Effect of PA-824 and of PA-824 Plus Moxifloxacin on the QTc Interval in Healthy Volunteers

This is a Phase I, single-center, double-blinded, randomized, placebo-controlled,
five-period cross-over clinical study of PA-824 to evaluate the effect of PA-824 and of
PA-824 plus moxifloxacin on cardiac repolarization (QT/QTc interval duration) in healthy
male and female participants. Moxifloxacin will be used as an active control. Participants
will be blinded to the treatments they will receive. The study consists of a screening
period up to 26 days; enrollment, 1 day; five in-patient treatment periods consisting of an
admission day (except in the first treatment period, when the pre-dose day is the baseline),
dosing day and two post-dosing days; an out-patient period of at least three days and not
more than 10 days between treatment periods; and a final visit 7 - 14 days after discharge
from the last treatment period. During the study, the subjects will receive each one of the
following five treatments: Treatment A: PA-824 placebo and moxifloxacin placebo; Treatment
B: PA-824 400 mg plus moxifloxacin placebo; Treatment C: PA-824 1000 mg plus moxifloxacin
placebo; Treatment D: PA-824 placebo plus moxifloxacin 400 mg; Treatment E: PA-824 400 mg
plus moxifloxacin 400 mg. The primary objective is to evaluate the effect of single-dose
administration of PA-824 400 mg and 1000 mg versus placebo on the QTcI interval. A total of
75 randomized (in order to have at least 60 evaluable) healthy male and female volunteers,
aged 18 to 45 years will be enrolled.

Inclusion Criteria:

- Subject must be 18 to 45 years of age (inclusive).

- Subject must be a healthy male or female volunteer as determined by medical history,
physical examination, 12-lead ECG and laboratory evaluations (hematology, clinical
chemistries and urinalysis tests) within study-defined ranges at Screening. (See
Appendix B for acceptable ranges of laboratory and vital signs assessments).

- Body Mass Index (BMI) must be between 18 and 30 kg/m^2 inclusive.

- Subject must be non-tobacco/nicotine using (3-month minimum).

- Subject must be Tuberculin Skin Test/Purified Protein Derivative (TST/PPD) negative
(within the previous 1 year) at Screening. The TST/PPD may be omitted if the subject
presents written evidence of having a negative test during the previous 12 months.

- Subject must be able to give voluntary written informed consent before any study
related procedure is performed.

- If female, has no childbearing potential (as defined below) or agrees to avoid
becoming pregnant from the day of screening through one week after the last dose by
using one of the following acceptable methods of birth control in addition to the use
of a barrier method (condom) by the male partner (even if vasectomized):

1. Hormonal contraceptives; or

2. intrauterine contraceptive device; or

3. diaphragm in combination with contraceptive jelly, cream, or foam; or

4. spermicide; or

5. abstinence. Non-childbearing potential is defined as being post-menopausal for
at least 2 years, status after bilateral tubal ligation for at least 1 year,
status after bilateral oophorectomy or status after hysterectomy.

If male, agrees to avoid fathering a child from the day of screening to three months after
the last dose.

- All female subjects must have a negative serum pregnancy test at Screening,
Enrollment (Day-2) and at check-in for each treatment period.

- Subject agrees not to donate blood during the study and up to 14 days after the end
of the last treatment period.

- Subject agrees to comply with all study requirements.

Exclusion Criteria:

- A history of clinically significant acute illness (resolved within 4 weeks of
screening) or history of cardiac arrhythmias or unexplained syncope or presence of
cardiac, vascular gastrointestinal, renal, hepatic, neurologic, hematologic,
endocrine, oncologic, pulmonary, immunologic, or psychiatric disease or any other
condition which, in the opinion of the Site Principal Investigator (PI), would
jeopardize the safety of the subject or impact the validity of the study results.

- Subject has had major surgery within 4 weeks of screening.

- has an uncontrolled intercurrent illness (i.e., active infection) or fever (oral
temperature >/=100 degrees Fahrenheit or >/= 37.7 degrees Celsius) at screening.

- History of lens opacity or evidence of lens opacity on screening ophthalmologic
examination or any other clinically significant ophthalmic dysfunction or disease.

- Subject has been on an abnormal diet during the 4 weeks preceding screening. Abnormal
diet is defined as a diet in which the subject has a significant change in eating
habits (e.g., liquid diet only) and an unbalanced diet (e.g., protein only, high fat,
low carbohydrate, etc.).

- Subject has engaged in strenuous physical activity or consumed alcohol, grapefruit,
and caffeine- or methylxanthine-containing beverages from 48 hours before reporting
to the clinic for enrollment until discharge from the clinical site in the last
treatment period.

- Previous participation in any other study of PA-824.

- History of seizures (other than febrile seizures during childhood) or known or
suspected Central Nervous System (CNS) disorders that may predispose to seizures.

- History of photosensitivity or phototoxicity reactions after use of quinolones or
other drugs.

- History of allergy or severe side-effects with nitroimidazoles (e.g., Flagyl and
related substances and azole antifungals or aromatase inhibitors).

- History of allergy to moxifloxacin or any fluoroquinolone antibiotic.

- History of tendinopathy associated with quinolones or other drugs, including
glucocorticoids, or a condition that predisposes to tendon rupture.

- Subject has received an investigational drug in a clinical trial within 30 days prior
to screening.

- Subject has used any over the counter (OTC) medication, including vitamins and herbal
supplements, antacids, cough and cold medications, within 7 days prior to Day 1 of
treatment with study drugs or during the study, unless in the opinion of the PI, the
substance would not likely impact on the conduct of this study.

- Subject has used any prescription medication, except hormonal contraceptives, within
30 days prior to Day 1 of treatment with study drugs or during the study, unless in
the opinion of the PI, the substance would not likely impact the conduct of this
study.

- Subject has any current medical condition requiring treatment with medication, either
prescription or OTC.

- Subject has been treated with any known CYP450 enzyme altering drugs, such as azoles,
antifungals, barbiturates, phenothiazines, cimetidine, carbamazepine, etc., except
hormonal contraceptives, within 30 days prior to Day 1 of treatment with study drugs.

- Subject has been treated with any drugs known to prolong the electrocardiographic QT
interval within 30 days prior to Day 1 of treatment with study drugs or has history
of excessive chronic caffeine (> 6-8 oz cups of brewed coffee daily), or theophylline
(> 600 mg/day), or ephedrine (>300 mg/day) use..

- Subject has a positive blood screen for HIV, hepatitis B surface antigen (HBsAg), or
hepatitis C antibody.

- Subject has a positive history for alcohol abuse or dependence and/or a positive
urine screen test for alcohol and drugs of abuse [amphetamines, barbiturates,
benzodiazepines, cocaine metabolites, marijuana, opiates, phencyclidine (PCP)] at
screening or at any check-in prior to receiving study drugs.

- Subject has a baseline QTcF interval >440 msec (males) or >450 msec (females) or a
history of prolonged QTc interval or a family history of Long QT Syndrome or
premature cardiac death or sudden death without a preceding diagnosis of a condition
that could be causative of sudden death (such as known coronary artery disease or CHF
or terminal cancer).

- Subject has any clinically significant ECG abnormality in the opinion of the site
principal investigator (PI) at Screening, Enrollment (Day-2), Baseline (Day-1), and
at any check-in day prior to receiving study drugs.

- Subject with ECGs deemed by the PI to have T -wave morphology unfavorable for
consistently accurate QT measurement and presence of artifacts that cannot be readily
eliminated.

- Subject has hypokalemia, hypomagnesemia, or hypocalcemia, or a history of eating
disorder.

- Subject has serum creatinine, blood urea nitrogen (BUN) or transaminase measurements
above the upper limit of the normal range at screening.

- Subject has lived with a person having active Tuberculosis (TB) or has traveled to an
area of endemic TB within the past 12 months prior to Screening.

- Women who are pregnant or breastfeeding.

- Subject has donated blood within the past 30 days prior to Day 1 of treatment with
study drugs.

- Subject is an employee of or family member of an employee of Quintiles, or DynPort
Vaccine Company LLC (DVC) or personnel participating in the conduct of the study.