Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 1, Double-Blind, Randomized, Placebo-Controlled Study To Evaluate The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of PNU-100480 (PF-02341272) After Administration Of Multiple Escalating Oral Doses To Healthy Adult Subjects
Brief Summary: The purpose of this study is to assess the safety, tolerability and pharmacokinetics of multiple doses of PNU-100480 given for 14 or 28 days. Killing activity against the bacterium that causes tuberculosis (TB) will also be measured. The effect of adding an additional tuberculosis (TB) agent (given for 2 days) in addition to PNU-100480 will be evaluated. Linezolid open label to determine activity in whole blood assay (WBA).


Options:
A: Inclusion Criteria:

* Presumptive diagnosis of sputum smear-positive pulmonary TB.
* Age: ≥18 years
* Seven (7) or fewer days of multidrug therapy for TB disease in the preceding 6 months.
* Seven (7) or fewer days of fluoroquinolone therapy in the preceding 3 months.
* Documentation of HIV infection status.
* For HIV seropositive individuals, a CD4 T lymphocyte count of greater than or equal to 200 cells/mm3.
* Documentation of study baseline laboratory parameters done at, or ≤ 14 days prior to screening:

  * AST less than or equal to 2.5 times upper limit of normal.
  * Total bilirubin level less than 2.5 times upper limit of normal.
  * Creatinine level less than 2 times upper limit of normal.
  * Hemoglobin level of at least 8.0 g/dl.
  * Platelet count of at least 75,000 mm3.
  * Potassium level of at least 3.5.
  * Negative pregnancy test (women of childbearing potential).
* Karnofsky score of at least 60 (requires occasional assistance but is able to care for most of his/her needs).
* Male or nonpregnant, nonnursing female.
* Provision of informed consent.

Exclusion Criteria:

* CD4 count \< 200 cells/cu mm.
* Presence of active AIDS-related opportunistic infection (other than TB) or active AIDS-related malignancy.
* Known intolerance to any of the study drugs.
* Concomitant disorders or conditions for which any of the study drugs is contraindicated. These include severe hepatic damage, acute liver disease of any cause, and acute uncontrolled gouty arthritis.
* Inability to take oral medication.
* Central nervous system TB.
* Pulmonary silicosis.
* Current or planned therapy, during study phase (intensive phase of TB treatment), with any one or more of the following drugs: quinidine, procainamide, amiodarone, sotalol, disopyramide, terfenadine, cisapride, erythromycin, clarithromycin, phenothiazines, haloperidol, olanzapine, ziprasidone, tricyclic antidepressants, chronic corticosteroids administered either orally or intravenously, chronic fluconazole,chronic itraconazole, chronic ketoconazole, oral or intravenous tacrolimus, oral or intravenous cyclosporine, HIV protease inhibitor, HIV non-nucleoside reverse transcriptase inhibitor.
* Concurrent severe and/or uncontrolled medical or psychiatric condition that, in the opinion of the investigator, could cause unacceptable safety risks or compromise compliance with the protocol.
* Unable or unwilling to receive directly observed therapy and/or adhere with follow-up (e.g. due to residence remote from the study site).
* Refusal of consent.
B: 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).
C: Inclusion Criteria

1. The patient has given free, signed written or witnessed oral informed consent for study participation prior to all trial-related procedures, including HIV testing if HIV serostatus is not known or the last documented negative is more than four weeks ago.
2. The patient has a diagnosis of pulmonary tuberculosis from a health clinic established by sputum smear and/or GeneXpert MTB/RIF® and/or chest X-ray.
3. An adequate sputum bacterial load is confirmed by a Ziehl-Neelsen stained smear in the study laboratory, done from concentrated sputum found at least 1+ on the IUATLD/WHO scale.
4. The patient has a valid rapid test result (GeneXpert MTB/RIF®) from the sputum positive for MTB complex, and indicating susceptibility to Rifampicin. This test must be done in the study laboratory.
5. The patient is aged at least 18 years at the day of informed consent.
6. The patient has a body weight in light clothing and without shoes of at least 35 kg, but not more than 90 kg.
7. Female patients of childbearing potential must have a negative serum pregnancy test, and consent to practise an effective method of birth control until week 26. Effective birth control for female patients has to include two methods, including methods that the patient's sexual partner(s) use. At least one must be a barrier method. Female patients are considered not to be of childbearing potential if they are post-menopausal with no menses for the last 12 months, or surgically sterile (this condition is fulfilled by bilateral oophorectomy, hysterectomy, and by tubal ligation which is done at least 12 months prior to enrolment).
8. Male patients must consent to use an effective contraceptive method, if their sexual partner(s) is/are of childbearing potential, and if they are not surgically sterile (see 6.). Contraception by male participants must be practised until at least week 24 to cover the period of spermatogenesis. Contraceptive methods used by male participants may include hormonal methods used by the partner(s).
9. The patient has a firm home address that is readily accessible for visiting and willingness to inform the study team of any change of address during trial participation, or will be compliant to study schedule, in the discretion of the investigator.

Exclusion Criteria

1. Circumstances that raise doubt about free, uncoerced consent to study participation (e.g. in a prisoner or mentally handicapped person)
2. Poor General Condition where delay in treatment cannot be tolerated or death within three months is likely.
3. The patient is pregnant or breast-feeding.
4. The patient has an HIV infection and is receiving antiretroviral treatment (ART), and/or is likely to require ART during the twelve weeks of experimental study treatment as per local guidelines.
5. The patient has a known intolerance to any of the study drugs, or concomitant disorders or conditions for which SQ109, rifampicin, moxifloxacin, or standard TB treatment are contraindicated.
6. The patient has an history or evidence of clinically relevant 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:

   clinically significant evidence of severe TB (e.g. miliary TB, TB meningitis. Limited lymph node involvement will not lead to exclusion); serious lung conditions other than TB or severe respiratory impairment in the discretion of the investigator; neuropathy, epilepsy or significant psychiatric disorder; uncontrolled and/or insulin-dependent diabetes; cardiovascular disease such as myocardial infarction, heart failure, coronary heart disease, uncontrolled hypertension (systolic blood pressure ≥160 mmHg and/or diastolic blood pressure of ≥100 mmHg on two occasions), arrhythmia, or tachyarrhythmia; long QT syndrome (see criterion 9.), or family history of long QT syndrome or sudden death of unknown or cardiac-related cause; Plasmodium spp. parasitemia as indicated by thick blood smear or a positive rapid test present at screening; Alcohol or other drug abuse that is sufficient to significantly compromise the safety or cooperation of the patient, includes substances prohibited by the protocol, or has led to significant organ damage at the discretion of the investigator.
7. History of previous TB within the last five years.
8. Laboratory: at screening one or more of the following abnormalities were observed for the patient in screening laboratory: Serum amino aspartate transferase (AST) and/or serum alanine aminotransferase (ALT) activity \>3x the upper limit of normal; Serum total bilirubin level \>2.5 times the upper limit of normal; Creatinine clearance (CrCl) level lower than 30 mls/min; Complete blood count with hemoglobin level \<7.0 g/dL; Platelet count \<50,000/mm3; Serum potassium below the lower level of normal;
9. ECG findings in the screening ECG: QTcB and/or QTcF of \>0.450 s; atrioventricular (AV) block with PR interval \> 0.20 s; prolongation of the QRS complex over 120 milliseconds; other changes in the ECG that are clinically relevant as per discretion of the investigator.
10. The patient has had treatment with any other investigational drug within 1 month prior to enrolment, or enrolment into other clinical (intervention) trials is planned during week 1-26
11. Previous anti-TB treatment: the patient has had previous treatment with drugs active against M. tuberculosis within the last 3 months, including but not limited to INH, EMB, RIF, PZA, amikacin, cycloserine, rifabutin, streptomycin, kanamycin, para-aminosalicylic acid, rifapentine, thioacetazone, capreomycin, fluoroquinolones, thioamides.
12. QT prolonging medications: Administration within 30 days prior to study start, anticipated administration during the study period, or during the 12 weeks of experimental treatment, of any QT-prolonging agents such as, but not limited to, azithromycin, bepridil chloroquine, chlorpromazine, cisapride, cisapride, clarithromycin, disopyramide dofetilide, domperidone, droperidol, erythromycin, halofantrine, haloperidol, ibutilide, levomethadyl, lumefantrine, mefloquine, mesoridazine, methadone, moxifloxacin, pentamidine, pimozide, procainamide, quinidine, quinine, roxithromycin, sotalol, sparfloxacin, terfenadine, thioridazine. Exceptions may be made for participants who have received 3 days or less of one of these drugs or substances, if there has been a wash-out period equivalent to at least 5 half-lives of that drug or substance.

    Patients who have ever received amiodarone will be excluded from study participation.
13. CYP 450 inducers/inhibitors: administration within 30 days prior to dosing, or planned administration until the end of week 12, of any drug(s) or substance(s) known to be strong inhibitors or inducers of cytochrome P450 enzymes, or specific inhibitors/inducers of SQ109-metabolizing enzymes as Exceptions may be made for subjects that have received 3 days or less of one of these drugs or substances, if a wash-out period equivalent to at least 5 half-lives of that drug or substance prior to study treatment is granted.
D: Inclusion Criteria:

* Male or female patients
* Aged 18 to 65 years
* Currently suffering from recently diagnosed microscopically proven pulmonary tuberculosis and providing informed consent for inclusion in the study.

Exclusion Criteria:

* Patients with history of tuberculosis treatment within the last 3 years
* History of diabetes mellitus or non insulin dependent diabetes mellitus requiring treatment
* Concomitant infection requiring additional anti-infective treatment (especially anti-retroviral therapy)
* HIV infected patients with WHO stage 3 infection - except those presenting with only the "loss of weight\>10% body weight" criterion - and all HIV infected patients at WHO stage 4.

Answer: B