Pharmacokinetic Study of Super-boosted Lopinavir/Ritonavir Given With Rifampin
- Registration Number
- NCT01700790
- Lead Sponsor
- University of Miami
- Brief Summary
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
- Detailed Description
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: 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 and rifampin 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 9
Not provided
- Non-compliance with DOTPlus. Alternatively DOT can be done by telephoning patient on a daily basis 5 times a week and having patient annotate taking drug in a log which would be reviewed by clinic staff
- History of being treated for tuberculosis in the prior 2 years unless there is DST, including PCR testing, showing sensitivity to rifamycin.
- Known hypersensitivity to rifampin or rifabutin.
- Liver enzymes greater than 2 times ULN.
- Bilirubin greater than 2 times ULN.
- Serum creatinine greater than 3 times ULN.
- Hemoglobin less than 7.0 gms even if receiving erythropoietin.
- Absolute neutrophil count less than 750 cells/mm3 even if receiving G-CSF.
- Fasting triglycerides greater than 400 mg/dL.
- Fasting cholesterol > 1.6 upper limits of normal.
- GI intolerance of tuberculosis medications requiring discontinuation of tuberculosis medications.
- Fasting glucose greater 150 mg/dL.
- Pregnant women.
- Use of one of the prohibited medications
- Any condition that the investigators feel could compromise the use of the current medication.
- Have a CD4 cell count of 50 cells/mm3or less
- Hepatitis B or C infection
- Alcohol or illicit drug use, which in the investigators opinion may affect participation in study.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Lopinavir/ritonavir and ritonavir 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.
- Primary Outcome Measures
Name Time Method Proportion of patients with expected pre dose concentration of lopinavir. Weeks 2 and 8: lopinavir time points at hours 0, 2, 4, 6 and 8. The expected pre dose concentration of lopinavir is \>1.0 mcg/mL.
- Secondary Outcome Measures
Name Time Method Proportion of patients with expected AUC of rifampin Approximatley 10-12 weeks The expected AUC of rifampin is 44-70 mcg•h/mL
Proportion of patients with expected Cmax of rifampin. Weeks 2 and 8: rifampin time points at hours 0, 2, 4, 6 and 8. Expected maximum concentration of rifampin is 8-24 mcg/mL
Proportion of patient with success of tuberculosis therapy Approximatly 10-12 weeks Success of treatment using criteria established by the Brazilian National Ttuberculosis Program.
Proportion of patients with successful treatment of HIV therapy. Approximately 10-12 weeks 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 Cmax and AUC of lopinavir 10-12 weeks The expected Cmax of lopinavir is 6-14 mcg/mL. The expected AUC lopinavir is 56-130 µg•h/mL
Trial Locations
- Locations (1)
Instituto Nacional de Infectologia Evandro Chagas - Fiocruz(INI), Laboratorio de Pesquisa Clinica em Micobacterioses(LAPCLINTB)
🇧🇷Rio de Janeiro, RJ, Brazil