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

Hepatic Impairment Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01767103
• Other study ID #: LA40-0412
• Status: Completed
• Phase: Phase 4
• First received: January 9, 2013
• Last updated: September 3, 2014
• Start date: January 2013
• Est. completion date: April 2014

Study information

• Verified date: April 2014
• Source: ApoPharma
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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®.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: April 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Hepatic Impairment
• Liver Diseases

Intervention

Drug:
• Ferriprox®

Locations

Country	Name	City	State
United States	University of Miami	Miami	Florida
United States	Orlando Clinical Research Center	Orlando	Florida

Sponsors (1)

Lead Sponsor	Collaborator
ApoPharma

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	AUC0-8 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	No
Primary	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	No
Primary	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	No
Primary	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	No
Secondary	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	Yes