An Evaluation of the Pharmacological Interaction of Lopinavir/r and Rifampin (A06-295)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2009 by Oswaldo Cruz Foundation.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Abbott
Information provided by:
Oswaldo Cruz Foundation
ClinicalTrials.gov Identifier:
NCT00771498
First received: October 10, 2008
Last updated: June 18, 2009
Last verified: June 2009
  Purpose

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.

Condition Intervention Phase
HIV Infection
Tuberculosis
Drug: Rifampin
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: An Evaluation of the Pharmacological Interaction of Lopinavir 800mg - Ritonavir 200mg Combination and Rifampin in Subjects Presenting Tuberculosis, With Contraindication for Antiretroviral Regimens Including Efavirenz

Resource links provided by NLM:


Further study details as provided by Oswaldo Cruz Foundation:

Primary Outcome Measures:
  • Plasma levels of rifampin and lopinavir-ritonavir (pharmacokinetics). [ Time Frame: 15, 45 and 180 days post-study treatment start ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • HIV response to treatment [ Time Frame: 90 and 180 days post-study treatment start ] [ Designated as safety issue: No ]
  • Adverse events [ Time Frame: Each study visit ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 30
Study Start Date: November 2008
Estimated Study Completion Date: February 2010
Estimated Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
I
Patients with HIV/TB co-infection will receive treatment for both infection, and PK of lopinavir/r will be evaluated
Drug: Rifampin
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
Other Names:
  • Lopinavir/r (Kaletra)
  • Rifampin

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00771498

Contacts
Contact: Valeria C Rolla, PhD 55 21 valeria.rolla@ipec.fiocruz.br

Locations
Brazil
University of Espirito Santo Recruiting
Vitoria, ES, Brazil
Principal Investigator: David J Haddad, PhD         
Sub-Investigator: Reynaldo Dietze, PhD         
Sub-Investigator: Rodrigo R Rodrigues, PhD         
Sub-Investigator: Moyses Palaci, PhD         
Instituto de Pesquisa Clinica Evandro Chagas (IPEC) Recruiting
Rio de Janeiro, RJ, Brazil
Principal Investigator: Valeria C Rolla, PhD         
Sub-Investigator: Marly Jane M Costa, PhD         
Sub-Investigator: Eduardo W Barroso, PhD         
Sub-Investigator: Maria Cristina S Lourenço, MSc         
Sub-Investigator: Luciane Velasque, MSc         
Instituto Oswaldo Cruz (IOC) Not yet recruiting
Rio de Janeiro, RJ, Brazil
Sub-Investigator: Mariza G Morgado, PhD         
Sponsors and Collaborators
Oswaldo Cruz Foundation
Abbott
Investigators
Principal Investigator: Valeria C Rolla, PhD Oswaldo Cruz Foundation
Study Chair: Valeria C Rolla, PhD Oswaldo Cruz Foundation
  More Information

No publications provided

Responsible Party: Valeria Cavalcante Rolla, Instituto de Pesquisa Clínica Evandro Chagas (IPEC) - Oswaldo Cruz Foundation
ClinicalTrials.gov Identifier: NCT00771498     History of Changes
Other Study ID Numbers: A06-295
Study First Received: October 10, 2008
Last Updated: June 18, 2009
Health Authority: Brazil: National Committee of Ethics in Research

Keywords provided by Oswaldo Cruz Foundation:
rifampin
lopinavir
drug interaction
pharmacokinetic

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Tuberculosis
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Lopinavir
Rifampin
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Antibiotics, Antitubercular
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on September 15, 2014