PanACEA - STEP2C -01

Inclusion Criteria:

1. Provide written, informed consent prior to all trial-related procedures including HIVtesting.
2. Male or female, aged between 18 and 65 years, inclusive.
3. Body weight (in light clothing and with no shoes) between 40 and 90 kg, inclusive.
4. Newly diagnosed, previously untreated, drug susceptible pulmonary TB: presence of MTBcomplex and rapid molecular tests result confirming susceptibility to RIF and INH suchas GeneXpert and/or HAIN MTBDR plus.
5. A chest X-ray (no older than 2 weeks) which, in the opinion of the Investigator, isconsistent with TB.
6. Sputum positive on microscopy from concentrated sputum for acid-fast bacilli on atleast one sputum sample (at least 1+ on the IUATLD/WHO scale).
7. The participant understands the interaction between the study drugs and certain foodsand is willing to forgo the consumption of foods high in tyramine for the period ofstudy medication, which will be necessary if randomized to arm 4.
8. The participant is not of child-bearing potential or is willing to use effectivemethods of contraception when engaging in heterosexual intercourse, as defined below:
9. Non-childbearing potential: i. Female participant/sexual partner of maleparticipant: Bilateral oophorectomy, and/or hysterectomy or bilateral tuballigation more than 12 months ago and/or has been postmenopausal with a history ofno menses for at least 12 consecutive months ii. Male participant/sexual partnerof female participant: Vasectomised or has had a bilateral orchidectomy minimallythree months prior to screening seen prior to 76 weeks after randomization iii.Male participants having a pregnant female partner or a male sexual partner: Atleast one barrier method has to be used in this case.
10. Effective contraception methods: i. Female participants: Two methods, includingmethods that the participant's sexual partner(s) use. At least one must be abarrier method. Contraception must be practised for at least until 12 weeks afterthe last dose of experimental treatment. ii. Male participants: Two methods,including methods that the participant's female sexual partner(s) use. At leastone must be a barrier method. Effective contraception must be ensured for atleast 16 weeks after the last dose of experimental treatment.

Exclusion Criteria:

1. Circumstances that raise doubt about free, unconstrained consent to studyparticipation (e.g., prisoner or mentally handicapped person)
2. Poor general condition where delay in treatment cannot be tolerated or death withinfour months is likely.
3. Poor social condition which would make it unlikely that the participant would be ableto complete follow-up:
4. The participant is pregnant or breast-feeding or planning to become pregnant in thestudy period.
5. The participant is infected with HIV with a CD4 count <220 cells/mm3. If >22 cells/mm3participants will be included only if any of the following is applicable:

• The participant is antiretroviral (ARV) naïve and able to postpone commencing HIVtreatment for 2 months after the trial has started and then restrict regimens tothose mentioned in section on ARVs Antiretroviral Therapy or
• The participant is ARV experienced (has been on ARV´s a minimum of 5 months),AND: ARV treatment is compliant to, or can be modified as described in the section onAntiretroviral Therapy

6. The participant has a known intolerance to any of the study drugs or concomitantdisorders or conditions for which study drugs or standard TB treatment arecontraindicated.
7. The participant has a history of, or current evidence of clinically relevantcardiovascular metabolic, gastrointestinal, neurological, psychiatric or endocrinediseases, malignancy, or any other condition that will influence treatment response,study adherence or survival in the judgement of the investigator, especially:
8. Neuropathy, or significant psychiatric disorder like depression or schizophrenia;especially if treatment for those has ever been required or is anticipated to berequired.
9. Evidence of clinically significant extra-pulmonary TB (e.g. miliary TB, TBmeningitis, but not limited lymph node involvement).
10. Serious lung conditions other than TB, or significant respiratory impairment inthe discretion of the investigator.
11. Uncontrolled diabetes mellitus.
12. Cardiovascular disease such as myocardial infarction, heart failure, coronaryheart disease, arrhythmia, tachyarrhythmia, or pulmonary hypertension
13. Uncontrolled arterial hypertension (systolic blood pressure ≥150 mmHg and/ordiastolic blood pressure of ≥95 mmHg on two occasions during screening).
14. Long QT syndrome or family history of long QT syndrome or family history ofsudden death of unknown or cardiac-related cause
15. Alcohol, regular opiate, or other drug abuse that is sufficient to significantlycompromise the safety or cooperation of the participant, that includes substancesprohibited by the protocol or has led to significant organ damage at thediscretion of the investigator.
16. Any of the following laboratory findings at screening:
17. Serum amino aspartate transferase (AST) and/or alanine aminotransferase (ALT) >3xthe upper limit of normal (ULN),
18. Serum alkaline phosphatase or y-glutamyl transferase > 2.5x the ULN,
19. Serum total bilirubin level >1.5x the ULN
20. Estimated creatinine clearance (eCrCl; using the Cockroft and Gault formula [57]lower than 30 ml/min)
21. Serum albumin < 2.8 mg/dl
22. Haemoglobin level <7.0 g/dl
23. Platelet count <50,000/mm3
24. Serum potassium below the lower level of normal for the laboratory
25. ECG findings in the screening ECG: (one or more):
26. QTcF of >0.450 s
27. Atrioventricular (AV) block with PR interval > 0.20 s,
28. QRS complex > 120 milliseconds
29. Any other changes in the ECG that are clinically relevant as per discretion ofthe investigator
30. Restricted medication:
31. Treatment with any other investigational drug within 1 month prior to enrolmentor enrolment into other clinical (intervention) trials during participation.
32. Previous anti-TB treatment with drugs active against MTB within the last 3 monthsprior to screening.
33. Unable or unwilling to abide by the requirements regarding restricted medicationor have taken restricted medication. Restricted medication includes the followingdrug classes, with relevant timing of intake. Exceptions may be permissible afterdiscussion with the sponsor medical expert. Anti-TB drugs other than study drugsMedication that increases the risk for serious cardiac arrhythmia (see 8.5.4).Drugs that affect monoamine oxidase or serotonin metabolism CYP 450 inhibitors orinducers.