search
Back to results

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

Primary Purpose

Renal Impairment

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Deflazacort
Sponsored by
PTC Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Renal Impairment

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • 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:

    • 18 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

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 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
  • Seated blood pressure is less than 90/40 mmHg or greater than 170/100 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 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, HBsAg or HCV
  • 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 ESRD
  • Is a regular user of any medication that would significantly alter glomerular filtration rate, e.g., cimetidine
  • Has presence of a renal carcinoma or acute renal disease caused by infection or drug toxicity
  • History of drug abuse within the past 2 years
  • Has a positive urine/breath alcohol or urine/serum/saliva drug testing Normal Renal Function
  • History or presence of alcoholism or drug abuse within the past 2 years
  • Positive urine drug or urine/breath alcohol results

Sites / Locations

  • University of Miami Division of Clinical Pharmacology
  • Orlando Clinical Research Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Renal Impairment

Healthy Volunteers

Arm Description

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

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Safety and tolerability of one dose of deflazacort in subjects with end stage renal disease as measured by capturing occurrence of adverse events.
Safety and tolerability of one dose of deflazacort in subjects with end stage renal disease as measured by capturing occurrence of adverse events.

Full Information

First Posted
November 4, 2014
Last Updated
August 15, 2017
Sponsor
PTC Therapeutics
search

1. Study Identification

Unique Protocol Identification Number
NCT02286622
Brief Title
A Single Dose Evaluation of the Effects of Renal Impairment on Deflazacort Pharmacokinetics
Official Title
A Single Dose Evaluation of the Effects of Renal Impairment on Deflazacort Pharmacokinetics
Study Type
Interventional

2. Study Status

Record Verification Date
August 2017
Overall Recruitment Status
Completed
Study Start Date
December 2014 (undefined)
Primary Completion Date
February 2015 (Actual)
Study Completion Date
February 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
PTC Therapeutics

4. Oversight

Data Monitoring Committee
No

5. Study Description

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).
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 ESRD to that of 8 healthy matched control subjects (age, body mass index [BMI], and gender). All subjects with ESRD will be on hemodialysis (HD). Dosing of deflazacort followed by PK evaluation of 21 desacetyl DFZ and, if data permits, deflazacort, will only be performed on a non-HD day. On Day 1, that will be scheduled on a non-HD day for subjects with ESRD, a single oral dose of deflazacort will be administered followed by serial blood sampling for 24 hours to assess the PK of 21 desacetyl-DFZ, and, if data permits, deflazacort. Safety will be monitored throughout the study by repeated clinical and laboratory evaluations. Subjects will return to the Clinical Research Unit (CRU) 3 days (± 1 day) following study drug administration to determine if any adverse events (AEs) have occurred since the last study visit. Subjects who terminate the study early will be contacted if the Principal Investigator (PI) deems necessary. A total of sixteen (16) adult male and female subjects will be enrolled. Renal Impaired Cohort: Eight (8) subjects with ESRD on HD. Healthy Match Control Cohort: 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. Each subject will receive a single oral dose of 18 mg (3 X 6 mg tablets) deflazacort, following an overnight fast. Study drug will be administered orally with approximately 240 mL of water.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Renal Impairment

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
16 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Renal Impairment
Arm Type
Experimental
Arm Description
Eight (8) subjects with ESRD on HD will receive one 18 mg dose of deflazacort.
Arm Title
Healthy Volunteers
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Deflazacort
Other Intervention Name(s)
DFZ
Intervention Description
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
Primary Outcome Measure Information:
Title
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.
Description
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.
Time Frame
1 day
Secondary Outcome Measure Information:
Title
Safety and tolerability of one dose of deflazacort in subjects with end stage renal disease as measured by capturing occurrence of adverse events.
Description
Safety and tolerability of one dose of deflazacort in subjects with end stage renal disease as measured by capturing occurrence of adverse events.
Time Frame
1 day

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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: 18 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 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 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 Seated blood pressure is less than 90/40 mmHg or greater than 170/100 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 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, HBsAg or HCV 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 ESRD Is a regular user of any medication that would significantly alter glomerular filtration rate, e.g., cimetidine Has presence of a renal carcinoma or acute renal disease caused by infection or drug toxicity History of drug abuse within the past 2 years Has a positive urine/breath alcohol or urine/serum/saliva drug testing Normal Renal Function History or presence of alcoholism or drug abuse within the past 2 years Positive urine drug or urine/breath alcohol results
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bioscience Center
Organizational Affiliation
Marathon Pharmaceuticals, LLC
Official's Role
Study Director
Facility Information:
Facility Name
University of Miami Division of Clinical Pharmacology
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Orlando Clinical Research Center
City
Orlando
State/Province
Florida
ZIP/Postal Code
32809
Country
United States

12. IPD Sharing Statement

Links:
URL
https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM204959.pdf
Description
Pharmacokinetics in patients with impaired ernal function
URL
http://www.oalib.com/references/12905458
Description
Treatment of DMD-Worsening of Cardiomyopathy

Learn more about this trial

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

We'll reach out to this number within 24 hrs