Safety of Saquinavir and High Doses of Lopinavir/Ritonavir in Children With HIV
|First Received Date ICMJE||June 4, 2004|
|Last Updated Date||May 17, 2012|
|Start Date ICMJE||Not Provided|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
|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
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|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|
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||Phase 1
|Study Design ICMJE||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Condition ICMJE||HIV Infections|
|Study Arm (s)||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Completion Date||December 2006|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages||2 Years to 17 Years|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States, Puerto Rico|
|Removed Location Countries|
|NCT Number ICMJE||NCT00084058|
|Other Study ID Numbers ICMJE||P1038, 10045, PACTG P1038|
|Has Data Monitoring Committee||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)|
|Information Provided By||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