TuberculosisPhase 2PETENCT00474435
Pharmacokinetics of Emtricitabine/Tenofovir/Efavirenz in HIV-infected Patients With Tuberculosis
A Phase 2 study testing Emtricitabine/tenofovir/efavirenz in people with Tuberculosis and HIV Infections, run by African Poverty Related Infection Oriented Research Initiative at 1 site in Tanzania.
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Tuberculosis, HIV Infections
- What is being tested?
- Emtricitabine/tenofovir/efavirenz
- Type of treatment
- Pill or oral medicine
- How many people
- 30 participants
- Where
- 1 siteTanzania
- Study dates
- Nov 2008to Dec 2009
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
Tanzania1 site, 1 recruiting
- Recruiting
Kibong'oto National Tuberculosis Hospital
Moshi, Kilimanjaro, P.O. Box 12
Liberate Mleoh, MD, 027 2756194, lmleoh@yahoo.com
Gibson Kibiki, MMed, PhD
About this study
Official title: The Pharmacokinetics of Co-formulated Emtricitabine/Tenofovir/Efavirenz in HIV-infected Patients With Smear-positive Pulmonary Tuberculosis in the Kilimanjaro Region, Tanzania
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.
Read the 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.
- Conditions
- Tuberculosis, HIV Infections
- Being tested
- Emtricitabine/tenofovir/efavirenz
- Keywords
- Tuberculosis, HIV, Coinfection, Pharmacokinetics, Emtricitabine, Tenofovir, Rifampin, Efavirenz, Treatment Naive
- Medical subject headings
- Tuberculosis, HIV Infections, Coinfection
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Emtricitabine/tenofovir/efavirenzDrug
Co-formulated in one tablet (taken once daily by oral administration):
- emtricitabine 200 mg
- tenofovir DF 300 mg
- efavirenz 600 mg
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetic parameters of emtricitabine, tenofovir and efavirenz
Measured: Two 24 hour pharmacokinetic (PK) curves (week 8 and 28)
Pharmacokinetic parameters of the tuberculostatic agents
Measured: Pharmacokinetic (PK) samples at 2 hours and 6 hours postdose (week 2 and 8)
Secondary outcomes (4)
Biochemistry and haematology samples for safety
Measured: Samples at screening, baseline, week 2, 4, 6, 8, 12, 16, 24, 28
Questioning about occurrence of adverse events
Measured: At baseline, week 2, 4, 6, 8, 12, 16, 24, 28
CD4 count and HIV-1 RNA
Measured: At screening, week 4, week 16 and week 28
Sputum staining and culture
Measured: At screening, week 4, 8, and 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2007 (estimated)
- Study startNov 2008
- Primary completionDec 2009 (estimated)
- Study completionDec 2009 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- African Poverty Related Infection Oriented Research Initiative
- Sponsor type
- University, hospital or other
- Collaborators
- Radboud University Medical Center, Kilimanjaro Christian Medical Centre, Tanzania
- Investigators
- Martin Boeree, MD, PhD, Principal investigator, University Lungcentre Dekkerswald, Groesbeek / University Medical Centre Nijmegen, the NetherlandsDavid Burger, PharmD, PhD, Principal investigator, University Medical Centre Nijmegen, the NetherlandsGibson Kibiki, MMed, PhD, Principal investigator, Kilimanjaro Christian Medical Centre,Moshi,Tanzania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00474435
- Sponsor's protocol ID
- UMCN-AKF 04.03
- Acronym
- PETE
- Status last verified
- Dec 2008
- First submitted
- 16 May 2007
- Last updated
- 17 Dec 2010
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 11081535Msamanga 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.
PubMed 9295244Dean 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.
PubMed 11741165Burman 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.
PubMed 11432536Finch 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.
PubMed 11996607Lopez-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.
PubMed 12126459Burger 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.
PubMed 8363370Gallicano 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.
PubMed 10417493Friedland 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.
PubMed 15156433Droste 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.
PubMed 12626888Holland 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.
PubMed 14982771Marzolini 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.
PubMed 11192870
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Pharmacokinetics of Co-formulated Emtricitabine/Tenofovir/Efavirenz in HIV-infected Patients With Smear-positive Pulmonary Tuberculosis in the Kilimanjaro Region, Tanzania
- ClinicalTrials.gov ID
- NCT00474435
- Acronym / sponsor ID
- PETE / UMCN-AKF 04.03
- Conditions
- Tuberculosis, HIV Infections
- Keywords
- Tuberculosis, HIV, Coinfection, Pharmacokinetics, Emtricitabine, Tenofovir, Rifampin, Efavirenz
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- African Poverty Related Infection Oriented Research InitiativeUniversity, hospital or other
- Collaborators
- Radboud University Medical Center, Kilimanjaro Christian Medical Centre, Tanzania
- Study start
- Nov 2008
- Primary completion
- Dec 2009 (estimated)
- Study completion
- Dec 2009 (estimated)
- First posted
- 17 May 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Emtricitabine/tenofovir/efavirenzCo-formulated in one tablet (taken once daily by oral administration): * emtricitabine 200 mg * tenofovir DF 300 mg * efavirenz 600 mg | Drug | – |
Primary outcome
Pharmacokinetic parameters of emtricitabine, tenofovir and efavirenz
Time frame: Two 24 hour pharmacokinetic (PK) curves (week 8 and 28)
Pharmacokinetic parameters of the tuberculostatic agents
Time frame: Pharmacokinetic (PK) samples at 2 hours and 6 hours postdose (week 2 and 8)
4 secondary outcomes
Biochemistry and haematology samples for safety
Time frame: Samples at screening, baseline, week 2, 4, 6, 8, 12, 16, 24, 28
Questioning about occurrence of adverse events
Time frame: At baseline, week 2, 4, 6, 8, 12, 16, 24, 28
CD4 count and HIV-1 RNA
Time frame: At screening, week 4, week 16 and week 28
Sputum staining and culture
Time frame: At screening, week 4, 8, and 28
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2010.
- Background: PubMed 11081535Bowen 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.
- Background: PubMed 9295244Msamanga 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.
- Background: PubMed 11741165Dean 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.
- Background: PubMed 11432536Burman 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.
- Background: PubMed 11996607Finch 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.
- Background: PubMed 12126459Lopez-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.
- Background: PubMed 8363370Burger 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.
- Background: PubMed 10417493Gallicano 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.
- Background: PubMed 15156433Friedland 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.
- Background: PubMed 12626888Droste 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.
- Background: PubMed 14982771Holland 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.
- Background: PubMed 11192870Marzolini 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Martin Boeree, MD, PhD principal investigator
University Lungcentre Dekkerswald, Groesbeek / University Medical Centre Nijmegen, the Netherlands
David Burger, PharmD, PhD principal investigator
University Medical Centre Nijmegen, the Netherlands
Gibson Kibiki, MMed, PhD principal investigator
Kilimanjaro Christian Medical Centre,Moshi,Tanzania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Emtricitabine/tenofovir/efavirenz in people with Tuberculosis and HIV Infections, run by African Poverty Related Infection Oriented Research Initiative at 1 site in Tanzania.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 17 Dec 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Tanzania. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Gibson Kibiki, MMed, PhD (+255 754 572767, gkibiki@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pharmacokinetic parameters of emtricitabine, tenofovir and efavirenz (time frame: Two 24 hour pharmacokinetic (PK) curves (week 8 and 28)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00474435, which also lists 12 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2010.