PETE: Pharmacokinetics of Emtricitabine/Tenofovir/Efavirenz in HIV-infected Patients With Tuberculosis

Sponsor

African Poverty Related Infection Oriented Research Initiative (Other)

Overall Status

Unknown status

CT.gov ID

NCT00474435

Collaborator

Radboud University Medical Center (Other), Kilimanjaro Christian Medical Centre, Tanzania (Other)

Enrollment

Location

Duration (Months)

2.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Tuberculosis HIV Infections	Drug: Emtricitabine/tenofovir/efavirenz	Phase 2

Detailed Description

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

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.
To determine the effect of the emtricitabine+tenofovir+efavirenz regimen on the pharmacokinetics of tuberculostatics in the same population.

The secondary objectives are:

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Nov 1, 2008

Anticipated Primary Completion Date :

Dec 1, 2009

Anticipated Study Completion Date :

Dec 1, 2009

Outcome Measures

Primary Outcome Measures

Pharmacokinetic parameters of emtricitabine, tenofovir and efavirenz [Two 24 hour pharmacokinetic (PK) curves (week 8 and 28)]
Pharmacokinetic parameters of the tuberculostatic agents [Pharmacokinetic (PK) samples at 2 hours and 6 hours postdose (week 2 and 8)]

Secondary Outcome Measures

Biochemistry and haematology samples for safety [Samples at screening, baseline, week 2, 4, 6, 8, 12, 16, 24, 28]
Questioning about occurrence of adverse events [At baseline, week 2, 4, 6, 8, 12, 16, 24, 28]
CD4 count and HIV-1 RNA [At screening, week 4, week 16 and week 28]
Sputum staining and culture [At screening, week 4, 8, and 28]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kibong'oto National Tuberculosis Hospital	Moshi	Kilimanjaro Region	Tanzania	P.O. Box 12

Sponsors and Collaborators

African Poverty Related Infection Oriented Research Initiative
Radboud University Medical Center
Kilimanjaro Christian Medical Centre, Tanzania

Investigators

Principal Investigator: Martin Boeree, MD, PhD, University Lungcentre Dekkerswald, Groesbeek / University Medical Centre Nijmegen, the Netherlands
Principal Investigator: David Burger, PharmD, PhD, University Medical Centre Nijmegen, the Netherlands
Principal Investigator: Gibson Kibiki, MMed, PhD, Kilimanjaro Christian Medical Centre,Moshi,Tanzania