Healthy Volunteers
Conditions
Keywords
Healthy, Deferiprone, DFP, L1
Brief summary
Single center, randomized, double-blind, placebo-controlled, adaptive sequential ascending-dose study for the evaluation of the safety, tolerability, and pharmacokinetics of single doses of deferiprone administered by intravenous infusion to healthy males and females. A bioavailability comparison will be included.
Interventions
DRUGDeferiprone
Deferiprone for infusion, 10mg/mL for intravenous infusion. Oral dose of deferiprone: 80mg/mL oral solution. (Cohort 2)
DRUGPlacebo
Placebo: normal saline solution.
Sponsors
ApoPharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
Main Inclusion Criteria: 1. Healthy adult males or females, at least 18 years old but not older than 50 years. 2. Body weight at least 60kg. 3. Body Mass Index (BMI) ≥ 18.50 and ≤ 30.00 kg/m2 4. Medically healthy with clinically insignificant screening results (e.g., laboratory profiles, medical history, ECG, vital signs, physical examination. 5. Non or ex-smoker (someone who has completely stopped smoking 6 months before study start) 6. For females, negative result on a serum pregnancy test. Main
Exclusion criteria
1. Absolute neutrophil count (ANC) \<1.5x10\^9/L. 2. History or presence of hypersensitivity to deferiprone or any related products. 3. 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. 4. Presence of significant cardiovascular, pulmonary, hematologic, neurologic, psychiatric, endocrine, immunologic or dermatologic disease. 5. Any history of tuberculosis (TB) or prophylaxis for TB. 6. Suicidal tendency, history of seizures, head trauma with coma or craniotomy/trepanation, state of confusion or relevant psychiatric disease. 7. Inadequate venous access in either arm. 8. Presence of out-of-range cardiac interval or clinically significant ECG abnormalities (PR \<110 msec or \> 220 msec, QRS \<60 msec or \>119 msec, QTcB \> 450 msec for males and \>460 msec for females). 9. Use of acetaminophen, acetylsalicylic acid (ASA), or non-steroidal anti-inflammatory drugs (NSAIDs) in the previous 7 days before study start. 10. Use of any enzyme-modifying drugs, including strong inhibitors of P450 (CYP) enzymes such as cimetidine, fluoxetine, quinidine, erythromycin, ciprofloxacin, fluconazole, ketoconazole, diltiazem, and HIV antivirals OR strong inducers of CYP enzymes such as: barbiturates, carbamazepine, glucocorticoids, phenytoin, rifampin, and St. John's wart within 28 days prior to study start. 11. Maintenance therapy with any drug, or significant history of drug dependency or alcohol abuse. 12. Had a clinically significant illness during the 28 days prior to study start. 13. Receipt of an investigational product in another clinical trial within 28 days prior prior to study start. 14. Enrolment in a previous cohort of this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of Single Ascending Doses of Deferiprone When Administered by Intravenous Infusion in Healthy Volunteers. | From start of intravenous dosing until Day 5 post-dose for all subjects; and from time of oral dose until 24 hours post-dose for subjects who additionally received oral deferiprone | The number of participants who experienced adverse events (including any changes of clinical significance in physical examinations, vital signs, 12-lead ECG, and clinical laboratory tests) following a single dose of intravenous deferiprone. |
| Time to Maximum Observed Serum Concentration (Tmax) for Serum Deferiprone and Deferiprone 3-O-glucuronide | 14-hour interval | Tmax was assessed over a 14-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite in healthy volunteers who received single intravenous doses of 500 mg, 1000 mg, 1500 mg, and 2000 mg of intravenous deferiprone. Blood samples were obtained pre-dose and at 0.17, 0.33, 0.50, 0.75, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 9, 12, and 14 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). |
| Area Under the Curve From Zero to Infinity (AUC0-∞) for Serum Deferiprone and Deferiprone 3-O-glucuronide | 14-hour interval | AUC0-∞ was assessed over a 14-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite in healthy volunteers who received single intravenous doses of 500 mg, 1000 mg, 1500 mg, and 2000 mg of intravenous deferiprone. Blood samples were obtained pre-dose and at 0.17, 0.33, 0.50, 0.75, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 9, 12, and 14 hours post-dose. |
| The Terminal Elimination Half-life (T1/2el) for Serum Deferiprone and Deferiprone 3-O-glucuronide | 14-hour interval | T1/2el was assessed over a 14-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite in healthy volunteers who received single intravenous doses of 500 mg, 1000 mg, 1500 mg, and 2000 mg of intravenous deferiprone. Blood samples were obtained pre-dose and at 0.17, 0.33, 0.50, 0.75, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 9, 12, and 14 hours post-dose. |
| Maximum Measured Serum Concentration (Cmax) for Serum Deferiprone and Deferiprone 3-O-glucuronide | 14-hour interval | Cmax was assessed over a 14-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite in healthy volunteers who received single intravenous doses of 500 mg, 1000 mg, 1500 mg, and 2000 mg of intravenous deferiprone. Blood samples were obtained pre-dose and at 0.17, 0.33, 0.50, 0.75, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 9, 12, and 14 hours post-dose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Bioavailability of Deferiprone | 14-hour interval | The pharmacokinetic profile was assessed over a 14-hour interval for deferiprone in healthy volunteers who received a single intravenous dose of 1000 mg and then one week later received a single oral dose of 1000 mg deferiprone oral solution. In both cases, blood samples were obtained pre-dose and at 0.17, 0.33, 0.50, 0.75, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 9, 12, and 14 hours post-dose. |
| Safety and Tolerability of a Single 1000 mg Oral Dose of Deferiprone | From dosing until 24 hours post-dose | The number of participants who experienced adverse events (including any changes of clinical significance in physical examinations, vital signs, 12-lead ECG, and clinical laboratory tests) following a single dose of oral deferiprone. Note: All subjects in the 1000 mg cohort received active product, including the 2 who had received placebo for the intravenous infusion. |
| Comparison of Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide Between Deferiprone for Infusion and Oral Deferiprone | 14-hour interval | Cmax was assessed over a 14-hour interval for deferiprone in healthy volunteers who received a single intravenous dose of 1000 mg and then one week later received a single oral dose of 1000 mg deferiprone oral solution. In both cases, blood samples were obtained pre-dose and at 0.17, 0.33, 0.50, 0.75, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 9, 12, and 14 hours post-dose. |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 500 mg Deferiprone for Infusion Single intravenous dose of 500 mg deferiprone (deferiprone for infusion, 10 mg/mL) | 14 |
| 1000 mg Deferiprone for Infusion Single intravenous dose of 1000 mg deferiprone (deferiprone for infusion, 10 mg/mL) | 14 |
| 1500 mg Deferiprone for Infusion Single intravenous dose of 1500 mg deferiprone (deferiprone for infusion, 10 mg/mL) | 14 |
| 2000 mg Deferiprone for Infusion Single intravenous dose of 2000 mg deferiprone (deferiprone for infusion, 10 mg/mL) | 14 |
| Placebo Single intravenous dose of placebo (normal saline solution). | 8 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Technical problems with infusion | 0 | 0 | 1 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | 2000 mg Deferiprone for Infusion | Placebo | Total | 500 mg Deferiprone for Infusion | 1000 mg Deferiprone for Infusion | 1500 mg Deferiprone for Infusion |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 8 Participants | 64 Participants | 14 Participants | 14 Participants | 14 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 1 Participants | 8 Participants | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 7 Participants | 54 Participants | 12 Participants | 11 Participants | 13 Participants |
| Region of Enrollment Canada | 14 participants | 8 participants | 64 participants | 14 participants | 14 participants | 14 participants |
| Sex: Female, Male Female | 6 Participants | 4 Participants | 21 Participants | 1 Participants | 4 Participants | 6 Participants |
| Sex: Female, Male Male | 8 Participants | 4 Participants | 43 Participants | 13 Participants | 10 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 10 / 14 | 7 / 14 | 8 / 14 | 10 / 14 | 3 / 8 | 2 / 14 |
| serious Total, serious adverse events | 0 / 14 | 0 / 14 | 0 / 14 | 0 / 14 | 0 / 8 | 0 / 14 |
Outcome results
Primary
Area Under the Curve From Zero to Infinity (AUC0-∞) for Serum Deferiprone and Deferiprone 3-O-glucuronide
AUC0-∞ was assessed over a 14-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite in healthy volunteers who received single intravenous doses of 500 mg, 1000 mg, 1500 mg, and 2000 mg of intravenous deferiprone. Blood samples were obtained pre-dose and at 0.17, 0.33, 0.50, 0.75, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 9, 12, and 14 hours post-dose.
Time frame: 14-hour interval
Population: The pharmacokinetic population included all subjects who had sufficient data to derive the value of at least one pharmacokinetic parameter.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 500 mg Deferiprone for Infusion | Area Under the Curve From Zero to Infinity (AUC0-∞) for Serum Deferiprone and Deferiprone 3-O-glucuronide | AUC0-∞ for serum deferiprone | 18.326 μg*h/mL | Standard Deviation 4.115 |
| 500 mg Deferiprone for Infusion | Area Under the Curve From Zero to Infinity (AUC0-∞) for Serum Deferiprone and Deferiprone 3-O-glucuronide | AUC0-∞ for serum deferiprone 3-O-glucuronide | 38.504 μg*h/mL | Standard Deviation 8.011 |
| 1000 mg Deferiprone for Infusion | Area Under the Curve From Zero to Infinity (AUC0-∞) for Serum Deferiprone and Deferiprone 3-O-glucuronide | AUC0-∞ for serum deferiprone 3-O-glucuronide | 79.210 μg*h/mL | Standard Deviation 15.686 |
| 1000 mg Deferiprone for Infusion | Area Under the Curve From Zero to Infinity (AUC0-∞) for Serum Deferiprone and Deferiprone 3-O-glucuronide | AUC0-∞ for serum deferiprone | 41.805 μg*h/mL | Standard Deviation 6.797 |
| 1500 mg Deferiprone for Infusion | Area Under the Curve From Zero to Infinity (AUC0-∞) for Serum Deferiprone and Deferiprone 3-O-glucuronide | AUC0-∞ for serum deferiprone | 69.390 μg*h/mL | Standard Deviation 8.937 |
| 1500 mg Deferiprone for Infusion | Area Under the Curve From Zero to Infinity (AUC0-∞) for Serum Deferiprone and Deferiprone 3-O-glucuronide | AUC0-∞ for serum deferiprone 3-O-glucuronide | 105.829 μg*h/mL | Standard Deviation 13.052 |
| 2000 mg Deferiprone for Infusion | Area Under the Curve From Zero to Infinity (AUC0-∞) for Serum Deferiprone and Deferiprone 3-O-glucuronide | AUC0-∞ for serum deferiprone | 89.250 μg*h/mL | Standard Deviation 17.223 |
| 2000 mg Deferiprone for Infusion | Area Under the Curve From Zero to Infinity (AUC0-∞) for Serum Deferiprone and Deferiprone 3-O-glucuronide | AUC0-∞ for serum deferiprone 3-O-glucuronide | 161.507 μg*h/mL | Standard Deviation 16.876 |
Primary
Maximum Measured Serum Concentration (Cmax) for Serum Deferiprone and Deferiprone 3-O-glucuronide
Cmax was assessed over a 14-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite in healthy volunteers who received single intravenous doses of 500 mg, 1000 mg, 1500 mg, and 2000 mg of intravenous deferiprone. Blood samples were obtained pre-dose and at 0.17, 0.33, 0.50, 0.75, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 9, 12, and 14 hours post-dose.
Time frame: 14-hour interval
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 500 mg Deferiprone for Infusion | Maximum Measured Serum Concentration (Cmax) for Serum Deferiprone and Deferiprone 3-O-glucuronide | Cmax for serum deferiprone | 7.406 μg/mL | Standard Deviation 1.889 |
| 500 mg Deferiprone for Infusion | Maximum Measured Serum Concentration (Cmax) for Serum Deferiprone and Deferiprone 3-O-glucuronide | Cmax for serum deferiprone-3-O-glucuronide | 8.037 μg/mL | Standard Deviation 1.374 |
| 1000 mg Deferiprone for Infusion | Maximum Measured Serum Concentration (Cmax) for Serum Deferiprone and Deferiprone 3-O-glucuronide | Cmax for serum deferiprone-3-O-glucuronide | 16.490 μg/mL | Standard Deviation 4.348 |
| 1000 mg Deferiprone for Infusion | Maximum Measured Serum Concentration (Cmax) for Serum Deferiprone and Deferiprone 3-O-glucuronide | Cmax for serum deferiprone | 17.835 μg/mL | Standard Deviation 2.162 |
| 1500 mg Deferiprone for Infusion | Maximum Measured Serum Concentration (Cmax) for Serum Deferiprone and Deferiprone 3-O-glucuronide | Cmax for serum deferiprone | 27.749 μg/mL | Standard Deviation 2.768 |
| 1500 mg Deferiprone for Infusion | Maximum Measured Serum Concentration (Cmax) for Serum Deferiprone and Deferiprone 3-O-glucuronide | Cmax for serum deferiprone-3-O-glucuronide | 20.032 μg/mL | Standard Deviation 3.757 |
| 2000 mg Deferiprone for Infusion | Maximum Measured Serum Concentration (Cmax) for Serum Deferiprone and Deferiprone 3-O-glucuronide | Cmax for serum deferiprone | 36.644 μg/mL | Standard Deviation 6.643 |
| 2000 mg Deferiprone for Infusion | Maximum Measured Serum Concentration (Cmax) for Serum Deferiprone and Deferiprone 3-O-glucuronide | Cmax for serum deferiprone-3-O-glucuronide | 30.517 μg/mL | Standard Deviation 3.947 |
Primary
Safety and Tolerability of Single Ascending Doses of Deferiprone When Administered by Intravenous Infusion in Healthy Volunteers.
The number of participants who experienced adverse events (including any changes of clinical significance in physical examinations, vital signs, 12-lead ECG, and clinical laboratory tests) following a single dose of intravenous deferiprone.
Time frame: From start of intravenous dosing until Day 5 post-dose for all subjects; and from time of oral dose until 24 hours post-dose for subjects who additionally received oral deferiprone
Population: The safety population included all subjects who received study product.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 500 mg Deferiprone for Infusion | Safety and Tolerability of Single Ascending Doses of Deferiprone When Administered by Intravenous Infusion in Healthy Volunteers. | 10 participants |
| 1000 mg Deferiprone for Infusion | Safety and Tolerability of Single Ascending Doses of Deferiprone When Administered by Intravenous Infusion in Healthy Volunteers. | 7 participants |
| 1500 mg Deferiprone for Infusion | Safety and Tolerability of Single Ascending Doses of Deferiprone When Administered by Intravenous Infusion in Healthy Volunteers. | 8 participants |
| 2000 mg Deferiprone for Infusion | Safety and Tolerability of Single Ascending Doses of Deferiprone When Administered by Intravenous Infusion in Healthy Volunteers. | 10 participants |
| Placebo | Safety and Tolerability of Single Ascending Doses of Deferiprone When Administered by Intravenous Infusion in Healthy Volunteers. | 3 participants |
Primary
The Terminal Elimination Half-life (T1/2el) for Serum Deferiprone and Deferiprone 3-O-glucuronide
T1/2el was assessed over a 14-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite in healthy volunteers who received single intravenous doses of 500 mg, 1000 mg, 1500 mg, and 2000 mg of intravenous deferiprone. Blood samples were obtained pre-dose and at 0.17, 0.33, 0.50, 0.75, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 9, 12, and 14 hours post-dose.
Time frame: 14-hour interval
Population: The pharmacokinetic population included all subjects who had sufficient data to derive the value of at least one pharmacokinetic parameter.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 500 mg Deferiprone for Infusion | The Terminal Elimination Half-life (T1/2el) for Serum Deferiprone and Deferiprone 3-O-glucuronide | T1/2el for serum deferiprone | 1.68 hour | Standard Deviation 0.22 |
| 500 mg Deferiprone for Infusion | The Terminal Elimination Half-life (T1/2el) for Serum Deferiprone and Deferiprone 3-O-glucuronide | T1/2el for serum deferiprone 3-O-glucuronide | 2.00 hour | Standard Deviation 0.25 |
| 1000 mg Deferiprone for Infusion | The Terminal Elimination Half-life (T1/2el) for Serum Deferiprone and Deferiprone 3-O-glucuronide | T1/2el for serum deferiprone 3-O-glucuronide | 1.94 hour | Standard Deviation 0.25 |
| 1000 mg Deferiprone for Infusion | The Terminal Elimination Half-life (T1/2el) for Serum Deferiprone and Deferiprone 3-O-glucuronide | T1/2el for serum deferiprone | 1.77 hour | Standard Deviation 0.32 |
| 1500 mg Deferiprone for Infusion | The Terminal Elimination Half-life (T1/2el) for Serum Deferiprone and Deferiprone 3-O-glucuronide | T1/2el for serum deferiprone | 1.83 hour | Standard Deviation 0.22 |
| 1500 mg Deferiprone for Infusion | The Terminal Elimination Half-life (T1/2el) for Serum Deferiprone and Deferiprone 3-O-glucuronide | T1/2el for serum deferiprone 3-O-glucuronide | 2.01 hour | Standard Deviation 0.18 |
| 2000 mg Deferiprone for Infusion | The Terminal Elimination Half-life (T1/2el) for Serum Deferiprone and Deferiprone 3-O-glucuronide | T1/2el for serum deferiprone | 1.85 hour | Standard Deviation 0.17 |
| 2000 mg Deferiprone for Infusion | The Terminal Elimination Half-life (T1/2el) for Serum Deferiprone and Deferiprone 3-O-glucuronide | T1/2el for serum deferiprone 3-O-glucuronide | 1.94 hour | Standard Deviation 0.26 |
Primary
Time to Maximum Observed Serum Concentration (Tmax) for Serum Deferiprone and Deferiprone 3-O-glucuronide
Tmax was assessed over a 14-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite in healthy volunteers who received single intravenous doses of 500 mg, 1000 mg, 1500 mg, and 2000 mg of intravenous deferiprone. Blood samples were obtained pre-dose and at 0.17, 0.33, 0.50, 0.75, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 9, 12, and 14 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: 14-hour interval
Population: The pharmacokinetic population included all subjects who had sufficient data to derive the value of at least one pharmacokinetic parameter.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 500 mg Deferiprone for Infusion | Time to Maximum Observed Serum Concentration (Tmax) for Serum Deferiprone and Deferiprone 3-O-glucuronide | Tmax for Serum Deferiprone | 1.00 hour |
| 500 mg Deferiprone for Infusion | Time to Maximum Observed Serum Concentration (Tmax) for Serum Deferiprone and Deferiprone 3-O-glucuronide | Tmax for Serum Deferiprone 3-O-glucuronide | 2.50 hour |
| 1000 mg Deferiprone for Infusion | Time to Maximum Observed Serum Concentration (Tmax) for Serum Deferiprone and Deferiprone 3-O-glucuronide | Tmax for Serum Deferiprone 3-O-glucuronide | 2.50 hour |
| 1000 mg Deferiprone for Infusion | Time to Maximum Observed Serum Concentration (Tmax) for Serum Deferiprone and Deferiprone 3-O-glucuronide | Tmax for Serum Deferiprone | 1.00 hour |
| 1500 mg Deferiprone for Infusion | Time to Maximum Observed Serum Concentration (Tmax) for Serum Deferiprone and Deferiprone 3-O-glucuronide | Tmax for Serum Deferiprone | 1.00 hour |
| 1500 mg Deferiprone for Infusion | Time to Maximum Observed Serum Concentration (Tmax) for Serum Deferiprone and Deferiprone 3-O-glucuronide | Tmax for Serum Deferiprone 3-O-glucuronide | 2.50 hour |
| 2000 mg Deferiprone for Infusion | Time to Maximum Observed Serum Concentration (Tmax) for Serum Deferiprone and Deferiprone 3-O-glucuronide | Tmax for Serum Deferiprone | 1.00 hour |
| 2000 mg Deferiprone for Infusion | Time to Maximum Observed Serum Concentration (Tmax) for Serum Deferiprone and Deferiprone 3-O-glucuronide | Tmax for Serum Deferiprone 3-O-glucuronide | 2.50 hour |
Secondary
Absolute Bioavailability of Deferiprone
The pharmacokinetic profile was assessed over a 14-hour interval for deferiprone in healthy volunteers who received a single intravenous dose of 1000 mg and then one week later received a single oral dose of 1000 mg deferiprone oral solution. In both cases, blood samples were obtained pre-dose and at 0.17, 0.33, 0.50, 0.75, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 9, 12, and 14 hours post-dose.
Time frame: 14-hour interval
Population: The pharmacokinetic population included all subjects who had sufficient data to derive the value of at least one pharmacokinetic parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 500 mg Deferiprone for Infusion | Absolute Bioavailability of Deferiprone | 41.805 μg*h/mL | Standard Deviation 6.797 |
| 1000 mg Deferiprone for Infusion | Absolute Bioavailability of Deferiprone | 30.796 μg*h/mL | Standard Deviation 7.182 |
90% CI: [68.83, 77.56]
Secondary
Comparison of Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide Between Deferiprone for Infusion and Oral Deferiprone
Cmax was assessed over a 14-hour interval for deferiprone in healthy volunteers who received a single intravenous dose of 1000 mg and then one week later received a single oral dose of 1000 mg deferiprone oral solution. In both cases, blood samples were obtained pre-dose and at 0.17, 0.33, 0.50, 0.75, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 9, 12, and 14 hours post-dose.
Time frame: 14-hour interval
Population: The pharmacokinetic population included all subjects who had sufficient data to derive the value of at least one pharmacokinetic parameter.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 500 mg Deferiprone for Infusion | Comparison of Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide Between Deferiprone for Infusion and Oral Deferiprone | Cmax for serum deferiprone | 17.835 μg/mL | Standard Deviation 2.162 |
| 500 mg Deferiprone for Infusion | Comparison of Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide Between Deferiprone for Infusion and Oral Deferiprone | Cmax for serum deferiprone-3-O-glucuronide | 16.490 μg/mL | Standard Deviation 4.348 |
| 1000 mg Deferiprone for Infusion | Comparison of Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide Between Deferiprone for Infusion and Oral Deferiprone | Cmax for serum deferiprone | 11.692 μg/mL | Standard Deviation 3.436 |
| 1000 mg Deferiprone for Infusion | Comparison of Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide Between Deferiprone for Infusion and Oral Deferiprone | Cmax for serum deferiprone-3-O-glucuronide | 18.806 μg/mL | Standard Deviation 5.659 |
Secondary
Safety and Tolerability of a Single 1000 mg Oral Dose of Deferiprone
The number of participants who experienced adverse events (including any changes of clinical significance in physical examinations, vital signs, 12-lead ECG, and clinical laboratory tests) following a single dose of oral deferiprone. Note: All subjects in the 1000 mg cohort received active product, including the 2 who had received placebo for the intravenous infusion.
Time frame: From dosing until 24 hours post-dose
Population: The safety population included all subjects who received study product.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 500 mg Deferiprone for Infusion | Safety and Tolerability of a Single 1000 mg Oral Dose of Deferiprone | 2 participants |