Evaluation of Early Bactericidal Activity in Pulmonary Tuberculosis With Clofazimine (C)-TMC207 (J)-PA-824 (Pa)-Pyrazinamide (Z)

Inclusion Criteria

• 1. Provide written, informed consent prior to all trial-related procedures including HIV testing.
• Male or female, aged between 18 and 65 years inclusive.
• Body weight (in light clothing and with no shoes) between 40 and 90 kg, inclusive.
• Newly diagnosed, previously untreated, sputum smear-positive pulmonary TB.
• A chest X-ray picture which in the opinion of the Investigator is compatible with TB.
• Sputum positive GeneXpert or TB Smear from TB clinic or site initial diagnosis
• Sputum positive on direct microscopy for acid-fast bacilli (at least 1+ on the IUATLD/WHO scale).
• Ability to produce an adequate volume of sputum as estimated from a spot assessment (estimated 10 ml or more overnight production).
• Be of non-childbearing potential or using an effective method of birth control as defined as:

Non-childbearing potential:

• Subject - Not heterosexually active or practice sexual abstinence or
• Female subject/sexual bilateral oophorectomy, bilateral tubal ligation, and/or hysterectomy or has been postmenopausal with a history of no menses for at least 12 consecutive months) or
• Male subject/sexual partner - vasectomised or has had a bilateral orchidectomy minimally three month prior to screening

Effective birth control methods:

• Double barrier method which can include a male condom, diaphragms, cervical cap, or female condom or
• Barrier method combined with hormone based contraceptives or an intra-uterine device for the female partner and are willing to continue practicing birth control methods throughout treatment and for 12 weeks (male participants) or 6 months (female participants) after the last dose of study medication or discontinuation from study medication in case of premature discontinuation

(Note: Hormone-based contraception alone may not be reliable when taking IMP; therefore, hormone-based contraceptives alone cannot be used by female participants to prevent pregnancy).

Exclusion Criteria

• Evidence of clinically significant (as judged by the investigator), metabolic, gastrointestinal, cardiovascular, musculoskeletal, ophthalmological, pulmonary, neurological, psychiatric or endocrine diseases, malignancy, or other abnormalities (other than the indication being studied) including malaria.
• Poor general condition where any delay in treatment cannot be tolerated per discretion of the Investigator.
• A history of previous TB.
• Clinically significant evidence of extrathoracic TB (miliary TB, abdominal TB, urogenital TB, osteoarthritic TB, TB meningitis), as judged by the Investigator.
• History of allergy to the IMP or related substances.
• Isoniazid-resistant and/or Rifampicin-resistant bacteria detected with a sputum specimen collected within the pre-treatment period and tested at the study laboratory.
• Known or suspected, current or history of within the past 2 years, alcohol or drug abuse, that is, in the opinion of the Investigator, sufficient to compromise the safety or cooperation of the participant.
• HIV infected participants:
• having a CD4+ count 450 ms at screening;
• History of additional risk factors for Torsade de Pointes, e.g., heart failure, hypokalemia, family history of Long QT Syndrome;
• Use of concomitant medications that prolong the QT/QTc interval (see exclusion criterion 19 and disallowed medications;
• Pathological Q waves (defined as >40ms or depth >0.4-0.5mV);
• ECG evidence of ventricular pre-excitation;
• ECG evidence of complete or incomplete left bundle branch block or right bundle branch block;
• ECG evidence of second or third degree heart block;
• Intraventricular conduction delay with QRS duration >120ms;
• Bradycardia as defined by sinus rate 1.5 times upper limit of normal [ULN]);
• lipase grade 3 or greater (>2.0 x ULN);
• hemoglobin grade 4 ( 8.0 x ULN) to be excluded, grade 3 (≥3.0 x ULN) must be discussed with the sponsor Medical Monitor;
• total bilirubin grade 3 or greater (>2.0 x ULN, or