The purpose of this study is to determine the safety and effectiveness of a soft-gel capsule formulation of saquinavir (SQV-SGC), a protease inhibitor, when given in combination with other anti-HIV drugs. SQV-SGC has been tested in adults for the treatment of HIV infection, but more information is still needed about SQV-SGC in children. Recent studies suggest that this soft-gel capsule form may be safer and more effective than other protease inhibitors.

Condition	Treatment or Intervention	Phase
HIV Infections	Drug: Ritonavir  Drug: Nelfinavir mesylate  Drug: Saquinavir	Phase II

Further Study Details: 

Expected Total Enrollment:  50

Clinical trials in adults and children suggest that SQV-SGC has advantages over other protease inhibitors in terms of tolerability, safety, and effectiveness in patients who have failed therapy with other protease inhibitors. [AS PER AMENDMENT 11/24/99: Pharmacokinetic data from this study demonstrate lower than expected plasma SQV exposures, particularly in Arm 1. Based on these data, patients in the study will be offered the opportunity to adjust their doses. Ritonavir added to the Arm 1 regimen is expected to significantly increase SQV-SGC plasma levels and allow twice-daily dosing for SQV-SGC.]

Patients are randomized to one of two study arms. Patients in Arm 1 receive SQV-SGC plus two [AS PER AMENDMENT 11/24/99: one or two] NRTIs of choice. Patients in Arm 2 receive SQV-SGC plus NFV plus one or two NRTIs of choice. All participants are evaluated by physical examinations and laboratory tests during the study and are followed for incidence of death, cancer, or fetal abnormality. NRTIs are not provided as part of this study. [AS PER AMENDMENT 11/24/99: This study is closed to accrual. All subjects on follow-up (Cohort 1) are given the option of either discontinuing participation in ACTG 397 or participating in the next phase of the study (version 2.0). Those electing to continue participation constitute Cohort 1A. The adjusted Arm 1 regimen consists of SQV-SGC plus ritonavir plus one or two NRTIs. Ritonavir is not provided as part of this study. The Arm 2 regimen study drugs have not changed but the maximum allowable dose of SQV-SGC has increased from 1,200 mg twice-daily to 1,600 mg twice-daily. Participants continue to be followed with physical examinations and laboratory evaluations that include an intensive pharmacokinetics study on Day 14 of the new regimen.]

Ages Eligible for Study:  3 Years   -   16 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria

Your child may be eligible for this study if he or she:

• Is HIV-positive.
• Is 3 to 16 years of age (consent of parent or guardian is required).
• Has an HIV level greater than 10,000 copies/ml.
• Has never taken at least one of the following anti-HIV drugs: lamivudine, zidovudine, stavudine, or didanosine.
• Is able to swallow capsules and tablets.

Exclusion Criteria

Your child will not be eligible if he or she:

• Has cancer requiring chemotherapy.
• Has an acute opportunistic (AIDS-related) infection requiring therapy.
• Has had two or more episodes of moderate or severe diarrhea or vomiting in the 3 months prior to study entry.
• Has ever taken SQV or NFV.
• Is pregnant or breast-feeding.
• Is taking certain medications, including those that would interfere with the study drugs.

Alabama
      Univ of Alabama at Birmingham - Pediatric, Birmingham,  Alabama,  35233,  United States
      Univ of Alabama at Birmingham / Childrens Hosp of AL, Birmingham,  Alabama,  352330011,  United States
California
      UCSF / Moffitt Hosp - Pediatric, San Francisco,  California,  941430105,  United States
      Children's Hosp of Oakland, Oakland,  California,  946091809,  United States
      Long Beach Memorial (Pediatric), Long Beach,  California,  90801,  United States
      Los Angeles County - USC Med Ctr, Los Angeles,  California,  90033,  United States
Connecticut
      Yale Univ Med School, New Haven,  Connecticut,  06504,  United States
District of Columbia
      Howard Univ Hosp, Washington,  District of Columbia,  20060,  United States
Florida
      Univ of Miami (Pediatric), Miami,  Florida,  33161,  United States
      Palm Beach County Health Dept, Riviera Beach,  Florida,  33404,  United States
Georgia
      Emory Univ Hosp / Pediatrics, Atlanta,  Georgia,  30306,  United States
Illinois
      Chicago Children's Memorial Hosp, Chicago,  Illinois,  606143394,  United States
      Cook County Hosp, Chicago,  Illinois,  60612,  United States
      Univ of Illinois College of Medicine / Pediatrics, Chicago,  Illinois,  60612,  United States
Louisiana
      Tulane Univ / Charity Hosp of New Orleans, New Orleans,  Louisiana,  701122699,  United States
Maryland
      Univ of Maryland at Baltimore / Univ Med Ctr, Baltimore,  Maryland,  21201,  United States
Massachusetts
      Children's Hosp of Boston, Boston,  Massachusetts,  021155724,  United States
      Baystate Med Ctr of Springfield, Springfield,  Massachusetts,  01199,  United States
Mississippi
      Univ of Mississippi Med Ctr, Jackson,  Mississippi,  39213,  United States
New Jersey
      Univ of Medicine & Dentistry of New Jersey / Univ Hosp, Newark,  New Jersey,  071032714,  United States
New York
      Harlem Hosp Ctr, New York,  New York,  10037,  United States
      Cornell Univ Med College, New York,  New York,  10021,  United States
      North Shore Univ Hosp, Great Neck,  New York,  11021,  United States
      Columbia Presbyterian Med Ctr, New York,  New York,  10032,  United States
      Bronx Municipal Hosp Ctr/Jacobi Med Ctr, Bronx,  New York,  10461,  United States
      Children's Hosp at Albany Med Ctr, Albany,  New York,  12208,  United States
      Bronx Lebanon Hosp Ctr, Bronx,  New York,  10457,  United States
      Incarnation Children's Ctr / Columbia Presbyterian Med Ctr, New York,  New York,  10032,  United States
      State Univ of New York at Stony Brook, Stony Brook,  New York,  117948111,  United States
Pennsylvania
      Saint Christopher's Hosp for Children, Philadelphia,  Pennsylvania,  191341095,  United States
South Carolina
      Med Univ of South Carolina, Charleston,  South Carolina,  294253312,  United States
Virginia
      Med College of Virginia, Richmond,  Virginia,  23219,  United States
Washington
      Children's Hospital & Medical Center / Seattle ACTU, Seattle,  Washington,  981050371,  United States
Puerto Rico
      San Juan City Hosp, San Juan,  009367344,  Puerto Rico
      Univ of Puerto Rico / Univ Children's Hosp AIDS, San Juan,  009365067,  Puerto Rico
      Ramon Ruiz Arnau Univ Hosp / Pediatrics, Bayamon,  00956,  Puerto Rico

Study chairs or principal investigators

Mark Kline,  Study Chair
Courtney Fletcher,  Study Chair

Study ID Numbers:  ACTG 397
Record last reviewed:  August 2004
Last Updated:  April 7, 2005
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00000913
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08