Clinical trial NCT00001040: Comparison of Ro 31-8959 Plus Zidovudine (AZT) Versus AZT Plus Zalcitabine (ddC) Versus Ro 31-8959 Plus AZT Plus ddC
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Keywords: Zalcitabine
Drug Therapy, Combination
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Zidovudine
Saquinavir
HIV Protease Inhibitors
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 300
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Univ of Alabama at Birmingham
state: Alabama
city: Stanford
country: United States
facility: Stanford Univ Med Ctr
state: California
city: Denver
country: United States
facility: Univ of Colorado Health Sciences Ctr
state: Colorado
city: Chicago
country: United States
facility: Northwestern Univ Med School
state: Illinois
city: New York
country: United States
facility: Bellevue Hosp / New York Univ Med Ctr
state: New York
city: Rochester
country: United States
facility: Univ of Rochester Med Ctr
state: New York
city: Columbus
country: United States
facility: Ohio State Univ Hosp
state: Ohio
city: Philadelphia
country: United States
facility: Girard Med Ctr
state: Pennsylvania
city: Galveston
country: United States
facility: Univ TX Galveston Med Branch
state: Texas
city: Seattle
country: United States
facility: Univ of Washington
state: Washington
Study officials:
name: Collier AC
role: STUDY_CHAIR
name: Corey L
role: STUDY_CHAIR
References:
citation: 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.
citation: 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)
citation: 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.
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)
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. doi: 10.2165/00003495-199652010-00007.
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. doi: 10.1128/AAC.41.11.2433.
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. doi: 10.1056/NEJM199604183341602.
citation: 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.
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)