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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Single Dose Crossover Comparative Bioavailability Study of Deferiprone 600 mg Delayed Release Tablets Versus Deferiprone Oral Solution in Healthy Male and Female Volunteers Following a 1200 mg Dose

Conditions
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Healthy

Intervention / Treatment
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* Drug: Deferiprone delayed release tablet formulation
* Drug: Deferiprone oral solution


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Delayed release, fed conditions<br>A single 1200 mg dose of deferiprone delayed release tablet formulation administered following a high-fat breakfast | Drug: Deferiprone delayed release tablet formulation<br>* Deferiprone 600 mg delayed release tablet formulation<br>* Other names: Deferiprone;|
| Experimental: Delayed release, fasting conditions<br>A single 1200 mg dose of deferiprone delayed release tablet formulation, administered following a 10-hour fast | Drug: Deferiprone delayed release tablet formulation<br>* Deferiprone 600 mg delayed release tablet formulation<br>* Other names: Deferiprone;|
| Experimental: Delayed release half-tablets<br>A single 1200 mg dose of deferiprone delayed release tablet formulation, following a high-fat breakfast | Drug: Deferiprone delayed release tablet formulation<br>* Deferiprone 600 mg delayed release tablet formulation<br>* Other names: Deferiprone;|
| Active Comparator: Oral solution, fasting conditions<br>A single 1200 mg dose of deferiprone oral solution, administered following a 10-hour fast | Drug: Deferiprone oral solution<br>* Deferiprone 100 mg/mL oral solution<br>* Other names: Ferriprox;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide | Maximum measured serum concentration. Blood samples will be collected pre-dose and over a 24-hour interval post-dose | 24-hour interval | 
| Tmax for Serum Deferiprone and Deferiprone 3-O-glucuronide | Time to maximum observed serum concentration. Blood samples will be collected pre-dose and over a 24-hour interval post-dose | 24-hour interval | 
| AUC0-∞for Serum Deferiprone and Deferiprone 3-O-glucuronide | 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 | 24-hour interval | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Adverse Events (AEs) | 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. | Throughout the trial, from the time of the first dose until the last study visit (Day 30 or early termination) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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deferiprone, deferiprone delayed release formulation, pharmacokinetics