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

This is an interventional basic science trial for Hepatic Impairment Read More

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.