Safety, Tolerability, and Effect of TMC207 and Efavirenz in Healthy Volunteers
Condition: Tuberculosis; HIV
MeSH terms: Tuberculosis
Study type: Interventional
Phase: Phase 1

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Efavirenz (EFV); TMC207
Intervention type(s): Drug; Drug
Intervention description(s): Oral dose of 600 mg daily, taken in the evening; Single oral dose of 400 mg in the morning
Other intervention name(s): Sustiva
Intervention MeSH terms: Efavirenz
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: ARV; Pharmacokinetics; TMC207; Efavirenz