Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Multi Center, Randomized, Double-blind, Placebo-controlled Phase 2 Trial to Evaluate the Safety, Efficacy and Pharmacokinetics of Multiple Doses of OPC 67683 in Patients With Pulmonary Sputum Culture-Positive, Multidrug-resistant Tuberculosis
Brief Summary: This is a clinical trial to evaluate the safety and efficacy of OPC-67683 in the treatment of multidrug resistant tuberculosis (MDR TB) for 56 days. In addition to an optimized background regimen (OBR), participants will be randomized to receive:

* 100 mg OPC-67683 twice daily (BID)
* 200 mg OPC-67683 BID
* Placebo BID

After 56 days participants will complete their optimized background regimen (OBR).


Options:
A: Inclusion Criteria:

* Signed written consent or witnessed oral consent in the case of illiteracy, before undertaking any trial related activity.
* Two sputum specimens positive for tubercle bacilli on smear microscopy at least one of which must be processed and positive at the study laboratory.
* Aged 18 years or over.
* No previous anti-tuberculosis chemotherapy.
* A firm home address that is readily accessible for visiting and willingness to inform the study team of any change of address during the treatment and follow-up period.
* Agreement to participate in the study and to give a sample of blood for HIV testing (see appendices 1 \& 2).
* Pre-menopausal women must be using a barrier form of contraception or be surgically sterilised or have an IUCD in place.
* Laboratory parameters performed up to 14 days before enrolment.

  * Serum aspartate transaminase (AST) and alanine transaminase (ALT) activity less than 3 times the upper limit of normal.
  * Serum total bilirubin level less than 2.5 times upper limit of normal. Creatinine clearance (CrCl) level greater than 30 mls/min.
  * Haemoglobin level of at least 7.0 g/dL.
  * Platelet count of at least 50x109cells/L.
  * Serum potassium greater than 3.5 mmol/L.
* Negative pregnancy test (women of childbearing potential).

Exclusion Criteria:

* Unable to take oral medication.
* Previously enrolled in this study.
* Received any investigational drug in the past 3 months.
* Received an antibiotic active against M. tuberculosis in the last 14 days (fluoroquinolones, macrolides, standard anti-tuberculosis drugs).
* Any condition that may prove fatal during the first two months of the study period.
* TB meningitis or other forms of severe tuberculosis with high risk of a poor outcome
* Pre-existing non-tuberculosis disease e.g. diabetes, liver or kidney disease, blood disorders,peripheral neuritis, chronic diarrhoeal disease in which the current clinical condition of the patient is likely to prejudice the response to, or assessment of treatment.
* Pregnant or breast feeding.
* Suffering from a condition likely to lead to uncooperative behaviour e.g. psychiatric illness or alcoholism.
* Contraindications to any medications in the study regimens.
* Known to have congenital or sporadic syndromes of QTc prolongation or receiving concomitant medication reported to increase the QTc interval (e.g. amiodarone, sotalol, disopyramide, quinidine, procainamide, terfenadine).
* Known allergy to any fluoroquinolone antibiotic or history of tendinopathy associated with quinolones.
* Patients already receiving anti-retroviral therapy.
* Patients whose initial isolate is shown to be multiple drug resistant (i.e. resistant to rifampicin and isoniazid) or monoresistant to rifampicin, or resistant to any fluoroquinolone)
* Weight less than 35kg
* HIV infection with CD4 count less than 250 cells/µL.
* End stage liver failure (class Child-Pugh C).
B: Inclusion Criteria:

* Provide written, informed consent prior to all trial-related procedures
* Male and female participants aged between 18 and 64 years, inclusive.
* Either mycobacterial culture of sputum positive for growth of Mycobacterium tuberculosis or sputum smear positive for acid fast bacilli within 60 days prior to the expected date of enrollment.
* Participant with TB caused by isolates of Mycobacterium tuberculosis complex confirmed to be resistant to treatment with isoniazid and rifampicin, or with positive rapid test for rifampicin resistance on direct sputum positive for acid fast bacilli within 60 days prior to the expected date of enrollment.
* Findings on chest radiograph consistent with TB.
* Able to produce sputum for mycobacterial culture.
* Female participants of childbearing potential must have a negative urine pregnancy test and agree to use a highly effective method of birth control (for example, two of the following precautions: tubal ligation, vaginal diaphragm, intrauterine device, oral contraceptives, contraceptive implant, combined hormonal patch, combined injectable contraceptive or depot-medroxyprogesterone acetate) throughout the participation in the trial and for 22 weeks after last dose (to cover duration of ovulation).
* Male participants must agree to use an adequate method of contraception (double barrier) throughout the participation in the trial and for 30 weeks after last dose (to cover duration of spermatogenesis).

Exclusion Criteria:

* A history of allergy to any nitro-imidazoles or nitro-imidazole derivates at any time.
* Use of the medications including: use of amiodarone at any time during the previous 12 months, use of other anti-arrhythmics for the previous 30 days, and use of certain other medications, including certain anti-depressants, anti-histamines, and macrolides, for the previous 14 days.
* Any current serious concomitant conditions or renal impairment characterized by serum creatinine levels ≥265 micromol/L or hepatic impairment characterized by alanine transaminase (ALT) and/or aspartate transferase (AST) levels 3 times the upper limit of the laboratory reference range.
* Current clinically relevant changes in the electrocardiogram (ECG) such as any atrioventricular (AV) block, prolongation of the QRS complex over 120 milliseconds (in both male and female participants), or of either the QT interval corrected by Fridericia's formula (QTcF) or QT interval corrected by Bazett's formula (QTcB) interval over 430 milliseconds in male participants and 450 milliseconds in female participants.
* Current clinically relevant cardiovascular disorder such as heart failure, coronary heart disease, hypertension, arrhythmia, tachyarrhythmia or status after myocardial infarction.
* For participants with human immunodeficiency virus (HIV) infection, cluster of differentiation 4 helper/inducer T cell\[s\] (CD4) cell count \< 350/mm3 or on treatment with anti-retroviral medication for HIV infection.
* Karnofsky score \< 60%.
* Any diseases or conditions in which the use of nitro-imidazoles or nitro-imidazole derivates is contra-indicated.
* Evidence of clinically significant metabolic, gastrointestinal, neurological, psychiatric or endocrine diseases, malignancy, or other abnormalities (other than the indication being studied).
* Known or suspected alcohol abuse, that is, abuse sufficient enough to compromise the safety or cooperation of the participant in the opinion of the investigator.
* Administered an investigational medicinal product (IMP) within 1 month prior to Visit 1 (Screening \[Days -9 to -3\]).
* Pregnant, breast-feeding, or planning to conceive or father a child within the timeframe described in the informed consent form.
* Recent use of methadone, benzodiazepines, cocaine, amphetamine/metamphetamine, tetrahydrocannabinol, barbiturates, tricyclic antidepressants, and opiates as determined by a urine drug screen unless evidence is provided that the positive drug screen is the result of authorized medications products prescribed by a physician for a non-abuse-related indication.
* Any disorder that in the judgment of the investigator makes the participant not a good candidate for the trial or may prevent the participant from reliably participating in the entire course of the trial.
C: Inclusion Criteria:

1. Is willing and able to give informed consent to participate in the trial treatment and follow-up (signed or witnessed consent if the patient is illiterate).
2. Is aged 18-65 years.
3. Has twice positive acid-fast bacilli(AFB) sputum smear or positive sputum culture result, along with chest x-ray imaging consistent with active pulmonary tuberculosis.
4. Newly diagnosed cases receiving anti-TB treatment for less than one month
5. Urine Human Chorionic Gonadotropin(U-HCG) negative and must agree to use effective contraception during the trial period.
6. Has Alanine aminotransferase（ALT）and Total bilirubin（TBil） less than 2 times the upper limit of normal ; has Creatinine clearance rate （CrCI） more than 30ml/min; has Hemoglobin more than 7.0g/dL; has Platelet（PLT）more than 50 x10\^9/L before study entry.

Exclusion Criteria:

1. Concomitant severe cardiovascular, liver, kidney, nervous system, hematopoietic system and other diseases, or concomitant neoplastic diseases. Or extensive lesion with respiratory insufficiency.
2. Uncontrolled diabetes mellitus.
3. Concomitant mental disorders.
4. Is HIV positive.
5. Is critically ill, and in the judgment of the investigator, not fit for the study or unlikely to complete the full course of study.
6. Is known to be pregnant or breast-feeding.
7. Is unable or unwilling to comply with the treatment, assessment, or follow-up schedule.
8. Is taking any medications contraindicated with the medicines in any trial regimen of the study.
9. Has a known allergy to any drug of treatment regimens.
10. Is currently taking part in another trial.
11. Has a QTc interval more than 480ms.
D: Inclusion Criteria:

* Healthy adult volunteers willing and able to be confined to the Clinical Research Unit and comply with study schedule.
* Women of non-childbearing potential only.

Exclusion Criteria:

* History of hypersensitivity to, or intolerance of, linezolid.
* Antibiotic treatment within 14 days prior to dosing, or any previous antibiotic use at the discretion of the investigator.
* Previous history of irritable bowel syndrome (IBS) or inflammatory bowel disease (IBD).

Answer: B