PanACEA DElpazolid Dose-finding and COmbination DEvelopment (DECODE)

Inclusion Criteria: 1. Provide written, informed consent prior to all trial-related procedures including HIV testing. 2. Male or female, aged between 18 and 65 years, inclusive. 3. Body weight between 40 and 90 kg, inclusive. 4. Newly diagnosed, previously untreated, drug susceptible pulmonary TB: presence of MTB complex and rapid molecular tests result confirming susceptibility to RIF and INH such as GeneXpert and/or HAIN MTBDR plus. 5. A chest X-ray (no older than 2 weeks) which, in the opinion of the Investigator, is consistent with TB. 6. Sputum positive on microscopy from concentrated sputum for acid-fast bacilli on at least one sputum sample (at least 1+ on the IUATLD/WHO scale). 7. The participant is willing to forgo consumption of foods high in tyramine for the period of taking study medication (See Appendix, section 20.2, page 92). 8. The participant is either unable to conceive/father children AND/OR his/her partner is unable to conceive/father children AND/OR they will consent to be using effective methods of contraception when engaging in heterosexual intercourse, as defined below: a. Non-childbearing potential: i. Female participant/sexual partner of male participant: Bilateral oophorectomy, and/or hysterectomy or bilateral tubal ligation more than 12 months ago and/or has been postmenopausal with a history of no menses for at least 12 consecutive months ii. Male participant/sexual partner of female participant: Vasectomised or has had a bilateral orchidectomy minimally three months prior to screening iii. Male participants having a pregnant female partner or a male sexual partner: At least one barrier method has to be used in this case. b. Effective contraception methods: i. Female participants: Two methods, including methods that the patient's sexual partner(s) use. At least one must be a barrier method. Contraception must be practised for at least until 12 weeks after the last dose of DZD. ii. Male participants: Two methods, including methods that the patient's female sexual partner(s) use. At least one must be a barrier method. Effective contraception must be ensured for at least 16 weeks after the last dose of DZD. Note: hormone-based contraception alone may not be reliable when taking RIF during continuation phase; therefore, hormone-based contraceptives alone cannot be used by female participants/female partners of male participants to prevent pregnancy. Exclusion Criteria: 1. Circumstances that raise doubt about free, unconstrained consent to study participation (e.g. prisoner or mentally handicapped person) 2. Poor general condition where delay in treatment cannot be tolerated or death within four months is likely. 3. Poor social condition which would make it unlikely that the patient would be able to complete follow-up 4. The patient is pregnant or breast-feeding. 5. The patient is infected with HIV with a CD4 count \<220 cells/mm3. If \>220 cells/mm3, patients will be included only if any of the following is applicable: * The patient is antiretroviral (ARV) naïve and able to postpone commencing HIV treatment for 2 months after the trial has started and then restrict regimens to those containing dolutegravir (see section 12.6.2 on ARVs) or The patient is ARV experienced (has been on ARV´s a minimum of 5 months) and able to switch to a dolutegravir-based regimen. * The patient is treated with nucleosidic reverse transcriptase inhibitors (are permitted as concomitant medication). * The patient is treated with protease inhibitors as part of antiretroviral treatment regimens, which will be stopped at least 3 days before the start of study treatment (WK01, day1) for a patient to be eligible. * The patient is treated with Efavirenz as part of antiretroviral treatment regimens which would have to be stopped 14 days before the start of study treatment (WK00, Day 01) for a patient to be eligible. 6. The patient has a known intolerance to any of the study drugs or concomitant disorders or conditions for which study drugs or standard TB treatment are contraindicated 7. The patient has a history of, or current evidence of clinically relevant cardiovascular metabolic, gastrointestinal, neurological, psychiatric or endocrine diseases, malignancy, or any other condition that will influence treatment response, study adherence or survival in the judgement of the investigator, especially: 1. Neuropathy, or significant psychiatric disorder like depression or schizophrenia; especially if treatment for those has ever been required or is anticipated to be required 2. Clinically significant evidence of extra-pulmonary TB (e.g. miliary TB, TB meningitis, but not limited lymph node involvement) 3. Serious lung conditions other than TB, or significant respiratory impairment in the discretion of the investigator 4. Any diabetes mellitus 5. Cardiovascular disease such as myocardial infarction, heart failure, coronary heart disease, arrhythmia, tachyarrhythmia, or pulmonary hypertension 6. Arterial hypertension (systolic blood pressure ≥140 mmHg and/or diastolic blood pressure of ≥90 mmHg on two occasions during screening). 7. Long QT syndrome or family history of long QT syndrome or sudden death of unknown or cardiac-related cause 8. Alcohol or other drug abuse that is sufficient to significantly compromise the safety or cooperation of the patient, that includes substances prohibited by the protocol or has led to significant organ damage at the discretion of the investigator. 8. Any of the following laboratory findings at screening: 1. Serum amino aspartate transferase (AST) and/or alanine aminotransferase (ALT) \>3x the upper limit of normal (ULN), 2. Serum alkaline phosphatase or y-glutamyl transferase \> 2.5x the ULN, 3. Serum total bilirubin level \>1.5x the ULN 4. Estimated creatinine clearance (eCrCl; using the Cockroft and Gault formula \[57\] lower than 30 ml/min 5. Serum albumin \< 2.8 mg/dl 6. Haemoglobin level \<7.0 g/dl 7. Platelet count \<50,000/mm3 8. Serum potassium below the lower level of normal for the laboratory 9. Blood glucose at screening of less than 70mg/dL (3.9mmol/L) 9. ECG findings in the screening ECG: (one or more): 1. QTcF of \>0.450 s 2. Atrioventricular (AV) block with PR interval \> 0.20 s, 3. QRS complex \> 120 milliseconds 4. Any other changes in the ECG that are clinically relevant as per discretion of the investigator 10. Restricted medication: 1. Treatment with any other investigational drug within 1 month prior to enrolment or enrolment into other clinical (intervention) trials during participation. 2. Previous anti-TB treatment with drugs active against MTB within the last 3 months prior to screening. 3. Unable or unwilling to abide by the requirements regarding restricted medication or have taken restricted medication as described under section 12.6, page 58. Restricted medication includes the following drug classes: * Anti-TB drugs other than study drugs * Medication that lowers the threshold for epileptic seizures * Medication that prolongs the QTc interval * Drugs that affect monoaminooxidase or serotonin metabolism * CYP 450 inhibitors or inducers, including grapefruit containing foods / beverages and St. John's Wort