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

NCT00474435 | Unknown Phase 2 DMC

• 1 other identifier: UMCN-AKF 04.03
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Tuberculosis; HIV Infections

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• 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

Interventions

Emtricitabine/tenofovir/efavirenz DRUG

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

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (1)

Kibong'oto National Tuberculosis Hospital

Moshi, Kilimanjaro, P.O. Box 12, Tanzania

RECRUITING

Related Publications (12)

• 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.

  PMID: 11081535 BACKGROUND

• 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.

  PMID: 9295244 BACKGROUND

• 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.

  PMID: 11741165 BACKGROUND

• 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.

  PMID: 11432536 BACKGROUND

• 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.

  PMID: 11996607 BACKGROUND

• 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.

  PMID: 12126459 BACKGROUND

• 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.

  PMID: 8363370 BACKGROUND

• 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.

  PMID: 10417493 BACKGROUND

• 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.

  PMID: 15156433 BACKGROUND

• 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.

  PMID: 12626888 BACKGROUND

• 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.

  PMID: 14982771 BACKGROUND

• 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.

  PMID: 11192870 BACKGROUND

MeSH Terms

Conditions

Tuberculosis; HIV Infections; Coinfection

Interventions

Emtricitabine

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gibson Kibiki, MMed, PhD

CONTACT

+255 754 572767; gkibiki@gmail.com

Jossy van den Boogaard, MD

CONTACT

+255 787 148431; jossyvandenboogaard@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: May 16, 2007
• First Posted: May 17, 2007
• Study Start: November 1, 2008
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2009
• Last Updated: December 17, 2010

Record last verified: 2008-12

Locations

TA (1)