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

NCT02286609 | Completed Phase 1

• 1 other identifier: MP-104-CL-023
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 2

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 classification, Grade B) to that of 8 healthy matched control subjects (age, body mass index \[BMI\], and gender).

Conditions

Hepatic Impairment

Outcome Measures

Primary Outcomes (1)

• Hepatic impairment on the pharmacokinetics (PK) of deflazacort in subjects with moderate hepatic impairment including the area under the plasma concentration time curve, from time 0 to the last measurable non-zero concentration.

  Hepatic impairment on the pharmacokinetics (PK) of deflazacort in subjects with moderate hepatic impairment including the area under the plasma concentration time curve, from time 0 to the last measurable non-zero concentration.

  1 day

Secondary Outcomes (1)

• Safety and tolerability of one dose of deflazacort in subjects with hepatic impairment as measured by capturing occurrence of adverse events.

  1 day

Study Arms (2)

Hepatic Impairment

EXPERIMENTAL

Eight (8) subjects with moderate hepatic insufficiency (a score of 7 to 9, on the Child-Pugh scale) will receive one 18 mg dose of deflazacort

Drug: Deflazacort

Healthy Volunteer

EXPERIMENTAL

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; will receive 18 mg dose of deflazacort

Drug: Deflazacort

Interventions

Deflazacort DRUG

Deflazacort, a glucocorticoid with anti-inflammatory and immunosuppressive effects, is used in treating a variety of diseases. Pharmacologically it is an inactive pro-drug which is metabolized immediately to the active metabolite, 21 desacetyl-DFZ. The elimination of this metabolite is primarily via the urine in humans. Its potency is approximately 70 to 90% of prednisone and 6 mg of deflazacort has approximately the same anti-inflammatory potency as 5 mg of prednisolone or prednisone.

Also known as: DFZ

Healthy Volunteer; Hepatic Impairment

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• PTC Therapeutics: lead

Study Sites (2)

University of Miami Division of Clinical Pharmacology

Miami, Florida, 33136, United States

Location

Orlando Clinical Research Center

Orlando, Florida, 32809, United States

Location

MeSH Terms

Interventions

deflazacort

Study Officials

• Bioscience Center

  Marathon Pharmaceuticals, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2014
• First Posted: November 10, 2014
• Study Start: December 1, 2014
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: August 18, 2017

Record last verified: 2017-08

Locations

US (2)