Pharmacokinetic Study of Super-boosted Lopinavir/Ritonavir Given With Rifampin
The object of this study is to evaluate the pharmacokinetic interactions, short term safety and efficacy of standard dose lopinavir/ritonavir 200mg/50 (two tablets twice daily) given with ritonavir 100 mg three tablets twice daily given in combination with rifampin in HIV-infected persons with tuberculosis
|Study Design:||Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Pharmacokinetic Study of Super-boosted Lopinavir/Ritonavir in Combination With Rifampin in HIV-1-infected Patients With Tuberculosis.|
- Proportion of patients with expected pre dose concentration of lopinavir. [ Time Frame: Weeks 2 and 10-12: lopinavir time points at hours 0, 2, 4, 6 and 8. ] [ Designated as safety issue: Yes ]The expected pre dose concentration of lopinavir is >1.0 mcg/mL.
- Proportion of patients with successful treatment of HIV therapy. [ Time Frame: 10-12 weeks ] [ Designated as safety issue: Yes ]HIV failure will be defined as failure to drop the viral load by 0.5 log 10 copies/mL drop by week 4 of treatment and a viral load drop >1 log 10 copies/ml by week 8.
- Proportion of patients with expected AUC of rifampin [ Time Frame: 10-12 weeks ] [ Designated as safety issue: No ]The expected AUC of rifampin is 44-70 mcg•h/mL
- Proportion of patient with success of tuberculosis therapy [ Time Frame: 10-12 weeks ] [ Designated as safety issue: No ]Success of treatment using criteria established by the Brazilian National Ttuberculosis Program.
- Proportion of patients with expected Cmax and AUC of lopinavir [ Time Frame: 10-12 weeks ] [ Designated as safety issue: No ]The expected Cmax of lopinavir is 6-14 mcg/mL. The expected AUC lopinavir is 56-130 µg•h/mL
- Proportion of patients with expected Cmax of rifampin. [ Time Frame: Weeks 2 and 10-12: rifampin time points at hours 0, 2, 4, 6 and 8. ] [ Designated as safety issue: No ]Expected maximum concentration of rifampin is 8-24 mcg/mL
|Study Start Date:||July 2014|
|Estimated Study Completion Date:||March 2017|
|Estimated Primary Completion Date:||February 2017 (Final data collection date for primary outcome measure)|
Experimental: Lopinavir/ritonavir and ritonavir
Two tablets of twice daily of Lopinavir/ritonavir 200 mg/50mg with 3 tablets of ritonavir 100 mg of twice daily given with rifampin 600 mg daily.
Drug: Lopinavir/ritonavir and ritonavir
Two tablets twice daily of Lopinavir/ritonavir 200 mg/50mg with 3 capsules of ritonavir 100 mg twice daily given with rifampin 600 mg daily
This will be an open label non-randomized pharmacokinetic study of 10-12 HIV-infected patients co-infected with Mycobacterium tuberculosis.
Enrollment: Potential subjects with active tuberculosis who have tolerated a rifampin containing regimen for at least 2 weeks. Potential subjects will be referred from the surrounding communities to Laboratorio de Pesquisa Clinica em Micobacterioses(LAPCLINTB)
Visit 1: Rifampin concentration sampling will be done. Subjects will then be started on lopinavir/ritonavir containing HAART regimen with standard twice daily dosing. Ritonavir 100 mg capsules will be added to the regimen and the dose escalated until the patient is taking 3 capsules twice daily. The time between enrollment and visit 1 will be determined by the treating physician.
Visit 2: They will return about 1 week after dose escalation has been completed to sample lopinavir concentrations.
Visit 3: Subject will return in 2 weeks to have repeat to review results of lopinavir concentrations and response to therapy. Ritonavir will be adjusted as needed.
Visit 4: Subject will then return in 4 weeks for last visit for evaluation. Lopinavir and rifampin PK will be done.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01700790
|Contact: Catherine V Boulanger, M.D.||305 243 firstname.lastname@example.org|
|Contact: Valeria Calvacanti Rolla, M.D.||55 21 email@example.com|
|Instituto Nacional de Infectologia Evandro Chagas - Fiocruz(INI), Laboratorio de Pesquisa Clinica em Micobacterioses(LAPCLINTB)||Recruiting|
|Rio de Janeiro, RJ, Brazil, 21040-900|
|Contact: Valeria Calvacanti Rolla, MD 55 21 38659601 firstname.lastname@example.org|
|Contact: Aline Benjamin, BSc, MSc 55 21 38659601 email@example.com|
|Principal Investigator: Valeria Calvacanti Rolla, M.D.|
|Principal Investigator:||Catherine Boulanger, MD.||University of Miami Miller Medical School of Medicine|
|Principal Investigator:||Valeria Calvicanti Rolla, MD||Oswaldo Cruz Foundation|