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

NCT ID: NCT00474435

Last Updated: 2010-12-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-11-30

Study Completion Date

2009-12-31

Brief Summary

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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

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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.

Conditions

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Tuberculosis HIV Infections

Keywords

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Tuberculosis HIV Coinfection Pharmacokinetics Emtricitabine Tenofovir Rifampin Efavirenz Treatment Naive

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Interventions

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Emtricitabine/tenofovir/efavirenz

Co-formulated in one tablet (taken once daily by oral administration):

* emtricitabine 200 mg
* tenofovir DF 300 mg
* efavirenz 600 mg

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Radboud University Medical Center

OTHER

Sponsor Role collaborator

Kilimanjaro Christian Medical Centre, Tanzania

OTHER

Sponsor Role collaborator

African Poverty Related Infection Oriented Research Initiative

OTHER

Sponsor Role lead

Responsible Party

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University Lungcentre Dekkerswald, Groesbeek, the Netherlands

Principal Investigators

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Martin Boeree, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

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

David Burger, PharmD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Medical Centre Nijmegen, the Netherlands

Gibson Kibiki, MMed, PhD

Role: PRINCIPAL_INVESTIGATOR

Kilimanjaro Christian Medical Centre,Moshi,Tanzania

Locations

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Kibong'oto National Tuberculosis Hospital

Moshi, Kilimanjaro, Tanzania

Site Status RECRUITING

Countries

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Tanzania

Central Contacts

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Gibson Kibiki, MMed, PhD

Role: CONTACT

Phone: +255 754 572767

Email: [email protected]

Jossy van den Boogaard, MD

Role: CONTACT

Phone: +255 787 148431

Email: [email protected]

Facility Contacts

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Liberate Mleoh, MD

Role: primary

References

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Bowen EF, Rice PS, Cooke NT, Whitfield RJ, Rayner CF. HIV seroprevalence by anonymous testing in patients with Mycobacterium tuberculosis and in tuberculosis contacts. Lancet. 2000 Oct 28;356(9240):1488-9. doi: 10.1016/S0140-6736(00)02876-2.

Reference Type BACKGROUND
PMID: 11081535 (View on PubMed)

Msamanga GI, Fawzi WW. The double burden of HIV infection and tuberculosis in sub-Saharan Africa. N Engl J Med. 1997 Sep 18;337(12):849-51. doi: 10.1056/NEJM199709183371210. No abstract available.

Reference Type BACKGROUND
PMID: 9295244 (View on PubMed)

Dean GL, Edwards SG, Ives NJ, Matthews G, Fox EF, Navaratne L, Fisher M, Taylor GP, Miller R, Taylor CB, de Ruiter A, Pozniak AL. Treatment of tuberculosis in HIV-infected persons in the era of highly active antiretroviral therapy. AIDS. 2002 Jan 4;16(1):75-83. doi: 10.1097/00002030-200201040-00010.

Reference Type BACKGROUND
PMID: 11741165 (View on PubMed)

Burman WJ, Gallicano K, Peloquin C. Comparative pharmacokinetics and pharmacodynamics of the rifamycin antibacterials. Clin Pharmacokinet. 2001;40(5):327-41. doi: 10.2165/00003088-200140050-00002.

Reference Type BACKGROUND
PMID: 11432536 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11996607 (View on PubMed)

Lopez-Cortes LF, Ruiz-Valderas R, Viciana P, Alarcon-Gonzalez A, Gomez-Mateos J, Leon-Jimenez E, Sarasanacenta M, Lopez-Pua Y, Pachon J. Pharmacokinetic interactions between efavirenz and rifampicin in HIV-infected patients with tuberculosis. Clin Pharmacokinet. 2002;41(9):681-90. doi: 10.2165/00003088-200241090-00004.

Reference Type BACKGROUND
PMID: 12126459 (View on PubMed)

Burger DM, Meenhorst PL, Koks CH, Beijnen JH. Pharmacokinetic interaction between rifampin and zidovudine. Antimicrob Agents Chemother. 1993 Jul;37(7):1426-31. doi: 10.1128/AAC.37.7.1426.

Reference Type BACKGROUND
PMID: 8363370 (View on PubMed)

Gallicano KD, Sahai J, Shukla VK, Seguin I, Pakuts A, Kwok D, Foster BC, Cameron DW. Induction of zidovudine glucuronidation and amination pathways by rifampicin in HIV-infected patients. Br J Clin Pharmacol. 1999 Aug;48(2):168-79. doi: 10.1046/j.1365-2125.1999.00987.x.

Reference Type BACKGROUND
PMID: 10417493 (View on PubMed)

Friedland G, Abdool Karim S, Abdool Karim Q, Lalloo U, Jack C, Gandhi N, El Sadr W. Utility of tuberculosis directly observed therapy programs as sites for access to and provision of antiretroviral therapy in resource-limited countries. Clin Infect Dis. 2004 Jun 1;38 Suppl 5:S421-8. doi: 10.1086/421407.

Reference Type BACKGROUND
PMID: 15156433 (View on PubMed)

Droste JA, Aarnoutse RE, Koopmans PP, Hekster YA, Burger DM. Evaluation of antiretroviral drug measurements by an interlaboratory quality control program. J Acquir Immune Defic Syndr. 2003 Mar 1;32(3):287-91. doi: 10.1097/00126334-200303010-00007.

Reference Type BACKGROUND
PMID: 12626888 (View on PubMed)

Holland DT, DiFrancesco R, Stone J, Hamzeh F, Connor JD, Morse GD; Adult and Pediatric AIDS Clinical Trials Group Pharmacology Laboratory Committees, Pediatric AIDS Clinical Trials Group. Quality assurance program for clinical measurement of antiretrovirals: AIDS clinical trials group proficiency testing program for pediatric and adult pharmacology laboratories. Antimicrob Agents Chemother. 2004 Mar;48(3):824-31. doi: 10.1128/AAC.48.3.824-831.2004.

Reference Type BACKGROUND
PMID: 14982771 (View on PubMed)

Marzolini C, Telenti A, Decosterd LA, Greub G, Biollaz J, Buclin T. Efavirenz plasma levels can predict treatment failure and central nervous system side effects in HIV-1-infected patients. AIDS. 2001 Jan 5;15(1):71-5. doi: 10.1097/00002030-200101050-00011.

Reference Type BACKGROUND
PMID: 11192870 (View on PubMed)

Other Identifiers

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UMCN-AKF 04.03

Identifier Type: -

Identifier Source: org_study_id