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

• Sponsor: ApoPharma (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01770652
• Collaborator: (none)
• Enrollment: 32
• Locations: 2
• Arms: 4
• Duration (Months): 7
• Patients Per Site: 16
• Patients Per Site Per Month: 2.3

Study Details

Study Description

Brief Summary

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®.

Condition or Disease	Intervention/Treatment	Phase
Renal Impairment	Drug: Deferiprone	Phase 4

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Official Title: An Open-label Study to Compare the Pharmacokinetic Profiles of a Single Dose of Ferriprox in Subjects With Impaired Renal Function and Healthy Volunteers
• Study Start Date: Jan 1, 2013
• Actual Primary Completion Date: Jul 1, 2013
• Actual Study Completion Date: Aug 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Normal renal function 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; Oral iron chelator; Other Names: Ferriprox L1 DFP
Experimental: Mild Renal Impairment 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; Oral iron chelator; Other Names: Ferriprox L1 DFP
Experimental: Moderate Renal Impairment 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; Oral iron chelator; Other Names: Ferriprox L1 DFP
Experimental: Severe Renal Impairment 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; Oral iron chelator; Other Names: Ferriprox L1 DFP

Outcome Measures

Primary Outcome Measures

1. Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide [24-hour interval]

   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.

2. Tmax for Serum Deferiprone and Deferiprone 3-O-glucuronide [24 hour interval]

   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).

3. AUC Zero to Infinity (AUC0-∞) for Serum Deferiprone and Deferiprone 3-O-glucuronide [24 hour interval]

   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.

4. T1/2 for Serum Deferiprone and Deferiprone 3-O-glucuronide [24 hour interval]

   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.

5. Ae24 for Urine Deferiprone and Deferiprone 3-O-glucuronide [24 hour interval]

   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.

6. Fe24 for Serum Deferiprone and Deferiprone 3-O-glucuronide [24-hour interval]

   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.

Secondary Outcome Measures

1. Safety and Tolerability of Ferriprox® in Subjects With Renal Impairment. [From time of dosing until 72 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 Ferriprox.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Main Inclusion Criteria:

All subjects:

1. Adult males or females, 18 - 75 years of age (inclusive);

2. Body weight ≥ 45 kg;

3. Body mass index (BMI) range of approximately 18.5-32 kg/m^2 (inclusive);

4. Absolute neutrophil count (ANC) of >1.5x10^9/L;

Healthy volunteers:

1. Medically healthy with clinically insignificant screening results (e.g., laboratory profiles, medical history, vital signs, physical examination);

2. eGFR ≥ 90 mL/min/1.73m^2;

Renally impaired subjects:

1. Considered clinically stable in the opinion of the Investigator;

2. 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:

1. History of renal transplant;

2. Subjects undergoing any method of dialysis;

3. 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;

4. 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.);

5. Clinically significant abnormalities on 12-lead ECG (e.g., QTcF≥430 ms in males or ≥450 ms in females);

6. Evidence of liver damage: hepatitis B and C; aspartate aminotransferase (AST), alanine aminotransferase (ALT) that is considered clinically significant by the Investigator;

7. Participation in another clinical trial within 28 days prior to the study drug administration;

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hôpital Maisonneuve-Rosemont	Montreal	Quebec	Canada	H1T2M4
2	Algorithme Pharma Inc.	Mount-Royal	Quebec	Canada	H3P3P1

Sponsors and Collaborators

• ApoPharma

Investigators

• Study Chair: Fernando Tricta, MD, ApoPharma

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: ApoPharma
• ClinicalTrials.gov Identifier: NCT01770652
• Other Study ID Numbers: LA39-0412
• First Posted: Jan 18, 2013
• Last Update Posted: Aug 26, 2014
• Last Verified: Aug 1, 2013

• Keywords provided by ApoPharma: Renal Impairment; Kidney Impairment; Kidney Disease; Ferriprox; Deferiprone; DFP (deferiprone); L1
• Additional relevant MeSH terms: Renal Insufficiency; Deferiprone

Study Results

Participant Flow

Arm/Group Title	Normal Hepatic Function (Healthy Volunteers)	Mild Renal Impairment	Moderate Renal Impairment	Severe Renal Impairment
Arm/Group Description	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	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	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	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
Period Title: Overall Study
STARTED	8	8	8	8
COMPLETED	8	8	8	8
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Normal Hepatic Function (Healthy Volunteers)	Mild Renal Impairment	Moderate Renal Impairment	Severe Renal Impairment	Total
Arm/Group Description	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	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	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	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	Total of all reporting groups
Overall Participants	8	8	8	8	32
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	7 87.5%	6 75%	4 50%	6 75%	23 71.9%
>=65 years	1 12.5%	2 25%	4 50%	2 25%	9 28.1%
Sex: Female, Male (Count of Participants)
Female	5 62.5%	3 37.5%	3 37.5%	2 25%	13 40.6%
Male	3 37.5%	5 62.5%	5 62.5%	6 75%	19 59.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	2 25%	0 0%	0 0%	2 6.3%
White	8 100%	6 75%	8 100%	8 100%	30 93.8%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	8 100%	8 100%	8 100%	8 100%	32 100%
Region of Enrollment (participants) [Number]
Canada	8 100%	8 100%	8 100%	8 100%	32 100%

Outcome Measures

1. Primary Outcome

Title	Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide
Description	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.
Time Frame	24-hour interval

Outcome Measure Data

Analysis Population Description

The pharmacokinetic population included all subjects who had sufficient data to derive the value of at least one pharmacokinetic parameter.

Arm/Group Title	Normal Renal Function (Healthy Volunteers)	Mild Renal Impairment	Moderate Renal Impairment	Severe Renal Impairment
Arm/Group Description	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	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	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	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
Measure Participants	8	8	8	8
Cmax for serum deferiprone	37.1 (12.0)	33.4 (9.5)	43.3 (22.9)	30.6 (16.2)
Cmax for serum deferiprone-3-o-glucuronide	47.8 (6.2)	60.8 (10.3)	118.8 (48.3)	150.8 (32.4)

2. Secondary Outcome

Title	Safety and Tolerability of Ferriprox® in Subjects With Renal Impairment.
Description	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.
Time Frame	From time of dosing until 72 hours post-dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Normal Renal Function	Mild Renal Impairment	Moderate Renal Impairment	Severe Renal Impairment
Arm/Group Description	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. Deferiprone: Oral iron chelator	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. Deferiprone: Oral iron chelator	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. Deferiprone: Oral iron chelator	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. Deferiprone: Oral iron chelator
Measure Participants	8	8	8	8
Number [participants]	2 25%	5 62.5%	1 12.5%	1 12.5%

3. Primary Outcome

Title	Tmax for Serum Deferiprone and Deferiprone 3-O-glucuronide
Description	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).
Time Frame	24 hour interval

Outcome Measure Data

Analysis Population Description

The pharmacokinetic population included all subjects who had sufficient data to derive the value of at least one pharmacokinetic parameter.

Arm/Group Title	Normal Renal Function	Mild Renal Impairment	Moderate Renal Impairment	Severe Renal Impairment
Arm/Group Description	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. Deferiprone: Oral iron chelator	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. Deferiprone: Oral iron chelator	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. Deferiprone: Oral iron chelator	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. Deferiprone: Oral iron chelator
Measure Participants	8	8	8	8
Tmax for Serum Deferiprone	0.50	0.75	1.00	0.75
Tmax for Serum Deferiprone 3-O-glucuronide	2.50	2.50	3.00	4.00

4. Primary Outcome

Title	AUC Zero to Infinity (AUC0-∞) for Serum Deferiprone and Deferiprone 3-O-glucuronide
Description	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.
Time Frame	24 hour interval

Outcome Measure Data

Analysis Population Description

The pharmacokinetic population included all subjects who had sufficient data to derive the value of at least one pharmacokinetic parameter.

Arm/Group Title	Normal Renal Function	Mild Renal Impairment	Moderate Renal Impairment	Severe Renal Impairment
Arm/Group Description	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. Deferiprone: Oral iron chelator	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. Deferiprone: Oral iron chelator	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. Deferiprone: Oral iron chelator	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. Deferiprone: Oral iron chelator
Measure Participants	8	8	8	8
AUC0-∞ for serum deferiprone 3-O-Glucuronide	78.1 (27.8)	76.9 (15.7)	74.9 (15.1)	70.9 (8.5)
AUC0-∞ for serum deferiprone	252.6 (35.4)	319.1 (54.1)	703.2 (229.6)	1438.5 (335.5)

5. Primary Outcome

Title	T1/2 for Serum Deferiprone and Deferiprone 3-O-glucuronide
Description	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.
Time Frame	24 hour interval

Outcome Measure Data

Analysis Population Description

The pharmacokinetic population included all subjects who had sufficient data to derive the value of at least one pharmacokinetic parameter.

Arm/Group Title	Normal Renal Function	Mild Renal Impairment	Moderate Renal Impairment	Severe Renal Impairment
Arm/Group Description	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. Deferiprone: Oral iron chelator	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. Deferiprone: Oral iron chelator	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. Deferiprone: Oral iron chelator	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. Deferiprone: Oral iron chelator
Measure Participants	8	8	8	8
T1/2 for Serum Deferiprone	1.68 (0.27)	1.77 (0.17)	2.03 (0.32)	2.20 (0.91)
T1/2 for Serum Deferiprone 3-O-Glucuronide	2.14 (0.32)	2.58 (0.45)	2.58 (0.38)	3.35 (0.48)

6. Primary Outcome

Title	Ae24 for Urine Deferiprone and Deferiprone 3-O-glucuronide
Description	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.
Time Frame	24 hour interval

Outcome Measure Data

Analysis Population Description

The pharmacokinetic population included all subjects who had sufficient data to derive the value of at least one pharmacokinetic parameter.

Arm/Group Title	Normal Renal Function	Mild Renal Impairment	Moderate Renal Impairment	Severe Renal Impairment
Arm/Group Description	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. Deferiprone: Oral iron chelator	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. Deferiprone: Oral iron chelator	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. Deferiprone: Oral iron chelator	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. Deferiprone: Oral iron chelator
Measure Participants	8	8	8	8
Ae24 for urine deferiprone	78 (33)	69 (20)	36 (12)	24 (10)
e24 for urine deferiprone 3-O-Glucuronide	5987 (1332)	6608 (1630)	5812 (929)	5318 (1683)

7. Primary Outcome

Title	Fe24 for Serum Deferiprone and Deferiprone 3-O-glucuronide
Description	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.
Time Frame	24-hour interval

Outcome Measure Data

Analysis Population Description

The pharmacokinetic population included all subjects who had sufficient data to derive the value of at least one pharmacokinetic parameter

Arm/Group Title	Normal Renal Function	Mild Renal Impairment	Moderate Renal Impairment	Severe Renal Impairment
Arm/Group Description	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. Deferiprone: Oral iron chelator	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. Deferiprone: Oral iron chelator	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. Deferiprone: Oral iron chelator	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. Deferiprone: Oral iron chelator
Measure Participants	8	8	8	8
Fe24 for urine deferiprone	3.5 (1.6)	2.9 (0.6)	1.5 (0.5)	1.0 (0.4)
Fe24 for urine deferiprone 3-O-glucuronide	115.0 (16.2)	123.2 (12.7)	104.5 (11.6)	97.9 (28.5)

Adverse Events

Time Frame	Up to 4 days: from the time of administration of study drug until a follow-up telephone call 48 to 72 hours after discharge
Arm/Group Title	Normal Hepatic Function (Healthy Volunteers)		Mild Renal Impairment		Moderate Renal Impairment		Severe Renal Impairment
Arm/Group Description	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		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		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		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
All Cause Mortality
	Normal Hepatic Function (Healthy Volunteers)		Mild Renal Impairment		Moderate Renal Impairment		Severe Renal Impairment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Normal Hepatic Function (Healthy Volunteers)		Mild Renal Impairment		Moderate Renal Impairment		Severe Renal Impairment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)
Other (Not Including Serious) Adverse Events
	Normal Hepatic Function (Healthy Volunteers)		Mild Renal Impairment		Moderate Renal Impairment		Severe Renal Impairment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/8 (25%)		5/8 (62.5%)		1/8 (12.5%)		1/8 (12.5%)
Gastrointestinal disorders
Nausea	0/8 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/8 (0%)	0
Abnormal faeces	0/8 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/8 (0%)	0
Abdominal discomfort	1/8 (12.5%)	1	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0
Musculoskeletal and connective tissue disorders
Muscle spasms	0/8 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/8 (0%)	0
Nervous system disorders
Headache	1/8 (12.5%)	1	1/8 (12.5%)	1	1/8 (12.5%)	1	1/8 (12.5%)	1
Somnolence	1/8 (12.5%)	1	3/8 (37.5%)	3	0/8 (0%)	0	0/8 (0%)	0
Dysgeusia	1/8 (12.5%)	1	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0
Chills	1/8 (12.5%)	1	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0
Renal and urinary disorders
Dysuria	1/8 (12.5%)	2	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.