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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00001040
• Other study ID #: ACTG 229
• Secondary ID: NV14255DFDA 123A
• Status: Completed
• Phase: Phase 2
• First received: November 2, 1999
• Last updated: February 28, 2011

Study information

• Verified date: February 2011
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Unspecified
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 300
• Est. primary completion date: May 1994
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 13 Years and older

Eligibility

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.

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Saquinavir

• Zidovudine

• Zalcitabine

Locations

Country	Name	City	State
United States	Univ of Alabama at Birmingham	Birmingham	Alabama
United States	Northwestern Univ Med School	Chicago	Illinois
United States	Ohio State Univ Hosp	Columbus	Ohio
United States	Univ of Colorado Health Sciences Ctr	Denver	Colorado
United States	Univ TX Galveston Med Branch	Galveston	Texas
United States	Bellevue Hosp / New York Univ Med Ctr	New York	New York
United States	Girard Med Ctr	Philadelphia	Pennsylvania
United States	Univ of Rochester Med Ctr	Rochester	New York
United States	Univ of Washington	Seattle	Washington
United States	Stanford Univ Med Ctr	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

United States, 

References & Publications (9)

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. — View Citation

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. — View Citation

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)

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. — View Citation

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. Review. — View Citation

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)

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. — View Citation

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. — View Citation

External Links

•   Click here for more information about Saquinavir
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