Comparison of Deferiprone Delayed Release Tablets and Deferiprone Oral Solution in Healthy Volunteers

Phase 1

Completed

Interventions: Drug: Deferiprone delayed release tablet formulation
Drug: Deferiprone oral solution

Brief Summary: The purpose of this study is to look at the pharmacokinetics of a new formulation of deferiprone (deferiprone delayed release tablets) under fed and fasting conditions.

Detailed Description: This is a single-center, open-label, randomized, 4-period crossover study of the pharmacokinetics of a new formulation of deferiprone, delayed release tablets in twenty healthy volunteers. In each study period, blood samples for pharmacokinetics assessment will be collected pre-dose and over 24 hours post-dose. Safety will be assessed throughout the study.

Recruitment & Eligibility

Inclusion Criteria

Male or female aged ≥18 to <50 years
A female volunteer of childbearing potential must agree to use an accepted contraceptive regimen from at least 28 days prior to the first administration of the study drug until at least 30 days after the last dose of the study drug
A sexually active male must agree that he and/or his female partner will use a medically acceptable method of contraception throughout the study and for at least 30 days following drug administration
Body mass index (BMI) greater than or equal to 18.5 kg/m^2 and below 30.0 kg/m^2
Non- or ex smoker
Clinical laboratory values within the laboratory's stated normal range; if not within this range, an abnormal value must be without any clinical significance
Have no clinically significant diseases captured in the medical history, or evidence of clinically significant findings on physical examination and/or clinical laboratory evaluations (hematology, general biochemistry, coagulation, ECG, and urinalysis)

Exclusion Criteria

Pregnant or breastfeeding
Absolute neutrophil count (ANC) < 1.8 x 109/L at screening (no repeat can be performed)
History of significant hypersensitivity to deferiprone or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (such as angioedema) to any drugs
History or presence of gastrointestinal, liver or kidney disease, or any other conditions known to interfere with the absorption, distribution, metabolism or excretion of drugs or known to potentiate or predispose to undesired effects
Presence of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic or dermatologic disease
Presence of out-of-range cardiac interval (PR < 110 msec, PR > 220 msec, QRS < 60 msec, QRS >119 msec and QTcF > 450 msec for males and > 460 msec for females) on the screening ECG or other clinically significant ECG abnormalities
Maintenance therapy with any drug or significant history of drug dependency or alcohol abuse (> 3 units of alcohol per day, intake of excessive alcohol, acute or chronic)
Any clinically significant illness in the previous 28 days before Day 1 of this study
Serum ferritin value below the normal limit of the reference laboratory at screening
Positive urine screening of alcohol and/or drugs of abuse
Positive results to HIV Ag/Ab Combo, Hepatitis B surface Antigen (HBsAG (B) (hepatitis B)) or anti-Hepatitis C Virus (HCV (C)) tests

Arm && Interventions

Group	Intervention	Description
Delayed release, fed conditions	Deferiprone delayed release tablet formulation	A single 1200 mg dose of deferiprone delayed release tablet formulation administered following a high-fat breakfast
Oral solution, fasting conditions	Deferiprone oral solution	A single 1200 mg dose of deferiprone oral solution, administered following a 10-hour fast
Delayed release, fasting conditions	Deferiprone delayed release tablet formulation	A single 1200 mg dose of deferiprone delayed release tablet formulation, administered following a 10-hour fast
Delayed release half-tablets	Deferiprone delayed release tablet formulation	A single 1200 mg dose of deferiprone delayed release tablet formulation, following a high-fat breakfast

Primary Outcome Measures

Name	Time	Method
Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide	24-hour interval	Maximum measured serum concentration. Blood samples will be collected pre-dose and over a 24-hour interval post-dose
Tmax for Serum Deferiprone and Deferiprone 3-O-glucuronide	24-hour interval	Time to maximum observed serum concentration. Blood samples will be collected pre-dose and over a 24-hour interval post-dose
AUC0-∞for Serum Deferiprone and Deferiprone 3-O-glucuronide	24-hour interval	Area under the serum concentration time curve extrapolated to infinity. Blood samples will be collected pre-dose and over a 24-hour interval post-dose

Secondary Outcome Measures

Name	Time	Method
Number of Subjects With Adverse Events (AEs)	Throughout the trial, from the time of the first dose until the last study visit (Day 30 or early termination)	Number of subjects with AEs, by frequency, severity, time to onset, duration, and relatedness to study product. AEs will include clinically significant changes from baseline in vital signs, 12-lead ECG, physical examinations, and laboratory tests.