Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase II, Placebo-controlled, Double-blind, Randomized Trial to Evaluate the Anti-bacterial Activity, Safety, and Tolerability of TMC207 in Subjects With Newly Diagnosed Sputum Smear-positive Pulmonary Infection With Multi-drug Resistant Mycobacterium Tuberculosis (MDR-TB).
Brief Summary: The objective of this study is to demonstrate that the antibacterial activity of TMC207 is better than placebo when added to a standardized Background Regimen (BR) for treatment of multi-drug resistant TB. Also safety and tolerability will be evaluated.


Options:
A: Inclusion Criteria:

* Suspected pulmonary tuberculosis with acid-fast bacilli in a stained smear of expectorated or induced sputum. Patients whose sputum cultures do not grow M. tuberculosis and those having an M. tuberculosis isolate resistant to (one or more) isoniazid, rifampin, fluoroquinolones, will be discontinued from the study, but followed for 14 days to detect late toxicities from study therapy. Patients having extra-pulmonary manifestations of tuberculosis, in addition to smear-positive pulmonary disease, are eligible for enrollment. Sputum must be expectorated or induced; smear results from respiratory secretions obtained by bronchoalveolar lavage or bronchial wash may not be used for assessment of study eligibility.
* Willingness to have HIV testing performed, if HIV serostatus is not known or if the last documented negative HIV test was more than 6 months prior to enrollment. HIV testing does not need to be repeated if there is written documentation of a positive test (positive ELISA and Western Blot or a plasma HIV-RNA level greater than 5000 copies/ml) at any time in the past.
* 7 (seven) or fewer days of multidrug therapy for tuberculosis disease in the 6 months preceding enrollment.
* 7 (seven) or fewer days of fluoroquinolone therapy in the 3 months preceding enrollment.
* Age \> 18 years
* Karnofsky score of at least 60 (requires occasional assistance but is able to care for most of his/her needs; see Appendix B).
* Signed informed consent
* Women with child-bearing potential must agree to practice an adequate (barrier) method of birth control or to abstain from heterosexual intercourse during study therapy.
* Laboratory parameters done at, or \<14 days prior to, screening:
* Serum amino aspartate transferase (AST) activity ≤ 3 times the upper limit of normal
* Serum total bilirubin level ≤ 2.5 times the upper limit of normal
* Serum creatinine level ≤ 2 times the upper limit of normal
* Complete blood count with hemoglobin level of at least 7.0 g/dL
* Complete blood count with platelet count of at least 50,000/mm3
* Serum potassium \> 3.5 meq/L
* Negative pregnancy test (women of childbearing potential)

Exclusion Criteria:

* Breast-feeding
* Known intolerance to any of the study drugs
* Known allergy to any fluoroquinolone antibiotic
* Concomitant disorders or conditions for which moxifloxacin (MXF), isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), or ethambutol (EMB) are contraindicated. These include severe hepatic damage, acute liver disease of any cause, and acute uncontrolled gouty arthritis.
* Current or planned therapy during the intensive phase of therapy using drugs having unacceptable interactions with rifampin (rifabutin can be substituted for rifampin during the continuation phase of therapy).
* Current or planned antiretroviral therapy during the intensive phase of therapy.
* History of prolonged QT syndrome or current or planned therapy with quinidine, procainamide, amiodarone, sotalol, disopyramide, ziprasidone, or terfenadine during the intensive phase of therapy.
* Pulmonary silicosis
* Central nervous system TB
B: 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.
C: 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.
D: 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

Answer: B