An Open-label, Non-randomized, Parallel Group Study in Su... | NCT01767103

NCT01767103

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Oversight Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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®

Name	Type	Description	Arm Group Labels	Other Names
Ferriprox®	Drug		Mild Hepatic Failure Moderate Hepatic Failure Normal Hepatic Function (healthy volunteers)

Outcomes Module

Primary Outcomes

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

Secondary Outcomes

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

Eligibility Module

Eligibility Criteria

Main Inclusion Criteria:

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.

Main Exclusion Criteria:

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;

Name	Affiliation	Role
Fernando Tricta, MD	ApoPharma	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
University of Miami		Miami	Florida	33136	United States
Orlando Clinical Research Center

Arm/Group Information

ID	Title	Description
FG000	Normal Hepatic Function (Healthy Volunteers)	Healthy volunteers with normal hepatic function. All subjects received a single 33 mg/kg oral dose of deferiprone.
FG001	Mild Hepatic Failure	Mild hepatic impairment as defined by Child-Pugh Class C: 5-6 points. All subjects received a single 33 mg/kg oral dose of deferiprone.
FG002	Moderate Hepatic Failure	Moderate hepatic impairment as defined by Child-Pugh Class : 7-9 points. All subjects received a single 33 mg/kg oral dose of deferiprone.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Normal Hepatic Function (Healthy Volunteers)	Healthy volunteers with normal hepatic function
BG001	Mild Hepatic Failure	Mild hepatic failure as defined by Child-Pugh Class C: 5-6 points

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical			Count of Participants

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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.

The PK Analysis Set consisted of all subjects who had sufficient data to derive at least one PK parameter

Posted

Mean

Standard Deviation

ug/mL

24-hour interval

ID	Title	Description
OG000	Normal Hepatic Function (Healthy Volunteers)	Healthy volunteers with normal hepatic function
OG001	Mild Hepatic Failure

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Normal Hepatic Function (Healthy Volunteers)	Healthy volunteers with normal hepatic function

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Liver injury	Hepatobiliary disorders	MedDRA (15.1)	Systematic Assessment

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Nausea	Gastrointestinal disorders	MedDRA (15.1)	Systematic Assessment

Title	Organization	Phone	Extension	Email
Fernando Tricta, MD	ApoPharma Inc.	416-401-7332		ftricta@apopharma.com

ID	Term
D008107	Liver Diseases

ID	Term
D004066	Digestive System Diseases

ID	Term
D000077543	Deferiprone
D007531	Isoflurophate
D020084	Long Interspersed Nucleotide Elements

ID	Term
D011728	Pyridones
D011725	Pyridines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds

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).