Pharmacokinetic Study of Super-boosted Lopinavir/Ritonavir Given With Rifampin

Sponsor

University of Miami (Other)

Overall Status

Terminated

CT.gov ID

NCT01700790

Collaborator

Oswaldo Cruz Foundation (Other)

Enrollment

Location

Arm

Actual Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
AIDS Tuberculosis	Drug: Lopinavir/ritonavir and ritonavir	Phase 4

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

9 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (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.

Actual Study Start Date :

Feb 1, 2016

Actual Primary Completion Date :

Nov 17, 2018

Actual Study Completion Date :

Dec 31, 2018

Arms and Interventions

Arm	Intervention/Treatment
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 Other Names: Kaletra Norvir

Arm

Intervention/Treatment

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

Other Names:

Kaletra

Norvir

Outcome Measures

Primary Outcome Measures

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

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 AUC of rifampin [Approximatley 10-12 weeks]
The expected AUC of rifampin is 44-70 mcg•h/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 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
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Antiretroviral naive
If not antiretroviral naïve they must meet the following criteria:
Taking Kaletra containing regimen with suppressed viral load.
Taking an NNRTI or integrase containing regimen without prior history of use of PI for more than 2 weeks
Taking an NNRTI or integrase containing regimen with prior exposure to PI greater than 2 weeks. It must be clearly stated in the source document that PI was switched to another agent for convenience.
Taking another PI containing regimens with suppressed viral load. It must be clearly stated in source document that if another PI was used for greater than 2 weeks the regimen was switched to another agent for convenience. Subjects with prior history of PI use may be enrolled, if there is a genotype showing no resistance to Kaletra Other Inclusion criteria
Be at least 18 years of age and able to give informed consent.
Diagnosed with TB by criteria per Brazilian Ministry of Health
Have a good clinical response to TB.
Tolerating tuberculosis therapy containing rifampin for the 2 weeks prior to screening,except for persons taking protease inhibitors at time of diagnosis of TB.,. Subjects taking protease inhibitors will be screened and initiate visit 1 within 3 days of starting TB medication
HIV positive with documentation present in source document.
Have a CD4 cell count greater than 50 cells/mm3if not taking ART. Persons with cd4 < 50 may be enrolled, if it is felt that in the best interest of the patient, that enrollment in the study will allow for quicker initiation of antiretroviral therapy than referral to another treatment center.

Exclusion Criteria:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Instituto Nacional de Infectologia Evandro Chagas - Fiocruz(INI), Laboratorio de Pesquisa Clinica em Micobacterioses(LAPCLINTB)	Rio de Janeiro	RJ	Brazil	21040-900

Sponsors and Collaborators

University of Miami
Oswaldo Cruz Foundation

Investigators

Principal Investigator: Catherine Boulanger, MD., University of Miami Miller Medical School of Medicine
Principal Investigator: Valeria Calvicanti Rolla, MD, Oswaldo Cruz Foundation