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Multi-center, non-randomized, open-label, single-dose, parallel group study to determine the effect of impaired renal function on the PK of deferiprone and its 3-O-glucuronide metabolite following a single oral dose of 33mg/kg Ferriprox®.
Post-marketing study to evaluate the effect of impaired renal function on the pharmacokinetics (PK) of deferiprone and its 3-O-glucuronide metabolite and on the safety of Ferriprox® in subjects with mild, moderate and severe renal impairment as compared to healthy volunteers.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Normal renal function | Experimental | Healthy volunteers, defined as having an estimated glomerular filtration rate (eGFR) ≥90 mL/min/1.73m^2. All subjects received a single 33 mg/kg oral dose of deferiprone. |
|
| Mild Renal Impairment | Experimental | Mild impairment, defined as having an eGFR 60-89 mL/min/1.73m^2. All subjects received a single 33 mg/kg oral dose of deferiprone. |
|
| Moderate Renal Impairment | Experimental | Mild impairment, defined as having an eGFR 30-59 mL/min/1.73m^2. All subjects received a single 33 mg/kg oral dose of deferiprone. |
|
| Severe Renal Impairment | Experimental | Severe impairment, defined as having an eGFR 15-19 mL/min/1.73m^2. All subjects received a single 33 mg/kg oral dose of deferiprone. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Deferiprone | Drug | Oral iron chelator |
|
| Measure | Description | Time Frame |
|---|---|---|
| Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide | Cmax was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite in subjects with normal, mild, moderate and severe renal impairment. Blood samples were obtained prior to dosing and at 0.25, 0.50, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 9, 12, 16, and 24 hours post-dose. | 24-hour interval |
| Tmax for Serum Deferiprone and Deferiprone 3-O-glucuronide | Tmax was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained prior to dosing and at 0.25, 0.50, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 9, 12, 16, and 24 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). | 24 hour interval |
| AUC Zero to Infinity (AUC0-∞) for Serum Deferiprone and Deferiprone 3-O-glucuronide | AUC0-∞ was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained prior to dosing and at 0.25, 0.50, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 9, 12, 16, and 24 hours post-dose. | 24 hour interval |
| T1/2 for Serum Deferiprone and Deferiprone 3-O-glucuronide | T1/2 was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained prior to dosing and at 0.25, 0.50, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 9, 12, 16, and 24 hours post-dose. | 24 hour interval |
| Ae24 for Urine Deferiprone and Deferiprone 3-O-glucuronide | Ae24 (the amount excreted in urine from time zero to 24 hours) was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite. Urine samples were collected at the intervals of -2 to 0 hours pre-dose and 0 to 2, 2 to 4, 4 to 8, 8 to 12, and 12 to 24 hours post-dose. |
| Measure | Description | Time Frame |
|---|---|---|
| Safety and Tolerability of Ferriprox® in Subjects With Renal Impairment. | 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 Ferriprox. | From time of dosing until 72 hours post-dose |
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Main Inclusion Criteria:
All subjects:
Healthy volunteers:
Renally impaired subjects:
Main Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Fernando Tricta, MD | ApoPharma | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hôpital Maisonneuve-Rosemont | Montreal | Quebec | H1T2M4 | Canada | ||
| Algorithme Pharma Inc. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Normal Hepatic Function (Healthy Volunteers) | Healthy volunteers as defined by an eGFR ≥90 mL/min/1.73m^2 as determined by the estimated glomerular filtration rate (eGFR) from the Modification of Diet in Renal Disease (MDRD) Study will receive a single 33mg/kg oral dose of deferiprone. Deferiprone |
| FG001 | Mild Renal Impairment | Mild renal impairment defined as eGFR 60-89 mL/min/1.73m^2 as determined by the estimated glomerular filtration rate (eGFR) from the Modification of Diet in Renal Disease (MDRD) Study will receive a single 33mg/kg oral dose of deferiprone. Deferiprone |
| FG002 | Moderate Renal Impairment | Moderate renal impairment as defined by eGFR 30-59 mL/min/1.73m^2 as determined by the estimated glomerular filtration rate (eGFR) from the Modification of Diet in Renal Disease (MDRD) Study will receive a single 33mg/kg oral dose of deferiprone. Deferiprone |
| FG003 | Severe Renal Impairment | Severe renal impairment as defined by an eGFR 15-19 mL/min/1.73m^2 as determined by the estimated glomerular filtration rate (eGFR) from the Modification of Diet in Renal Disease (MDRD) Study will receive a single 33mg/kg oral dose of deferiprone. Deferiprone |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Normal Hepatic Function (Healthy Volunteers) | Healthy volunteers as defined by an eGFR ≥90 mL/min/1.73m^2 as determined by the estimated glomerular filtration rate (eGFR) from the Modification of Diet in Renal Disease (MDRD) Study will receive a single 33mg/kg oral dose of deferiprone. Deferiprone |
| BG001 |
| 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 | Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide | Cmax was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite in subjects with normal, mild, moderate and severe renal impairment. Blood samples were obtained prior to dosing and at 0.25, 0.50, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 9, 12, 16, and 24 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 | 24-hour interval |
|
Up to 4 days: from the time of administration of study drug until a follow-up telephone call 48 to 72 hours after discharge
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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 | Normal Hepatic Function (Healthy Volunteers) | Healthy volunteers as defined by an eGFR ≥90 mL/min/1.73m^2 as determined by the estimated glomerular filtration rate (eGFR) from the Modification of Diet in Renal Disease (MDRD) Study will receive a single 33mg/kg oral dose of deferiprone. Deferiprone |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MedDRA | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Fernando Tricta, MD | ApoPharma Inc. | Phone: 416-401-7332 | ftricta@apopharma.com |
Not provided
| ID | Term |
|---|---|
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| ID | Term |
|---|---|
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
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| ID | Term |
|---|---|
| D000077543 | Deferiprone |
| D020084 | Long Interspersed Nucleotide Elements |
| D007531 | Isoflurophate |
| ID | Term |
|---|---|
| D011728 | Pyridones |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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|
| 24 hour interval |
| Fe24 for Serum Deferiprone and Deferiprone 3-O-glucuronide | Fe24 (fraction of dose excreted in urine from time zero to 24 hours) was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite. Urine samples were collected at the intervals of -2 to 0 hours pre-dose and 0 to 2, 2 to 4, 4 to 8, 8 to 12, and 12 to 24 hours post-dose. Some of the Fe24 values were over 100% which could be explained by variability in urine collection (e.g. incomplete collection of urine into the container) and volume measurement, as well as analytical imprecision. | 24-hour interval |
| Mount Royal |
| Quebec |
| H3P3P1 |
| Canada |
| Mild Renal Impairment |
Mild renal impairment defined as eGFR 60-89 mL/min/1.73m^2 as determined by the estimated glomerular filtration rate (eGFR) from the Modification of Diet in Renal Disease (MDRD) Study will receive a single 33mg/kg oral dose of deferiprone. Deferiprone |
| BG002 | Moderate Renal Impairment | Moderate renal impairment as defined by eGFR 30-59 mL/min/1.73m^2 as determined by the estimated glomerular filtration rate (eGFR) from the Modification of Diet in Renal Disease (MDRD) Study will receive a single 33mg/kg oral dose of deferiprone. Deferiprone |
| BG003 | Severe Renal Impairment | Severe renal impairment as defined by an eGFR 15-19 mL/min/1.73m^2 as determined by the estimated glomerular filtration rate (eGFR) from the Modification of Diet in Renal Disease (MDRD) Study will receive a single 33mg/kg oral dose of deferiprone. Deferiprone |
| BG004 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Mild Renal Impairment | Mild renal impairment defined as eGFR 60-89 mL/min/1.73m^2 as determined by the estimated glomerular filtration rate (eGFR) from the Modification of Diet in Renal Disease (MDRD) Study will receive a single 33mg/kg oral dose of deferiprone. Deferiprone |
| OG002 | Moderate Renal Impairment | Moderate renal impairment as defined by eGFR 30-59 mL/min/1.73m^2 as determined by the estimated glomerular filtration rate (eGFR) from the Modification of Diet in Renal Disease (MDRD) Study will receive a single 33mg/kg oral dose of deferiprone. Deferiprone |
| OG003 | Severe Renal Impairment | Severe renal impairment as defined by an eGFR 15-19 mL/min/1.73m^2 as determined by the estimated glomerular filtration rate (eGFR) from the Modification of Diet in Renal Disease (MDRD) Study will receive a single 33mg/kg oral dose of deferiprone. Deferiprone |
|
|
| Secondary | Safety and Tolerability of Ferriprox® in Subjects With Renal Impairment. | 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 Ferriprox. | Posted | Number | participants | From time of dosing until 72 hours post-dose |
|
|
|
| Primary | Tmax for Serum Deferiprone and Deferiprone 3-O-glucuronide | Tmax was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained prior to dosing and at 0.25, 0.50, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 9, 12, 16, and 24 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 | 24 hour interval |
|
|
|
| Primary | AUC Zero to Infinity (AUC0-∞) for Serum Deferiprone and Deferiprone 3-O-glucuronide | AUC0-∞ was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained prior to dosing and at 0.25, 0.50, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 9, 12, 16, and 24 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 | 24 hour interval |
|
|
|
| Primary | T1/2 for Serum Deferiprone and Deferiprone 3-O-glucuronide | T1/2 was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained prior to dosing and at 0.25, 0.50, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 9, 12, 16, and 24 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 | 24 hour interval |
|
|
|
| Primary | Ae24 for Urine Deferiprone and Deferiprone 3-O-glucuronide | Ae24 (the amount excreted in urine from time zero to 24 hours) was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite. Urine samples were collected at the intervals of -2 to 0 hours pre-dose and 0 to 2, 2 to 4, 4 to 8, 8 to 12, and 12 to 24 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 | mg | 24 hour interval |
|
|
|
| Primary | Fe24 for Serum Deferiprone and Deferiprone 3-O-glucuronide | Fe24 (fraction of dose excreted in urine from time zero to 24 hours) was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite. Urine samples were collected at the intervals of -2 to 0 hours pre-dose and 0 to 2, 2 to 4, 4 to 8, 8 to 12, and 12 to 24 hours post-dose. Some of the Fe24 values were over 100% which could be explained by variability in urine collection (e.g. incomplete collection of urine into the container) and volume measurement, as well as analytical imprecision. | The pharmacokinetic population included all subjects who had sufficient data to derive the value of at least one pharmacokinetic parameter | Posted | Mean | Standard Deviation | % of dose excreted in urine from 0-24 hr | 24-hour interval |
|
|
|
| 0 |
| 8 |
| 2 |
| 8 |
| EG001 | Mild Renal Impairment | Mild renal impairment defined as eGFR 60-89 mL/min/1.73m^2 as determined by the estimated glomerular filtration rate (eGFR) from the Modification of Diet in Renal Disease (MDRD) Study will receive a single 33mg/kg oral dose of deferiprone. Deferiprone | 0 | 8 | 5 | 8 |
| EG002 | Moderate Renal Impairment | Moderate renal impairment as defined by eGFR 30-59 mL/min/1.73m^2 as determined by the estimated glomerular filtration rate (eGFR) from the Modification of Diet in Renal Disease (MDRD) Study will receive a single 33mg/kg oral dose of deferiprone. Deferiprone | 0 | 8 | 1 | 8 |
| EG003 | Severe Renal Impairment | Severe renal impairment as defined by an eGFR 15-19 mL/min/1.73m^2 as determined by the estimated glomerular filtration rate (eGFR) from the Modification of Diet in Renal Disease (MDRD) Study will receive a single 33mg/kg oral dose of deferiprone. Deferiprone | 0 | 8 | 1 | 8 |
| Nausea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Abnormal faeces | Gastrointestinal disorders | MedDRA | Systematic Assessment | Soft stool |
|
| Somnolence | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment | Cramp in right calf |
|
| Dysuria | Renal and urinary disorders | MedDRA | Systematic Assessment | Difficulty urinating |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA | Systematic Assessment | Metallic taste in mouth |
|
| Chills | Nervous system disorders | MedDRA | Systematic Assessment | Shivering |
|
Not provided
| D052801 | Male Urogenital Diseases |
| 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 |
| D063066 | Organofluorophosphonates |
| D063065 | Organophosphonates |
| D009943 | Organophosphorus Compounds |
| D009930 | Organic Chemicals |
| Tmax for Serum Deferiprone 3-O-glucuronide |
|
| AUC0-∞ for serum deferiprone |
|
| T1/2 for Serum Deferiprone 3-O-Glucuronide |
|
| e24 for urine deferiprone 3-O-Glucuronide |
|
| Fe24 for urine deferiprone 3-O-glucuronide |
|