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

HIV Infections Clinical Trial

— 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00474435
• Other study ID #: UMCN-AKF 04.03
• Status: Recruiting
• Phase: Phase 2
• First received: May 16, 2007
• Last updated: December 16, 2010
• Start date: November 2008
• Est. completion date: December 2009

Study information

• Verified date: December 2008
• Source: African Poverty Related Infection Oriented Research Initiative
• Contact: Gibson Kibiki, MMed, PhD
• Phone: +255 754 572767
• Email: gkibiki[@]gmail.com
• Is FDA regulated: No
• Health authority: Tanzania: Food & Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 2009
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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.

Study Design

Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections
• Tuberculosis

Intervention

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

Locations

Country	Name	City	State
Tanzania	Kibong'oto National Tuberculosis Hospital	Moshi	Kilimanjaro Region

Sponsors (3)

Lead Sponsor	Collaborator
African Poverty Related Infection Oriented Research Initiative	Kilimanjaro Christian Medical Centre, Tanzania, Radboud University

Country where clinical trial is conducted

Tanzania, 

References & 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. — View Citation

Burger DM, Meenhorst PL, Koks CH, Beijnen JH. Pharmacokinetic interaction between rifampin and zidovudine. Antimicrob Agents Chemother. 1993 Jul;37(7):1426-31. — View Citation

Burman WJ, Gallicano K, Peloquin C. Comparative pharmacokinetics and pharmacodynamics of the rifamycin antibacterials. Clin Pharmacokinet. 2001;40(5):327-41. Review. — View Citation

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. — View Citation

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. — View 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. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

López-Cortés LF, Ruiz-Valderas R, Viciana P, Alarcón-González A, Gómez-Mateos J, León-Jimenez E, Sarasanacenta M, López-Pua Y, Pachón J. Pharmacokinetic interactions between efavirenz and rifampicin in HIV-infected patients with tuberculosis. Clin Pharmacokinet. 2002;41(9):681-90. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetic parameters of emtricitabine, tenofovir and efavirenz		Two 24 hour pharmacokinetic (PK) curves (week 8 and 28)	No
Primary	Pharmacokinetic parameters of the tuberculostatic agents		Pharmacokinetic (PK) samples at 2 hours and 6 hours postdose (week 2 and 8)	No
Secondary	Biochemistry and haematology samples for safety		Samples at screening, baseline, week 2, 4, 6, 8, 12, 16, 24, 28	Yes
Secondary	Questioning about occurrence of adverse events		At baseline, week 2, 4, 6, 8, 12, 16, 24, 28	Yes
Secondary	CD4 count and HIV-1 RNA		At screening, week 4, week 16 and week 28	Yes
Secondary	Sputum staining and culture		At screening, week 4, 8, and 28	Yes