Study Assessing Pharmacokinetics and Bioavailability of Three Novel Triazine Compounds

This is an open-label, randomized, fixed-sequence, microdose study of three Carbon-14 radio
labeled (14C) triazine compounds WR826647, WR909388, WR909390 designed in accordance with ICH
Guidance for Industry M3(R2) (ICH 2009). Subjects will be randomized to one of three groups
to receive 100 mcg WR826647, WR909388, or WR909390 at an exposure no greater than 250 nCi per
dose, administered both IV (bolus) and PO with a six half-life wash-out period between IV and
PO administration. Interim analyses will be done at Day 14 following the IV dosing groups in
order to assess half-lives of the three compounds to ensure the wash-out period between IV
and PO dosing is at least six half-lives long.

Pharmacokinetic parameters of the 3 compounds will be calculated from the plasma-time data
using Phoenix WinNonlin version 6.3 or higher, and descriptive statistics assessed using SAS
version 9.3 or higher. No statistical significance inferences will be made. An analysis of
variance (ANOVA) will be performed on the natural logarithm (ln) transformed dose-adjusted
AUCinf to estimate the bioavailability. The sample size of 6 subjects per group is considered
adequate to obtain useful data to compute descriptive statistics. Interim analyses will be
done after the IV dosing groups in order to assess half-lives of the 3 compounds to ensure
the wash-out period between IV bolus and oral dosing is at least 6 half-lives long.

Inclusion Criteria:

- Male or non-breastfeeding female of non-childbearing potential (defined as either
surgically sterilized by bilateral tubal ligation or hysterectomy with bilateral
ophorectomy at least 6 months before dosing, or is one year post-menopausal, confirmed
by screening follicle-stimulating hormone [FSH] serum levels consistent with
postmenopausal status >30mIU/mL)

- Between the ages of 19 and 50, inclusive, at the time of screening.

- Medically healthy with no clinically significant medical history, physical
examination, laboratory profiles, vital signs, or EKGs, as deemed by the PI or
designee.

- Body Mass Index (BMI) ≥ 18.5 and ≤ 32.0 kg/m2 at screening.

- Continuous non smoker who has not used nicotine containing products for at least 90
days prior to the first dose and throughout the study.

- A non vasectomized, male subject must agree to use a condom with spermicide or abstain
from sexual intercourse during the study until 90 days beyond the last dose of study
drug. (No restrictions are required for a vasectomized male provided his vasectomy has
been performed 4 months or more prior to first dose/dosing of study drug. A male who
has been vasectomized less than 4 months prior to study first dose/dosing must follow
the same restrictions as a non vasectomized male).

- Male volunteers must agree not to donate sperm from the first dose until 90 days after
last dose.

- Ability to comprehend and willingness to sign informed consent, which includes the
Authorization for the Release of Health Information document

- Willingness to comply with all study procedures including two 24-hour inpatient stays
at the study clinic and returning to the clinic for scheduled follow-up visits

Exclusion Criteria:

- History of any medical or psychiatric illness that, in the opinion of the PI or
designee, might confound the results of the study or poses an additional risk to the
subject by their participation in the study.

- History or presence of alcoholism or drug abuse within the past 2 years prior to the
first dose.

- History or presence of hypersensitivity or idiosyncratic reaction to the study drug or
related compounds (i.e., compound in the same family).

- Positive urine drug results for alcohol, amphetamines, methamphetamines, cocaine, or
opioids at screening or first check in.

- Positive results at screening for HIV, hepatitis B surface antigen (HBsAg) or
hepatitis C virus (HCV).

- Received any other investigational drug within 30 days prior to study entry. The 30
day window will be derived from the date of the last blood collection or dosing,
whichever is later, in the previous study to Day 1 of Period 1 of the current study.

- An employee of the study site involved with the study

- Inability to comply with the study procedures

- Unable to refrain from or anticipate the use of any drug, including prescription and
non prescription medications, herbal remedies, or vitamin supplements beginning 14
days prior to the first dose and throughout the study. Acetaminophen (up to 2 g per 24
hour period may be permitted during the study but only for dosing as needed to treat
adverse events (AEs).

- Unable to refrain from or anticipate the use of any drugs known to be significant
inducers of cytochrome P450 (CYP) enzymes and/or permeability glycoprotein (P gp),
including St. John's Wort, for 30 days prior to the first dose/dosing and throughout
the study. Appropriate sources will be consulted by the PI or designee to confirm lack
of PK/pharmacodynamics interaction with study drug.

- Has been on a diet incompatible with the on study diet, in the opinion of the PI or
designee, within the 30 days prior to the first dose and throughout the study.

- Donation of blood or significant blood loss within 56 days prior to the first dose.

- Plasma donation within 7 days prior to the first dose.

- Subjects with tattoo(s) or scarring at or near the site of IV infusion or any other
condition which may interfere with infusion site examination(s), in the opinion of the
Investigator or designee.

- Participation in another clinical trial in which a 14C-labeled drug was administered
within 1 year prior to Day 1.

- Any other significant finding that in the opinion of the clinical investigators would
make the subject's participation in the study unsafe.