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

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

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02189941

Enrollment

Registered

2014-07-15

Start date

2014-05-31

Completion date

2014-06-30

Last updated

2016-05-20

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy

Keywords

Deferiprone, Deferiprone sustained-release tablets, Pharmacokinetics

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.

Interventions

DRUGDeferiprone sustained-release

Deferiprone sustained-release tablets

DRUGDeferiprone immediate-release

Deferiprone immediate-release tablets

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 55 Years

Healthy volunteers

Yes

Inclusion criteria

Main 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.

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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

Countries

Canada

Participant flow

Recruitment details

Subjects were dosed at the clinic between May and June of 2014

Pre-assignment details

Subjects were randomized to receive 3 single-dose treatments in different sequences, with a washout of 7 days between doses. Twenty (20) subjects were screened and 12 were randomized. One subject experienced a medical event prior to the first dosing and was excluded from the study, so only 11 subjects received at least 1 dose of study product.

Participants by arm

Arm	Count
Healthy Volunteers Subjects received one dose of deferiprone sustained-release tablets under fed conditions, one dose of deferiprone sustained-release tablets under fasting conditions, and one dose of deferiprone immediate-release tablets under fasting conditions, 7 days apart	11
Total	11

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Non-compliance	0	0	1

Baseline characteristics

Characteristic	Healthy Volunteers
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	0 Participants
Age, Categorical Between 18 and 65 years	11 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	1 Participants
Race (NIH/OMB) Black or African American	5 Participants
Race (NIH/OMB) More than one race	2 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	3 Participants
Region of Enrollment Canada	11 participants
Sex: Female, Male Female	4 Participants
Sex: Female, Male Male	7 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	5 / 10	5 / 10	6 / 11
serious Total, serious adverse events	0 / 10	0 / 10	0 / 11

Outcome results

Primary

AUCinf for Serum Deferiprone and Deferiprone 3-O-glucuronide

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.

Time frame: 24-hour interval