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

• Register: ClinicalTrials.gov
• Last refreshed on: 17 October 2012
• Main ID: NCT00771498
• Date of registration: 10/10/2008
• Primary sponsor: Oswaldo Cruz Foundation
• Public title: An Evaluation of the Pharmacological Interaction of Lopinavir/r and Rifampin A06-295
• Scientific 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
• Date of first enrolment: November 2008
• Target sample size: 30
• Recruitment status: Recruiting
• URL: http://clinicaltrials.gov/show/NCT00771498
• Study type: Interventional
• Study design: Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label

Countries of recruitment

Brazil

Contacts

• Name: Valeria C Rolla, PhD

• Name: Valeria C Rolla, PhD
• Affiliation: Oswaldo Cruz Foundation

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

HIV Infection

Tuberculosis

Intervention(s)

Drug: Rifampin

Primary Outcome(s)

Plasma levels of rifampin and lopinavir-ritonavir (pharmacokinetics). [Time Frame: 15, 45 and 180 days post-study treatment start]

Secondary Outcome(s)

Adverse events [Time Frame: Each study visit]

HIV response to treatment [Time Frame: 90 and 180 days post-study treatment start]

Secondary ID(s)

A06-295

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Abbott