Trial Outcomes & Findings for Pilot Study of the Pharmacokinetic Profile of Deferiprone Sustained-Release Formulation in Healthy Volunteers (NCT NCT02189941)
NCT ID: NCT02189941
Last Updated: 2016-05-20
Results Overview
AUCt (Area Under the Curve to the last measured time) 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, 0.5, 0.75, 1, 1.3333, 1.6667, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16 and 24 hours post-dose.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
11 participants
Primary outcome timeframe
24-hour interval
Results posted on
2016-05-20
Participant Flow
Subjects were dosed at the clinic between May and June of 2014
Subjects were randomized to receive 3 single-dose treatments in different sequences, with a washout of 7 days between doses. Twenty (20) subjects were screened and 12 were randomized. One subject experienced a medical event prior to the first dosing and was excluded from the study, so only 11 subjects received at least 1 dose of study product.
Participant milestones
| Measure |
DFP-SR Fed, Then DFP-SR Fasting, Then Ferriprox Fasting
Subjects received 3 treatments in the following order, with a 7-day washout period between treatments:
1. One dose of deferiprone sustained-release (DFP-SR) tablets under fed conditions
2. One dose of deferiprone sustained-release tablets under fasting conditions
3. One dose of Ferriprox immediate-release (IR) tablets under fasting conditions
|
DFP-SR Fasting, Then Ferriprox Fasting, Then DFP-SR Fed
Subjects received 3 treatments in the following order, with a 7-day washout period between treatments:
1. One dose of deferiprone sustained-release tablets under fasting conditions
2. One dose of Ferriprox immediate-release tablets under fasting conditions
3. One dose of deferiprone sustained-release tablets under fed conditions
|
Ferriprox Fasting, Then DFP-SR Fed, Then DFP-SR Fasting
Subjects received 3 treatments in the following order, with a 7-day washout period between treatments:
1. One dose of Ferriprox immediate-release tablets under fasting conditions
2. One dose of deferiprone sustained-release tablets under fed conditions
3. One dose of deferiprone sustained-release tablets under fasting conditions
|
|---|---|---|---|
|
Overall Study
STARTED
|
4
|
4
|
3
|
|
Overall Study
COMPLETED
|
4
|
4
|
2
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
1
|
Reasons for withdrawal
| Measure |
DFP-SR Fed, Then DFP-SR Fasting, Then Ferriprox Fasting
Subjects received 3 treatments in the following order, with a 7-day washout period between treatments:
1. One dose of deferiprone sustained-release (DFP-SR) tablets under fed conditions
2. One dose of deferiprone sustained-release tablets under fasting conditions
3. One dose of Ferriprox immediate-release (IR) tablets under fasting conditions
|
DFP-SR Fasting, Then Ferriprox Fasting, Then DFP-SR Fed
Subjects received 3 treatments in the following order, with a 7-day washout period between treatments:
1. One dose of deferiprone sustained-release tablets under fasting conditions
2. One dose of Ferriprox immediate-release tablets under fasting conditions
3. One dose of deferiprone sustained-release tablets under fed conditions
|
Ferriprox Fasting, Then DFP-SR Fed, Then DFP-SR Fasting
Subjects received 3 treatments in the following order, with a 7-day washout period between treatments:
1. One dose of Ferriprox immediate-release tablets under fasting conditions
2. One dose of deferiprone sustained-release tablets under fed conditions
3. One dose of deferiprone sustained-release tablets under fasting conditions
|
|---|---|---|---|
|
Overall Study
Non-compliance
|
0
|
0
|
1
|
Baseline Characteristics
Pilot Study of the Pharmacokinetic Profile of Deferiprone Sustained-Release Formulation in Healthy Volunteers
Baseline characteristics by cohort
| Measure |
Healthy Volunteers
n=11 Participants
Subjects received one dose of deferiprone sustained-release tablets under fed conditions, one dose of deferiprone sustained-release tablets under fasting conditions, and one dose of deferiprone immediate-release tablets under fasting conditions, 7 days apart
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
11 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
9 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
11 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 24-hour intervalPopulation: All subjects who contributed evaluable pharmacokinetics data
AUCt (Area Under the Curve to the last measured time) 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, 0.5, 0.75, 1, 1.3333, 1.6667, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16 and 24 hours post-dose.
Outcome measures
| Measure |
Deferiprone Sustained-release (Fed)
n=10 Participants
A single 2000 mg dose of deferiprone sustained-release following a high fat high calorie breakfast.
Deferiprone sustained-release: Deferiprone sustained-release tablets
|
Deferiprone Sustained-release (Fasting)
n=10 Participants
A single 2000 mg dose of deferiprone sustained-release under fasting conditions.
Deferiprone sustained-release: Deferiprone sustained-release tablets
|
Deferiprone Immediate-release (Fasting)
n=11 Participants
A single 2000 mg dose of Deferiprone immediate-release under fasting conditions.
Deferiprone immediate-release: Deferiprone immediate-release tablets
|
|---|---|---|---|
|
AUCt for Serum Deferiprone and Deferiprone 3-O-glucuronide
Deferiprone
|
63.5 mcg*h/mL
Standard Deviation 10.0
|
52.3 mcg*h/mL
Standard Deviation 14.8
|
71.1 mcg*h/mL
Standard Deviation 10.9
|
|
AUCt for Serum Deferiprone and Deferiprone 3-O-glucuronide
Deferiprone 3-O-glucuronide
|
171.9 mcg*h/mL
Standard Deviation 33.4
|
147.2 mcg*h/mL
Standard Deviation 41.5
|
192.7 mcg*h/mL
Standard Deviation 32.8
|
PRIMARY outcome
Timeframe: 24-hour intervalPopulation: All subjects who contributed evaluable pharmacokinetics data
AUCinf (Area Under the Curve to infinity) 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, 0.5, 0.75, 1, 1.3333, 1.6667, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16 and 24 hours post-dose.
Outcome measures
| Measure |
Deferiprone Sustained-release (Fed)
n=10 Participants
A single 2000 mg dose of deferiprone sustained-release following a high fat high calorie breakfast.
Deferiprone sustained-release: Deferiprone sustained-release tablets
|
Deferiprone Sustained-release (Fasting)
n=10 Participants
A single 2000 mg dose of deferiprone sustained-release under fasting conditions.
Deferiprone sustained-release: Deferiprone sustained-release tablets
|
Deferiprone Immediate-release (Fasting)
n=11 Participants
A single 2000 mg dose of Deferiprone immediate-release under fasting conditions.
Deferiprone immediate-release: Deferiprone immediate-release tablets
|
|---|---|---|---|
|
AUCinf for Serum Deferiprone and Deferiprone 3-O-glucuronide
Deferiprone
|
66.2 mcg*h/mL
Standard Deviation 11.1
|
57.2 mcg*h/mL
Standard Deviation 16.1
|
71.6 mcg*h/mL
Standard Deviation 11.0
|
|
AUCinf for Serum Deferiprone and Deferiprone 3-O-glucuronide
Deferiprone 3-O-glucuronide
|
181.3 mcg*h/mL
Standard Deviation 39.9
|
169.2 mcg*h/mL
Standard Deviation 62.3
|
193.4 mcg*h/mL
Standard Deviation 32.5
|
PRIMARY outcome
Timeframe: 24-hour intervalPopulation: All subjects who contributed evaluable pharmacokinetics data
Cmax (maximum concentration in the serum) 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, 0.5, 0.75, 1, 1.3333, 1.6667, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16 and 24 hours post-dose.
Outcome measures
| Measure |
Deferiprone Sustained-release (Fed)
n=10 Participants
A single 2000 mg dose of deferiprone sustained-release following a high fat high calorie breakfast.
Deferiprone sustained-release: Deferiprone sustained-release tablets
|
Deferiprone Sustained-release (Fasting)
n=10 Participants
A single 2000 mg dose of deferiprone sustained-release under fasting conditions.
Deferiprone sustained-release: Deferiprone sustained-release tablets
|
Deferiprone Immediate-release (Fasting)
n=11 Participants
A single 2000 mg dose of Deferiprone immediate-release under fasting conditions.
Deferiprone immediate-release: Deferiprone immediate-release tablets
|
|---|---|---|---|
|
Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide
Deferiprone
|
8.7 mcg/mL
Standard Deviation 1.8
|
5.8 mcg/mL
Standard Deviation 1.6
|
21.9 mcg/mL
Standard Deviation 6.9
|
|
Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide
Deferiprone 3-O-glucuronide
|
18.5 mcg/mL
Standard Deviation 4.2
|
14.3 mcg/mL
Standard Deviation 2.9
|
33.2 mcg/mL
Standard Deviation 5.0
|
PRIMARY outcome
Timeframe: 24-hour intervalPopulation: All subjects who contributed evaluable pharmacokinetics data
Tmax (the time to Cmax) 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, 0.5, 0.75, 1, 1.3333, 1.6667, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16 and 24 hours post-dose.
Outcome measures
| Measure |
Deferiprone Sustained-release (Fed)
n=10 Participants
A single 2000 mg dose of deferiprone sustained-release following a high fat high calorie breakfast.
Deferiprone sustained-release: Deferiprone sustained-release tablets
|
Deferiprone Sustained-release (Fasting)
n=10 Participants
A single 2000 mg dose of deferiprone sustained-release under fasting conditions.
Deferiprone sustained-release: Deferiprone sustained-release tablets
|
Deferiprone Immediate-release (Fasting)
n=10 Participants
A single 2000 mg dose of Deferiprone immediate-release under fasting conditions.
Deferiprone immediate-release: Deferiprone immediate-release tablets
|
|---|---|---|---|
|
Tmax for Serum Deferiprone and Deferiprone 3-O-glucuronide
Deferiprone
|
4.4 h
Standard Deviation 0.9
|
3.3 h
Standard Deviation 1.4
|
1.3 h
Standard Deviation 1.1
|
|
Tmax for Serum Deferiprone and Deferiprone 3-O-glucuronide
Deferiprone 3-O-glucuronide
|
6.0 h
Standard Deviation 1.5
|
4.5 h
Standard Deviation 1.5
|
3.0 h
Standard Deviation 0.9
|
PRIMARY outcome
Timeframe: 24-hour intervalPopulation: All subjects who contributed evaluable pharmacokinetics data
Thalf (the apparent terminal elimination half-life of the drug) 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, 0.5, 0.75, 1, 1.3333, 1.6667, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16 and 24 hours post-dose.
Outcome measures
| Measure |
Deferiprone Sustained-release (Fed)
n=10 Participants
A single 2000 mg dose of deferiprone sustained-release following a high fat high calorie breakfast.
Deferiprone sustained-release: Deferiprone sustained-release tablets
|
Deferiprone Sustained-release (Fasting)
n=10 Participants
A single 2000 mg dose of deferiprone sustained-release under fasting conditions.
Deferiprone sustained-release: Deferiprone sustained-release tablets
|
Deferiprone Immediate-release (Fasting)
n=11 Participants
A single 2000 mg dose of Deferiprone immediate-release under fasting conditions.
Deferiprone immediate-release: Deferiprone immediate-release tablets
|
|---|---|---|---|
|
Thalf for Serum Deferiprone and Deferiprone 3-O-glucuronide
Deferiprone
|
2.8 h
Standard Deviation 1.4
|
5.0 h
Standard Deviation 3.5
|
1.9 h
Standard Deviation 0.3
|
|
Thalf for Serum Deferiprone and Deferiprone 3-O-glucuronide
Deferiprone 3-O-glucuronide
|
3.7 h
Standard Deviation 3.4
|
6.1 h
Standard Deviation 4.9
|
2.4 h
Standard Deviation 0.5
|
SECONDARY outcome
Timeframe: From time of dose until 24 hours post dosePopulation: All subjects who received at least one dose of study medication and had at least one safety assessment
The number of participants who experienced adverse events between the time of dosing up to 24 hours post-dose, including any changes of clinical significance in vital signs, 12-lead ECG, and clinical laboratory tests
Outcome measures
| Measure |
Deferiprone Sustained-release (Fed)
n=10 Participants
A single 2000 mg dose of deferiprone sustained-release following a high fat high calorie breakfast.
Deferiprone sustained-release: Deferiprone sustained-release tablets
|
Deferiprone Sustained-release (Fasting)
n=10 Participants
A single 2000 mg dose of deferiprone sustained-release under fasting conditions.
Deferiprone sustained-release: Deferiprone sustained-release tablets
|
Deferiprone Immediate-release (Fasting)
n=11 Participants
A single 2000 mg dose of Deferiprone immediate-release under fasting conditions.
Deferiprone immediate-release: Deferiprone immediate-release tablets
|
|---|---|---|---|
|
Safety and Tolerability of Deferiprone Sustained Release Tablets
|
5 participants
|
5 participants
|
6 participants
|
Adverse Events
Deferiprone Sustained-release (Fed)
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Deferiprone Sustained-release (Fasting)
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Deferiprone Immediate-release (Fasting)
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Deferiprone Sustained-release (Fed)
n=10 participants at risk
A single 2000 mg dose of deferiprone sustained-release following a high fat high calorie breakfast.
Deferiprone sustained-release: Deferiprone sustained-release tablets
|
Deferiprone Sustained-release (Fasting)
n=10 participants at risk
A single 2000 mg dose of deferiprone sustained-release under fasting conditions.
Deferiprone sustained-release: Deferiprone sustained-release tablets
|
Deferiprone Immediate-release (Fasting)
n=11 participants at risk
A single 2000 mg dose of Deferiprone immediate-release under fasting conditions.
Deferiprone immediate-release: Deferiprone immediate-release tablets
|
|---|---|---|---|
|
Investigations
Heart rate decreased
|
20.0%
2/10 • Number of events 3 • 1 day
Safety data were collected from the time of dosing up to 24 hours post-dose
|
20.0%
2/10 • Number of events 2 • 1 day
Safety data were collected from the time of dosing up to 24 hours post-dose
|
18.2%
2/11 • Number of events 3 • 1 day
Safety data were collected from the time of dosing up to 24 hours post-dose
|
|
Investigations
Blood pressure decreased
|
0.00%
0/10 • 1 day
Safety data were collected from the time of dosing up to 24 hours post-dose
|
0.00%
0/10 • 1 day
Safety data were collected from the time of dosing up to 24 hours post-dose
|
9.1%
1/11 • Number of events 1 • 1 day
Safety data were collected from the time of dosing up to 24 hours post-dose
|
|
Investigations
Blood pressure increased
|
10.0%
1/10 • Number of events 1 • 1 day
Safety data were collected from the time of dosing up to 24 hours post-dose
|
10.0%
1/10 • Number of events 1 • 1 day
Safety data were collected from the time of dosing up to 24 hours post-dose
|
9.1%
1/11 • Number of events 1 • 1 day
Safety data were collected from the time of dosing up to 24 hours post-dose
|
|
Investigations
Blood urine present
|
10.0%
1/10 • Number of events 1 • 1 day
Safety data were collected from the time of dosing up to 24 hours post-dose
|
0.00%
0/10 • 1 day
Safety data were collected from the time of dosing up to 24 hours post-dose
|
9.1%
1/11 • Number of events 1 • 1 day
Safety data were collected from the time of dosing up to 24 hours post-dose
|
|
Cardiac disorders
Sinus bradycardia
|
0.00%
0/10 • 1 day
Safety data were collected from the time of dosing up to 24 hours post-dose
|
0.00%
0/10 • 1 day
Safety data were collected from the time of dosing up to 24 hours post-dose
|
9.1%
1/11 • Number of events 1 • 1 day
Safety data were collected from the time of dosing up to 24 hours post-dose
|
|
Investigations
White blood cells urine positive
|
10.0%
1/10 • Number of events 2 • 1 day
Safety data were collected from the time of dosing up to 24 hours post-dose
|
0.00%
0/10 • 1 day
Safety data were collected from the time of dosing up to 24 hours post-dose
|
0.00%
0/11 • 1 day
Safety data were collected from the time of dosing up to 24 hours post-dose
|
|
Investigations
Alanine aminotransferase increased
|
10.0%
1/10 • Number of events 1 • 1 day
Safety data were collected from the time of dosing up to 24 hours post-dose
|
20.0%
2/10 • Number of events 2 • 1 day
Safety data were collected from the time of dosing up to 24 hours post-dose
|
0.00%
0/11 • 1 day
Safety data were collected from the time of dosing up to 24 hours post-dose
|
|
Investigations
Body temperature increased
|
0.00%
0/10 • 1 day
Safety data were collected from the time of dosing up to 24 hours post-dose
|
10.0%
1/10 • Number of events 1 • 1 day
Safety data were collected from the time of dosing up to 24 hours post-dose
|
0.00%
0/11 • 1 day
Safety data were collected from the time of dosing up to 24 hours post-dose
|
|
Investigations
Amylase increased
|
0.00%
0/10 • 1 day
Safety data were collected from the time of dosing up to 24 hours post-dose
|
10.0%
1/10 • Number of events 1 • 1 day
Safety data were collected from the time of dosing up to 24 hours post-dose
|
0.00%
0/11 • 1 day
Safety data were collected from the time of dosing up to 24 hours post-dose
|
|
General disorders
Catheter site bruise
|
10.0%
1/10 • Number of events 1 • 1 day
Safety data were collected from the time of dosing up to 24 hours post-dose
|
0.00%
0/10 • 1 day
Safety data were collected from the time of dosing up to 24 hours post-dose
|
0.00%
0/11 • 1 day
Safety data were collected from the time of dosing up to 24 hours post-dose
|
|
Investigations
Serum ferritin decreased
|
10.0%
1/10 • Number of events 1 • 1 day
Safety data were collected from the time of dosing up to 24 hours post-dose
|
0.00%
0/10 • 1 day
Safety data were collected from the time of dosing up to 24 hours post-dose
|
0.00%
0/11 • 1 day
Safety data were collected from the time of dosing up to 24 hours post-dose
|
|
Metabolism and nutrition disorders
C-reactive protein increased
|
10.0%
1/10 • Number of events 1 • 1 day
Safety data were collected from the time of dosing up to 24 hours post-dose
|
0.00%
0/10 • 1 day
Safety data were collected from the time of dosing up to 24 hours post-dose
|
0.00%
0/11 • 1 day
Safety data were collected from the time of dosing up to 24 hours post-dose
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place