Trial Outcomes & Findings for An Open-label, Non-randomized, Parallel Group Study in Subjects With Mild and Moderate Hepatic Insufficiency and Healthy Volunteers (NCT NCT01767103)
NCT ID: NCT01767103
Last Updated: 2014-09-10
Results Overview
Cmax was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite in subjects with normal hepatic function, mild hepatic impairment, or moderate hepatic 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.
COMPLETED
PHASE4
21 participants
24-hour interval
2014-09-10
Participant Flow
Participant milestones
| Measure |
Normal Hepatic Function (Healthy Volunteers)
Healthy volunteers with normal hepatic function. All subjects received a single 33 mg/kg oral dose of deferiprone.
|
Mild Hepatic Failure
Mild hepatic impairment as defined by Child-Pugh Class C: 5-6 points. All subjects received a single 33 mg/kg oral dose of deferiprone.
|
Moderate Hepatic Failure
Moderate hepatic impairment as defined by Child-Pugh Class : 7-9 points. All subjects received a single 33 mg/kg oral dose of deferiprone.
|
|---|---|---|---|
|
Overall Study
STARTED
|
7
|
7
|
7
|
|
Overall Study
COMPLETED
|
7
|
7
|
7
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
An Open-label, Non-randomized, Parallel Group Study in Subjects With Mild and Moderate Hepatic Insufficiency and Healthy Volunteers
Baseline characteristics by cohort
| Measure |
Normal Hepatic Function (Healthy Volunteers)
n=7 Participants
Healthy volunteers with normal hepatic function
|
Mild Hepatic Failure
n=7 Participants
Mild hepatic failure as defined by Child-Pugh Class C: 5-6 points
|
Moderate Hepatic Failure
n=7 Participants
Moderate hepatic failure as defined by Child-Pugh Class B: 7-9 points
|
Total
n=21 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=157 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
7 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
7 Participants
n=206 Participants
|
20 Participants
n=157 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
1 Participants
n=157 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
5 Participants
n=157 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=99 Participants
|
7 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
16 Participants
n=157 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=157 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=157 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=157 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
2 Participants
n=157 Participants
|
|
Race (NIH/OMB)
White
|
6 Participants
n=99 Participants
|
7 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
19 Participants
n=157 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=157 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=157 Participants
|
|
Region of Enrollment
United States
|
7 participants
n=99 Participants
|
7 participants
n=107 Participants
|
7 participants
n=206 Participants
|
21 participants
n=157 Participants
|
PRIMARY outcome
Timeframe: 24-hour intervalPopulation: The PK Analysis Set consisted of all subjects who had sufficient data to derive at least one PK parameter
Cmax was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite in subjects with normal hepatic function, mild hepatic impairment, or moderate hepatic 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.
Outcome measures
| Measure |
Normal Hepatic Function (Healthy Volunteers)
n=7 Participants
Healthy volunteers with normal hepatic function
|
Mild Hepatic Failure
n=7 Participants
Mild hepatic failure as defined by Child-Pugh Class C: 5-6 points
|
Moderate Hepatic Failure
n=7 Participants
Moderate hepatic failure as defined by the Child-Pugh Class B: 7-9 points
|
|---|---|---|---|
|
Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide
Cmax for serum deferiprone
|
49.00 ug/mL
Standard Deviation 24.081
|
36.26 ug/mL
Standard Deviation 8.4799
|
35.94 ug/mL
Standard Deviation 7.8407
|
|
Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide
Cmax for serum deferiprone 3-O-glucuronide
|
69.03 ug/mL
Standard Deviation 9.9153
|
56.91 ug/mL
Standard Deviation 11.416
|
55.33 ug/mL
Standard Deviation 25.335
|
PRIMARY outcome
Timeframe: 24-hour intervalPopulation: The PK Analysis Set consisted of all subjects who had sufficient data to derive at least one PK parameter
Tmax was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite in subjects with normal hepatic function, mild hepatic impairment, or moderate hepatic 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.
Outcome measures
| Measure |
Normal Hepatic Function (Healthy Volunteers)
n=7 Participants
Healthy volunteers with normal hepatic function
|
Mild Hepatic Failure
n=7 Participants
Mild hepatic failure as defined by Child-Pugh Class C: 5-6 points
|
Moderate Hepatic Failure
n=7 Participants
Moderate hepatic failure as defined by the Child-Pugh Class B: 7-9 points
|
|---|---|---|---|
|
Tmax for Serum Deferiprone and Deferiprone 3-O-glucuronide
Tmax of deferiprone 3-O-glucuronide
|
2.000 hour
Interval 1.0 to 3.0
|
3.000 hour
Interval 1.67 to 4.0
|
3.000 hour
Interval 3.0 to 4.0
|
|
Tmax for Serum Deferiprone and Deferiprone 3-O-glucuronide
Tmax of deferiprone
|
0.7500 hour
Interval 0.5 to 2.0
|
0.7500 hour
Interval 0.5 to 1.0
|
0.7500 hour
Interval 0.5 to 1.33
|
PRIMARY outcome
Timeframe: 24-hour intervalPopulation: The PK Analysis Set consisted of all subjects who had sufficient data to derive at least one PK parameter
AUC (area under the curve) from zero to infinity was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite in subjects with normal hepatic function, mild hepatic impairment, or moderate hepatic 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.
Outcome measures
| Measure |
Normal Hepatic Function (Healthy Volunteers)
n=7 Participants
Healthy volunteers with normal hepatic function
|
Mild Hepatic Failure
n=7 Participants
Mild hepatic failure as defined by Child-Pugh Class C: 5-6 points
|
Moderate Hepatic Failure
n=7 Participants
Moderate hepatic failure as defined by the Child-Pugh Class B: 7-9 points
|
|---|---|---|---|
|
AUC0-∞ for Serum Deferiprone and Deferiprone 3-O-glucuronide
AUC0-∞ for serum deferiprone 3-O-glucuronide
|
337.3 ug*hr/mL
Standard Deviation 45.343
|
305.1 ug*hr/mL
Standard Deviation 53.651
|
305.9 ug*hr/mL
Standard Deviation 111.75
|
|
AUC0-∞ for Serum Deferiprone and Deferiprone 3-O-glucuronide
AUC0-∞ for serum deferiprone
|
92.64 ug*hr/mL
Standard Deviation 19.221
|
82.02 ug*hr/mL
Standard Deviation 28.213
|
105.5 ug*hr/mL
Standard Deviation 41.684
|
PRIMARY outcome
Timeframe: 24-hour intervalPopulation: The PK Analysis Set consisted of all subjects who had sufficient data to derive at least one PK parameter
T1/2 was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite in subjects with normal hepatic function, mild hepatic impairment, or moderate hepatic 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.
Outcome measures
| Measure |
Normal Hepatic Function (Healthy Volunteers)
n=7 Participants
Healthy volunteers with normal hepatic function
|
Mild Hepatic Failure
n=7 Participants
Mild hepatic failure as defined by Child-Pugh Class C: 5-6 points
|
Moderate Hepatic Failure
n=7 Participants
Moderate hepatic failure as defined by the Child-Pugh Class B: 7-9 points
|
|---|---|---|---|
|
T1/2 for Serum Deferiprone and Deferiprone 3-O-glucuronide
T1/2 for serum deferiprone
|
1.994 hour
Standard Deviation 0.26971
|
1.855 hour
Standard Deviation 0.45370
|
2.180 hour
Standard Deviation 0.83153
|
|
T1/2 for Serum Deferiprone and Deferiprone 3-O-glucuronide
T1/2 for deferiprone 3-O-glu
|
2.621 hour
Standard Deviation 0.35653
|
2.518 hour
Standard Deviation 0.55679
|
2.479 hour
Standard Deviation 0.67212
|
PRIMARY outcome
Timeframe: 24-hour intervalPopulation: The PK Analysis Set consisted of all subjects who had sufficient data to derive at least one PK parameter. The data of one subject in the moderate hepatic failure group were dropped due to low or zero volume of urine samples.
Cumulative amount of deferiprone and deferiprone 3-O-glucuronide excreted in the urine. Urine samples were collected at the intervals of -2 to 0 hours pre-dose, and 0-2, 2-4, 4-8, 8-12 ,and 12- 24 hours post-dose. Note: For unknown reasons, the urine samples for one subject in the moderate hepatic failure group had low or zero volume and there were no measurable levels of deferiprone or its metabolite in any of the samples. Accordingly, the urine PK results were derived both with and without this subject's data, and are here presented without them (i.e., N=6 rather than 7).
Outcome measures
| Measure |
Normal Hepatic Function (Healthy Volunteers)
n=7 Participants
Healthy volunteers with normal hepatic function
|
Mild Hepatic Failure
n=7 Participants
Mild hepatic failure as defined by Child-Pugh Class C: 5-6 points
|
Moderate Hepatic Failure
n=6 Participants
Moderate hepatic failure as defined by the Child-Pugh Class B: 7-9 points
|
|---|---|---|---|
|
CumAe for Urine Deferiprone and Deferiprone 3-O-glucuronide
CumAe of urine deferiprone
|
69.0 mg
Standard Deviation 25.9
|
59.5 mg
Standard Deviation 19.4
|
62.9 mg
Standard Deviation 31.1
|
|
CumAe for Urine Deferiprone and Deferiprone 3-O-glucuronide
CumAe of urine deferiprone 3-O-glucuronide
|
6670 mg
Standard Deviation 2520
|
6787 mg
Standard Deviation 619
|
5979 mg
Standard Deviation 887
|
PRIMARY outcome
Timeframe: 24-hour intervalPopulation: The PK Analysis Set consisted of all subjects who had sufficient data to derive at least one PK parameter. The data of one subject in the moderate hepatic failure group were dropped due to low or zero volume of urine samples.
Cumulative fraction of Ferriprox dose excreted in urine as deferiprone or deferiprone 3-O-glucuronide. Urine samples were collected at the intervals of -2 to 0 hours pre-dose, and 0-2, 2-4, 4-8, 8-12 ,and 12- 24 hours post-dose. Note: For unknown reasons, the urine samples for one subject in the moderate hepatic failure group had low or zero volume and there were no measurable levels of deferiprone or its metabolite in any of the samples. Accordingly, the urine PK results were derived both with and without this subject's data, and are here presented without them (i.e., N=6 rather than 7).
Outcome measures
| Measure |
Normal Hepatic Function (Healthy Volunteers)
n=7 Participants
Healthy volunteers with normal hepatic function
|
Mild Hepatic Failure
n=7 Participants
Mild hepatic failure as defined by Child-Pugh Class C: 5-6 points
|
Moderate Hepatic Failure
n=6 Participants
Moderate hepatic failure as defined by the Child-Pugh Class B: 7-9 points
|
|---|---|---|---|
|
Fe% for Urine Deferiprone and Deferiprone 3-O-glucuronide
Fe of urine deferiprone
|
2.56 percentage of dose excreted in urine
Standard Deviation 0.773
|
2.18 percentage of dose excreted in urine
Standard Deviation 0.669
|
2.36 percentage of dose excreted in urine
Standard Deviation 1.20
|
|
Fe% for Urine Deferiprone and Deferiprone 3-O-glucuronide
Fe of urine 3-O-glucuronide
|
109 percentage of dose excreted in urine
Standard Deviation 32.4
|
110 percentage of dose excreted in urine
Standard Deviation 14.0
|
97.7 percentage of dose excreted in urine
Standard Deviation 13.7
|
SECONDARY outcome
Timeframe: Time of dosing until 48 hours post-dosePopulation: The Safety Analysis Set consisted of all subjects who received study medication and had at least one safety assessment
The number of participants who experienced adverse events following a single dose of Ferriprox, between the time of dosing and the follow-up visit (including any changes of clinical significance in physical examinations, vital signs, 12-lead ECG, and clinical laboratory tests).
Outcome measures
| Measure |
Normal Hepatic Function (Healthy Volunteers)
n=7 Participants
Healthy volunteers with normal hepatic function
|
Mild Hepatic Failure
n=7 Participants
Mild hepatic failure as defined by Child-Pugh Class C: 5-6 points
|
Moderate Hepatic Failure
n=7 Participants
Moderate hepatic failure as defined by the Child-Pugh Class B: 7-9 points
|
|---|---|---|---|
|
Safety and Tolerability of Ferriprox in Subjects With or Without Hepatic Impairment.
|
0 participants
|
1 participants
|
3 participants
|
Adverse Events
Normal Hepatic Function (Healthy Volunteers)
Mild Hepatic Failure
Moderate Hepatic Failure
Serious adverse events
| Measure |
Normal Hepatic Function (Healthy Volunteers)
n=7 participants at risk
Healthy volunteers with normal hepatic function
|
Mild Hepatic Failure
n=7 participants at risk
Mild hepatic failure as defined by the Child-Pugh Class C: 5-6 points
|
Moderate Hepatic Failure
n=7 participants at risk
Moderate hepatic failure as defined by the Child-Pugh Class B: 7-9 points
|
|---|---|---|---|
|
Hepatobiliary disorders
Liver injury
|
0.00%
0/7 • 2 days
Safety data were collected from the time of dosing up to the follow-up visit 48 hours post-dose
|
0.00%
0/7 • 2 days
Safety data were collected from the time of dosing up to the follow-up visit 48 hours post-dose
|
14.3%
1/7 • Number of events 1 • 2 days
Safety data were collected from the time of dosing up to the follow-up visit 48 hours post-dose
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/7 • 2 days
Safety data were collected from the time of dosing up to the follow-up visit 48 hours post-dose
|
0.00%
0/7 • 2 days
Safety data were collected from the time of dosing up to the follow-up visit 48 hours post-dose
|
14.3%
1/7 • Number of events 1 • 2 days
Safety data were collected from the time of dosing up to the follow-up visit 48 hours post-dose
|
Other adverse events
| Measure |
Normal Hepatic Function (Healthy Volunteers)
n=7 participants at risk
Healthy volunteers with normal hepatic function
|
Mild Hepatic Failure
n=7 participants at risk
Mild hepatic failure as defined by the Child-Pugh Class C: 5-6 points
|
Moderate Hepatic Failure
n=7 participants at risk
Moderate hepatic failure as defined by the Child-Pugh Class B: 7-9 points
|
|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/7 • 2 days
Safety data were collected from the time of dosing up to the follow-up visit 48 hours post-dose
|
0.00%
0/7 • 2 days
Safety data were collected from the time of dosing up to the follow-up visit 48 hours post-dose
|
14.3%
1/7 • Number of events 1 • 2 days
Safety data were collected from the time of dosing up to the follow-up visit 48 hours post-dose
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/7 • 2 days
Safety data were collected from the time of dosing up to the follow-up visit 48 hours post-dose
|
0.00%
0/7 • 2 days
Safety data were collected from the time of dosing up to the follow-up visit 48 hours post-dose
|
14.3%
1/7 • Number of events 1 • 2 days
Safety data were collected from the time of dosing up to the follow-up visit 48 hours post-dose
|
|
Investigations
Hepatic enzyme increased
|
0.00%
0/7 • 2 days
Safety data were collected from the time of dosing up to the follow-up visit 48 hours post-dose
|
0.00%
0/7 • 2 days
Safety data were collected from the time of dosing up to the follow-up visit 48 hours post-dose
|
14.3%
1/7 • Number of events 1 • 2 days
Safety data were collected from the time of dosing up to the follow-up visit 48 hours post-dose
|
|
Metabolism and nutrition disorders
Gout
|
0.00%
0/7 • 2 days
Safety data were collected from the time of dosing up to the follow-up visit 48 hours post-dose
|
14.3%
1/7 • Number of events 1 • 2 days
Safety data were collected from the time of dosing up to the follow-up visit 48 hours post-dose
|
0.00%
0/7 • 2 days
Safety data were collected from the time of dosing up to the follow-up visit 48 hours post-dose
|
|
Nervous system disorders
Headache
|
0.00%
0/7 • 2 days
Safety data were collected from the time of dosing up to the follow-up visit 48 hours post-dose
|
0.00%
0/7 • 2 days
Safety data were collected from the time of dosing up to the follow-up visit 48 hours post-dose
|
14.3%
1/7 • Number of events 1 • 2 days
Safety data were collected from the time of dosing up to the follow-up visit 48 hours post-dose
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Sponsor retained title to and the right to publish all documentation, records, raw data, specimens or other work product generated in connection with the trial. Such publications shall not be made without the prior written consent of Sponsor. Neither Party will use the other Party's name in connection with any publication or promotion without the other Party's prior written consent. However, Sponsor has the right to publish appropriate information in order to satisfy regulatory requirements.
- Publication restrictions are in place
Restriction type: OTHER