A Comparison of Three Anti-HIV Drug Combinations Containing Saquinavir Soft Gelatin Capsules Used in HIV-1 Infected Patients

HIV Infections Clinical Trial

Official title:

A Randomized Phase IIIB Comparative Study to Evaluate Saquinavir Soft Gel Capsule (SGC) TID Regimen in Combination With Two NRTIs Versus Saquinavir Soft Gel Capsule (SGC) BID Regimen in Combination With Two NRTIs Versus Saquinavir Soft Gel Capsule (SGC) BID Plus Nelfinavir BID Plus a NRTI in HIV-1 Infected Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002378
• Other study ID #: 229H
• Secondary ID: NR15520M6101
• Status: Completed
• Phase: Phase 3
• First received: November 2, 1999
• Last updated: June 23, 2005

Study information

• Verified date: December 1998
• Source: NIH AIDS Clinical Trials Information Service
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

To determine the proportion of patients whose plasma HIV-1 RNA level falls below the level of detection (< 400 copies/ml) at week 24 of study therapy. To determine the absolute change in plasma HIV-1 RNA during the 24 weeks of study treatment. To collect safety data on the treatment regimens.

AS PER AMENDMENT 12/12/97: To compare the virologic response of Fortovase (FTV) (Saquinavir) Soft Gel Capsule (SGC) tid plus nucleoside reverse transcriptase inhibitors (NRTIs) versus FTV bid plus NRTIs. Further, to compare the virologic response of FTV tid plus NRTIs versus FTV bid plus Nelfinavir bid plus a NRTI with respect to: the percentage of patients whose plasma HIV-1 RNA level falls below the Amplicor assay level of detection (< 400 copies/ml) at week 24 and week 48.

Description:

Patients will be randomized to receive 1 of 3 study regimens: Group A - Saquinavir (SQV) sgc plus 2 new reverse transcriptase inhibitors (RTIs), Group B - SQV sgc plus delavirdine plus new RTI, and Group C - SQV sgc plus nelfinavir plus new RTI, or SQV sgc plus ritonavir plus 2 new RTIs.

NOTE: "New RTI" is defined for this study as any reverse transcriptase inhibitor to which the patient has never been exposed.

AS PER AMENDMENT 12/12/97: In this open-label, multicenter, Phase IIIB, comparative study, 825 patients are randomized to treatment arms. (NOTE: 50% of the patients will be treatment naive and 50% will be NRTI experienced.) Further, patients are randomized with stratification based on HIV-1 RNA level (5,000-30,000 copies/ml vs. greater than 30,000 copies/ml) and prior antiretroviral therapy to one of the three study arms.

The drug regimens for the three treatment arms are as follows:

ARM A: Fortovase (FTV), plus 2 new NRTIs*. ARM B: FTV plus 2 new NRTIs*. ARM C: FTV plus nelfinavir plus new NRTI**.

• Naive patients in Arm A and Arm B will take: d4T (or zidovudine) plus 3TC unless contraindicated.

** Naive patients in Arm C will take: d4T, unless contraindicated.

• NRTI experienced patients in Arms A & B should be treated with 2 NRTIs to which he/she has not been previously exposed. If the patient has only 1 NRTI to which he/she has never been exposed, then the second NRTI can be one that the patient has been previously exposed to from the most distant past.

Therapy is administered for an initial 24 weeks and may be extended for an additional 24 weeks.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 825
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years and older

Eligibility

Inclusion Criteria

Patients must have:

• HIV-1 infection.

• HIV RNA >= 5000 copies/ml by Amplicor assay.

• Signed, informed consent from parent or legal guardian for patients less than 18 years old.

Prior Medication:

Required:

(Note:

• 50% of the patients will be treatment naive).

• > 3 months cumulative therapy with antiretrovirals other than non-nucleoside reverse transcriptase inhibitors and/or protease inhibitors.

• Stable antiretroviral therapy for at least 4 weeks prior to enrollment.

Allowed:

• <= 2 weeks cumulative treatment with protease inhibitors.

AS PER AMENDMENT 12/12/97:

Required:

NRTI experienced patients:

• > 3 months cumulative therapy with antiretrovirals.

• <= 2 weeks cumulative previous treatment with non-nucleoside analogue reverse transcriptase inhibitors (NNRTIs).

• <= 2 weeks cumulative previous treatment with protease inhibitors.

• Must have at least one NRTI (preferably two) to which he/she has not been previously exposed.

• Stable antiretroviral therapy defined as within (+/-) 1 log HIV-1 RNA between the 2 most recent values greater than 8 weeks apart (may include screening visit) prior to study enrollment. (NOTE:

• If patient does not have a previous HIV-1 RNA value, screening will be accepted.)

Required:

• Note:

• 50% of the patients will be treatment naive and 50% will be NRTI experienced. AS PER AMENDMENT 12/12/97.

Study Design

Endpoint Classification: Safety Study, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Ritonavir

• Nelfinavir mesylate

• Saquinavir

• Delavirdine mesylate

• Lamivudine

• Stavudine

• Zidovudine

Locations

Country	Name	City	State
Germany	Medizinische Einrichtungen der Heinrich U	Duesseldorf
Italy	Ospedale S Raffaele	Milano
Puerto Rico	San Juan Veterans Administration Med Ctr	San Juan
Spain	Hosp Valle D Hebron	Barcelona
United Kingdom	Royal Liverpool Univ Hosp	Liverpool
United States	Albany Med College / Division of HIV Medicine A158	Albany	New York
United States	Lehigh Valley Hosp	Allentown	Pennsylvania
United States	IDC Research Initiative	Altamonte Springs	Florida
United States	ASC Inc	Aniston	Alabama
United States	Infectious Disease Physicians Inc	Annandale	Virginia
United States	AIDS Research Consortium of Atlanta	Atlanta	Georgia
United States	Austin Infectious Disease Consultants	Austin	Texas
United States	Alta Bates Med Ctr	Berkeley	California
United States	Montefiore Med Ctr	Bronx	New York
United States	Community Research Initiative	Brookline	Massachusetts
United States	Brookdale Univ Med Ctr	Brooklyn	New York
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	UMDNJ - New Jersey Med School / Cooper Hosp	Camden	New Jersey
United States	Carolinas Research Associates	Charlotte	North Carolina
United States	Nalle Clinic	Charlotte	North Carolina
United States	Northwestern Univ Med Ctr	Chicago	Illinois
United States	Univ of Cincinnati Med Ctr / Holmes Division	Cincinnati	Ohio
United States	Burnside Clinic	Columbia	South Carolina
United States	Dr Nicholaos Bellos	Dallas	Texas
United States	North Texas Infectious Disease Consultants	Dallas	Texas
United States	Univ of Texas Southwestern Med Ctr of Dallas	Dallas	Texas
United States	Infectious Disease Specialists of Atlanta	Decatur	Georgia
United States	Denver Public Health Dept / Disease Control Services	Denver	Colorado
United States	Kaiser Permanente, Infectious Disease	Denver	Colorado
United States	Harper Hosp	Detroit	Michigan
United States	Nassau County Med Ctr	East Meadow	New York
United States	VAMC New Jersey Healthcare System	East Orange	New Jersey
United States	Elmhurst Hosp	Elmhurst	New York
United States	Stratogen of Ft Lauderdale	Fort Lauderdale	Florida
United States	Urgent Care Ctr	Fort Lauderdale	Florida
United States	Dr Robert Schwartz	Fort Myers	Florida
United States	East Carolina Univ School of Medicine	Greenville	North Carolina
United States	Houston Clinical Research Network	Houston	Texas
United States	Houston Clinical Research Network	Houston	Texas
United States	Houston Med Ctr	Houston	Texas
United States	ONCOL Med Associates / PA	Houston	Texas
United States	Indiana Univ Hosp	Indianapolis	Indiana
United States	Ctr for Special Immunology	Irving	California
United States	Duval County Health Dept	Jacksonville	Florida
United States	Antibiotic Research Associates	Kansas City	Missouri
United States	Univ of Missouri at Kansas City School of Medicine	Kansas City	Missouri
United States	HIV Wellness Ctr / Univ Med Ctr	Las Vegas	Nevada
United States	Dartmouth-Hitchcock Med Ctr	Lebanon	New Hampshire
United States	Univ of Kentucky / Kentucky Clinic Annex #	Lexington	Kentucky
United States	AIDS Healthcare Foundation Labs	Los Angeles	California
United States	Beer Med Group	Los Angeles	California
United States	Dr Charles Farthing	Los Angeles	California
United States	North Shore Univ Hosp	Manhasset	New York
United States	Steinhart Medical Associates	Miami	Florida
United States	Aurora Med Group	Milwaukee	Wisconsin
United States	Abbott Northwestern Hosp	Minneapolis	Minnesota
United States	Mt Vernon Hosp	Mt. Vernon	New York
United States	AIDS Clinical Trials Unit	New York	New York
United States	Dr Douglas Dieterich	New York	New York
United States	Dr Michael Mullen	New York	New York
United States	Dr Ron Grossman	New York	New York
United States	Harlem Hosp Ctr	New York	New York
United States	Howard Grossman	New York	New York
United States	Liberty Med Group	New York	New York
United States	New York / Cornell Med Ctr	New York	New York
United States	New York Hosp - Cornell Med Ctr	New York	New York
United States	New York Hosp / Cornell Med Ctr	New York	New York
United States	Peter Krueger Clinic	New York	New York
United States	St Lukes / Roosevelt Hosp / HIV Center	New York	New York
United States	New Jersey Community Research Initiative	Newark	New Jersey
United States	Gottlieb Med Group	North Hollywood	California
United States	Oklahoma Univ Health Science Ctr	Oklahoma City	Oklahoma
United States	Stratogen Health of Palm Beach	Palm Beach Gardens	Florida
United States	Dr Wilbert Jordan	Paramount	California
United States	St Joseph's Hosp & Med Center	Paterson	New Jersey
United States	Allegheny Univ Hosp	Philadelphia	Pennsylvania
United States	Dr Jay Kostman	Philadelphia	Pennsylvania
United States	CIGNA	Phoenix	Arizona
United States	Roger Williams Med Ctr	Providence	Rhode Island
United States	AIDS Community Research Consortium	Redwood City	California
United States	Mayo Clinic	Rochester	Minnesota
United States	Dr Daniel Pearce	San Francisco	California
United States	Kaiser Permanente Med Ctr	San Francisco	California
United States	QUEST Clinical Research	San Francisco	California
United States	UCSF - San Francisco Gen Hosp	San Francisco	California
United States	Marin County Specialty Clinic	San Rafael	California
United States	Swedish Med Ctr / Dr Peter Shalit	Seattle	Washington
United States	SIU School of Medicine	Springfield	Illinois
United States	Ctr for Quality Care	Tampa	Florida
United States	Infectious Disease Research Institute Inc	Tampa	Florida
United States	Univ of South Florida	Tampa	Florida
United States	Shared Med Research Foundation	Tarzana	California
United States	Arizona Clinical Research Ctr Inc	Tucson	Arizona
United States	Univ of Arizona	Tucson	Arizona
United States	Carle Clinic Association	Urbana	Illinois
United States	Treasure Coast Infectious Disease Consultants	Vero Beach	Florida
United States	Anderson Clinical Research	Washington	District of Columbia
United States	Georgetown Univ Med Ctr	Washington	District of Columbia
United States	Providence Hosp	Washington	District of Columbia
United States	Bowman Gray School of Medicine	Winston Salem	North Carolina
United States	Univ of Massachusetts Med Ctr	Worcester	Massachusetts
United States	Saint Joseph's / Mercy Hosp	Ypsilanti	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Germany,  Italy,  Puerto Rico,  Spain,  United Kingdom,