An Open-label, Non-randomized, Parallel Group Study in Subjects With Mild, Moderate, Severe, or No Renal Impairment

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
ApoPharma
ClinicalTrials.gov Identifier:
NCT01770652
First received: January 16, 2013
Last updated: August 25, 2014
Last verified: August 2013
  Purpose

Multi-center, non-randomized, open-label, single-dose, parallel group study to determine the effect of impaired renal function on the PK of deferiprone and its 3-O-glucuronide metabolite following a single oral dose of 33mg/kg Ferriprox®.


Condition Intervention Phase
Renal Impairment
Drug: Deferiprone
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: An Open-label Study to Compare the Pharmacokinetic Profiles of a Single Dose of Ferriprox in Subjects With Impaired Renal Function and Healthy Volunteers

Resource links provided by NLM:


Further study details as provided by ApoPharma:

Primary Outcome Measures:
  • Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide [ Time Frame: 24-hour interval ] [ Designated as safety issue: No ]
    Cmax was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite in subjects with normal, mild, moderate and severe renal impairment. Blood samples were obtained prior to dosing and at 0.25, 0.50, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 9, 12, 16, and 24 hours post-dose.

  • Tmax for Serum Deferiprone and Deferiprone 3-O-glucuronide [ Time Frame: 24 hour interval ] [ Designated as safety issue: No ]

    Tmax 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, 0.50, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 9, 12, 16, and 24 hours post-dose.

    The results of the Tmax parameter are reported as the median and range (other parameters are reported as mean and standard deviation).


  • AUC Zero to Infinity (AUC0-∞) for Serum Deferiprone and Deferiprone 3-O-glucuronide [ Time Frame: 24 hour interval ] [ Designated as safety issue: No ]
    AUC0-∞ 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, 0.50, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 9, 12, 16, and 24 hours post-dose.

  • T1/2 for Serum Deferiprone and Deferiprone 3-O-glucuronide [ Time Frame: 24 hour interval ] [ Designated as safety issue: No ]
    T1/2 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, 0.50, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 9, 12, 16, and 24 hours post-dose.

  • Ae24 for Urine Deferiprone and Deferiprone 3-O-glucuronide [ Time Frame: 24 hour interval ] [ Designated as safety issue: No ]
    Ae24 (the amount excreted in urine from time zero to 24 hours) was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite. Urine samples were collected at the intervals of -2 to 0 hours pre-dose and 0 to 2, 2 to 4, 4 to 8, 8 to 12, and 12 to 24 hours post-dose.

  • Fe24 for Serum Deferiprone and Deferiprone 3-O-glucuronide [ Time Frame: 24-hour interval ] [ Designated as safety issue: No ]

    Fe24 (fraction of dose excreted in urine from time zero to 24 hours) was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite. Urine samples were collected at the intervals of -2 to 0 hours pre-dose and 0 to 2, 2 to 4, 4 to 8, 8 to 12, and 12 to 24 hours post-dose.

    Some of the Fe24 values were over 100% which could be explained by variability in urine collection (e.g. incomplete collection of urine into the container) and volume measurement, as well as analytical imprecision.



Secondary Outcome Measures:
  • Safety and Tolerability of Ferriprox® in Subjects With Renal Impairment. [ Time Frame: From time of dosing until 72 hours post-dose ] [ Designated as safety issue: Yes ]
    The number of participants who experienced adverse events (including any changes of clinical significance in physical examinations, vital signs, 12-lead ECG, and clinical laboratory tests) following a single dose of Ferriprox.


Enrollment: 32
Study Start Date: January 2013
Study Completion Date: August 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Normal renal function
Healthy volunteers, defined as having an estimated glomerular filtration rate (eGFR) ≥90 mL/min/1.73m^2. All subjects received a single 33 mg/kg oral dose of deferiprone.
Drug: Deferiprone
Oral iron chelator
Other Names:
  • Ferriprox
  • L1
  • DFP
Experimental: Mild Renal Impairment
Mild impairment, defined as having an eGFR 60-89 mL/min/1.73m^2. All subjects received a single 33 mg/kg oral dose of deferiprone.
Drug: Deferiprone
Oral iron chelator
Other Names:
  • Ferriprox
  • L1
  • DFP
Experimental: Moderate Renal Impairment
Mild impairment, defined as having an eGFR 30-59 mL/min/1.73m^2. All subjects received a single 33 mg/kg oral dose of deferiprone.
Drug: Deferiprone
Oral iron chelator
Other Names:
  • Ferriprox
  • L1
  • DFP
Experimental: Severe Renal Impairment
Severe impairment, defined as having an eGFR 15-19 mL/min/1.73m^2. All subjects received a single 33 mg/kg oral dose of deferiprone.
Drug: Deferiprone
Oral iron chelator
Other Names:
  • Ferriprox
  • L1
  • DFP

Detailed Description:

Post-marketing study to evaluate the effect of impaired renal function on the pharmacokinetics (PK) of deferiprone and its 3-O-glucuronide metabolite and on the safety of Ferriprox® in subjects with mild, moderate and severe renal impairment as compared to healthy volunteers.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Main Inclusion Criteria:

All subjects:

  1. Adult males or females, 18 - 75 years of age (inclusive);
  2. Body weight ≥ 45 kg;
  3. Body mass index (BMI) range of approximately 18.5-32 kg/m^2 (inclusive);
  4. Absolute neutrophil count (ANC) of >1.5x10^9/L;

Healthy volunteers:

  1. Medically healthy with clinically insignificant screening results (e.g., laboratory profiles, medical history, vital signs, physical examination);
  2. eGFR ≥ 90 mL/min/1.73m^2;

Renally impaired subjects:

  1. Considered clinically stable in the opinion of the Investigator;
  2. Subjects with mild renal impairment (eGFR 60-89 mL/min/1.73m^E2) OR moderate renal impairment (eGFR 30-59 mL/min/1.73m^2) OR severe renal impairment (eGFR 15-29 mL/min/1.73m^2).

Main Exclusion Criteria:

  1. History of renal transplant;
  2. Subjects undergoing any method of dialysis;
  3. History or presence of clinically unstable significant respiratory, cardiovascular, pulmonary, hepatic, renal (except for subjects assigned to one of the renally impaired groups), hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease;
  4. Disorders or surgery of the gastrointestinal tract which may interfere with drug absorption or may otherwise influence the PK of the investigational medicinal product (e.g. cholecystectomy, resections of the small or large intestine, febrile conditions, chronic diarrhea, chronic vomiting, endocrine disease, severe infections, acute inflammations, etc.);
  5. Clinically significant abnormalities on 12-lead ECG (e.g., QTcF≥430 ms in males or ≥450 ms in females);
  6. Evidence of liver damage: hepatitis B and C; aspartate aminotransferase (AST), alanine aminotransferase (ALT) that is considered clinically significant by the Investigator;
  7. Participation in another clinical trial within 28 days prior to the study drug administration;
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01770652

Locations
Canada, Quebec
Hôpital Maisonneuve-Rosemont
Montreal, Quebec, Canada, H1T2M4
Algorithme Pharma Inc.
Mount-Royal, Quebec, Canada, H3P3P1
Sponsors and Collaborators
ApoPharma
Investigators
Study Chair: Fernando Tricta, MD ApoPharma
  More Information

No publications provided

Responsible Party: ApoPharma
ClinicalTrials.gov Identifier: NCT01770652     History of Changes
Other Study ID Numbers: LA39-0412
Study First Received: January 16, 2013
Results First Received: July 18, 2014
Last Updated: August 25, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by ApoPharma:
Renal Impairment
Kidney Impairment
Kidney Disease
Ferriprox
Deferiprone
DFP (deferiprone)
L1

Additional relevant MeSH terms:
Renal Insufficiency
Kidney Diseases
Urologic Diseases
Deferiprone
Chelating Agents
Iron Chelating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Sequestering Agents

ClinicalTrials.gov processed this record on October 23, 2014