Evaluating the Safety and Drug Interaction of PA-824, an Investigational Tuberculosis Medication, Together With Efavirenz, Ritonavir-Boosted Lopinavir, or Rifampin
Condition: Tuberculosis
MeSH terms: Tuberculosis
Study type: Interventional
Phase: Phase 1

Summary: 
      Tuberculosis (TB) is a global public health concern and developing new treatment regimens is
      an important research priority. PA-824 is an experimental TB medication. This study will
      evaluate the safety and tolerability of PA-824 when combined with efavirenz (EFV) or
      ritonavir-boosted lopinavir (LPV/r), which are medications used to treat HIV infection, or
      rifampin (RIF), which is a medication used to treat TB. Study researchers will examine the
      safety and tolerability of these drug combinations and how the medications affect the levels
      of PA-824 in the blood.
    

Detailed description: 
      TB is a global public health threat. In 2009, there were an estimated 9.4 million cases of TB
      and 1.8 million deaths from the disease. TB treatment regimens are often lengthy and complex,
      and multidrug-resistant (MDR) TB is emerging as a worldwide epidemic. TB is also one of the
      most common causes of death among people infected with HIV. PA-824 is an experimental drug
      developed for the treatment of TB. This study will evaluate the safety, tolerability, and
      pharmacokinetic (PK) drug interactions between PA-824 and EFV, LPV/r, or RIF.

      This study will enroll healthy adults who are not infected with HIV or TB. Participants will
      be enrolled into one of three arms, with Arms 1 and 2 each consisting of two groups.
      Participants in Arm 1 will be randomly assigned to receive PA-824 alone or EFV alone followed
      by EFV plus PA-824 in one of two sequences. Participants in Arm 2 will be randomly assigned
      to receive PA-824 alone or LPV/r alone followed by LPV/r plus PA-824 in one of two sequences.
      For participants in Arms 1 and 2, there will be a 14-day washout period between treatments,
      where participants will not receive any medication. Participants in Arm 3 will receive PA-824
      alone, followed by RIF alone, and then RIF plus PA-824. Participants in Arms 1 and 2 will
      attend outpatient study visits at study entry and either Days 3, 22, and 29 or Days 7, 36,
      and 39, depending on which group they are in. Participants in Arm 3 will attend outpatient
      study visits at study entry and Days 3, 10, and 15. At most study visits, participants will
      undergo a physical examination, vital sign measurements, medication and medical history
      review, and blood collection. Participants will complete a medication and symptom diary
      throughout the study.

      All participants also will be admitted to an inpatient clinical research unit two or three
      times during the study, depending on which arm they are enrolled in. Each inpatient visit
      will last 1 or 2 days. During the inpatient visits, participants will undergo several blood
      collections throughout the day; select visits also will include an electrocardiogram (ECG).

      Participants in Arms 1 and 2 will receive the last dose of their assigned medication on Day
      42. Participants in Arm 3 will receive the last dose of their assigned medication on Day 21.
      A final study visit will occur for all participants 1 to 2 weeks later.
    

Intervention name(s): PA-824; Efavirenz (EFV); Lopinavir/Ritonavir (LPV/r); Rifampin (RIF)
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): 200-mg tablets once a day; 600-mg tablets once a day; 400-mg/100-mg tablets twice a day; 300-mg capsules once a day
Intervention MeSH terms: Ritonavir; Lopinavir; Efavirenz; Rifampin
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment