Trial Outcomes & Findings for Pharmacokinetic Study of Deferiprone in Paediatric Patients (NCT NCT01740713)
NCT ID: NCT01740713
Last Updated: 2017-01-11
Results Overview
Plasma clearance after oral administration. The parameter was estimated through a population pharmacokinetic model, during which concentration data obtained after single oral dose ( at 3 dose levels) of DFP in patients aged from 1 month to less than 6 years of age.
COMPLETED
PHASE2
23 participants
Day 1 of single dose treatment (6 sampling time range: from predose up to 8h post first administration)
2017-01-11
Participant Flow
A total of 23 children affected by transfusion-dependent haemoglobinopathies were enrolled in this study. Of these 23 children, 2 were screening failures and 3 early terminations.
Participant milestones
| Measure |
Deferiprone 25 mg/kg/Day
Deferiprone will be administered at 25 mg/kg/day
Deferiprone, dose level 1: deferiprone liquid oral solution (80 mg/ml)
|
Deferiprone 50 mg/kg/da
Deferiprone will be administered at 50 mg/kg/day
Deferiprone, dose level 2: deferiprone liquid oral solution (80 mg/ml)
|
Deferiprone 100 mg/kg/Day
Deferiprone will be administered at 100 mg/kg/day
Deferiprone, dose level 3: deferiprone liquid oral solution (80 mg/ml)
|
|---|---|---|---|
|
Overall Study
STARTED
|
6
|
8
|
7
|
|
Overall Study
COMPLETED
|
6
|
6
|
6
|
|
Overall Study
NOT COMPLETED
|
0
|
2
|
1
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Pharmacokinetic Study of Deferiprone in Paediatric Patients
Baseline characteristics by cohort
| Measure |
Deferiprone 25 mg/kg/Day
n=6 Participants
Deferiprone will be administered at 25 mg/kg/day
Deferiprone, dose level 1: deferiprone liquid oral solution (80 mg/ml)
|
Deferiprone 50 mg/kg/Day
n=8 Participants
Deferiprone will be administered at 50 mg/kg/day
Deferiprone, dose level 2: deferiprone liquid oral solution (80 mg/ml)
|
Deferiprone 100 mg/kg/Day
n=7 Participants
Deferiprone will be administered at 100 mg/kg/day
Deferiprone, dose level 3: deferiprone liquid oral solution (80 mg/ml)
|
Total
n=21 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
6 Participants
n=99 Participants
|
8 Participants
n=107 Participants
|
7 Participants
n=206 Participants
|
21 Participants
n=7 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Gender
Female
|
3 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
11 Participants
n=7 Participants
|
|
Gender
Male
|
3 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
10 Participants
n=7 Participants
|
|
Region of Enrollment
Italy
|
6 participants
n=99 Participants
|
8 participants
n=107 Participants
|
7 participants
n=206 Participants
|
21 participants
n=7 Participants
|
PRIMARY outcome
Timeframe: Day 1 of single dose treatment (6 sampling time range: from predose up to 8h post first administration)Plasma clearance after oral administration. The parameter was estimated through a population pharmacokinetic model, during which concentration data obtained after single oral dose ( at 3 dose levels) of DFP in patients aged from 1 month to less than 6 years of age.
Outcome measures
| Measure |
PK Population
n=18 Participants
Deferiprone liquid oral solution (80 mg/ml) has been administered at 25/50/100 mg/kg/day
|
Deferiprone 50 mg/kg/Day
Deferiprone will be administered at 50 mg/kg/day
Deferiprone, dose level 2: deferiprone liquid oral solution (80 mg/ml)
|
Deferiprone 100 mg/kg/Day
Deferiprone will be administered at 100 mg/kg/day
Deferiprone, dose level 3: deferiprone liquid oral solution (80 mg/ml)
|
|---|---|---|---|
|
CL/F
|
8.3 litre/h
Standard Error 0.569
|
—
|
—
|
PRIMARY outcome
Timeframe: Day 1 of single dose treatment (6 sampling time range: from predose up to 8h post first administration)Area under concentration versus time curve from 0 to 8 h post dosing. Secondary pharmacokinetic parameter derived on the basis of the individual predicted concentration vs. time profiles, through the pop-PK model.
Outcome measures
| Measure |
PK Population
n=6 Participants
Deferiprone liquid oral solution (80 mg/ml) has been administered at 25/50/100 mg/kg/day
|
Deferiprone 50 mg/kg/Day
n=6 Participants
Deferiprone will be administered at 50 mg/kg/day
Deferiprone, dose level 2: deferiprone liquid oral solution (80 mg/ml)
|
Deferiprone 100 mg/kg/Day
n=6 Participants
Deferiprone will be administered at 100 mg/kg/day
Deferiprone, dose level 3: deferiprone liquid oral solution (80 mg/ml)
|
|---|---|---|---|
|
AUC (0-8h)
|
116.7 micromol*h/L
Interval 90.6 to 129.0
|
210.0 micromol*h/L
Interval 173.1 to 266.6
|
428.8 micromol*h/L
Interval 291.4 to 547.8
|
PRIMARY outcome
Timeframe: Day 1 of single dose treatment (6 sampling time range: from predose up to 8h post first administration)volume of distribution after oral administration. The parameter was estimated through a population pharmacokinetic model, during which concentration data obtained after single oral dose ( at 3 dose levels) of DFP in patients aged from 1 month to less than 6 years of age
Outcome measures
| Measure |
PK Population
n=18 Participants
Deferiprone liquid oral solution (80 mg/ml) has been administered at 25/50/100 mg/kg/day
|
Deferiprone 50 mg/kg/Day
Deferiprone will be administered at 50 mg/kg/day
Deferiprone, dose level 2: deferiprone liquid oral solution (80 mg/ml)
|
Deferiprone 100 mg/kg/Day
Deferiprone will be administered at 100 mg/kg/day
Deferiprone, dose level 3: deferiprone liquid oral solution (80 mg/ml)
|
|---|---|---|---|
|
V/F
|
18.7 litres
Standard Error 1.16
|
—
|
—
|
PRIMARY outcome
Timeframe: Day 1 of single dose treatment (6 sampling time range: from predose up to 8h post first administration)Time at which the maximum concentration (Cmax) is reached. Secondary pharmacokinetic parameters such as Cmax, Min, Tmax, Css and AUC (0-8h) were derived based on the individual predicted concentration vs. time profiles.
Outcome measures
| Measure |
PK Population
n=6 Participants
Deferiprone liquid oral solution (80 mg/ml) has been administered at 25/50/100 mg/kg/day
|
Deferiprone 50 mg/kg/Day
n=6 Participants
Deferiprone will be administered at 50 mg/kg/day
Deferiprone, dose level 2: deferiprone liquid oral solution (80 mg/ml)
|
Deferiprone 100 mg/kg/Day
n=6 Participants
Deferiprone will be administered at 100 mg/kg/day
Deferiprone, dose level 3: deferiprone liquid oral solution (80 mg/ml)
|
|---|---|---|---|
|
Tmax
|
0.33 hour
Interval 0.19 to 0.92
|
0.33 hour
Interval 0.21 to 0.63
|
0.37 hour
Interval 0.27 to 0.42
|
PRIMARY outcome
Timeframe: Day 1 of single dose treatment (6 sampling time range: from predose up to 8h post first administration)Absorption rate constant. The parameter was estimated through a population pharmacokinetic model, during which concentration data obtained after single oral dose ( at 3 dose levels) of DFP in patients aged from 1 month to less than 6 years of age.
Outcome measures
| Measure |
PK Population
n=18 Participants
Deferiprone liquid oral solution (80 mg/ml) has been administered at 25/50/100 mg/kg/day
|
Deferiprone 50 mg/kg/Day
Deferiprone will be administered at 50 mg/kg/day
Deferiprone, dose level 2: deferiprone liquid oral solution (80 mg/ml)
|
Deferiprone 100 mg/kg/Day
Deferiprone will be administered at 100 mg/kg/day
Deferiprone, dose level 3: deferiprone liquid oral solution (80 mg/ml)
|
|---|---|---|---|
|
Ka
|
9.13 h^-1
Standard Error 1.41
|
—
|
—
|
PRIMARY outcome
Timeframe: Day 1 of single dose treatment (6 sampling time range: from predose up to 8h post first administration)Maximum concentration reached in plasma. Secondary pharmacokinetic parameter derived on the basis of the individual predicted concentration vs. time profiles, through the pop-PK model.
Outcome measures
| Measure |
PK Population
n=6 Participants
Deferiprone liquid oral solution (80 mg/ml) has been administered at 25/50/100 mg/kg/day
|
Deferiprone 50 mg/kg/Day
n=6 Participants
Deferiprone will be administered at 50 mg/kg/day
Deferiprone, dose level 2: deferiprone liquid oral solution (80 mg/ml)
|
Deferiprone 100 mg/kg/Day
n=6 Participants
Deferiprone will be administered at 100 mg/kg/day
Deferiprone, dose level 3: deferiprone liquid oral solution (80 mg/ml)
|
|---|---|---|---|
|
Cmax
|
61.7 microM
Interval 45.1 to 80.7
|
119.8 microM
Interval 106.0 to 154.0
|
229.5 microM
Interval 179.7 to 278.1
|
PRIMARY outcome
Timeframe: Day 1 of single dose treatment (6 sampling time range: from predose up to 8h post first administration)Plasma concentration reached at steady state. Secondary pharmacokinetic parameter derived on the basis of the individual predicted concentration vs. time profiles, through the pop-PK model.
Outcome measures
| Measure |
PK Population
n=6 Participants
Deferiprone liquid oral solution (80 mg/ml) has been administered at 25/50/100 mg/kg/day
|
Deferiprone 50 mg/kg/Day
n=6 Participants
Deferiprone will be administered at 50 mg/kg/day
Deferiprone, dose level 2: deferiprone liquid oral solution (80 mg/ml)
|
Deferiprone 100 mg/kg/Day
n=6 Participants
Deferiprone will be administered at 100 mg/kg/day
Deferiprone, dose level 3: deferiprone liquid oral solution (80 mg/ml)
|
|---|---|---|---|
|
Css
|
2.1 microM
Interval 1.6 to 2.3
|
3.7 microM
Interval 3.1 to 4.9
|
7.7 microM
Interval 5.1 to 10.0
|
PRIMARY outcome
Timeframe: Day 1 of single dose treatment (6 sampling time range: from predose up to 8h post first administration)Minimum plasma concentration. Secondary pharmacokinetic parameter derived on the basis of the individual predicted concentration vs. time profiles, through the pop-PK model.
Outcome measures
| Measure |
PK Population
n=6 Participants
Deferiprone liquid oral solution (80 mg/ml) has been administered at 25/50/100 mg/kg/day
|
Deferiprone 50 mg/kg/Day
n=6 Participants
Deferiprone will be administered at 50 mg/kg/day
Deferiprone, dose level 2: deferiprone liquid oral solution (80 mg/ml)
|
Deferiprone 100 mg/kg/Day
n=6 Participants
Deferiprone will be administered at 100 mg/kg/day
Deferiprone, dose level 3: deferiprone liquid oral solution (80 mg/ml)
|
|---|---|---|---|
|
Cmin
|
1.5 microM
Interval 0.92 to 2.6
|
1.9 microM
Interval 0.79 to 5.5
|
6.8 microM
Interval 3.1 to 13.9
|
SECONDARY outcome
Timeframe: from drug administration up to 8 days post treatmentAll the medical occurrences that started after the administration of the drug
Outcome measures
| Measure |
PK Population
n=21 Participants
Deferiprone liquid oral solution (80 mg/ml) has been administered at 25/50/100 mg/kg/day
|
Deferiprone 50 mg/kg/Day
Deferiprone will be administered at 50 mg/kg/day
Deferiprone, dose level 2: deferiprone liquid oral solution (80 mg/ml)
|
Deferiprone 100 mg/kg/Day
Deferiprone will be administered at 100 mg/kg/day
Deferiprone, dose level 3: deferiprone liquid oral solution (80 mg/ml)
|
|---|---|---|---|
|
Adverse Events
|
3 participants
|
—
|
—
|
Adverse Events
Deferiprone 25mg/kg/Day
Deferiprone 50 mg/kg/Day
Deferiprone 100 mg/kg/Day
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Deferiprone 25mg/kg/Day
n=6 participants at risk
Deferiprone will be administered at 25 mg/kg/day
Deferiprone, dose level 1: deferiprone liquid oral solution (80 mg/ml)
|
Deferiprone 50 mg/kg/Day
n=8 participants at risk
Deferiprone will be administered at 50 mg/kg/day
Deferiprone, dose level 2: deferiprone liquid oral solution (80 mg/ml)
|
Deferiprone 100 mg/kg/Day
n=7 participants at risk
Deferiprone will be administered at 100 mg/kg/day
Deferiprone, dose level 3: deferiprone liquid oral solution (80 mg/ml)
|
|---|---|---|---|
|
Pregnancy, puerperium and perinatal conditions
Infantile spitting up
|
0.00%
0/6 • All the medical occurrences that started after the administration of the drug under investigation have been recorded as AEs till the follow -up visit at 8 days post dosing.
|
0.00%
0/8 • All the medical occurrences that started after the administration of the drug under investigation have been recorded as AEs till the follow -up visit at 8 days post dosing.
|
28.6%
2/7 • Number of events 2 • All the medical occurrences that started after the administration of the drug under investigation have been recorded as AEs till the follow -up visit at 8 days post dosing.
|
|
Skin and subcutaneous tissue disorders
Rash trunk
|
16.7%
1/6 • Number of events 1 • All the medical occurrences that started after the administration of the drug under investigation have been recorded as AEs till the follow -up visit at 8 days post dosing.
|
0.00%
0/8 • All the medical occurrences that started after the administration of the drug under investigation have been recorded as AEs till the follow -up visit at 8 days post dosing.
|
0.00%
0/7 • All the medical occurrences that started after the administration of the drug under investigation have been recorded as AEs till the follow -up visit at 8 days post dosing.
|
Additional Information
Clinical Research Coordinator
Consorzio per Valutazioni Biologiche e Farmacologiche
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place