Comparison of Deferiprone Extended Release Tablets and Ferriprox Immediate Release Tablets in Healthy Volunteers

Phase 1

Completed

Conditions: Healthy

Interventions: Drug: Deferiprone extended release
Drug: Deferiprone immediate release

Registration Number: NCT02465489

Lead Sponsor: ApoPharma

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

Detailed Description: This is a single-center, open-label, randomized, 5-period, 5-sequence study of the pharmacokinetics of a new formulation of deferiprone, extended 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

Status: COMPLETED

Sex: All

Target Recruitment: 20

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
Body weight of at least 60 kg
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
Suicidal tendency, history of seizures, history of head trauma with coma or craniotomy/trepanation, state of confusion, or clinically relevant psychiatric diseases
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
Use of any enzyme-modifying drugs, including strong inhibitors of cytochrome P450 (CYP) enzymes (such as cimetidine, fluoxetine, quinidine, erythromycin, ciprofloxacin, fluconazole, ketoconazole, diltiazem and HIV antivirals) and strong inducers of CYP enzymes (such as barbiturates, carbamazepine, glucocorticoids, phenytoin, rifampin and St John's Wort), in the previous 28 days before Day 1 of this study
Any history of tuberculosis and/or prophylaxis for tuberculosis
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 on HIV Ag/Ab Combo, Hepatitis B surface Antigen (HBsAG (B) (hepatitis B)) or anti-Hepatitis C Virus (HCV (C)) tests
Positive result on a serum pregnancy test
Receipt of an investigational product in another clinical trial in the previous 28 days before Day 1 of this study
Donation of 50 mL or more of blood in the previous 28 days before Day 1 of this study or donation of 500 mL or more of blood (Canadian Blood Services, Hema-Quebec, clinical studies, etc.) in the previous 56 days before Day 1 of this study

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
ER, fasting conditions	Deferiprone extended release	A single 1000 mg dose of deferiprone extended release tablet formulation administered under fasting conditions
ER half-tablets, fed conditions	Deferiprone extended release	A single 1000 mg dose of deferiprone extended release tablet formulation (one 1000 mg tablet divided in two) administered under fed conditions
ER, fed conditions	Deferiprone extended release	A single 1000 mg dose of deferiprone extended release tablet formulation administered under fed conditions
IR, fasting conditions	Deferiprone immediate release	A single 1000 mg dose of deferiprone immediate release tablet formulation administered under fasting conditions
IR, fed conditions	Deferiprone immediate release	A single 1000 mg dose of deferiprone immediate release tablet formulation administered under fed conditions

Primary Outcome Measures

Name	Time	Method
Cmax for Serum Deferiprone	Samples were collected pre-dose and at 0.25, 0.5, 0.75, 1.0, 1.33, 1.66, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 8.0, 12.0, 16.0, and 24.0 hours post-dose.	Maximum measured serum concentration. Blood samples will be collected pre-dose and over a 24-hour interval post-dose
Tmax for Serum Deferiprone	Samples were collected pre-dose and at 0.25, 0.5, 0.75, 1.0, 1.33, 1.66, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 8.0, 12.0, 16.0, and 24.0 hours post-dose.	Time of maximum observed serum concentration. Blood samples will be collected pre-dose and over a 24-hour interval post-dose
AUC0-∞for Serum Deferiprone	Samples were collected pre-dose and at 0.25, 0.5, 0.75, 1.0, 1.33, 1.66, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 8.0, 12.0, 16.0, and 24.0 hours post-dose.	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 36 or early termination)	Number of subjects with AEs. AEs will include clinically significant changes from baseline in vital signs, 12-lead ECG, physical examinations, and laboratory tests.