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Pilot Study of the Pharmacokinetic Profile of Deferiprone Sustained-Release Formulation in Healthy Volunteers

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ClinicalTrials.gov Identifier: NCT02189941
Recruitment Status : Completed
First Posted : July 15, 2014
Results First Posted : May 20, 2016
Last Update Posted : May 20, 2016
Sponsor:
Information provided by (Responsible Party):
ApoPharma

Tracking Information
First Submitted Date  ICMJE July 11, 2014
First Posted Date  ICMJE July 15, 2014
Results First Submitted Date  ICMJE December 23, 2015
Results First Posted Date  ICMJE May 20, 2016
Last Update Posted Date May 20, 2016
Study Start Date  ICMJE May 2014
Actual Primary Completion Date June 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 14, 2016)
  • AUCt for Serum Deferiprone and Deferiprone 3-O-glucuronide [ Time Frame: 24-hour interval ]
    AUCt (Area Under the Curve to the last measured time) was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained prior to dosing and at 0.25, 0.5, 0.75, 1, 1.3333, 1.6667, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16 and 24 hours post-dose.
  • AUCinf for Serum Deferiprone and Deferiprone 3-O-glucuronide [ Time Frame: 24-hour interval ]
    AUCinf (Area Under the Curve to infinity) was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained prior to dosing and at 0.25, 0.5, 0.75, 1, 1.3333, 1.6667, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16 and 24 hours post-dose.
  • Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide [ Time Frame: 24-hour interval ]
    Cmax (maximum concentration in the serum) was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained prior to dosing and at 0.25, 0.5, 0.75, 1, 1.3333, 1.6667, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16 and 24 hours post-dose.
  • Tmax for Serum Deferiprone and Deferiprone 3-O-glucuronide [ Time Frame: 24-hour interval ]
    Tmax (the time to Cmax) was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained prior to dosing and at 0.25, 0.5, 0.75, 1, 1.3333, 1.6667, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16 and 24 hours post-dose.
  • Thalf for Serum Deferiprone and Deferiprone 3-O-glucuronide [ Time Frame: 24-hour interval ]
    Thalf (the apparent terminal elimination half-life of the drug) was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained prior to dosing and at 0.25, 0.5, 0.75, 1, 1.3333, 1.6667, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16 and 24 hours post-dose.
Original Primary Outcome Measures  ICMJE
 (submitted: July 11, 2014)
  • AUCt from serum deferiprone and deferiprone 3-O-glucuronide concentration-time profiles. [ Time Frame: pre-dose and 0.25, 0.5, 0.75, 1, 1.3333, 1.6667, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16 and 24 hours post-dose ]
  • AUCinf from serum deferiprone and deferiprone 3-O-glucuronide concentration-time profiles. [ Time Frame: pre-dose and 0.25, 0.5, 0.75, 1, 1.3333, 1.6667, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16 and 24 hours post-dose ]
  • Cmax from serum deferiprone and deferiprone 3-O-glucuronide concentration-time profiles. [ Time Frame: pre-dose and 0.25, 0.5, 0.75, 1, 1.3333, 1.6667, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16 and 24 hours post-dose ]
  • Tmax from serum deferiprone and deferiprone 3-O-glucuronide concentration-time profiles. [ Time Frame: pre-dose and 0.25, 0.5, 0.75, 1, 1.3333, 1.6667, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16 and 24 hours post-dose ]
  • Thalf from serum deferiprone and deferiprone 3-O-glucuronide concentration-time profiles. [ Time Frame: pre-dose and 0.25, 0.5, 0.75, 1, 1.3333, 1.6667, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16 and 24 hours post-dose ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 14, 2016)
Safety and Tolerability of Deferiprone Sustained Release Tablets [ Time Frame: From time of dose until 24 hours post dose ]
The number of participants who experienced adverse events between the time of dosing up to 24 hours post-dose, including any changes of clinical significance in vital signs, 12-lead ECG, and clinical laboratory tests
Original Secondary Outcome Measures  ICMJE
 (submitted: July 11, 2014)
To evaluate the safety and tolerability of deferiprone sustained release tablets [ Time Frame: Prior to dosing until 24 hrs post-dose ]
Safety and tolerability will be assessed based on changes in: vital signs, 12-lead ECG, clinical laboratory tests, and frequency of adverse events (AEs)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pilot Study of the Pharmacokinetic Profile of Deferiprone Sustained-Release Formulation in Healthy Volunteers
Official Title  ICMJE Pilot Study of the Pharmacokinetic Profile of a Single Dose of Deferiprone Sustained-Release Formulation in Healthy Volunteers
Brief Summary The purpose of this study was to evaluate the pharmacokinetic and safety profile of the sustained-release formulation of deferiprone under both fasting and fed conditions, and evaluate the relative bioavailability of this sustained-release formulation when compared to immediate-release formulation of deferiprone under fasting conditions.
Detailed Description

This was an open-label, single-dose, randomized, three-way crossover study under fed and fasting conditions designed to determine the pharmacokinetics, safety, and tolerability of deferiprone sustained-release tablets in healthy volunteers. Subjects were randomized to receive the following 3 treatments in different orders, with a washout period of 7 days between treatments:

  • 2000 mg of deferiprone sustained-release tablets under fed conditions
  • 2000 mg of deferiprone sustained-release tablets under fasted conditions
  • 2000 mg of Ferriprox immediate-release tablets under fasted conditions

In each period, blood samples for pharmacokinetics (PK) assessment were collected prior to dosing and at specified time points up to 24 hours post-dose. Safety assessments were conducted throughout the study.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Healthy
Intervention  ICMJE
  • Drug: Deferiprone sustained-release
    Deferiprone sustained-release tablets
    Other Name: Deferiprone
  • Drug: Deferiprone immediate-release
    Deferiprone immediate-release tablets
    Other Name: Ferriprox
Study Arms  ICMJE
  • Experimental: Deferiprone sustained-release (fed)
    A single 1000 mg dose of deferiprone sustained-release following a high fat high calorie breakfast.
    Intervention: Drug: Deferiprone sustained-release
  • Experimental: Deferiprone sustained-release (fasting)
    A single 1000 mg dose of deferiprone sustained-release under fasting conditions.
    Intervention: Drug: Deferiprone sustained-release
  • Active Comparator: Deferiprone immediate-release (fasting)
    A single 1000 mg dose of Deferiprone immediate-release under fasting conditions.
    Intervention: Drug: Deferiprone immediate-release
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: April 14, 2016)
11
Original Actual Enrollment  ICMJE
 (submitted: July 11, 2014)
12
Actual Study Completion Date  ICMJE June 2014
Actual Primary Completion Date June 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Main Inclusion Criteria:

  • Meeting the age, body mass index (BMI) and weight requirements.
  • Signing the Informed Consent Form.
  • Acceptable alcohol and/or drug screen at check-in of each period.
  • Acceptable health, blood pressure, pulse rate and temperature at check-in.
  • Being a non-smoker.
  • Female subjects of childbearing potential should be either sexually inactive (abstinent) for 60 days prior to the first dose of the study and throughout the study, and for 30 days after completion of the study, or be using an acceptable method of birth control.

Exclusion Criteria:

  • A history of presence of significant asthma, chronic bronchitis, seizure, diabetes, migraine, hypertension, cardiovascular, pulmonary, neurological conditions, psychiatric conditions, hepatic, renal, hematopoietic or gastrointestinal diseases or ongoing infectious diseases, or any other significant abnormality as evidenced by a medical history and physical examination.
  • Blood chemistry, hematology, international normalized ratio, partial thromboplastin time and urinalysis values outside clinically acceptable limits.
  • A positive screen for Hepatitis B surface antigens, Hepatitis C antibodies or HIV.
  • Significant abnormality found on ECG.
  • Known sensitivity to deferiprone or any components of the Ferriprox tablets.
  • Requiring other medication at the time of the study. Oral, injectable or topical contraceptives, and contraceptive implants are permitted as they are acceptable methods of contraception.
  • Acetaminophen use within 2 weeks prior to dosing and for the duration of the study.
  • History of drug or alcohol abuse within the last 6 months.
  • Any known enzyme inducing or inhibiting drug taken within 30 days before the study.
  • History of long QT syndrome, cardiac arrhythmias.
  • Infection within two weeks prior to dosing.
  • Participation in an investigational drug study within 30 days prior to first dosing in this study.
  • Blood donation of 50 mL to 499 mL of whole blood within 30 days, or more than 499 mL of whole blood within 56 days prior to drug administration.
  • Positive test for pregnancy at medical screening or prior to dosing in either period.
  • Female subjects who are breast-feeding.
  • Absolute neutrophil count (ANC) <= 1.0 x 10E9 cells/L prior to dosing for each period.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02189941
Other Study ID Numbers  ICMJE LA43-0114
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party ApoPharma
Study Sponsor  ICMJE ApoPharma
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Gurinder Rai, MD Apotex Inc.
PRS Account ApoPharma
Verification Date April 2016

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