Status:

COMPLETED

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

Lead Sponsor:

PTC Therapeutics

Conditions:

Hepatic Impairment

Eligibility:

All Genders

18-80 years

Phase:

PHASE1

Brief 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 ...

Detailed Description

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 ...

Eligibility Criteria

Inclusion

  • 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

  • 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.

Key Trial Info

Start Date :

December 1 2014

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

February 1 2015

Estimated Enrollment :

16 Patients enrolled

Trial Details

Trial ID

NCT02286609

Start Date

December 1 2014

End Date

February 1 2015

Last Update

August 18 2017

Active Locations (2)

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Page 1 of 1 (2 locations)

1

University of Miami Division of Clinical Pharmacology

Miami, Florida, United States, 33136

2

Orlando Clinical Research Center

Orlando, Florida, United States, 32809