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Ensayos clínicos

Ensayos clínicos

Safety, Tolerability, and Effect of TMC207 and Efavirenz in Healthy Volunteers

Patrocinador(es) del estudio: National Institute of Allergy and Infectious Diseases (NIAID)
Números de identificación: NCT00992069, ACTG A5267
  • Concluido

Propósito del estudio

Common treatments for tuberculosis (TB) can interfere with certain antiretroviral (ARV) medications used to treat HIV. People whose immune systems are weakened by HIV infection are susceptible to TB, so it is important to find treatments for both that can be given in combination. This study will test the safety of combining a new medication for TB with an already approved HIV medication in healthy adults.

Afección:Fase:
Tuberculosis
VIH-1
Fase 1

Detalles del estudio

Tuberculosis (TB) is the second most deadly infectious disease after HIV.

Multidrug-resistant TB (MDR-TB) has emerged as a worldwide epidemic, limiting treatment

options. HIV infected people with suppressed immune systems are particularly susceptible to

TB, and TB is the leading cause of death among people with HIV. Treating people infected

with both HIV and TB is particularly problematic because rifamycins, the drug class usually

used to treat TB, lower the effectiveness of certain anti-HIV medications. Studies of

pharmacokinetics (PK), the interactions between drugs and body, are needed to determine

which anti-TB and anti-HIV medications can be safely and effectively combined. This study

will examine TMC207, a new anti-TB medication with the potential to shorten TB treatment

time, combined with efavirenz (EFV), an antiretroviral (ARV) medication used in many

first-line treatment regimens for HIV. The study will test PK and safety of this combination

in healthy volunteers.



Participation in this study will last 49 days. At entry, participants will complete basic

assessments, including taking a medical history and completing a physical exam, an eye exam,

an electrocardiogram (ECG) to measure heartbeat, a pregnancy test, and a blood test. Certain

behaviors and substances will be prohibited during the study, including consuming

grapefruit, alcohol, or caffeine (on PK visit days); taking nutritional supplements,

over-the-counter herbal medicines, and certain medicines and drugs from other studies; and

excessive smoking. Participants will also be asked to keep a medication diary to record all

medications they take during the study.



All participants will receive study medications on the same schedule: a single dose of

TMC207 on Days 1 and 29, and daily dosing of EFV on Days 15 to 43.



Participants will complete two PK visits, one from Days 1 to 3, and one from Days 28 to 31.

During PK visits, participants will have their vital signs checked and undergo an ECG, and

they may also complete a limited physical exam, give a medication history, and report on

symptoms. They will have multiple blood samples taken via a catheter left in place for the

3-day visit. Blood samples will be taken before receiving TMC207; 1, 2, 3, 4, 5, 6, 8, and

12 hours after receiving TMC207; and again on the mornings of Days 2 and 3.



Participants will complete six outpatient visits over the 11 days following each PK visit

and one outpatient visit on Day 21, between PK visits. At outpatient visits participants

will complete a blood draw and may complete a limited physical exam and medical history,

record symptoms, and review their medication diaries.



On Day 49 participants will complete their last study visit, repeating many of the

assessments from baseline testing. In the case of side effects or abnormal blood tests,

participants may be monitored longer for safety reasons.Tuberculosis (TB) is the second most deadly infectious disease after HIV.

Multidrug-resistant TB (MDR-TB) has emerged as a worldwide epidemic, limiting treatment

options. HIV infected people with suppressed immune systems are particularly susceptible to

TB, and TB is the leading cause of death among people with HIV. Treating people infected

with both HIV and TB is particularly problematic because rifamycins, the drug class usually

used to treat TB, lower the effectiveness of certain anti-HIV medications. Studies of

pharmacokinetics (PK), the interactions between drugs and body, are needed to determine

which anti-TB and anti-HIV medications can be safely and effectively combined. This study

will examine TMC207, a new anti-TB medication with the potential to shorten TB treatment

time, combined with efavirenz (EFV), an antiretroviral (ARV) medication used in many

first-line treatment regimens for HIV. The study will test PK and safety of this combination

in healthy volunteers.



Participation in this study will last 49 days. At entry, participants will complete basic

assessments, including taking a medical history and completing a physical exam, an eye exam,

an electrocardiogram (ECG) to measure heartbeat, a pregnancy test, and a blood test. Certain

behaviors and substances will be prohibited during the study, including consuming

grapefruit, alcohol, or caffeine (on PK visit days); taking nutritional supplements,

over-the-counter herbal medicines, and certain medicines and drugs from other studies; and

excessive smoking. Participants will also be asked to keep a medication diary to record all

medications they take during the study.



All participants will receive study medications on the same schedule: a single dose of

TMC207 on Days 1 and 29, and daily dosing of EFV on Days 15 to 43.



Participants will complete two PK visits, one from Days 1 to 3, and one from Days 28 to 31.

During PK visits, participants will have their vital signs checked and undergo an ECG, and

they may also complete a limited physical exam, give a medication history, and report on

symptoms. They will have multiple blood samples taken via a catheter left in place for the

3-day visit. Blood samples will be taken before receiving TMC207; 1, 2, 3, 4, 5, 6, 8, and

12 hours after receiving TMC207; and again on the mornings of Days 2 and 3.



Participants will complete six outpatient visits over the 11 days following each PK visit

and one outpatient visit on Day 21, between PK visits. At outpatient visits participants

will complete a blood draw and may complete a limited physical exam and medical history,

record symptoms, and review their medication diaries.



On Day 49 participants will complete their last study visit, repeating many of the

assessments from baseline testing. In the case of side effects or abnormal blood tests,

participants may be monitored longer for safety reasons.

Criterios de inclusión

    • Females not of reproductive potential, defined as women who have been postmenopausal for at least 24 consecutive months or women who have undergone hysterectomy, bilateral oophorectomy, or bilateral tubal ligation
    • Females who have been surgically sterilized and all males must agree to use contraceptives if participating in sexual activity that could lead to pregnancy while receiving the protocol-specified medications and for 4 weeks after stopping the medication
    • Absence of HIV-1 infection, as documented by any licensed enzyme-linked immunosorbent assay (ELISA) test kit, within 21 days prior to study entry
    • Estimated creatinine clearance of more than 50 ml/min, within 21 days prior to study entry, calculated by the Cockcroft-Gault method
    • Laboratory test results obtained within 21 days prior to entry, including negative pregnancy test, negative hepatitis B and C tests, and certain blood values

Criterios de exclusión

    :
    • Use of any prescription medication known to inhibit or induce CYP3A metabolizing
    enzymes within 30 days prior to entry
    • Planned use during the study, from day 0 through the last PK blood draw, of any of
    the following: prescription medication(s), herbal supplement(s), nutritional supplement(s), or over-the-counter medication(s). Multivitamins and acetaminophen, up to 650 mg every 6 hours as an analgesic, are permitted.
    • Hospitalization for any reason, pharmacotherapy for serious illness, or use of any
    prescription medication(s) within 14 days prior to study entry
    • Receipt of any investigational study drug within 21 days prior to study entry
    • Known allergy, sensitivity, or hypersensitivity to EFV or TMC207 or components of
    their formulations, including cyclodextrin allergy
    • Significant previous or active history of cardiovascular, renal, liver, hematologic,
    neurologic, gastrointestinal, psychiatric, endocrine, or immunologic disease(s), as determined by the site investigator. This is inclusive of chronic illnesses or gastrointestinal conditions that may affect drug absorption, etc. Additionally, any medical condition that, in the opinion of the site investigator, would interfere with the volunteer's ability to participate in the protocol will exclude participation.
    • Active illicit drug use or dependence that, in the opinion of the site investigator,
    would interfere with adherence to study requirements
    • Suspicion of active tuberculosis (TB) by the site investigator
    • Inability to abstain from alcoholic beverages, grapefruit, and grapefruit juice for
    the duration of the study
    • For smokers, inability to smoke 5 cigarettes per day or less for the duration of the
    study
    • Breastfeeding
    • Electrocardiogram (ECG) showing first-degree or greater heart block or QT interval
    (QTc) greater than 440 ms within 21 days prior to study entry. First-degree heart block is defined as PR interval greater than 200 ms.

Centros de estudio/contactos

California

    Ucsf Aids Crs, San Francisco, California, 94110, United States

Maryland

    Johns Hopkins Adult AIDS CRS, Baltimore, Maryland, 21287, United States

North Carolina

    Unc Aids Crs, Chapel Hill, North Carolina, 27514, United States

Ohio

    The Ohio State Univ. AIDS CRS, Columbus, Ohio, 43210, United States

Tennessee

    Vanderbilt Therapeutics CRS, Nashville, Tennessee, 37232-2582, United States

Actualizado: 10 de noviembre del 2009

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