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

NCT00771498 | Completed Phase 4

• 1 other identifier: A06-295
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

HIV Infection; Tuberculosis

Keywords

rifampin; lopinavir; drug interaction; pharmacokinetic

Outcome Measures

Primary Outcomes (1)

• Plasma levels of rifampin and lopinavir-ritonavir (pharmacokinetics).

  15, 45 and 180 days post-study treatment start

Secondary Outcomes (2)

• HIV response to treatment

  90 and 180 days post-study treatment start

• Adverse events

  Each study visit

Study Arms (1)

lopinavir

OTHER

Patients with HIV/TB co-infection will receive treatment for both infection, and PK of lopinavir 800mg + ritonavir 200mg (PO BID) during 5 months will be performed

Drug: Lopinavir

Interventions

Lopinavir DRUG

ARV treatment: 2 NRTIs + lopinavir/r 800mg / 200 mg (4 tablets of Kaletra) every 12 hours, daily and orally Antituberculosis treatment: rifampin (600 mg/daily) + isoniazide (400 mg/daily) for 6 months, both in fasting condition + pirazinamide (2000 mg) for the first two months

Also known as: Kaletra

lopinavir

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Oswaldo Cruz Foundation: lead
• Abbott: collaborator

Study Sites (3)

University of Espirito Santo

Vitória, Espírito Santo, Brazil

Location

Instituto de Pesquisa Clinica Evandro Chagas (IPEC)

Rio de Janeiro, Rio de Janeiro, Brazil

Location

Instituto Oswaldo Cruz (IOC)

Rio de Janeiro, Rio de Janeiro, Brazil

Location

MeSH Terms

Conditions

HIV Infections; Tuberculosis

Interventions

Lopinavir; lopinavir-ritonavir drug combination

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Valeria C Rolla, PhD

  Oswaldo Cruz Foundation

  PRINCIPAL INVESTIGATOR

• Valeria C Rolla, PhD

  Oswaldo Cruz Foundation

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Laboratorio de Pesquisa Clinica em Micobacterioses, IPEC

Study Record Dates

• First Submitted: October 10, 2008
• First Posted: October 13, 2008
• Study Start: November 1, 2008
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: May 19, 2015

Record last verified: 2015-05

Locations

BR (3)