An Evaluation of the Pharmacological Interaction of Lopinavir/r and Rifampin

• Status: Completed
• Trial end date: 2012-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a pharmacokinetic, descriptive, open-label, prospective, multicentric, national study in Aids and tuberculosis co-infected patients, to be laboratory and clinically monitored during the treatment with lopinavir-ritonavir and rifampin medications.

Study population: Thirty patients older than 18 years, both male and female, which present active tuberculosis and failure or contraindication for any motive to an efavirenz will be selected to participate in the study.

Objectives:

• Evaluate the pharmacokinetics of lopinavir-800mg / ritonavir-200mg combination (every 12 h) in association with rifampin-containing anti-tuberculosis regimens, in patients presenting tuberculosis and HIV-infected with indication to antiretroviral treatment according to Brazilian Ministry of Health's guidelines, with contraindication to the use of NNTRI.

• Describe the adverse events observed during the tuberculosis treatment period with rifampin associated with antiretroviral therapy consisting of lopinavir-800mg / ritonavir-200mg every 12 hours.

• Describe clinical, immunological and virological endpoints throughout the study with these drugs.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Oswaldo Cruz Foundation
• Collaborator: Abbott
• Treatments: Lopinavir; Rifampin

Criteria

Inclusion Criteria:

• Male and female subjects, with HIV infection and an active tuberculosis diagnosis. Women must have a negative pregnancy test and use a birth control method (barrier or Depo-Provera contraceptive) throughout the study and at investigator's discretion considered as reliable. To guarantee the security of the volunteers the pregnancy test in urine will be repeated to each visit.

• Patients who present contraindication for NNRTI use. Contraindication may be obtained through a history of virologic resistance (prior use of efavirenz with comproved virologic failure in a subject with good adherence), genotyping test indicative of mutations that provide resistance to these drugs, intolerance, or hypersensitivity.

• Patients must be older than 18 years.

• HIV infection documented by two positive ELISA tests for HIV and one confirmatory test (immunoblot or immunofluorescence), which may be replaced by a plasma VL using Roche-PCR test, Chiron Branched DNA or NASBA (BioMerrieux).

• The tuberculosis diagnostic can be proved through one positive culture with identification of M. tuberculosis. Besides, a patient will be eligible if he/she presents clinical signs and symptoms suggestive of tuberculosis, the radiological aspects are compatible, and other oportunistic deseases are excluded, even if specimen baciloscopy is negative, according to Brazilian Guidelines (BRASIL, Ministério da Saúde, 2004);

• Patients who do not require the use of medications with established contraindication for concomitant use with lopinavir-ritonavir, such as: amiodarone, astemizole, bepridil, bupropione, cisapride, clorazepate, clozapim, diazepam, encainide, flecainide, flurazepam, meperidine, midazolam, primozide, piroxicam, propafenone, propoxifeno, quinidine, rifabutin, terfenadine, triazolam, zolpidem, dihydroergotamine and ergotamine.

• Patient agrees not to use any medication (even herbal medications or natural products) without previous knowledgement and consent from investigator throughout the study. Patient also agrees to notify the investigator of any medication that has been changed (started or replaced) during the study.

• Patients should date and sign volunteer the informed consent before entering in the study and after a full explanation of the study nature. If the patient is unable, his/her legally authorized representative will sign on his/her behalf.

Exclusion Criteria:

• Patient has a previous history of hypersensitivity or known resistance or acquired to rifampin or to lopinavir-ritonavir.

2. Evidence of toxic substances abuse, such as alcohol and/or illicit drugs (Attachment B).

• Viral B and/or C hepatitis co-infection.

• Patient presents one or more abnormalities in the following blood laboratory tests:

STGO and/or STGP and/or alkaline phosphatase > 5,1 fold upper normal limit, or bilirrubin > 1.5 mg/dl. If the patient is not eligible at this moment due the risk of hepatotoxicity, an alternative treatment for tuberculosis will be offered (according to the recommendations of the Ministry of Health) in order to reduce the risk of serious hepatopaty and to allow the use of any concomitant antiretroviral scheme. This patient will be excluded of the study, but he will be able to be treated and accompanied in the responsible sites for the study up to the end of the tuberculosis treatment if it is the wish of the patient.

• Documented genotypic resistance to lopinavir/ritonavir on the screening sample.

• In the investigator's opinion, patient predicts a low compliance to the proposed study according to the clinical history for a given subject.

• Patient with history of prior use of Kaletra® (lopinavir, ritonavir) with comproved virologic or genotypic failure or serious intolerance needing change of antiretroviral treatment.