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A Pharmacokinetic Study of Oral Deflazacort in Children and Adolescent Subjects With Duchenne Muscular Dystrophy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02251600
Recruitment Status : Completed
First Posted : September 29, 2014
Last Update Posted : August 18, 2017
Sponsor:
Information provided by (Responsible Party):
PTC Therapeutics

Tracking Information
First Submitted Date  ICMJE September 22, 2014
First Posted Date  ICMJE September 29, 2014
Last Update Posted Date August 18, 2017
Study Start Date  ICMJE December 2014
Actual Primary Completion Date October 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 15, 2017)
  • The area under the plasma concentration time curve, from time 0 to the last measurable concentration non-zero, for single-state pharmacokinetics on Day 1 of deflazacort and 21-desacetyl-DFZ, the active metabolite [ Time Frame: Day 1, Day 8 ]
    The area under the plasma concentration time curve, from time 0 to the last measurable concentration non-zero, for single-state pharmacokinetics on Day 1 of deflazacort and 21-desacetyl-DFZ, the active metabolite
  • The area under the plasma concentration versus time curve over the final dosing interval for steady state pharmacokinetics on Day 8 of deflazacort and 21-desacetyl-DFZ, the active metabolite [ Time Frame: Day 8 ]
    The area under the plasma concentration versus time curve over the final dosing interval for steady state pharmacokinetics on Day 8 of deflazacort and 21-desacetyl-DFZ, the active
Original Primary Outcome Measures  ICMJE
 (submitted: September 25, 2014)
  • The area under the plasma concentration time curve, from time 0 to the last measurable concentration non-zero, for single-state pharmacokinetics on Day 1 of deflazacort and 21-desacetyl-DFZ, the active metabolite [ Time Frame: Day 1, Day 8 ]
  • The area under the plasma concentration versus time curve over the final dosing interval for steady state pharmacokinetics on Day 8 of deflazacort and 21-desacetyl-DFZ, the active metabolite [ Time Frame: Day 8 ]
Change History Complete list of historical versions of study NCT02251600 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 15, 2017)
Number of participants with adverse events as a measure of safety and tolerability [ Time Frame: Day 1-8 ]
To assess the safety and tolerability of single-dose and steady-state deflazacort in DMD subjects.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 25, 2014)
Number of participants with adverse events as a measure of safety and tolerability [ Time Frame: Day 1-8 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Pharmacokinetic Study of Oral Deflazacort in Children and Adolescent Subjects With Duchenne Muscular Dystrophy
Official Title  ICMJE A Multi-center Study to Evaluate the Pharmacokinetics of 21-Desacetyldeflazacort and the Safety of Deflazacort After Oral Administration of Deflazacort Tablets to Children and Adolescent Subjects With Duchenne Muscular Dystrophy
Brief Summary Study to characterize the single-state and steady-state dosing of oral deflazacort in pediatric and adolescents subjects.
Detailed Description

This is an open label, single period study in 24 male DMD subjects consisting of children (ages 4-12, inclusive) and adolescents (ages 13-16, inclusive) with at least 12 subjects between the ages of 4-12 (children). Subjects taking maintenance corticosteroid therapy will be required to take their dose of corticosteroid 24 hours (± 2 hours) prior to the first dose of deflazacort on Day 1. Subjects receiving deflazacort as maintenance corticosteroid therapy must take their last dose at least 30 days prior to the first dose of deflazacort on Day 1. Concomitant corticosteroid therapy will be prohibited during the study while the subject is taking deflazacort. On Day 1, a single oral dose of deflazacort under fasting conditions will be administered in the CRU followed by blood sampling for plasma analysis of DFZ and 21-desacetyl-DFZ for 8 hours. Following the 8 hour PK sample on Day 1, subjects will be given medication to take at home for once-daily, morning dosing on Days 2 through 7 (+2 days). On Day 8 (+2 days), subjects will return for a PK sample predose and an 8th oral dose of deflazacort under fasting conditions which will be administered in the CRU followed by PK sampling for 8 hours.

Safety will be monitored throughout the study by repeated clinical and laboratory evaluations on Days 1 and 8 (+2 days). Subjects will be contacted via telephone approximately 7 days (± 1 day) following study drug administration on Day 8 (+2 days) for a follow-up assessment to determine if any adverse event (AE) has occurred since the last study visit. Subjects who terminate the study early will be contacted if the Principal Investigator (PI) deems necessary.

Subjects that complete this study or receive at least one dose of study medication will be eligible for an open-label extension study with deflazacort treatment conducted under a separate protocol.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Duchenne Muscular Dystrophy
Intervention  ICMJE Drug: Deflazacort
Oral deflazacort administered once daily at 0.9 mg/kg for eight days
Other Name: DFZ
Study Arms  ICMJE Experimental: Deflazacort
This is an open label and single period study , dosed with 0.9mg/kg Deflazacort.
Intervention: Drug: Deflazacort
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 25, 2014)
24
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE October 2015
Actual Primary Completion Date October 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • In the opinion of the investigator, the subject is capable of understanding and complying with protocol requirements.
  • The subject or, when applicable, the subject's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
  • If above the age of 7, the subject signs and dates a written, informed assent form (IAF) and any required privacy authorization prior to the initiation of any study procedures.
  • The subject must have confirmed diagnosis of Duchenne Muscular Dystrophy defined as muscle biopsy and dystrophin analyses consistent with DMD or DNA mutation and analysis by PCR or Southern blot techniques to detect gene deletions as well as:

    1. onset of weakness before 5 years of age;
    2. proximal muscle weakness;
    3. increased serum creatine kinase more than 10 times the upper limit of normal (ULN);
  • The subject is male and aged 4 to 16 years, inclusive.
  • The subject weighs at least 13 kg and has a Body Mass Index (BMI) of ≤ 40.
  • Willingness and ability to comply with scheduled visits, oral drug administration, and study procedures including blood sample draws (total blood volume collected not to exceed 50 mL for the study duration or 25 mL on any single study day [≤ 3 mL/kg])
  • The subject has a life expectancy of >1 year.
  • Up to date on all childhood vaccinations, specifically varicella vaccine (chicken pox).
  • Baseline health is judged to be stable based on medical history, physical examination, laboratory profiles, vital signs, or ECGs at screening, as deemed by the Investigator.
  • Continuous non smoker who has not used nicotine containing products for at least 3 months prior to the first dose.
  • The subject is able to take tablets.

Exclusion Criteria:

  • The subject has received any investigational compound and/or has participated in another clinical study within 90 days prior to study treatment with the exception of observational cohort studies or non-interventional studies.
  • The subject has received deflazacort within 30 days or previous discontinued deflazacort due to an intolerable reaction.
  • The subject is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in the conduct of this study (e.g. spouse, parent, child, sibling) or may consent under duress.
  • Any significant finding on the Columbia suicide severity rating scale (C SSRS) for subjects (ages 12-16, inclusive), in the opinion of the PI, warrants exclusion from this study.
  • The subject has, in the judgment of the investigator, clinically significant abnormal clinical chemistry laboratory parameters that may affect safety at Screening.
  • The subject has, in the judgment of the investigator, a history or current medical condition that could affect safety including, but not limited to:

    1. Major renal or hepatic impairment
    2. Immunosuppression or other contraindications for corticosteroid treatment
    3. History of chronic systemic fungal or viral infections
    4. Diabetes mellitus
    5. Idiopathic hypocalcuria
    6. Symptomatic cardiomyopathy at screening
  • The subject has a history of hypersensitivity or allergic reaction to steroids or their formulations including, but not limited to lactose, sucrose, etc.
  • Inability to take tablets as assessed by site investigator.
  • Unable to refrain from or anticipates the use of:

    • Any medications at least 4 hours before and after dosing on PK Days 1 and 8.
    • Any vitamins, vitamins with minerals, and/or meal supplementation (e.g., Ensure, Boost, etc.) at least 4 hours before and after dosing on PK Days 1 and 8.
    • Any drug, including prescription and non prescription medications, and herbal remedies known to be significant inhibitors of CYP 3A4 enzymes and/or P gp for 14 days prior to the first dose of study drug and throughout the study. Appropriate sources will be consulted by the PI or designee to confirm lack of pharmacokinetic/pharmacodynamic interaction with study drug. Acetaminophen may be permitted during the study (doses to be based upon appropriate age/weight ranges.
    • Any drugs known to be significant inducers of CYP 3A4 enzymes and/or P gp for 28 days prior to the first dose of study drug and throughout the study. Appropriate sources will be consulted by the PI or designee to confirm lack of PK/pharmacodynamics interaction with study drug.
  • Subject is mentally or legally incapacitated or has significant emotional problems at the time of screening visit or expected during the conduct of the study.
  • History of any illness that, in the opinion of the PI, might confound the results of the study or poses an additional risk to the subject by their participation in the study.
  • Positive urine drug or alcohol results at screening or check in.
  • Positive urine cotinine at screening.
  • Positive results at screening for HIV, HBsAg, or HCV.
  • Hemoglobin level below the lower limit of normal at screening.
  • Donation of blood or significant blood loss within 56 days prior to the first dose of study drug.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 4 Years to 16 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02251600
Other Study ID Numbers  ICMJE MP-104-CL-005
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party PTC Therapeutics
Study Sponsor  ICMJE PTC Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Katherine Smith, MD Drug Safety Solutions/Celerion
PRS Account PTC Therapeutics
Verification Date August 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP