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

NCT01767103 | Completed Phase 4 Results

• 1 other identifier: LA40-0412
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 2

Brief Summary

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®.

Conditions

Hepatic Impairment

Keywords

Hepatic Impairment; Liver Impairment; Liver Disease; Ferriprox®; LI; DFP; Deferiprone

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (1)

• Safety and Tolerability of Ferriprox in Subjects With or Without Hepatic Impairment.

  Time of dosing until 48 hours post-dose

Study Arms (3)

Normal Hepatic Function (healthy volunteers)

EXPERIMENTAL

Healthy volunteers with normal hepatic function received a single 33 mg/kg dose of Ferriprox®.

Drug: Ferriprox®

Mild Hepatic Failure

EXPERIMENTAL

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®

Moderate Hepatic Failure

EXPERIMENTAL

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®

Interventions

Ferriprox® DRUG

Also known as: DFP, Deferiprone, L1

Mild Hepatic Failure; Moderate Hepatic Failure; Normal Hepatic Function (healthy volunteers)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All subjects:
• Adult males or females, 18 - 75 years of age (inclusive);
• Body weight ≥ 50 kg;
• Body mass index (BMI) between 19 and 32 kg/mE2 (inclusive);
• Absolute neutrophil count (ANC) of \>1.5x10E9/L ;
• Healthy volunteers:
• Medically healthy with clinically insignificant screening results (e.g., laboratory profiles, medical history, vital signs, physical examination);
• Matched to hepatically impaired subjects in the study by age (+/- 10 years), sex and weight (+/- 15% BMI).
• Hepatically impaired subjects:
• Considered clinically stable in the opinion of the Investigator;
• 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.

You may not qualify if:

• 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).
• 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;
• 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;
• 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.);
• Received a pharmacological agent in another clinical trial within 28 days prior to the first dose of the study;

Sponsors & Collaborators

• ApoPharma: lead

Study Sites (2)

University of Miami

Miami, Florida, 33136, United States

Location

Orlando Clinical Research Center

Orlando, Florida, 32809, United States

Location

MeSH Terms

Conditions

Liver Diseases

Interventions

Deferiprone; Isoflurophate; Long Interspersed Nucleotide Elements

Condition Hierarchy (Ancestors)

Digestive System Diseases

Intervention Hierarchy (Ancestors)

Pyridones; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Organofluorophosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Retroelements; Interspersed Repetitive Sequences; Repetitive Sequences, Nucleic Acid; Base Sequence; Molecular Structure; Biochemical Phenomena; Chemical Phenomena; Genetic Structures; Genetic Phenomena; Genome Components; Genome

Results Point of Contact

• Title: Fernando Tricta, MD
• Organization: ApoPharma Inc.

ftricta@apopharma.com

416-401-7332

Study Officials

• Fernando Tricta, MD

  ApoPharma

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2013
• First Posted: January 14, 2013
• Study Start: January 1, 2013
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: September 10, 2014
• Results First Posted: September 10, 2014

Record last verified: 2014-04

Locations

US (2)