Clinical trial NCT00474435: Pharmacokinetics of Emtricitabine/Tenofovir/Efavirenz in HIV-infected Patients With Tuberculosis
Official title: The Pharmacokinetics of Co-formulated Emtricitabine/Tenofovir/Efavirenz in HIV-infected Patients With Smear-positive Pulmonary Tuberculosis in the Kilimanjaro Region, Tanzania
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Tuberculosis
HIV Infections
Keywords: Tuberculosis
HIV
Coinfection
Pharmacokinetics
Emtricitabine
Tenofovir
Rifampin
Efavirenz
Treatment Naive
Lead sponsor: African Poverty Related Infection Oriented Research Initiative
Sponsor class: OTHER
Collaborators: name: Radboud University Medical Center
name: Kilimanjaro Christian Medical Centre, Tanzania
First posted: 2007-05-17
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: In this pilot study the pharmacokinetics and safety of the antiretroviral combination of co-formulated emtricitabine/tenofovir/efavirenz will be studied in HIV-positive patients with pulmonary tuberculosis (TB) who are concomitantly treated with a standard rifampin-containing tuberculostatic regimen. It is expected that this antiretroviral combination causes minimal drug interactions with the rifampin-containing anti-tuberculosis medication.

Detailed description: The primary objectives of this pilot study in 30 patients are:

1. To determine the effect of rifampin-containing tuberculostatic treatment on the pharmacokinetic profile of emtricitabine+tenofovir+efavirenz, when co-formulated in one tablet, in HIV-infected patients with smear-positive pulmonary tuberculosis in Tanzania.
2. To determine the effect of the emtricitabine+tenofovir+efavirenz regimen on the pharmacokinetics of tuberculostatics in the same population.

The secondary objectives are:

1. To determine the safety of co-administration of emtricitabine+tenofovir+efavirenz with treatment for smear-positive pulmonary tuberculosis.
2. To determine the short-term (24 weeks) virological efficacy on HIV of an emtricitabine+tenofovir+efavirenz regimen in patients with smear-positive pulmonary tuberculosis.
3. To determine the short-term bacteriological efficacy on smear-positive tuberculosis of the co-administration of a standard regimen for tuberculosis and an emtricitabine+tenofovir+efavirenz regimen.

Eligibility criteria: Inclusion Criteria:

* A smear-positive pulmonary tuberculosis, based on positive smear of at least two sputum samples with Ziehl-Neelsen (ZN) staining.
* HIV-infected as documented by positive HIV antibody test.
* Subject is at least 18 years of age at the day of the first dosing of study medication.
* Subject is able and willing to sign the Informed Consent Form prior to screening evaluations.
* CD4 cell count \> 50 copies/mm3.
* Karnofsky score \> 40.
* Willing and able to regularly attend the Kibung'oto National Tuberculosis Hospital (KNTH) clinic.

Exclusion Criteria:

* History of sensitivity/idiosyncrasy to the drug or chemically related compounds or excipients, which may be employed in the trial.
* Previously treated for HIV infection with antiretroviral agents.
* Pregnant or breastfeeding.
* Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion.
* A history of severe psychiatric disease such as psychosis, schizophrenia, etc.
* Inability to understand the nature and extent of the trial and the procedures required.
* Abnormal serum transaminases or creatinine, determined as levels being \> 5 times upper limit of normal.
* Active hepatobiliary or hepatic disease (Non B Chronic Hepatitis B/C co-infection is allowed).
* CD4 cell count \> 350 cells/mm3.

Primary outcomes:
measure: Pharmacokinetic parameters of emtricitabine, tenofovir and efavirenz
timeFrame: Two 24 hour pharmacokinetic (PK) curves (week 8 and 28)
measure: Pharmacokinetic parameters of the tuberculostatic agents
timeFrame: Pharmacokinetic (PK) samples at 2 hours and 6 hours postdose (week 2 and 8)
Secondary outcomes:
measure: Biochemistry and haematology samples for safety
timeFrame: Samples at screening, baseline, week 2, 4, 6, 8, 12, 16, 24, 28
measure: Questioning about occurrence of adverse events
timeFrame: At baseline, week 2, 4, 6, 8, 12, 16, 24, 28
measure: CD4 count and HIV-1 RNA
timeFrame: At screening, week 4, week 16 and week 28
measure: Sputum staining and culture
timeFrame: At screening, week 4, 8, and 28
Other outcomes:
Locations:
city: Moshi
country: Tanzania
facility: Kibong'oto National Tuberculosis Hospital
state: Kilimanjaro Region
Study officials:
affiliation: University Lungcentre Dekkerswald, Groesbeek / University Medical Centre Nijmegen, the Netherlands
name: Martin Boeree, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Medical Centre Nijmegen, the Netherlands
name: David Burger, PharmD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Kilimanjaro Christian Medical Centre,Moshi,Tanzania
name: Gibson Kibiki, MMed, PhD
role: PRINCIPAL_INVESTIGATOR
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