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

Primary Purpose

Tuberculosis, HIV Infections

Status

Unknown status

Phase

Phase 2

Locations

Tanzania

Study Type

Interventional

Intervention

Emtricitabine/tenofovir/efavirenz

About this trial

This is an interventional treatment trial for Tuberculosis focused on measuring Tuberculosis, HIV, Coinfection, Pharmacokinetics, Emtricitabine, Tenofovir, Rifampin, Efavirenz, Treatment Naive

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

Kibong'oto National Tuberculosis HospitalRecruiting

Outcomes

Primary Outcome Measures

Pharmacokinetic parameters of emtricitabine, tenofovir and efavirenz

Pharmacokinetic parameters of the tuberculostatic agents

Secondary Outcome Measures

Biochemistry and haematology samples for safety

Questioning about occurrence of adverse events

CD4 count and HIV-1 RNA

Sputum staining and culture

Full Information

NCT ID

NCT00474435

First Posted

May 16, 2007

Last Updated

December 16, 2010

Sponsor

African Poverty Related Infection Oriented Research Initiative

Collaborators

Radboud University Medical Center, Kilimanjaro Christian Medical Centre, Tanzania

1. Study Identification

Unique Protocol Identification Number

NCT00474435

Brief Title

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

Acronym

PETE

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

2. Study Status

Record Verification Date

December 2008

Overall Recruitment Status

Unknown status

Study Start Date

November 2008 (undefined)

Primary Completion Date

December 2009 (Anticipated)

Study Completion Date

December 2009 (Anticipated)

3. Sponsor/Collaborators

Name of the Sponsor

African Poverty Related Infection Oriented Research Initiative

Collaborators

Radboud University Medical Center, Kilimanjaro Christian Medical Centre, Tanzania

4. Oversight

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Tuberculosis, HIV Infections

Keywords

Tuberculosis, HIV, Coinfection, Pharmacokinetics, Emtricitabine, Tenofovir, Rifampin, Efavirenz, Treatment Naive

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type

Drug

Intervention Name(s)

Emtricitabine/tenofovir/efavirenz

Intervention Description

Co-formulated in one tablet (taken once daily by oral administration): emtricitabine 200 mg tenofovir DF 300 mg efavirenz 600 mg

Primary Outcome Measure Information:

Title

Pharmacokinetic parameters of emtricitabine, tenofovir and efavirenz

Time Frame

Two 24 hour pharmacokinetic (PK) curves (week 8 and 28)

Title

Pharmacokinetic parameters of the tuberculostatic agents

Time Frame

Pharmacokinetic (PK) samples at 2 hours and 6 hours postdose (week 2 and 8)

Secondary Outcome Measure Information:

Title

Biochemistry and haematology samples for safety

Time Frame

Samples at screening, baseline, week 2, 4, 6, 8, 12, 16, 24, 28

Title

Questioning about occurrence of adverse events

Time Frame

At baseline, week 2, 4, 6, 8, 12, 16, 24, 28

Title

CD4 count and HIV-1 RNA

Time Frame

At screening, week 4, week 16 and week 28

Title

Sputum staining and culture

Time Frame

At screening, week 4, 8, and 28

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Gibson Kibiki, MMed, PhD

Phone

+255 754 572767

gkibiki@gmail.com

First Name & Middle Initial & Last Name or Official Title & Degree

Jossy van den Boogaard, MD

Phone

+255 787 148431

jossyvandenboogaard@gmail.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Martin Boeree, MD, PhD

Organizational Affiliation

University Lungcentre Dekkerswald, Groesbeek / University Medical Centre Nijmegen, the Netherlands

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

David Burger, PharmD, PhD

Organizational Affiliation

University Medical Centre Nijmegen, the Netherlands

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Gibson Kibiki, MMed, PhD

Organizational Affiliation

Kilimanjaro Christian Medical Centre,Moshi,Tanzania

Official's Role

Principal Investigator

Facility Information:

Facility Name

Kibong'oto National Tuberculosis Hospital

City

Moshi

State/Province

Kilimanjaro Region

ZIP/Postal Code

P.O. Box 12

Country

Tanzania

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Liberate Mleoh, MD

Phone

027 2756194

lmleoh@yahoo.com

First Name & Middle Initial & Last Name & Degree

Gibson Kibiki, MMed, PhD

First Name & Middle Initial & Last Name & Degree

Elton Kisanga, B-Pharm, PhD

First Name & Middle Initial & Last Name & Degree

Liberate Mleoh, MD

First Name & Middle Initial & Last Name & Degree

Jossy van den Boogaard, MD

First Name & Middle Initial & Last Name & Degree

Hadija Semvua, B-Pharm, MPH

First Name & Middle Initial & Last Name & Degree

Charles Mtabho, MD, MPH

12. IPD Sharing Statement

Citations:

PubMed Identifier

11081535

Citation

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Results Reference

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Citation

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Citation

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PubMed Identifier

11432536

Citation

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PubMed Identifier

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Citation

Finch CK, Chrisman CR, Baciewicz AM, Self TH. Rifampin and rifabutin drug interactions: an update. Arch Intern Med. 2002 May 13;162(9):985-92. doi: 10.1001/archinte.162.9.985.

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PubMed Identifier

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Citation

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Citation

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

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