Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomised Open-Label Controlled Trial of a 4-Month Gatifloxacin-Containing Regimen Versus Standard Regimen for the Treatment of Adult Patients With Pulmonary Tuberculosis
Brief Summary: Tuberculosis is currently treated with a 6-month course regimen. During this time many patients might fail to adhere to treatment and default, increasing the risk of recurrent disease which might be multidrug resistant. A shorter duration of treatment is expected to provide improved patient compliance and at least equal or better clinical outcome. The aim of the trial is to evaluate the efficacy and safety of a gatifloxacin-containing regimen of four months duration for the treatment of pulmonary tuberculosis,


Options:
A: Inclusion Criteria:

* Females of non-childbearing potential
* Patients with newly diagnosed sputum smear-positive pulmonary MDR-TB infection
* Patients must consent to HIV-testing
* Patients must be willing to discontinue all TB drugs to allow 7 days washout
* Patients having normal weight
* Patients are willing to be hospitalized per standard of care.

Exclusion Criteria:

* Previously having been treated for MDR-TB
* Having a significant cardiac arrhythmia that requires medication
* For HIV infected patients, having a CD4+ count \< 300 cells/µL
* Patients with complicated or severe extrapulmonary manifestations of TB or neurological manifestations of TB
* Patients who will require surgical procedure for management of their TB
* Evidence of chorioretinitis, optic neuritis, or uveitis at screening
* Having had a drug susceptibility test performed prior to screening and being not susceptible to at least 3 of the 5 classes of TB drugs used to treat MDR-TB
* Women who are pregnant and/or breastfeeding.
B: 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.
C: Inclusion Criteria:

* Presumptive diagnosis of smear-positive pulmonary TB within 2 weeks of study entry. Patients with both pulmonary and extrapulmonary disease are eligible.
* Documentation of HIV infection status. If HIV status is unknown at study entry, the participant must consent to testing and results must be available prior to study participation.
* Agree to use acceptable methods of contraception

Exclusion Criteria:

* History of adverse drug reaction to MOX, INH, RIF, PZA, or EMB
* Disease or condition for which MOX, INH, RIF, PZA, or EMB is contraindicated
* History of more than 14 days of continuous antituberculosis therapy during the previous 2 years or more than 2 months of antituberculosis therapy ever
* Active AIDS-related opportunistic infection or malignancy
* Currently receiving or planning to receive HIV protease inhibitors or nonnucleoside reverse transcriptase inhibitors in the first 2 months after study entry
* Silicotuberculosis
* Central nervous system TB
* Pregnant or breastfeeding
* Unable to take oral medication
* Electrocardiogram (EKG) QTc interval greater than 450 msec
* Taking classes IA or III antiarrhythmic agents (quinidine, procainamide, amiodarone, sotalol), cisapride, erythromycin, perphenazine/amitriptyline, phenothiazines, or tricyclic antidepressant
* Diseases or conditions for which treatment with other drugs with antituberculosis activity (e.g., rifabutin for MAC prophylaxis) is anticipated during the course of the study
D: 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 (in light clothing and with no shoes) between 40 and 90 kg, inclusive.
4. Newly diagnosed, previously untreated, sputum smear-positive pulmonary TB.
5. A chest X-ray picture which in the opinion of the Investigator is compatible with TB.
6. Sputum positive on direct microscopy for acid-fast bacilli (at least 1+ on the IUATLD/WHO scale).
7. Ability to produce an adequate volume of sputum as estimated from a spot assessment (estimated 10 ml or more overnight production).
8. Females may participate if they are: 1) of non-childbearing potential (have had a bilateral oophorectomy and/or hysterectomy or have been postmenopausal for at least 12 consecutive months), 2) if they are using effective birth control methods and are willing to continue practicing birth control methods throughout treatment or 3) be non-heterosexually active, practice sexual abstinence or have a vasectomized partner (confirmed sterile). Therefore to be eligible for this study women of childbearing potential should either: 1) use a double barrier method to prevent pregnancy (i.e. use a condom with either diaphragm or cervical cap) or 2) use hormonal based contraceptives in combination with a barrier contraceptive, or 3) use an intrauterine device in combination with a barrier contraceptive. They must also be willing to continue these contraceptive measures until 6 months after the last dose of study medication or 6 months after discontinuation from study medication in case of premature discontinuation. (Note: Hormone-based contraception alone may not be reliable when taking IMP; therefore, hormone-based contraceptives alone cannot be used by female participants to prevent pregnancy).
9. Male participants who are having heterosexual intercourse with females of child-bearing potential are required to use one of the following birth control methods during their participation in the trial and for 12 weeks after their last dose of study medication to prevent pregnancy:

   * a double barrier method which can include a male condom, diaphragm, cervical cap, or female condom; or
   * a barrier method combined with hormone-based contraceptives or an intra-uterine device for the female partner.

The use of the above mentioned birth control method does not apply if the male participant has been vasectomised or has had a bilateral orchidectomy minimally one month prior to screening, or is not heterosexually active, or practice sexual abstinence or if the female sexual partner has had a bilateral oophorectomy and/or hysterectomy or has been postmenopausal for at least 12 consecutive months.

Exclusion Criteria

Medical History

1. Evidence of clinically significant (as judged by the investigator), metabolic, gastrointestinal, cardiovascular, musculoskeletal, ophthalmological, pulmonary, neurological, psychiatric or endocrine diseases, malignancy, or other abnormalities (other than the indication being studied).
2. Poor general condition where any delay in treatment cannot be tolerated per discretion of the Investigator.
3. A history of previous TB.
4. Clinically significant evidence of extrathoracic TB (miliary TB, abdominal TB, urogenital TB, osteoarthritic TB, TB meningitis), as judged by the Investigator.
5. History of allergy to the IMP or related substances, including a known allergy to any fluoroquinolone antibiotic, history of tendinopathy associated with quinolones or suspected hypersensitivity to any rifamycin antibiotics.
6. Isoniazid-resistant and Rifampicin-resistant bacteria detected with a sputum specimen collected within the pre-treatment period and tested at the study laboratory.
7. Known or suspected, current or history of within the past 2 years, alcohol or drug abuse, that is, in the opinion of the Investigator, sufficient to compromise the safety or cooperation of the participant.
8. HIV infected participants:

   1. having a CD4+ count \<300 cells/µL;
   2. or having received antiretroviral therapy medication within the last 90 days;
   3. or having received oral or intravenous antifungal medication within the last 90 days;
   4. or with an AIDS-defining opportunistic infection or malignancies (except pulmonary TB).
9. Having participated in other clinical studies with investigational agents within 8 weeks prior to trial start.
10. Significant cardiac arrhythmia requiring medication.
11. Participants with the following at screening:

    1. Marked prolongation of QT/QTc interval, e.g., confirmed demonstration of QTcF (Fridericia correction) or QTcB (Bazett correction) interval \>450 ms at screening;
    2. History of additional risk factors for Torsade de Pointes, e.g., heart failure, hypokalemia, family history of Long QT Syndrome;
    3. Use of concomitant medications that prolong the QT/QTc interval (see exclusion criterion 22 as well as list of disallowed medication in Section 4.7.2);
    4. Pathological Q waves (defined as \>40ms or depth \>0.4-0.5mV);
    5. ECG evidence of ventricular pre-excitation;
    6. ECG evidence of complete or incomplete left bundle branch block or right bundle branch block;
    7. ECG evidence of second or third degree heart block;
    8. Intraventricular conduction delay with QRS duration \>120ms;
    9. Bradycardia as defined by sinus rate \<50bpm.
12. Females who are pregnant, breast-feeding, or planning to conceive a child within 6 months of cessation of treatment.
13. Males planning to conceive a child within twelve weeks of cessation of treatment.
14. History and/or presence (or evidence) of neuropathy or epilepsy.
15. Diabetes Mellitus requiring insulin.
16. History of lens opacity or evidence of lens opacity on slit lamp ophthalmologic examination.
17. For males, any evidence or history of a clinically significant abnormality in the reproductive system, including but not limited to the following: serum testosterone, luteinizing hormone (LH), and/or follicle-stimulating hormone (FSH) levels outside the laboratory reference range. An evaluation resulting in an isolated abnormal value (i.e., only 1 of the 3 hormones is abnormal) may be repeated using a morning (ideally, 8am) serum specimen. If the laboratory value on the repeat specimen is outside the laboratory reference range, unless the result is deemed not clinically significant by the Investigator in consultation with the Sponsor Medical Monitor, the participant should be excluded.

    Specific Treatments
18. Previously received treatment with TMC207 or PA-824 as part of a clinical trial.
19. Treatment received with any drug active against MTB within the 3 months prior to Visit 1 (e.g. isoniazid, ethambutol, amikacin, cycloserine, rifabutin, rifampicin, streptomycin, kanamycin, para-aminosalicylic acid, rifapentine, pyrazinamide, thioacetazone, capreomycin, fluoroquinolones, thioamides, metronidazole).
20. Any diseases or conditions in which the use of the standard TB drugs or any of their components is contra-indicated, including but not limited to allergy to any TB drug, their component or to the IMP.
21. Any disease or conditions in which any of the medicinal products listed in the section pertaining to prohibited medications is used.
22. Concomitant use of any drug known to prolong QTc interval (including amiodarone, bepridil, chloroquine, chlorpromazine, cisapride, clarithromycin, disopyramide dofetilide, domperidone, droperidol, erythromycin, halofantrine, haloperidol, ibutilide, levomethadyl, mesoridazine, methadone, pentamidine, pimozide, procainamide, quinidine, sotalol, sparfloxacin, thioridazine). The exception is moxifloxacin which is one of the drugs being evaluated in this study, with extensive ECG monitoring to help ensure patient safety.
23. Use of any drugs or substances within 30 days prior to dosing known to be strong inhibitors or inducers of cytochrome P450 enzymes (such as quinidine, tyramine, ketoconazole, testosterone, quinine, gestodene, metyrapone, phenelzine, doxorubicin, troleandomycin, cyclobenzaprine, erythromycin, cocaine, furafylline, cimetidine, dextromethorphan). Exceptions may be made for participants that have received 3 days or less of one of these drugs or substances, if there has been a wash-out period before administration of IMP equivalent to at least 5 half-lives of that drug or substance.
24. Use of any therapeutic agents known to alter any major organ function (e.g., barbiturates, opiates, phenothiazines, cimetidine) within 30 days prior to dosing.
25. Use of systemic glucocorticoids within one year prior to dosing.

    Based on Laboratory Abnormalities
26. Participants with the following toxicities at screening as defined by the enhanced Division of Microbiology and Infectious Disease (DMID) adult toxicity table (November 2007):

    1. creatinine grade 2 or greater (\>1.5 times upper limit of normal \[ULN\]);
    2. lipase grade 3 or greater (\>2.0 x ULN);
    3. hemoglobin grade 4 (\<6.5 g/dL);
    4. platelets grade 2 or greater (under 50x109 cells/L);
    5. serum potassium grade 2 or greater (\<3.5 mEq/L);
    6. aspartate aminotransferase (AST) grade 3 (≥3.0 x ULN) to be excluded;
    7. alanine aminotransferase (ALT) grade 3 (≥3.0 x ULN) to be excluded;
    8. alkaline phosphatase (ALP) grade 4 (\>8.0 x ULN) to be excluded, grade 3 (≥3.0 x ULN) must be discussed with the sponsor Medical Monitor;
    9. total bilirubin grade 3 or greater (\>2.0 x ULN, or \>1.50 x ULN when accompanied by any increase in other liver function test) to be excluded, grade 2 (\>1.50 x ULN, or \>1.25 x ULN when accompanied by any increase in other liver function test) must be discussed with the sponsor Medical Monitor.

Answer: B