A Single Dose Evaluation of the Effects of Moderate Hepatic Impairment on Deflazacort Pharmacokinetics

This is a non-randomized, open-label, single-dose study to compare the PK of
21-desacetyl-DFZ and, if data permits, deflazacort in 8 subjects with moderate hepatic
impairment (based on the Child Pugh classification, Grade B) to that of 8 healthy matched
control subjects (age, body mass index [BMI], and gender).

On Day 1, a single oral dose of deflazacort will be administered followed by serial blood
sampling for 24 hours to assess the PK of 21-desacetyl-DFZ and, if data permits,
deflazacort.

Safety will be monitored throughout the study by repeated clinical and laboratory
evaluations.

Subjects will return to the Clinical Research Unit (CRU) 3 days (± 1 day) following study
drug administration to determine if any adverse events (AEs) have occurred since the last
study visit. Subjects who terminate the study early will be contacted if the Principal
Investigator (PI) deems necessary.

A total of sixteen (16) adult male and female subjects will be enrolled. Hepatic Impaired
Cohort: Eight (8) subjects with moderate hepatic insufficiency (a score of 7 to 9, on the
Child-Pugh scale).

Healthy Match Control Cohort: Eight (8) healthy subjects. Subjects will be matched for age
[± 15 years], BMI [± 15 %], and gender [1:1] to the subjects in the moderate hepatic
impaired cohort.

Inclusion Criteria:

All Subjects

- Continuous non-smokers or moderate smokers.

- For a female of non-childbearing potential: must have undergone one a sterilization
procedures or be postmenopausal with amenorrhea for at least 1 year prior to dosing
and FSH serum levels consistent with postmenopausal status

- A non vasectomized, male subject must agree to use a condom with spermicide or
abstain from sexual intercourse during the study until 90 days

- If male, must agree not to donate sperm from dosing until 90 days Subject with
Moderate Hepatic Impairment

- Adult male or female, 18 80 years of age

- BMI ≥ 18.5 and ≤ 40.0 kg/m2

- Subject's score on the Child-Pugh scale must range from 7 to 9 (moderate hepatic
insufficiency)

- Subject has a diagnosis of chronic (> 6 months), stable (no acute episodes of illness
within the previous 2 months due to deterioration in hepatic function) hepatic
insufficiency with features of cirrhosis due to any etiology.

Healthy Subject

- Healthy adult male and female subjects will be matched 1:1 to a specific subject in the
moderate hepatic impairment cohort based upon age, BMI, and gender.

Exclusion Criteria:

- Subject is mentally or legally incapacitated or has significant emotional problems at
the time of the screening visit or expected during the conduct of the study.

- History or presence of hypersensitivity or idiosyncratic reaction to the study drug,
related compounds (e.g., steroids or their formulations including lactose and corn
starch).

- History (within the last year prior to dosing) or presence of peptic ulcers.

- History or presence of:

- Gastritis or esophagitis, diverticulitis, ulcerative colitis (if there is
probability of impending perforation), abscess or pyogenic infections, or fresh
intestinal anastomosis;

- Previous corticoids-induced myopathy;

- Ocular herpes simplex;

- Symptomatic cardiomyopathy at screening;

- Immunosuppression or other contraindications for corticosteroid treatment;

- History of chronic systemic fungal or viral infections;

- Galactose intolerance, Lapp lactose deficiency, or glucose-galactose
malabsorption;

- Osteoporosis;

- Myasthenia gravis;

- Epilepsy;

- Idiopathic hypocalcuria.

- Seated blood pressure is less than 90/40 mmHg or greater than 160/95 mmHg

- Seated heart rate is lower than 40 bpm or higher than 99 bpm

- QTcF interval is > 500 msec

- Has received any live or live-attenuated vaccine within 30 days

- Has received any immunosuppressive agents, coal tar, and/or radiation therapies
within 30 days

- Has received injectable corticoids in the 12 weeks prior to dosing or any oral form
of corticoids in 30 days

- Unable to refrain from or anticipates the use of:

- Any drug known to be moderate or strong inhibitors or inducers of cytochrome
P450 (CYP) 3A or P-glycoprotein (P-gp) for 14 days or 28 days, respectively

- Any medication or substance, vitamin supplements, natural or herbal supplements
which cannot be discontinued at least 14 days

- Female subjects of childbearing potential.

- Female subjects who are pregnant or lactating.

- Positive results at screening for HIV.

- Has been on a diet incompatible with the on study diet within 28 days

- Donation of blood or significant blood loss within 56 days

- Plasma donation within 7 days

- Participation in another clinical trial within 28 days Subject with Moderate Hepatic
Impairment

- Has history of organ transplant.

- History of drug abuse within the past 2 years

- Has a positive urine drug or urine/breath alcohol testing Healthy Subject

- History or presence of alcoholism or drug abuse within the past 2 years

- Positive urine drug or urine/breath alcohol testing results at screening or check in.

- Positive results at screening for HBsAg or HCV.