Evaluation of Early Bactericidal Activity in Pulmonary Tuberculosis (CL-010)
Condition: Pulmonary Tuberculosis
MeSH terms: Tuberculosis; Tuberculosis, Pulmonary
Intervention: PA-824; PA-824; PA-824; Rifafour e-275 mg; PA-824
Intervention description: 50mg; 100mg; 150 mg; 275 mg; 200 mg
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 69.0
Sex: All
Minimum age: 18 Years
Maximum age: 64 Years
Healthy volunteers: No
Keywords: Early Bactericidal Activity; EBA; Pulmonary Tuberculosis; PA-824; pretomanid

Summary:

      The trial will evaluate the extended bactericidal activity of 14 consecutive days of oral
      administration of PA-824 at 50, 100, 150 and 200 mg per day in adult patients with newly
      diagnosed, uncomplicated, smear positive tuberculosis (TB). A control group will receive
      standard TB treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Informed Consent

          -  Body weight between 40 and 90 kg, inclusive.

          -  Newly diagnosed, previously untreated, uncomplicated, sputum smear-positive, pulmonary
             TB.

          -  A chest X-ray compatible with TB.

          -  Sputum positive

          -  Adequate volume of sputum

          -  Female participants of childbearing potential negative serum pregnancy and agree to
             use birth control

          -  Male participants must agree to use contraception throughout participation in the
             trial and for 12 weeks after last dose.

        Exclusion Criteria:

          -  Poor general condition

          -  Rifampicin-resistant and/or Isoniazid-resistant

          -  MTB Treatment received within the 3 months prior

          -  Allergy to the IMP or related substances

          -  Evidence of extrathoracic TB

          -  A history of previous TB

          -  Evidence of serious lung conditions other than TB or uncontrolled obstructive
             bronchial disease

          -  History of lens opacity or evidence of lens opacity on slit lamp ophthalmologic
             examination

          -  Any evidence of renal impairment

          -  For males, any evidence or history of abnormality in the reproductive system

          -  History and/or presence (or evidence) of neuropathy or epilepsy.

          -  Clinically relevant changes in the ECG

          -  A history of or current clinically relevant cardiovascular disorder

          -  Concomitant use of any drug known to prolong QTc interval

          -  Diabetics using insulin

          -  Evidence of clinically significant metabolic, gastrointestinal, neurological,
             psychiatric or endocrine diseases, malignancy, or other abnormalities (other than the
             indication being studied).

          -  Any diseases or conditions in which the use of the standard TB drugs or any of their
             components is contra-indicated, including but not limited to allergy to any TB drug,
             their component or to the IMP.

          -  Any disease or conditions in which any of the medicinal products listed in the section
             pertaining to prohibited medication is used.

          -  alcohol or drug abuse

          -  Administration of an IMP prior to Visit 1, within 5 half-lives for that IMP if known.
             If the half-life of the IMP is unknown within 1 month.

          -  Pregnant, breast-feeding, or planning to conceive or father a child within twelve
             weeks of cessation of treatment for males and within one week of cessation of
             treatment for females.

          -  Use of any drugs or substances within 30 days prior to dosing known to be strong
             inhibitors or inducers of cytochrome P450 enzymes

          -  Any therapeutic agents known to alter any major organ function (e.g., barbiturates,
             opiates, phenothiazines, cimetidine) within 30 days prior to dosing.

          -  glucocorticoids within one year prior to dosing.

          -  HIV infection with helper/inducer T lymphocyte (CD4 cell) count of less than or equal
             to 300x10-6/L.

          -  Receiving antiretroviral therapy (ART).