Evaluating the Safety, Tolerance, Drug Interactions, and Effective Dosing of a Raltegravir-Containing Antiretroviral Therapy (ART) Regimen in ART-Naive Children Infected With HIV and TB
People who are infected with HIV and tuberculosis (TB) need to receive medications that treat both diseases safely and effectively. This study will enroll children infected with HIV and TB and evaluate the safety and tolerance of an antiretroviral (ARV) treatment regimen for HIV that contains raltegravir when administered with a TB treatment regimen that includes rifampicin. Study researchers will also determine the most effective dose of raltegravir for children when it is taken with rifampicin.
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/II Dose-Finding, Safety, Tolerance, Drug-Drug Interaction and Pharmacokinetics Study of a Raltegravir-Containing Antiretroviral Therapy (ART) Regimen in ART-Naive HIV-Infected and TB Co-Infected Children ≥ 3 Years to < 12 Years of Age|
- Termination from treatment due to a suspected adverse drug reaction (SADR), including death and adverse events of greater than or equal to Grade 3, attributable to raltegravir [ Time Frame: Measured through a participant's last study visit, at approximately Month 4 to 9 ] [ Designated as safety issue: Yes ]
- Early termination of TB therapy if there is multi-drug-resistant (MDR)/extensively drug-resistant (XDR) TB detected subsequent to starting ARV treatment or if due to toxicity attributable to TB medication [ Time Frame: Measured through a participant's last study visit, at approximately Month 4 to 9 ] [ Designated as safety issue: Yes ]
- Failure to respond at Week 8, which includes HIV RNA (copies/mL) greater than 400 copies/mL AND less than 1-log10 drop from baseline [ Time Frame: Measured at Week 8 ] [ Designated as safety issue: No ]
- Development of new opportunistic infections (OIs) [ Time Frame: Measured through a participant's last study visit, at approximately Month 4 to 9 ] [ Designated as safety issue: Yes ]
|Estimated Primary Completion Date:||March 2015 (Final data collection date for primary outcome measure)|
Experimental: 3 to Less than 12 Years of Age
Participants will receive chewable raltegravir tablets, initially dosed at 12 mg/kg (up to a maximum of 800 mg) twice daily, in addition to two NRTIs to treat HIV and a rifampicin-containing regimen to treat TB. Participants will be enrolled into the study into two cohorts: Cohort I: 3 years of age to less than 6 years of age and Cohort II: 6 years of age to less than 12 years of age. After a study visit at Day 5 to 8, efavirenz will be added to the regimen.
Chewable raltegravir tablets, initially dosed at 12 mg/kg (up to a maximum of 800 mg) twice daily.
People who are infected with HIV are also at risk for becoming infected with TB, particularly in many resource-limited settings, including Sub-Saharan Africa. Rifampicin is a medication commonly used to treat TB. There is a need for HIV treatment regimens that contain newer ARV medications that are well-tolerated and have minimal interactions with rifampicin-containing TB medication regimens. This study will enroll HIV-infected children who have never taken any ARV medications and who are infected with TB and are taking or will be starting a TB medication regimen that includes rifampicin. The purpose of this study is to evaluate the safety and tolerance of raltegravir-containing ARV regimens to treat HIV when administered with a rifampicin-containing regimen to treat TB in children. Study researchers will also evaluate the pharmacokinetics of the medications (i.e., how medication is absorbed and processed in the body) and determine the most effective dose of raltegravir when it is administered with a TB regimen that contains rifampicin.
During the study, researchers will continuously monitor participant data for safety and other factors. Researchers may adjust the dose of raltegravir given to participants prior to enrolling additional participants.
At study entry, participants will undergo a medical and medication history review, physical examination, medication adherence assessment, blood collection, and urine collection for pregnancy testing. Participants will receive chewable raltegravir tablets two or three times a day, and they will also take their TB medications, including rifampicin, and two nucleoside reverse transcriptase inhibitor (NRTI) ARV medications that will be chosen by participants' doctors. This study will provide raltegravir to participants; all other medications will be provided by participants' own doctors.
At study visits at Days 5 to 8 and at Week 4, participants will remain in the clinic for about 12 hours. During these two visits, participants will take part in the same study procedures that occurred at the entry visit, but they will also have small amounts of blood collected several times throughout the 12 hours to measure the amount of medication in the blood. After the Day 5 to 8 visit, participants will begin receiving efavirenz, which is an ARV medication, in addition to the other medications. Participants will continue receiving raltegravir until they stop taking their TB medications. They will continue to take efavirenz and the other two ARV medications for 3 months after they stop receiving raltegravir and the TB medications.
Additional study visits will occur at Week 8, every 4 weeks until the participant stops receiving raltegravir and the TB medications, and 4 and 12 weeks after stopping raltegravir and the TB medications. These study visits will include the same study procedures that occurred at study entry. Participants will be enrolled in the study for a total of about 4 to 9 months.
|Study Chair:||Tammy Meyers, MD||Bamboo Grove, Wan Chai, Hong Kong, People's Republic of China|
|Study Chair:||Paul Krogstad, MD||University of California, Los Angeles|