Prior Medication:

Excluded:

• Any antiretroviral agent (other than AZT) or immunomodulatory therapy within 14 days prior to study entry.
• Prior treatment with an HIV proteinase inhibitor.

Contacts and Locations

Locations

United States, Alabama

Univ of Alabama at Birmingham

Birmingham, Alabama, United States, 35294

United States, California

Stanford Univ Med Ctr

Stanford, California, United States, 943055107

United States, Colorado

Univ of Colorado Health Sciences Ctr

Denver, Colorado, United States, 80262

United States, Illinois

Northwestern Univ Med School

Chicago, Illinois, United States, 60611

United States, New York

Bellevue Hosp / New York Univ Med Ctr

New York, New York, United States, 10016

Univ of Rochester Med Ctr

Rochester, New York, United States, 14642

United States, Ohio

Ohio State Univ Hosp

Columbus, Ohio, United States, 432101228

United States, Pennsylvania

Girard Med Ctr

Philadelphia, Pennsylvania, United States, 191046073

United States, Texas

Univ TX Galveston Med Branch

Galveston, Texas, United States, 775550882

United States, Washington

Univ of Washington

Seattle, Washington, United States, 98122

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

• Study Chair: Collier AC
• Study Chair: Corey L

More Information

Publications:

Schapiro JM, Lawrence J, Speck R, Winters MA, Efron B, Coombs RW, Collier AC, Merigan TC. Resistance mutations to zidovudine and saquinavir in patients receiving zidovudine plus saquinavir or zidovudine and zalcitabine plus saquinavir in AIDS clinical trials group 229. J Infect Dis. 1999 Jan;179(1):249-53. doi: 10.1086/314541.

Brambilla D, Coombs R, Bremer JW, Reichelderfer PS, Kalish L, Shapiro DE. The contributions of assay variation and biological variation to the variability of HIV RNA measurements in serially collected clinical specimens. Int Conf AIDS. 1998;12:805 (abstract no 42163)

Collier AC, Coombs RW, Schoenfeld DA, Bassett R, Baruch A, Corey L. Combination therapy with zidovudine, didanosine and saquinavir. Antiviral Res. 1996 Jan;29(1):99. doi: 10.1016/0166-3542(95)00928-0.

Collier AC, Coombs RW, Timpone J, Schoenfeld DA, Bassett R, Baruch A, Corey L. Comparative study of Ro 31-8959 and zidovudine (ZDV) vs. ZDV and zalcitabine (ddC) vs. Ro 31-8959, ZDV, and ddC. The ACTG 229 Protocol Team. Int Conf AIDS. 1994 Aug 7-12;10(1):21 (abstract no 058B)

Noble S, Faulds D. Saquinavir. A review of its pharmacology and clinical potential in the management of HIV infection. Drugs. 1996 Jul;52(1):93-112. doi: 10.2165/00003495-199652010-00007.

Vanhove GF, Gries JM, Verotta D, Sheiner LB, Coombs R, Collier AC, Blaschke TF. Exposure-response relationships for saquinavir, zidovudine, and zalcitabine in combination therapy. Antimicrob Agents Chemother. 1997 Nov;41(11):2433-8. doi: 10.1128/AAC.41.11.2433.

Collier AC, Coombs RW, Schoenfeld DA, Bassett RL, Timpone J, Baruch A, Jones M, Facey K, Whitacre C, McAuliffe VJ, Friedman HM, Merigan TC, Reichman RC, Hooper C, Corey L. Treatment of human immunodeficiency virus infection with saquinavir, zidovudine, and zalcitabine. AIDS Clinical Trials Group. N Engl J Med. 1996 Apr 18;334(16):1011-7. doi: 10.1056/NEJM199604183341602.

Fischl MA, Stanley K, Collier AC, Arduino JM, Stein DS, Feinberg JE, Allan JD, Goldsmith JC, Powderly WG. Combination and monotherapy with zidovudine and zalcitabine in patients with advanced HIV disease. The NIAID AIDS Clinical Trials Group. Ann Intern Med. 1995 Jan 1;122(1):24-32. doi: 10.7326/0003-4819-122-1-199501010-00004.

Schapiro JM, Lawrence J, Speck R, Winters MA, Coombs R, Collier AC, Efron B, Merigan TC. HIV RNA and resistance mutations to saquinavir and zidovudine in patients receiving dual versus triple combination therapy. Conf Retroviruses Opportunistic Infect. 1998 Feb 1-5;5th:154 (abstract no 401)

• ClinicalTrials.gov Identifier: NCT00001040
• Other Study ID Numbers: ACTG 229; NV14255D; FDA 123A
• First Posted: August 31, 2001
• Last Update Posted: March 1, 2011
• Last Verified: February 2011

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Zalcitabine; Drug Therapy, Combination; Acquired Immunodeficiency Syndrome; AIDS-Related Complex; Zidovudine; Saquinavir; HIV Protease Inhibitors

Additional relevant MeSH terms:

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Zidovudine; Zalcitabine; Saquinavir; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antiviral Agents; Anti-Infective Agents; Anti-HIV Agents; Anti-Retroviral Agents; HIV Protease Inhibitors; Viral Protease Inhibitors; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors