| City: |
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Baltimore |
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State:
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MD |
| Zip Code: |
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21287 |
| Conditions: |
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Tuberculosis - HIV |
| Purpose: |
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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.
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| Study summary: |
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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. |
| Criteria: |
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Inclusion Criteria:
- 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
Exclusion Criteria:
- 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. |
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If you are interested in this clinical trial please use the contact information above. If you would like to get additional information about this clinical trial please visit ClinicalTrials.gov.
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| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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November 11, 2010 |
Modifications to
this listing: |
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Only selected fields are shown, please use the link
above to view all information about this clinical trial. |
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