Sickle Cell Disease
Conditions
Keywords
sickle cell disease, iron overload, pharmacokinetics, Ferriprox, deferiprone
Brief summary
The objective of this study is to evaluate the pharmacokinetics of deferiprone and its 3-O-glucuronide metabolite following administration of a single 1500 mg dose of Ferriprox in patients with sickle cell disease.
Detailed description
This is a single-arm, single-dose study of Ferriprox in patients with sickle cell disease. Patients found to be eligible will visit the clinic the day before receiving the drug, in order to reconfirm eligibility and to undergo baseline assessments, and will receive a single dose of 1500 mg Ferriprox under fasting conditions. Blood and urine samples for pharmacokinetic assessment will be collected over a 10-hour period. Standard safety assessments will be performed throughout the study, and patients will return for a safety follow-up.
Interventions
DRUGsingle 1500 mg dose of Ferriprox
A single dose of 1500mg of Ferriprox (three 500mg tablets) administered under fasting conditions
Sponsors
ApoPharma
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female, 18-45 years of age (inclusive) 2. Diagnosis of sickle cell disease, confirmed by Hb electrophoresis 3. Body weight ≥ 50 kg 4. Body mass index (BMI) ≥ 18 and ≤ 32 kg/m\^2 5. Absolute neutrophil count (ANC) of \>1.5 x 10\^9/L 6. Women of childbearing potential must agree to either be sexually inactive or use an acceptable method of birth control for 14 days prior to dosing and for 30 days afterwards 7. A fertile heterosexual male must agree that he or his partner will use an effective method of contraception for 14 days prior to dosing and for 30 days afterwards
Exclusion criteria
1. History or presence of hypersensitivity or idiosyncratic reaction to Ferriprox 2. Use of Ferriprox within the past 3 months 3. History of malignancy 4. Evidence of abnormal liver function (serum Alanine Transaminase (ALT)level \> 5 times upper limit of normal or creatinine levels \>2 times upper limit of normal) 5. A serious, unstable illness, as judged by the Investigator, within the past 3 months before screening visit including but not limited to hepatic, renal, gastro-enterologic, respiratory, cardiovascular, endocrinologic, neurologic or immunologic disease 6. Hemodialysis during the week prior to dosing or planned for the day of dosing 7. Known difficulty in providing blood samples 8. Disorders or surgery of the gastrointestinal tract that may interfere with drug absorption or may otherwise influence the Pharmacokinetic (PK) results (e.g., resection of the small or large intestine, febrile conditions, chronic diarrhea, chronic vomiting, endocrine disease, severe infections, acute inflammations, etc.) 9. Clinically significant abnormalities on 12-lead ECG (e.g., QT interval corrected using Fridericia's formula (QTcF) ≥ 430 ms in males or ≥ 450 ms in females) 10. Use of tobacco/nicotine-containing products for at least 3 months prior to study drug administration 11. Use of any drugs within the past 14 days that are metabolized by the Uridine diphosphate glucosyltransferase enzyme (UGT1A6) and hence could affect the PK of Ferriprox 12. Treatment with an investigational drug within the past 30 days or 5 half-lives of that drug (whichever is longer) prior to study drug administration 13. Pregnant or nursing female
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide | 10-hour interval | Cmax (maximum measured serum concentration) was assessed over a 10-hour interval for deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained pre-dose and at 0.25, 0.50, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 8, and 10 hours post-dose. |
| Tmax for Deferiprone and Deferiprone 3-O-glucuronide | 10-hour interval | Tmax (time to the maximum measured serum concentration) was assessed over a 10-hour interval for deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained pre-dose and at 0.25, 0.50, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 8, and 10 hours post-dose. The results of the Tmax parameter are reported as the median and range (other parameters are reported as mean and standard deviation). |
| AUC0-∞ for Serum Deferiprone and Deferiprone 3-O-glucuronide | 10-hour interval | AUC0-∞ (area under the curve, zero to infinity) was assessed over a 10-hour interval for deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained pre-dose and at 0.25, 0.50, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 8, and 10 hours post-dose. |
| T1/2 for Serum Deferiprone and Deferiprone 3-O-glucuronide | 10-hour interval | T1/2 (apparent terminal elimination half-life) was assessed over a 10-hour interval for deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained pre-dose and at 0.25, 0.50, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 8, and 10 hours post-dose. |
Secondary
| Measure | Time frame |
|---|---|
| Frequency of Adverse Events | From Day 1 (Dosing) to Day 7 plus/minus 3 days (Follow-up) |
| Frequency of Serious Adverse Events | From Day 1 (Dosing) to Day 30 post-dose |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ferriprox A single dose of 1500 mg of Ferriprox (three 500 mg tablets) administered under fasting conditions | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | Ferriprox |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants |
| Age, Continuous | 33.0 years STANDARD_DEVIATION 5.9 |
| Region of Enrollment Canada | 8 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2 / 8 |
| serious Total, serious adverse events | 0 / 8 |
Outcome results
Primary
AUC0-∞ for Serum Deferiprone and Deferiprone 3-O-glucuronide
AUC0-∞ (area under the curve, zero to infinity) was assessed over a 10-hour interval for deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained pre-dose and at 0.25, 0.50, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 8, and 10 hours post-dose.
Time frame: 10-hour interval
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ferriprox | AUC0-∞ for Serum Deferiprone and Deferiprone 3-O-glucuronide | AUC0-∞ for serum deferiprone | 43.37 µg*hr/mL | Standard Deviation 5.39 |
| Ferriprox | AUC0-∞ for Serum Deferiprone and Deferiprone 3-O-glucuronide | AUC0-∞ for serum deferiprone 3-O-glucuronide | 142.7 µg*hr/mL | Standard Deviation 47.02 |
Primary
Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide
Cmax (maximum measured serum concentration) was assessed over a 10-hour interval for deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained pre-dose and at 0.25, 0.50, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 8, and 10 hours post-dose.
Time frame: 10-hour interval
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ferriprox | Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide | Cmax for serum deferiprone | 17.56 μg/mL | Standard Deviation 5.76 |
| Ferriprox | Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide | Cmax for serum deferiprone 3-O-glucuronide | 32.95 μg/mL | Standard Deviation 11.85 |
Primary
T1/2 for Serum Deferiprone and Deferiprone 3-O-glucuronide
T1/2 (apparent terminal elimination half-life) was assessed over a 10-hour interval for deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained pre-dose and at 0.25, 0.50, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 8, and 10 hours post-dose.
Time frame: 10-hour interval
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ferriprox | T1/2 for Serum Deferiprone and Deferiprone 3-O-glucuronide | T1/2 for serum deferiprone | 1.458 hr | Standard Deviation 0.207 |
| Ferriprox | T1/2 for Serum Deferiprone and Deferiprone 3-O-glucuronide | T1/2 for serum deferiprone 3-O-glucuronide | 1.575 hr | Standard Deviation 0.217 |
Primary
Tmax for Deferiprone and Deferiprone 3-O-glucuronide
Tmax (time to the maximum measured serum concentration) was assessed over a 10-hour interval for deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained pre-dose and at 0.25, 0.50, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 8, and 10 hours post-dose. The results of the Tmax parameter are reported as the median and range (other parameters are reported as mean and standard deviation).
Time frame: 10-hour interval
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Ferriprox | Tmax for Deferiprone and Deferiprone 3-O-glucuronide | Tmax for serum seferiprone | 1.000 hr |
| Ferriprox | Tmax for Deferiprone and Deferiprone 3-O-glucuronide | Tmax for serum deferiprone 3-O-glucuronide | 2.750 hr |
Secondary
Frequency of Adverse Events
Time frame: From Day 1 (Dosing) to Day 7 plus/minus 3 days (Follow-up)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ferriprox | Frequency of Adverse Events | 2 participants |
Secondary
Frequency of Serious Adverse Events
Time frame: From Day 1 (Dosing) to Day 30 post-dose
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ferriprox | Frequency of Serious Adverse Events | 0 participants |