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

An Open-Label Study to Compare the Pharmacokinetic Profiles of a Single Dose of Ferriprox® in Subjects With Impaired Hepatic Function and Healthy Volunteers

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®.

Study Overview

• Status: Completed
• Conditions: Hepatic Impairment
• Intervention / Treatment: Drug: Ferriprox®

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.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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;

Study Plan

How is the study designed?

Design Details

• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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: L1; DFP; Deferiprone
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: L1; DFP; Deferiprone
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: L1; DFP; Deferiprone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide	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.	24-hour interval
Tmax for Serum Deferiprone and Deferiprone 3-O-glucuronide	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.	24-hour interval
AUC0-∞ for Serum Deferiprone and Deferiprone 3-O-glucuronide	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.	24-hour interval
T1/2 for Serum Deferiprone and Deferiprone 3-O-glucuronide	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.	24-hour interval
CumAe for Urine Deferiprone and Deferiprone 3-O-glucuronide	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).	24-hour interval
Fe% for Urine Deferiprone and Deferiprone 3-O-glucuronide	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).	24-hour interval

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability of Ferriprox in Subjects With or Without Hepatic Impairment.	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).	Time of dosing until 48 hours post-dose

Collaborators and Investigators

• Sponsor: ApoPharma
• Investigators: Study Chair: Fernando Tricta, MD, ApoPharma

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: January 9, 2013
• First Submitted That Met QC Criteria: January 10, 2013
• First Posted (Estimate): January 14, 2013

Study Record Updates

• Last Update Posted (Estimate): September 10, 2014
• Last Update Submitted That Met QC Criteria: September 3, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: Liver Disease; Hepatic Impairment; Deferiprone; DFP; Liver Impairment; Ferriprox®; LI
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Iron Chelating Agents; Deferiprone
• Other Study ID Numbers: LA40-0412