Pilot Study of the Pharmacokinetic Profile of Deferiprone Sustained-Release Formulation in Healthy Volunteers

Phase 1

Completed

Conditions: Healthy

Interventions: Drug: Deferiprone immediate-release
Drug: Deferiprone sustained-release

Registration Number: NCT02189941

Lead Sponsor: ApoPharma

Brief Summary: The purpose of this study was to evaluate the pharmacokinetic and safety profile of the sustained-release formulation of deferiprone under both fasting and fed conditions, and evaluate the relative bioavailability of this sustained-release formulation when compared to immediate-release formulation of deferiprone under fasting conditions.

Detailed Description: This was an open-label, single-dose, randomized, three-way crossover study under fed and fasting conditions designed to determine the pharmacokinetics, safety, and tolerability of deferiprone sustained-release tablets in healthy volunteers. Subjects were randomized to receive the following 3 treatments in different orders, with a washout period of 7 days between treatments:

* 2000 mg of deferiprone sustained-release tablets under fed conditions

* 2000 mg of deferiprone sustained-release tablets under fasted conditions

* 2000 mg of Ferriprox immediate-release tablets under fasted conditions

In each period, blood samples for pharmacokinetics (PK) assessment were collected prior to dosing and at specified time points up to 24 hours post-dose. Safety assessments were conducted throughout the study.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 11

Inclusion Criteria

Meeting the age, body mass index (BMI) and weight requirements.
Signing the Informed Consent Form.
Acceptable alcohol and/or drug screen at check-in of each period.
Acceptable health, blood pressure, pulse rate and temperature at check-in.
Being a non-smoker.
Female subjects of childbearing potential should be either sexually inactive (abstinent) for 60 days prior to the first dose of the study and throughout the study, and for 30 days after completion of the study, or be using an acceptable method of birth control.

Exclusion Criteria

A history of presence of significant asthma, chronic bronchitis, seizure, diabetes, migraine, hypertension, cardiovascular, pulmonary, neurological conditions, psychiatric conditions, hepatic, renal, hematopoietic or gastrointestinal diseases or ongoing infectious diseases, or any other significant abnormality as evidenced by a medical history and physical examination.
Blood chemistry, hematology, international normalized ratio, partial thromboplastin time and urinalysis values outside clinically acceptable limits.
A positive screen for Hepatitis B surface antigens, Hepatitis C antibodies or HIV.
Significant abnormality found on ECG.
Known sensitivity to deferiprone or any components of the Ferriprox tablets.
Requiring other medication at the time of the study. Oral, injectable or topical contraceptives, and contraceptive implants are permitted as they are acceptable methods of contraception.
Acetaminophen use within 2 weeks prior to dosing and for the duration of the study.
History of drug or alcohol abuse within the last 6 months.
Any known enzyme inducing or inhibiting drug taken within 30 days before the study.
History of long QT syndrome, cardiac arrhythmias.
Infection within two weeks prior to dosing.
Participation in an investigational drug study within 30 days prior to first dosing in this study.
Blood donation of 50 mL to 499 mL of whole blood within 30 days, or more than 499 mL of whole blood within 56 days prior to drug administration.
Positive test for pregnancy at medical screening or prior to dosing in either period.
Female subjects who are breast-feeding.
Absolute neutrophil count (ANC) <= 1.0 x 10E9 cells/L prior to dosing for each period.

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Deferiprone immediate-release (fasting)	Deferiprone immediate-release	A single 1000 mg dose of Deferiprone immediate-release under fasting conditions.
Deferiprone sustained-release (fed)	Deferiprone sustained-release	A single 1000 mg dose of deferiprone sustained-release following a high fat high calorie breakfast.
Deferiprone sustained-release (fasting)	Deferiprone sustained-release	A single 1000 mg dose of deferiprone sustained-release under fasting conditions.

Primary Outcome Measures

Name	Time	Method
AUCt for Serum Deferiprone and Deferiprone 3-O-glucuronide	24-hour interval	AUCt (Area Under the Curve to the last measured time) was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained prior to dosing and at 0.25, 0.5, 0.75, 1, 1.3333, 1.6667, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16 and 24 hours post-dose.
AUCinf for Serum Deferiprone and Deferiprone 3-O-glucuronide	24-hour interval	AUCinf (Area Under the Curve to infinity) was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained prior to dosing and at 0.25, 0.5, 0.75, 1, 1.3333, 1.6667, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16 and 24 hours post-dose.
Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide	24-hour interval	Cmax (maximum concentration in the serum) was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained prior to dosing and at 0.25, 0.5, 0.75, 1, 1.3333, 1.6667, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16 and 24 hours post-dose.
Tmax for Serum Deferiprone and Deferiprone 3-O-glucuronide	24-hour interval	Tmax (the time to Cmax) was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained prior to dosing and at 0.25, 0.5, 0.75, 1, 1.3333, 1.6667, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16 and 24 hours post-dose.
Thalf for Serum Deferiprone and Deferiprone 3-O-glucuronide	24-hour interval	Thalf (the apparent terminal elimination half-life of the drug) was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained prior to dosing and at 0.25, 0.5, 0.75, 1, 1.3333, 1.6667, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16 and 24 hours post-dose.

Secondary Outcome Measures

Name	Time	Method
Safety and Tolerability of Deferiprone Sustained Release Tablets	From time of dose until 24 hours post dose	The number of participants who experienced adverse events between the time of dosing up to 24 hours post-dose, including any changes of clinical significance in vital signs, 12-lead ECG, and clinical laboratory tests