An Open-label, Non-randomized, Parallel Group Study in Subjects With Mild, Moderate, Severe, or No Renal Impairment

Study Overview
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Brief Summary
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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®.

Detailed Description
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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.

Official Title
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An Open-label Study to Compare the Pharmacokinetic Profiles of a Single Dose of Ferriprox in Subjects With Impaired Renal Function and Healthy Volunteers

Conditions
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Renal Impairment

Intervention / Treatment
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* Drug: Deferiprone


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: All subjects: Adult males or females, 18 - 75 years of age (inclusive); Body weight ≥ 45 kg; Body mass index (BMI) range of approximately 18.5-32 kg/m^2 (inclusive); Absolute neutrophil count (ANC) of >1.5x10^9/L; Healthy volunteers: Medically healthy with clinically insignificant screening results (e.g., laboratory profiles, medical history, vital signs, physical examination); eGFR ≥ 90 mL/min/1.73m^2; Renally impaired subjects: Considered clinically stable in the opinion of the Investigator; Subjects with mild renal impairment (eGFR 60-89 mL/min/1.73m^E2) OR moderate renal impairment (eGFR 30-59 mL/min/1.73m^2) OR severe renal impairment (eGFR 15-29 mL/min/1.73m^2). Main Exclusion Criteria: History of renal transplant; Subjects undergoing any method of dialysis; History or presence of clinically unstable significant respiratory, cardiovascular, pulmonary, hepatic, renal (except for subjects assigned to one of the renally impaired groups), hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease; Disorders or surgery of the gastrointestinal tract which may interfere with drug absorption or may otherwise influence the PK of the investigational medicinal product (e.g. cholecystectomy, resections of the small or large intestine, febrile conditions, chronic diarrhea, chronic vomiting, endocrine disease, severe infections, acute inflammations, etc.); Clinically significant abnormalities on 12-lead ECG (e.g., QTcF≥430 ms in males or ≥450 ms in females); Evidence of liver damage: hepatitis B and C; aspartate aminotransferase (AST), alanine aminotransferase (ALT) that is considered clinically significant by the Investigator; Participation in another clinical trial within 28 days prior to the study drug administration;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Normal renal function<br>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. | Drug: Deferiprone<br>* Oral iron chelator<br>* Other names: DFP;|
| Experimental: Mild Renal Impairment<br>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. | Drug: Deferiprone<br>* Oral iron chelator<br>* Other names: DFP;|
| Experimental: Moderate Renal Impairment<br>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. | Drug: Deferiprone<br>* Oral iron chelator<br>* Other names: DFP;|
| Experimental: Severe Renal Impairment<br>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. | Drug: Deferiprone<br>* Oral iron chelator<br>* Other names: DFP;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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. | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Renal Impairment, Kidney Impairment, Kidney Disease, Ferriprox, Deferiprone, DFP (deferiprone), L1