Evaluation of the Efficacy and Safety of a 4-month Daily Regimen (2HZPM/2HPM) for Treatment of Pulmonary TB
Evaluation of the Efficacy and Safety of a 4-month Daily Regimen (2HZPM/2HPM) for Treatment of Pulmonary TB
The development of efficacious, safe, and shorter treatment regimens could significantly
 improve TB management and treatment success rates. This prospective, 3-year, single arm study
 is to evaluate the efficacy and safety of a short-course, 4-month regimen including
 isoniazid(H), pyrazinamide(P), rifapentine (P), and moxifloxacin(M) (2HZPM/2HPM) for the
 treatment of drug-susceptible, pulmonary tuberculosis, and compared with a historical control
 group receiving the standard six-month regimen.
Shorter regimens have the potential to impact on TB control by reducing TB incidence and
 mortality, and improve outcomes by increasing patient adherence to treatments and decreasing
 duration to cure, in addition to reducing costs to the health system and the patient. The
 purpose of this prospective, three year, single arm study is to evaluate whether a short
 course, four-month regimen containing rifapentine and moxifloxacin (2HZPM/2HPM) are as
 effective and/or as tolerable as the standard six-month regimen for the treatment of
 drug-susceptible, pulmonary tuberculosis (TB). A historical group receiving the standard
 six-month regimen is used as control. The pharmacokinetic and pharmacodynamic profile of
 rifapentine in Asian patients. Analysis of of histocompatibility leucocyte antigen (HLA)
 associations with adverse events and changes in biomarkers will be done.
Inclusion Criteria:

 1. Suspected newly diagnosed pulmonary TB plus one of the following: a) at least one
 sputum specimen positive for acid-fast bacilli on smear microscopy OR b) at least one
 sputum specimen positive for Mycobacterium tuberculosis by culture or "Gene Xpert
 MTB/RIF" testing, with rifamycin resistance not detected, OR c) histopathologic
 findings compatible with mycobacterial infection including a positive acid-fast stain

 2. Patient with a history of being untreated for 3 years after cure from a previous
 episode of TB can be included.

 3. Age 20 years or older

 4. For women of childbearing potential, a negative pregnancy test at or within seven (7)
 days prior to screening is required, and must agree to practice a barrier method of
 contraception during study drug treatment, or be surgically sterilized or have an
 intrauterine contraceptive device in place.

 5. Laboratory parameters performed at or within 14 days prior to enrollment:

 -  Serum or plasma alanine aminotransferase (ALT) less than or equal to 3 times the
 upper limit of normal

 -  Serum or plasma total bilirubin less than or equal to 2.5 times the upper limit
 of normal

 -  Serum or plasma creatinine level less than or equal to 2 times the upper limit of
 normal or Creatinine clearance (CrCl) level greater than 30 mL/min.

 -  Serum or plasma potassium level greater than or equal to 3.5 milliequivalent/L

 -  Hemoglobin level of 7.0 g/dL or greater

 -  Platelet count of 100,000/mm3 or greater

 6. Patient signed a written informed consent

 Exclusion Criteria:

 1. Pregnant or breast-feeding.

 2. Unable to take oral medications.

 3. Previously enrolled in this study.

 4. Received any investigational drug in the past 3 months.

 5. More than 14 days of systemic treatment with any antituberculous drugs preceding
 initiation of study drugs.

 6. Known history of prolonged QT syndrome.

 7. Suspected or documented TB involving the central nervous system and/or bones and/or
 joints, and/or miliary tuberculosis and/or pericardial tuberculosis.

 8. Weight less than 40.0 kg.

 9. Known allergy or intolerance to any of the study medications.

 10. Individuals will be excluded from enrollment if, at the time of enrollment, their M.
 tuberculosis isolate is already known to be resistant to any one or more of the
 following: rifampin, isoniazid, pyrazinamide, ethambutol, or fluoroquinolones.

 11. Medical conditions, including HIV infection and others conditions that, in the
 investigator's judgment, make study participation not in the individual's best
 interest.

 12. Late exclusions: Drug-resistant TB by either rapid sputum based test (Gene Expert) or
 resistance testing using an indirect susceptibility test in liquid culture to
 isoniazid, rifampin, ethambutol, pyrazinamide or resistance to moxifloxacin or
 rifapentine by microdilution agar proportion test.