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

• Status: Completed
• Trial end date: 2015-02-01
• Target enrollment: 0
• Participant gender: All

Summary

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).

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Marathon Pharmaceuticals, LLC; PTC Therapeutics
• Treatments: Deflazacort

Criteria

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.