An Open-label, Non-randomized, Parallel Group Study in Subjects With Mild and Moderate Hepatic Insufficiency and Healthy Volunteers

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
ApoPharma
ClinicalTrials.gov Identifier:
NCT01767103
First received: January 9, 2013
Last updated: September 3, 2014
Last verified: April 2014
  Purpose

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


Condition Intervention Phase
Hepatic Impairment
Drug: Ferriprox®
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 Hepatic 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 hepatic function, mild hepatic impairment, or moderate hepatic 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 in subjects with normal hepatic function, mild hepatic impairment, or moderate hepatic 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.

  • AUC0-∞ for Serum Deferiprone and Deferiprone 3-O-glucuronide [ Time Frame: 24-hour interval ] [ Designated as safety issue: No ]
    AUC (area under the curve) from zero to infinity was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite in subjects with normal hepatic function, mild hepatic impairment, or moderate hepatic 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.

  • 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 in subjects with normal hepatic function, mild hepatic impairment, or moderate hepatic 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.

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

    Cumulative amount of deferiprone and deferiprone 3-O-glucuronide excreted in the urine. Urine samples were collected at the intervals of -2 to 0 hours pre-dose, and 0-2, 2-4, 4-8, 8-12 ,and 12- 24 hours post-dose.

    Note: For unknown reasons, the urine samples for one subject in the moderate hepatic failure group had low or zero volume and there were no measurable levels of deferiprone or its metabolite in any of the samples. Accordingly, the urine PK results were derived both with and without this subject's data, and are here presented without them (i.e., N=6 rather than 7).


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

    Cumulative fraction of Ferriprox dose excreted in urine as deferiprone or deferiprone 3-O-glucuronide. Urine samples were collected at the intervals of -2 to 0 hours pre-dose, and 0-2, 2-4, 4-8, 8-12 ,and 12- 24 hours post-dose.

    Note: For unknown reasons, the urine samples for one subject in the moderate hepatic failure group had low or zero volume and there were no measurable levels of deferiprone or its metabolite in any of the samples. Accordingly, the urine PK results were derived both with and without this subject's data, and are here presented without them (i.e., N=6 rather than 7).



Secondary Outcome Measures:
  • Safety and Tolerability of Ferriprox in Subjects With or Without Hepatic Impairment. [ Time Frame: Time of dosing until 48 hours post-dose ] [ Designated as safety issue: Yes ]
    The number of participants who experienced adverse events following a single dose of Ferriprox, between the time of dosing and the follow-up visit (including any changes of clinical significance in physical examinations, vital signs, 12-lead ECG, and clinical laboratory tests).


Enrollment: 21
Study Start Date: January 2013
Study Completion Date: April 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Normal Hepatic Function (healthy volunteers)
Healthy volunteers with normal hepatic function received a single 33 mg/kg dose of Ferriprox®.
Drug: Ferriprox®
Other Names:
  • DFP
  • Deferiprone
  • L1
Experimental: Mild Hepatic Failure
Subjects with mild hepatic failure as defined by the Child-Pugh Class C: 5-6 points received a single 33 mg/kg dose of Ferriprox®.
Drug: Ferriprox®
Other Names:
  • DFP
  • Deferiprone
  • L1
Experimental: Moderate Hepatic Failure
Subjects with moderate hepatic failure as defined by the Child-Pugh Class B: 7-9 points received a single 33 mg/kg dose of Ferriprox®.
Drug: Ferriprox®
Other Names:
  • DFP
  • Deferiprone
  • L1

Detailed Description:

Post-marketing study to evaluate the effect of impaired hepatic function on the pharmacokinetics (PK) of deferiprone and its 3-O-glucuronide metabolite and on the safety of Ferriprox® in subjects with mild and moderate hepatic 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 ≥ 50 kg;
  3. Body mass index (BMI) between 19 and 32 kg/mE2 (inclusive);
  4. Absolute neutrophil count (ANC) of >1.5x10E9/L ;

Healthy volunteers:

  1. Medically healthy with clinically insignificant screening results (e.g., laboratory profiles, medical history, vital signs, physical examination);
  2. Matched to hepatically impaired subjects in the study by age (+/- 10 years), sex and weight (+/- 15% BMI).

Hepatically impaired subjects:

  1. Considered clinically stable in the opinion of the Investigator;
  2. Subjects with different degrees of impaired hepatic function as assessed by a Child-Pugh classification score: mild (Class A: 5-6 points) and moderate (Class B: 7-9 points) impaired hepatic function.

Main Exclusion Criteria:

  1. For subjects with hepatic impairment, fluctuating or rapidly deteriorating hepatic function as indicated by clinical and/or laboratory signs of hepatic impairment (e.g. advanced ascites, infection of ascites, fever, or active gastrointestinal bleeding).
  2. Evidence of liver impairment in healthy volunteers: hepatitis B and C; or aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin, clotting factors, serum protein that is considered clinically significant by the Investigator;
  3. History or presence of significant clinically unstable respiratory, cardiovascular, pulmonary, hepatic (except for subjects assigned to one of the hepatically impaired groups), renal, hematologic, gastrointestinal, endocrine (except for subjects with hepatic impairment with clinically stable and treated diabetes, hypertension and thyroid disorders), 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. resections of the small or large intestine, febrile conditions, chronic diarrhea, chronic vomiting, clinically unstable endocrine disease, severe infections, acute inflammations, etc.);
  5. Received a pharmacological agent in another clinical trial within 28 days prior to the first dose of the study;
  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: NCT01767103

Locations
United States, Florida
University of Miami
Miami, Florida, United States, 33136
Orlando Clinical Research Center
Orlando, Florida, United States, 32809
Sponsors and Collaborators
ApoPharma
Investigators
Study Chair: Fernando Tricta, MD ApoPharma
  More Information

No publications provided

Responsible Party: ApoPharma
ClinicalTrials.gov Identifier: NCT01767103     History of Changes
Other Study ID Numbers: LA40-0412
Study First Received: January 9, 2013
Results First Received: September 3, 2014
Last Updated: September 3, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by ApoPharma:
Hepatic Impairment
Liver Impairment
Liver Disease
Ferriprox®
LI
DFP
Deferiprone

Additional relevant MeSH terms:
Liver Diseases
Digestive System Diseases
Deferiprone
Iron Chelating Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 16, 2014