A Single Dose Evaluation of the Effects of Renal Impairment on Deflazacort Pharmacokinetics

NCT02286622 | Completed Phase 1

• 1 other identifier: MP-104-CL-024
• 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 ESRD to that of 8 healthy matched control subjects (age, body mass index \[BMI\], and gender).

Conditions

Renal Impairment

Outcome Measures

Primary Outcomes (1)

• Renal impairment on the pharmacokinetics (PK) of deflazacort in subjects with end-stage renal disease including the area under the plasma concentration time curve, from time 0 to the last measurable non-zero concentration.

  Renal impairment on the pharmacokinetics (PK) of deflazacort in subjects with end-stage renal disease 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 end stage renal disease as measured by capturing occurrence of adverse events.

  1 day

Study Arms (2)

Renal Impairment

EXPERIMENTAL

Eight (8) subjects with ESRD on HD will receive one 18 mg dose of deflazacort.

Drug: Deflazacort

Healthy Volunteers

EXPERIMENTAL

Eight (8) healthy subjects with estimated creatinine clearance (CLcr) ≥ 90 mL/min. Subjects will be matched for age \[± 15 years\], BMI \[± 15 %\], and gender \[1:1\] to the subjects in the ESRD cohort. Subjects will receive one 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 Volunteers; Renal 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:

• Continuous non-smokers or moderate smokers
• For a female of non-childbearing potential: must have undergone a sterilization procedures or be postmenopausal with amenorrhea for at least 1 year prior to the first dose 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 ESRD on Hemodialysis
• Adult male or female, 18 80 years of age
• BMI ≥ 18.5 and ≤ 40.0 kg/m2 - Subject is maintained on a stable regimen of HD at least 3 months Healthy Subject
• Healthy adult male and female subjects will be matched 1:1 to a specific subject in the ESRD cohort based upon age, BMI, and gender \[1:1\]. The following criteria should be fulfilled:
• to 80 years of age. Age must be within ± 15 years of the matched subject's age in the ESRD cohort
• BMI ≥ 18.5 and ≤ 40.0 kg/m2. BMI must be within ± 15% of the matched subject's BMI in the ESRD cohort
• Has a CLcr ≥ 90 mL/min

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 drugs or related compounds (e.g., steroids or their formulations including lactose and corn starh)
• 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

Related Links

• Methylprednisolone effect on Dystrophin levels
• Pharmacokinetics in patients with impaired ernal function
• Deflazacort fefect on Laminin and Myogenic repair.
• Treatment of DMD-Worsening of Cardiomyopathy
• Deflazacort Vs Prednisone in DMD

MeSH Terms

Conditions

Renal Insufficiency

Interventions

deflazacort

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

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)