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Trial record 54 of 3132 for:    HIV Infections | NIH

Safety of Saquinavir and High Doses of Lopinavir/Ritonavir in Children With HIV

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00084058
Recruitment Status : Completed
First Posted : June 7, 2004
Last Update Posted : May 21, 2012
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Tracking Information
First Submitted Date  ICMJE June 4, 2004
First Posted Date  ICMJE June 7, 2004
Last Update Posted Date May 21, 2012
Study Start Date  ICMJE Not Provided
Primary Completion Date Not Provided
Current Primary Outcome Measures  ICMJE
 (submitted: August 18, 2005)
  • Life-threatening adverse events attributable to study drugs
  • dose-limiting toxicity, defined as adverse events of Grade 3 or greater attributable to study drug and require dose reduction or interruption but are not judged to be life-threatening by the protocol team
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00084058 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 18, 2005)
  • Pharmacological success, defined as achieving an inhibitory quotient (IQ) of 15 after 2 weeks on high-dose LPV/r without life-threatening or dose-limiting toxicity
  • virologic success, defined by optimal response (undetectable viral load) at Week 24 or adequate response (0.75 log drop in viral load or more) from baseline to Week 24
  • immunologic success, defined as a CD4% increase from baseline of 5% or more points by Week 24
  • minimal criterion for overall success, defined as a 0.75 log drop in viral load or more or 5% point increase in CD4% from baseline to Week 24
  • virologic failure, defined as an inadequate (less than 0.75 log drop in viral load) or suboptimal (confirmed viral load of greater than 400 copies/ml) response at Week 24
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety of Saquinavir and High Doses of Lopinavir/Ritonavir in Children With HIV
Official Title  ICMJE A Phase I/II Safety, Tolerability, and Pharmacokinetic Study of High Dose Lopinavir/Ritonavir With or Without Saquinavir in HIV-Infected Pediatric Subjects Previously Treated With Protease Inhibitors
Brief Summary The purpose of this study is to determine the effect of increased doses of lopinavir/ritonavir (LPV/r) and saquinavir (SQV) in HIV infected children who are failing their current antiretroviral regimen
Detailed Description

Since current drugs cannot cure HIV infection, lifelong therapy is required. Development of drug resistance is common, with 30% to 80% of patients with initial viral load decreases following a potent anti-HIV regimen experiencing regimen failure within the first year of therapy. Dose intensification (increasing dosing of treatment medications) has been used successfully in pediatric oncology. Dose intensification in HIV infected patients may overcome resistance and, as similarly observed in cancer, may result in a greater rate of viral inhibition, maximizing the degree and durability of viral suppression. This study will evaluate dose intensification in HIV infected children and adolescents who are failing their current antiretroviral regimen and have significant genotypic and phenotypic resistance.

Participants in this 3-step study will have previously undergone genotypic resistance testing as part of their regular clinical care. Participants will have phenotypic resistance testing done at screening or within 6 months prior to study entry. Participants in this study will have either a genotypic profile with at least 4 of the required protease mutations or phenotypic resistance to LPV that is at least fivefold greater than wild type while on a failing regimen within 6 months of study screening.

In Step 1, Group 1 participants will be randomly assigned to either a drug regimen without a nonnucleoside reverse transcriptase inhibitor (NNRTI) or a drug regimen with an NNRTI for Group 2 participants. Participants and their doctors will work with study investigators to select the best treatment regimen possible. All participants in the study will receive LPV/r as part of their drug regimens. Participants in Group 1 will take a higher dose of LPV/r than participants in Group 2 because NNRTIs lower LPV/r levels in the blood.

At Week 2, participants will undergo a 12-hour pharmacokinetic (PK) test to evaluate the drug levels in their blood. If LPV/r levels are not high enough to control HIV and the participant can swallow tablets, hard gel capsules, or the contents of hard gel capsules with food or milk, the participant will begin taking SQV as part of his or her drug regimen and enter Step 2. After two weeks of taking SQV, participants will again undergo PK testing at Week 6. Based on these test results, the dose of SQV will then be increased, decreased, or maintained. Participants who do not add SQV to their regimen will continue taking LPV/r for the remainder of the study and stay in Step 1. If the PK test indicates SQV blood concentrations are sufficient, the participant will remain in Step 2. If the PK test indicates SQV blood concentrations are too low, the SQV dose will be increased and the participant will enter Step 3. After 2 weeks of taking elevated doses of SQV, participants will undergo PK testing at Week 10. If the PK test indicates that SQV blood concentrations are too high, the SQV dose will be decreased. At Week 14, participants who receive a reduced SQV dose will again undergo PK testing to verify that SQV blood concentrations are optimal.

Participants will have study visits at Weeks 2, 4, 6, 7, and 8, then every 4 weeks through the end of the study at Week 48. Study visits will include a physical exam, health history assessment, and blood collection. Blood collection for PK studies will occur at selected visits. Study visits at Weeks 2 and 12 will include an electrocardiogram (ECG or EKG).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE HIV Infections
Intervention  ICMJE
  • Drug: Lopinavir/ritonavir
  • Drug: Saquinavir
Study Arms  ICMJE Not Provided
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 3, 2012)
26
Original Enrollment  ICMJE
 (submitted: June 23, 2005)
48
Actual Study Completion Date  ICMJE December 2006
Primary Completion Date Not Provided
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • HIV infected
  • HIV RNA viral load greater than 5,000 copies/ml
  • At least 6 months of continuous therapy with a protease inhibitor (PI) prior to study entry
  • No change in antiretroviral therapy since genotypic resistance testing
  • Genotypic resistance testing indicating a primary protease mutation at position 32, 47, 48, 50, 82, or 84 and at least three other mutations in positions 10, 20, 24, 30, 32, 33, 36, 46, 47, 48, 50, 53, 54, 71, 73, 77, 82, 84, or 90 OR phenotypic resistance testing, within 6 months of screening while on a failing regimen, indicating at least a fivefold increase in LPV as compared to wild type HIV
  • Parent or legal guardian willing to provide informed consent
  • If sexually active, agree to use acceptable methods of contraception
  • Have a telephone, pager, or other method of reliable communication with study staff
  • Able and willing to swallow study medications

Exclusion Criteria:

  • Any drug toxicity greater than Grade 3 at screening
  • Certain abnormal laboratory values
  • Acute opportunistic or serious bacterial infection requiring treatment
  • Chemotherapy for active cancer
  • Any significant diseases (other than HIV infection) that may, in the opinion of the investigator, interfere with the study
  • Require certain medications
  • History of heart problems
  • Family history of prolonged QTc-Interval Syndrome or prolonged QTc-interval at study entry
  • Pregnancy or breastfeeding
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 2 Years to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Puerto Rico,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00084058
Other Study ID Numbers  ICMJE P1038
10045 ( Registry Identifier: DAIDS ES )
PACTG P1038
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Institute of Allergy and Infectious Diseases (NIAID)
Study Sponsor  ICMJE National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators  ICMJE Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators  ICMJE
Study Chair: Peter L. Havens, MD Medical College of Wisconsin
PRS Account National Institute of Allergy and Infectious Diseases (NIAID)
Verification Date May 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP