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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 | Experimental | Single dose of 500mg deferiprone or placebo administered via intravenous infusion. First 2 subjects to enroll: 1 will be randomized to receive deferiprone and the other to receive placebo. Next 14 subjects enrolled: 13 will be randomized to receive deferiprone and 1 to receive placebo. |
|
| Cohort 2 | Experimental | Single dose of 1000mg deferiprone or placebo administered via intravenous infusion and oral solution. Randomization will be done for all 16 subjects at the same time: 14 will be randomized to receive deferiprone and 2 to receive placebo. Subjects enrolled to cohort 2 will receive an oral dose of deferiprone. |
|
| Cohort 3 | Experimental | Single dose of 1500mg deferiprone or placebo administered via intravenous infusion. Randomization will be done for all 16 subjects at the same time, 14 will be randomized to receive deferiprone and 2 to receive placebo. |
|
| Cohort 4 | Experimental | Single dose of 2000mg deferiprone or placebo administered via intravenous infusion. First 2 subjects to enroll: 1 will be randomized to receive deferiprone and the other to receive placebo. Next 14 subjects enrolled: 13 will be randomized to receive deferiprone and 1 to receive placebo. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Deferiprone | Drug | Deferiprone for infusion, 10mg/mL for intravenous infusion. Oral dose of deferiprone: 80mg/mL oral solution. (Cohort 2) |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 14-hour interval |
| 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). | 14-hour interval |
| 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. | 14-hour interval |
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Main Inclusion Criteria:
Main Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Fernando Tricta, MD | ApoPharma Inc. | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Algorithme Pharma Inc. | Mount Royal | Quebec | H3P3P1 | Canada |
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| ID | Title | Description |
|---|---|---|
| FG000 | 500 mg Deferiprone | Single intravenous dose of 500 mg deferiprone (deferiprone for infusion, 10 mg/mL) |
| FG001 | 1000 mg Deferiprone | Single intravenous dose of 1000 mg deferiprone (deferiprone for infusion, 10 mg/mL), followed one week later by a single oral dose of 1000 mg deferiprone oral solution, 80 mg/mL |
| FG002 | 1500 mg Deferiprone | Single intravenous dose of 1500 mg deferiprone (deferiprone for infusion, 10 mg/mL) |
| FG003 | 2000 mg Deferiprone | Single intravenous dose of 2000 mg deferiprone (deferiprone for infusion, 10 mg/mL) |
| FG004 | Placebo | Single intravenous dose of placebo (normal saline solution). |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Healthy volunteers
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| ID | Title | Description |
|---|---|---|
| BG000 | 500 mg Deferiprone for Infusion | Single intravenous dose of 500 mg deferiprone (deferiprone for infusion, 10 mg/mL) |
| BG001 | 1000 mg Deferiprone for Infusion | Single intravenous dose of 1000 mg deferiprone (deferiprone for infusion, 10 mg/mL) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Posted | Mean | Standard Deviation | μg/mL | 14-hour interval |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 500 mg Deferiprone for Infusion | Single intravenous dose of 500 mg deferiprone (deferiprone for infusion, 10 mg/mL) |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Somnolence | Nervous system disorders | MedDRA v 16.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Caroline Fradette, PhD | ApoPharma Inc. | 416-401-7543 | cfradett@apopharma.com |
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| ID | Term |
|---|---|
| D000077543 | Deferiprone |
| D007531 | Isoflurophate |
| D020084 | Long Interspersed Nucleotide Elements |
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D011728 | Pyridones |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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|
| Placebo | Drug | Placebo: normal saline solution. |
|
|
| 14-hour interval |
| 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. | 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 |
| 14-hour interval |
| 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. | 14-hour interval |
| 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. | From dosing until 24 hours post-dose |
| Withdrawal by Subject |
|
| Technical problems with infusion |
|
| BG002 | 1500 mg Deferiprone for Infusion | Single intravenous dose of 1500 mg deferiprone (deferiprone for infusion, 10 mg/mL) |
| BG003 | 2000 mg Deferiprone for Infusion | Single intravenous dose of 2000 mg deferiprone (deferiprone for infusion, 10 mg/mL) |
| BG004 | Placebo | Single intravenous dose of placebo (normal saline solution). |
| BG005 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
Single intravenous dose of 1000 mg deferiprone (deferiprone for infusion, 10 mg/mL)
| OG002 | 1500 mg Deferiprone for Infusion | Single intravenous dose of 1500 mg deferiprone (deferiprone for infusion, 10 mg/mL) |
| OG003 | 2000 mg Deferiprone for Infusion | Single intravenous dose of 2000 mg deferiprone (deferiprone for infusion, 10 mg/mL) |
|
|
| 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). | The pharmacokinetic population included all subjects who had sufficient data to derive the value of at least one pharmacokinetic parameter. | Posted | Median | Full Range | hour | 14-hour interval |
|
|
|
| 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. | The pharmacokinetic population included all subjects who had sufficient data to derive the value of at least one pharmacokinetic parameter. | Posted | Mean | Standard Deviation | μg*h/mL | 14-hour interval |
|
|
|
| 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. | The pharmacokinetic population included all subjects who had sufficient data to derive the value of at least one pharmacokinetic parameter. | Posted | Mean | Standard Deviation | hour | 14-hour interval |
|
|
|
| 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. | The safety population included all subjects who received study product. | Posted | Number | participants | 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 |
|
|
|
| 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. | The pharmacokinetic population included all subjects who had sufficient data to derive the value of at least one pharmacokinetic parameter. | Posted | Mean | Standard Deviation | μg/mL | 14-hour interval |
|
|
|
| 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. | The pharmacokinetic population included all subjects who had sufficient data to derive the value of at least one pharmacokinetic parameter. | Posted | Mean | Standard Deviation | μg*h/mL | 14-hour interval |
|
|
|
|
| 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. | The safety population included all subjects who received study product. | Posted | Number | participants | From dosing until 24 hours post-dose |
|
|
|
| 0 |
| 14 |
| 10 |
| 14 |
| EG001 | 1000 mg Deferiprone for Infusion | Single intravenous dose of 1000 mg deferiprone (deferiprone for infusion, 10 mg/mL) | 0 | 14 | 7 | 14 |
| EG002 | 1500 mg Deferiprone for Infusion | Single intravenous dose of 1500 mg deferiprone (deferiprone for infusion, 10 mg/mL) | 0 | 14 | 8 | 14 |
| EG003 | 2000 mg Deferiprone for Infusion | Single intravenous dose of 2000 mg deferiprone (deferiprone for infusion, 10 mg/mL) | 0 | 14 | 10 | 14 |
| EG004 | Placebo | Single intravenous dose of placebo (normal saline solution). | 0 | 8 | 3 | 8 |
| EG005 | 1000 mg Oral Deferiprone | Single oral dose of 1000 mg deferiprone (deferiprone oral solution, 80 mg/mL) | 0 | 14 | 2 | 14 |
| Headache | Nervous system disorders | MedDRA v 16.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 16.1 | Systematic Assessment |
|
| Head discomfort | Nervous system disorders | MedDRA 16.1 | Systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA 16.1 | Systematic Assessment |
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| Vertigo | Nervous system disorders | MedDRA v 16.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA v 16.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA v 16.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA v 16.1 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA v 16.1 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA v 16.1 | Systematic Assessment |
|
| Feeling hot | General disorders | MedDRA v 16.1 | Systematic Assessment |
|
| Feeling of body temperature change | General disorders | MedDRA v 16.1 | Systematic Assessment |
|
| Catheter site swelling | Injury, poisoning and procedural complications | MedDRA v 16.1 | Systematic Assessment |
|
| Procedural complication | Injury, poisoning and procedural complications | MedDRA v 16.1 | Systematic Assessment |
|
| Procedural dizziness | Injury, poisoning and procedural complications | MedDRA v 16.1 | Systematic Assessment |
|
| Vessel puncture site pain | Injury, poisoning and procedural complications | MedDRA v 16.1 | Systematic Assessment |
|
| Vessel puncture site reaction | Injury, poisoning and procedural complications | MedDRA v 16.1 | Systematic Assessment |
|
| Catheter site pain | Injury, poisoning and procedural complications | MedDRA v 16.1 | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA v 16.1 | Systematic Assessment |
|
| Generalized erythema | Skin and subcutaneous tissue disorders | MedDRA v 16.1 | Systematic Assessment |
|
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA v 16.1 | Systematic Assessment |
|
| Sneezing | Respiratory, thoracic and mediastinal disorders | MedDRA v 16.1 | Systematic Assessment |
|
| C-reactive protein increased | Investigations | MedDRA v 16.1 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA v 16.1 | Systematic Assessment |
|
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| D063066 |
| Organofluorophosphonates |
| D063065 | Organophosphonates |
| D009943 | Organophosphorus Compounds |
| D009930 | Organic Chemicals |
| D018626 | Retroelements |
| D020071 | Interspersed Repetitive Sequences |
| D012091 | Repetitive Sequences, Nucleic Acid |
| D001483 | Base Sequence |
| D015394 | Molecular Structure |
| D001669 | Biochemical Phenomena |
| D055598 | Chemical Phenomena |
| D040342 | Genetic Structures |
| D055614 | Genetic Phenomena |
| D040481 | Genome Components |
| D016678 | Genome |
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |
| Tmax for Serum Deferiprone 3-O-glucuronide |
|
| AUC0-∞ for serum deferiprone 3-O-glucuronide |
|
| T1/2el for serum deferiprone 3-O-glucuronide |
|