Evaluation of Early Bactericidal Activity in Pulmonary Tuberculosis (TMC207-CL001)

Inclusion Criteria: * 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, uncomplicated, sputum smear-positive, pulmonary TB. * A chest X-ray picture which in the opinion of the Investigator is compatible with TB. * Sputum positive on direct microscopy for acid-fast bacilli …(at least 1+ on the International Union Against Tuberculosis and Lung Disease (IUATLD)/World Health Organization (WHO) scale). * Ability to produce an adequate volume of sputum as estimated from a spot assessment (estimated 10 ml or more overnight production). * Females may participate if they are of non-childbearing potential, if they are using effective birth control methods and are willing to continue practicing birth control methods throughout treatment or if they are non-heterosexually active or willing to practice sexual abstinence throughout the treatment period or have a vasectomized partner (confirmed sterile). Therefore to be eligible for this study women of childbearing potential should either:1) use a double barrier method to prevent pregnancy (i.e. use a condom with either diaphragm or cervical cap) or 2) use hormonal based contraceptives in combination with a barrier contraceptive, or 3) use an intrauterine device in combination with a barrier contraceptive. They must also be willing to continue these contraception until 6 months after last study drug or 6 months after discontinuation from study medication in case of premature discontinuation. (Note: Hormone-based contraception may not be reliable when taking TMC207; therefore, hormone-based contraceptives cannot be used by female patients to prevent pregnancy). * Male patients must be willing to use a condom with spermicide when having heterosexual intercourse throughout treatment and until 1 month after last study drug administration or 1 month after discontinuation from study medication in case of premature discontinuation. Exclusion Criteria: 1. Evidence of clinically significant metabolic, gastrointestinal neurological, psychiatric or endocrine diseases, malignancy, or other abnormalities (other than the indication being studied). 2. Known or suspected hypersensitivity to study medications (including any rifamycin antibiotics) 3. Rifampicin-resistant and/or isoniazid-resistant bacteria detected with a sputum specimen collected within the pre-treatment period and tested at the study laboratory. 4. Clinically significant evidence of extrathoracic TB (miliary TB, abdominal TB, urogenital TB, osteoarthritic TB, TB meningitis), as judged by the investigator. 5. Current or past history of alcohol and/or drug use that, in the investigator's opinion, would compromise the participant's safety or compliance to the study protocol procedures. 6. HIV infected patients: 1. having a cluster of differentiation 4 (CD4)+ count \<300 cells/µL; 2. or having received antiretroviral therapy medication within the last 90 days: 3. or having received oral or intravenous antifungal medication within the last 90 days; 4. or with an AIDS-defining opportunistic infection or malignancies (except pulmonary TB). 7. Significant cardiac arrhythmia requiring medication 8. Having participated in other clinical studies with investigational agents within 8 weeks prior to trial start. 9. Patients with the following QT/corrected QT(QTc) interval characteristics at screening: 1. Marked prolongation of QT/QTc interval, e.g., confirmed demonstration of QT corrected for heart rate using Fridericia's method (QTcF) interval \>450 ms at screening; 2. History of additional risk factors for Torsade de Pointes, e.g., heart failure, hypokalemia, family history of Long QT Syndrome; 3. Use of concomitant medications that prolong the QT/QTc interval listed as disallowed medication in Section 2.10.2; 4. Pathological Q waves (defined as \>40ms or depth \>0.4-0.5mV); 5. Evidence of ventricular pre-excitation; 6. ECG evidence of complete or incomplete left bundle branch block or right bundle branch block; 7. Evidence of second or third degree heart block; 8. Intraventricular conduction delay with QRS duration \>120ms; 9. Bradycardia as defined by sinus rate \<50bpm 10. Women who are pregnant or breastfeeding 11. History and/or presence (or evidence) of neuropathy or epilepsy. 12. Diabetics using insulin 13. Poor general condition where any delay in treatment cannot be tolerated per discretion of Investigator. 14. Previously received treatment with TMC207 as part of a clinical trial. 15. Treatment received with any drug active against Mycobacterium tuberculosis within 3 months prior to Visit 1. 16. Any disease or conditions in which any of the medicinal products listed in the section pertaining to prohibited medications is used. 17. Patients with the following toxicities at screening as defined by the enhanced Division of Microbiology and Infectious Disease (DMID) adult toxicity table (November 2007): 1. creatinine grade 2 or greater (\>1.5 times upper limit of normal \[ULN\]); 2. lipase grade 3 or greater (\>2.0 x ULN); 3. hemoglobin grade 4 (\<6.5 g/dL) except after discussion with the Medical Monitor; 4. aspartate aminotransferase (AST) grade 4 (\>8.0 x ULN) to be excluded, grade 3 (≥3.0 x ULN) must be discussed with Medical Monitor; 5. alanine aminotransferase (ALT) grade 4 (\>8.0 x ULN) to be excluded, grade 3 (≥3.0 x ULN) must be discussed with Medical Monitor; 6. alkaline phosphatase (ALP) grade 4 (\>8.0 x ULN) to be excluded, grade 3 (≥3.0 x ULN) must be discussed with Medical Monitor; 7. total bilirubin grade 3 or greater (\>2.00 x ULN, or \>1.50 x ULN when accompanied by any increase in other liver function test) to be excluded, grade 2 (\>1.50 x ULN, or \>1.25 x ULN when accompanied by any increase in other liver function test) must be discussed with the Medical Monitor