Shortening Treatment by Advancing Novel Drugs

Inclusion Criteria

• Signed written consent or witnessed oral consent in the case of illiteracy, prior to undertaking any trial-related procedures.
• Male or female, aged 18 years or over.
• Body weight (in light clothing and no shoes) ≥ 30 kg.
• Sputum positive for tubercule bacilli (at least 1+ on the International Union Against Tuberculosis and Lung Disease (IUATLD) and World Health Organization (WHO) scale on smear microscopy at the trial laboratory.
• Drug-Sensitive TB treatment arms subjects should be:
• sensitive to rifampicin by rapid sputum based test (may be sensitive or resistant to isoniazid) AND
• either newly diagnosed for TB or have a patient history of being untreated for at least 3 years after cure from a previous episode of TB. If they are entered into the trial due to being sensitive to rifampicin by rapid sputum based test, however on receipt of the rifampicin resistance testing using an indirect susceptibility test in liquid culture this shows they are rifampicin resistant, they will be:
• Excluded as late exclusions;
• Possibly replaced as determined by the sponsor.
• MDR-TB treatment arm subjects should be resistant to rifampicin by rapid sputum based test (may be sensitive or resistant to isoniazid).
• A chest x-ray which in the opinion of the investigator is compatible with pulmonary TB.
• Be of non-childbearing potential or using effective methods of birth control, as defined below:

Non-childbearing potential:

• Subject - not heterosexually active or practice sexual abstinence; or
• Female subject or male subjects female sexual partner - 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 or female subjects male sexual partner - vasectomised or has had a bilateral orchidectomy minimally three months prior to screening;

Effective birth control methods:

• Double barrier method which can include a male condom, diaphragm, cervical cap, or female condom; or
• Female subject: Barrier method combined with hormone-based contraceptives or an intra-uterine device for the female patient.
• Male subjects' female sexual partner: Double barrier method or hormone-based contraceptives or an intra-uterine device for the female partner.

and are willing to continue practising birth control methods and are not planning to conceive throughout treatment and for 12 weeks (male subjects) or 1 week (female subjects) after the last dose of trial medication or discontinuation from trial medication in case of premature discontinuation.

(Note: Hormone-based contraception alone may not be reliable when taking IMP; therefore,

Exclusion Criteria

• Any non TB related condition (including myasthenia gravis) where participation in the trial, as judged by the investigator, could compromise the well-being of the subject or prevent, limit or confound protocol specified assessments.
• Being or about to be treated for Malaria.
• Is critically ill and, in the judgment of the investigator, has a diagnosis likely to result in death during the trial or the follow-up period.
• TB meningitis or other forms of extrapulmonary tuberculosis with high risk of a poor outcome, or likely to require a longer course of therapy (such as TB of the bone or joint), as judged by the investigator.
• History of allergy or hypersensitivity to any of the trial IMP or related substances, including known allergy to any fluoroquinolone antibiotic, history of tendinopathy associated with quinolones or suspected hypersensitivity to any rifampicin antibiotics.
• For HIV infected subjects any of the following:
• CD4+ count 450 ms;
• History of additional risk factors for Torsade de Pointes, (e.g., heart failure, hypokalemia, family history of Long QT Syndrome);
• Any clinically significant ECG abnormality, in the opinion of the investigator.
• Unstable Diabetes Mellitus which required hospitalization for hyper- or hypo-