A Phase 3 Trial Assessing Safety and Efficacy of B-Pa-L in Participants With DR-TB

Exclusion Criteria

• •1. Karnofsky score \< 50 within 30 days prior to entry.
• •2. Body Mass index (BMI) \< 17 kg/m²
• •3. History of allergy or known hypersensitivity to any of the trial Investigational Medicinal Products or related substances.
• •4. HIV infected Subjects having a CD4+ count ≤ 50 cells/μL
• •5. Having participated in other clinical studies with dosing of investigational agents within 8 weeks prior to trial start or currently enrolled in an investigational study that includes treatment with medicinal agents. Subjects who are participating in observational studies or who are in a follow up period of a trial that included drug therapy may be considered for inclusion.
• •6. Significant cardiac arrhythmia requiring medication.
• •7. Subjects with the following at Screening:
• •1. QTcF interval on ECG \>500 msec.
• •2. History of additional risk factors for Torsade de Pointes, (e.g., heart failure, hypokalemia, family history of Long QT Syndrome);
• •3. Clinically significant ventricular arrhythmias;
• •4. Subjects with other cardiac abnormalities that may place them at risk of arrhythmias must be discussed with the sponsor medical monitor before enrolment. Such abnormalities include: Evidence of ventricular pre-excitation (e.g., Wolff Parkinson White syndrome); Electrocardiographic evidence of complete or clinically significant incomplete left bundle branch block or right bundle branch block; Evidence of second or third degree heart block; Intraventricular conduction delay with QRS duration more than 120 msec.
• •8. Females who have a positive pregnancy test at Screening or already known to be pregnant, breastfeeding, or planning to conceive a child during the study or within 6 months of cessation of treatment. Males planning to conceive a child during the study or within 6 months of cessation of treatment.
• •9. A peripheral neuropathy of Grade 3 or 4, according to DMID (Appendix 2). Or, subjects with a Grade 1 or 2 neuropathy which is likely to progress/worsen over the course of the study, in the opinion of the Investigator.
• •10. Concomitant use of Monoamine Oxidase Inhibitors (MAOIs) or prior use within 2 weeks of treatment assignment.
• •11. Subjects with the following toxicities at Screening as defined by the enhanced Division of Microbiology and Infectious Disease (DMID) adult toxicity table (November 2007):
• •a. serum potassium less than the lower limit of normal for the laboratory; b. Hemoglobin level grade 2 or greater (\< 8.0 g/dL); c. Platelets grade 2 or greater(\<75,000/mm3); d. Absolute neutrophil count (ANC) \< 1000/ mm3; e. Aspartate aminotransferase (AST) \> 3 x ULN g. Total bilirubin \> or = to 2xULN h. Direct bilirubin \> ULN i. Serum creatinine level greater than 2 times upper limit of normal j. Albumin \<32 g/L