Healthy
Conditions
Keywords
deferiprone, deferiprone delayed release formulation, pharmacokinetics
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.
Interventions
DRUGDeferiprone delayed release tablet formulation
Deferiprone 600 mg delayed release tablet formulation
Deferiprone 100 mg/mL oral solution
Sponsors
Algorithme Pharma Inc
ApoPharma
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 49 Years
Healthy volunteers
Yes
Inclusion criteria
1. Male or female aged ≥18 to \<50 years 2. 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 3. 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 4. Body mass index (BMI) greater than or equal to 18.5 kg/m\^2 and below 30.0 kg/m\^2 5. Non- or ex smoker 6. Clinical laboratory values within the laboratory's stated normal range; if not within this range, an abnormal value must be without any clinical significance 7. 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
1. Pregnant or breastfeeding 2. Absolute neutrophil count (ANC) \< 1.8 x 109/L at screening (no repeat can be performed) 3. 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 4. 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 5. Presence of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic or dermatologic disease 6. 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 7. 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) 8. Any clinically significant illness in the previous 28 days before Day 1 of this study 9. Serum ferritin value below the normal limit of the reference laboratory at screening 10. Positive urine screening of alcohol and/or drugs of abuse 11. Positive results to HIV Ag/Ab Combo, Hepatitis B surface Antigen (HBsAG (B) (hepatitis B)) or anti-Hepatitis C Virus (HCV (C)) tests
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Healthy Volunteers Subjects were randomized to receive the following four treatments in different orders, with a 7-day washout period between treatments:
* Deferiprone delayed release tablets under fed conditions.
* Deferiprone delayed release tablets under fasting conditions.
* Deferiprone delayed release tablets administered as half-tablets, under fed conditions.
* Deferiprone oral solution under fasting conditions | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Withdrawal by Subject | 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 | 20 Participants |
| Region of Enrollment Canada | 20 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 18 | 4 / 18 | 5 / 19 | 6 / 17 |
| serious Total, serious adverse events | 0 / 18 | 0 / 18 | 0 / 19 | 0 / 17 |
Outcome results
Primary
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
Time frame: 24-hour interval
Population: The pharmacokinetics population included all subjects who provided evaluable data for at least one of the comparisons of interest
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Delayed Release, Fed Conditions | AUC0-∞for Serum Deferiprone and Deferiprone 3-O-glucuronide | AUC0-∞ for serum deferiprone | 36.70 ug*h/mL | Standard Deviation 9.37 |
| Delayed Release, Fed Conditions | AUC0-∞for Serum Deferiprone and Deferiprone 3-O-glucuronide | AUC0-∞ for serum deferiprone 3-O-glucuronide | 97.52 ug*h/mL | Standard Deviation 11.47 |
| Delayed Release, Fasting Conditions | AUC0-∞for Serum Deferiprone and Deferiprone 3-O-glucuronide | AUC0-∞ for serum deferiprone | 35.77 ug*h/mL | Standard Deviation 8.74 |
| Delayed Release, Fasting Conditions | AUC0-∞for Serum Deferiprone and Deferiprone 3-O-glucuronide | AUC0-∞ for serum deferiprone 3-O-glucuronide | 100.44 ug*h/mL | Standard Deviation 13.49 |
| Delayed Release Half-tablets | AUC0-∞for Serum Deferiprone and Deferiprone 3-O-glucuronide | AUC0-∞ for serum deferiprone | 37.18 ug*h/mL | Standard Deviation 9.72 |
| Delayed Release Half-tablets | AUC0-∞for Serum Deferiprone and Deferiprone 3-O-glucuronide | AUC0-∞ for serum deferiprone 3-O-glucuronide | 98.23 ug*h/mL | Standard Deviation 10.64 |
| Oral Solution, Fasting Conditions | AUC0-∞for Serum Deferiprone and Deferiprone 3-O-glucuronide | AUC0-∞ for serum deferiprone 3-O-glucuronide | 101.34 ug*h/mL | Standard Deviation 13.99 |
| Oral Solution, Fasting Conditions | AUC0-∞for Serum Deferiprone and Deferiprone 3-O-glucuronide | AUC0-∞ for serum deferiprone | 40.61 ug*h/mL | Standard Deviation 10.72 |
Primary
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
Time frame: 24-hour interval
Population: The pharmacokinetics population included all subjects who provided evaluable data for at least one of the comparisons of interest
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Delayed Release, Fed Conditions | Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide | Cmax for serum deferiprone | 8.05 μg/mL | Standard Deviation 2.85 |
| Delayed Release, Fed Conditions | Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide | Cmax for serum deferiprone 3-O-glucuronide | 15.77 μg/mL | Standard Deviation 3.8 |
| Delayed Release, Fasting Conditions | Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide | Cmax for serum deferiprone 3-O-glucuronide | 19.27 μg/mL | Standard Deviation 3.73 |
| Delayed Release, Fasting Conditions | Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide | Cmax for serum deferiprone | 8.21 μg/mL | Standard Deviation 2.18 |
| Delayed Release Half-tablets | Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide | Cmax for serum deferiprone | 7.43 μg/mL | Standard Deviation 2 |
| Delayed Release Half-tablets | Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide | Cmax for serum deferiprone 3-O-glucuronide | 15.40 μg/mL | Standard Deviation 4.33 |
| Oral Solution, Fasting Conditions | Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide | Cmax for serum deferiprone | 16.71 μg/mL | Standard Deviation 4.54 |
| Oral Solution, Fasting Conditions | Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide | Cmax for serum deferiprone 3-O-glucuronide | 21.87 μg/mL | Standard Deviation 4.34 |
Primary
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
Time frame: 24-hour interval
Population: The pharmacokinetics population included all subjects who provided evaluable data for at least one of the comparisons of interest
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Delayed Release, Fed Conditions | Tmax for Serum Deferiprone and Deferiprone 3-O-glucuronide | Tmax for serum deferiprone 3-O-glucuronide | 4.63 Hour | Standard Deviation 1.48 |
| Delayed Release, Fed Conditions | Tmax for Serum Deferiprone and Deferiprone 3-O-glucuronide | Tmax for serum deferiprone | 3.93 Hour | Standard Deviation 1.77 |
| Delayed Release, Fasting Conditions | Tmax for Serum Deferiprone and Deferiprone 3-O-glucuronide | Tmax for serum deferiprone | 2.05 Hour | Standard Deviation 0.6 |
| Delayed Release, Fasting Conditions | Tmax for Serum Deferiprone and Deferiprone 3-O-glucuronide | Tmax for serum deferiprone 3-O-glucuronide | 3.03 Hour | Standard Deviation 0.52 |
| Delayed Release Half-tablets | Tmax for Serum Deferiprone and Deferiprone 3-O-glucuronide | Tmax for serum deferiprone 3-O-glucuronide | 4.75 Hour | Standard Deviation 1.87 |
| Delayed Release Half-tablets | Tmax for Serum Deferiprone and Deferiprone 3-O-glucuronide | Tmax for serum deferiprone | 3.49 Hour | Standard Deviation 1.68 |
| Oral Solution, Fasting Conditions | Tmax for Serum Deferiprone and Deferiprone 3-O-glucuronide | Tmax for serum deferiprone 3-O-glucuronide | 1.87 Hour | Standard Deviation 0.34 |
| Oral Solution, Fasting Conditions | Tmax for Serum Deferiprone and Deferiprone 3-O-glucuronide | Tmax for serum deferiprone | 0.52 Hour | Standard Deviation 0.16 |
Secondary
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.
Time frame: Throughout the trial, from the time of the first dose until the last study visit (Day 30 or early termination)
Population: The safety population included all subjects who received at least one of the investigational products under study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Delayed Release, Fed Conditions | Number of Subjects With Adverse Events (AEs) | 3 participants |
| Delayed Release, Fasting Conditions | Number of Subjects With Adverse Events (AEs) | 4 participants |
| Delayed Release Half-tablets | Number of Subjects With Adverse Events (AEs) | 5 participants |
| Oral Solution, Fasting Conditions | Number of Subjects With Adverse Events (AEs) | 6 participants |