Pharmacokinetic Study of Deferiprone in Paediatric Patients (DEEP-1)

• ClinicalTrials.gov Identifier: NCT01740713
• Recruitment Status: Completed
• First Posted: December 4, 2012
• Results First Posted: January 11, 2017
• Last Update Posted: January 11, 2017
• Sponsor: Consorzio per Valutazioni Biologiche e Farmacologiche
• Collaborator: European Commission
• Information provided by (Responsible Party): Consorzio per Valutazioni Biologiche e Farmacologiche

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Investigator)
• Condition: Chronic Iron Overload
• Interventions: Drug: Deferiprone, dose level 1; Drug: Deferiprone, dose level 2; Drug: Deferiprone, dose level 3
• Enrollment: 23

Participant Flow

Recruitment Details	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.
Pre-assignment Details

Arm/Group Title	Deferiprone 25 mg/kg/Day	Deferiprone 50 mg/kg/da	Deferiprone 100 mg/kg/Day
Arm/Group Description	Deferiprone will be administered at 25 mg/kg/day Deferiprone, dose level 1: deferiprone liquid oral solution (80 mg/ml)	Deferiprone will be administered at 50 mg/kg/day Deferiprone, dose level 2: deferiprone liquid oral solution (80 mg/ml)	Deferiprone will be administered at 100 mg/kg/day Deferiprone, dose level 3: deferiprone liquid oral solution (80 mg/ml)
Period Title: Overall Study
Started	6	8	7
Completed	6	6	6
Not Completed	0	2	1

Baseline Characteristics

Arm/Group Title		Deferiprone 25 mg/kg/Day	Deferiprone 50 mg/kg/Day	Deferiprone 100 mg/kg/Day	Total
Arm/Group Description		Deferiprone will be administered at 25 mg/kg/day Deferiprone, dose level 1: deferiprone liquid oral solution (80 mg/ml)	Deferiprone will be administered at 50 mg/kg/day Deferiprone, dose level 2: deferiprone liquid oral solution (80 mg/ml)	Deferiprone will be administered at 100 mg/kg/day Deferiprone, dose level 3: deferiprone liquid oral solution (80 mg/ml)	Total of all reporting groups
Overall Number of Baseline Participants		6	8	7	21
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	6 participants	8 participants	7 participants	21 participants
	<=18 years	6 100.0%	8 100.0%	7 100.0%	21 100.0%
	Between 18 and 65 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	>=65 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Gender; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	6 participants	8 participants	7 participants	21 participants
	Female	3 50.0%	4 50.0%	4 57.1%	11 52.4%
	Male	3 50.0%	4 50.0%	3 42.9%	10 47.6%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
Italy	Number Analyzed	6 participants	8 participants	7 participants	21 participants
		6	8	7	21

Outcome Measures

1. Primary Outcome

Title	CL/F
Description	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.
Time Frame	Day 1 of single dose treatment (6 sampling time range: from predose up to 8h post first administration)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	PK Population
Arm/Group Description:	Deferiprone liquid oral solution (80 mg/ml) has been administered at 25/50/100 mg/kg/day
Overall Number of Participants Analyzed	18
Mean (Standard Error); Unit of Measure: litre/h
	8.3 (0.569)

2. Primary Outcome

Title	AUC (0-8h)
Description	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.
Time Frame	Day 1 of single dose treatment (6 sampling time range: from predose up to 8h post first administration)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Deferiprone 25 mg/kg/Day	Deferiprone 50 mg/kg/Day	Deferiprone 100 mg/kg/Day
Arm/Group Description:	Deferiprone will be administered at 25 mg/kg/day Deferiprone, dose level 1: deferiprone liquid oral solution (80 mg/ml)	Deferiprone will be administered at 50 mg/kg/day Deferiprone, dose level 2: deferiprone liquid oral solution (80 mg/ml)	Deferiprone will be administered at 100 mg/kg/day Deferiprone, dose level 3: deferiprone liquid oral solution (80 mg/ml)
Overall Number of Participants Analyzed	6	6	6
Median (Inter-Quartile Range); Unit of Measure: micromol*h/L
	116.7; (90.6 to 129.0)	210.0; (173.1 to 266.6)	428.8; (291.4 to 547.8)

3. Primary Outcome

Title	V/F
Description	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
Time Frame	Day 1 of single dose treatment (6 sampling time range: from predose up to 8h post first administration)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	PK Population
Arm/Group Description:	Deferiprone liquid oral solution (80 mg/ml) has been administered at 25/50/100 mg/kg/day
Overall Number of Participants Analyzed	18
Mean (Standard Error); Unit of Measure: litres
	18.7 (1.16)

4. Primary Outcome

Title	Tmax
Description	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.
Time Frame	Day 1 of single dose treatment (6 sampling time range: from predose up to 8h post first administration)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Deferiprone 25 mg/kg/Day	Deferiprone 50 mg/kg/Day	Deferiprone 100 mg/kg/Day
Arm/Group Description:	Deferiprone will be administered at 25 mg/kg/day Deferiprone, dose level 1: deferiprone liquid oral solution (80 mg/ml)	Deferiprone will be administered at 50 mg/kg/day Deferiprone, dose level 2: deferiprone liquid oral solution (80 mg/ml)	Deferiprone will be administered at 100 mg/kg/day Deferiprone, dose level 3: deferiprone liquid oral solution (80 mg/ml)
Overall Number of Participants Analyzed	6	6	6
Median (Inter-Quartile Range); Unit of Measure: hour
	0.33; (0.19 to 0.92)	0.33; (0.21 to 0.63)	0.37; (0.27 to 0.42)

5. Primary Outcome

Title	Ka
Description	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.
Time Frame	Day 1 of single dose treatment (6 sampling time range: from predose up to 8h post first administration)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	PK Population
Arm/Group Description:	Deferiprone liquid oral solution (80 mg/ml) has been administered at 25/50/100 mg/kg/day
Overall Number of Participants Analyzed	18
Mean (Standard Error); Unit of Measure: h^-1
	9.13 (1.41)

6. Primary Outcome

Title	Cmax
Description	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.
Time Frame	Day 1 of single dose treatment (6 sampling time range: from predose up to 8h post first administration)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Deferiprone 25 mg/kg/Day	Deferiprone 50 mg/kg/Day	Deferiprone 100 mg/kg/Day
Arm/Group Description:	Deferiprone will be administered at 25 mg/kg/day Deferiprone, dose level 1: deferiprone liquid oral solution (80 mg/ml)	Deferiprone will be administered at 50 mg/kg/day Deferiprone, dose level 2: deferiprone liquid oral solution (80 mg/ml)	Deferiprone will be administered at 100 mg/kg/day Deferiprone, dose level 3: deferiprone liquid oral solution (80 mg/ml)
Overall Number of Participants Analyzed	6	6	6
Median (Inter-Quartile Range); Unit of Measure: microM
	61.7; (45.1 to 80.7)	119.8; (106 to 154)	229.5; (179.7 to 278.1)

7. Primary Outcome

Title	Css
Description	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.
Time Frame	Day 1 of single dose treatment (6 sampling time range: from predose up to 8h post first administration)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Deferiprone 25 mg/kg/Day	Deferiprone 50 mg/kg/Day	Deferiprone 100 mg/kg/Day
Arm/Group Description:	Deferiprone will be administered at 25 mg/kg/day Deferiprone, dose level 1: deferiprone liquid oral solution (80 mg/ml)	Deferiprone will be administered at 50 mg/kg/day Deferiprone, dose level 2: deferiprone liquid oral solution (80 mg/ml)	Deferiprone will be administered at 100 mg/kg/day Deferiprone, dose level 3: deferiprone liquid oral solution (80 mg/ml)
Overall Number of Participants Analyzed	6	6	6
Median (Inter-Quartile Range); Unit of Measure: microM
	2.1; (1.6 to 2.3)	3.7; (3.1 to 4.9)	7.7; (5.1 to 10)

8. Primary Outcome

Title	Cmin
Description	Minimum plasma concentration. Secondary pharmacokinetic parameter derived on the basis of the individual predicted concentration vs. time profiles, through the pop-PK model.
Time Frame	Day 1 of single dose treatment (6 sampling time range: from predose up to 8h post first administration)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Deferiprone 25 mg/kg/Day	Deferiprone 50 mg/kg/Day	Deferiprone 100 mg/kg/Day
Arm/Group Description:	Deferiprone will be administered at 25 mg/kg/day Deferiprone, dose level 1: deferiprone liquid oral solution (80 mg/ml)	Deferiprone will be administered at 50 mg/kg/day Deferiprone, dose level 2: deferiprone liquid oral solution (80 mg/ml)	Deferiprone will be administered at 100 mg/kg/day Deferiprone, dose level 3: deferiprone liquid oral solution (80 mg/ml)
Overall Number of Participants Analyzed	6	6	6
Median (Inter-Quartile Range); Unit of Measure: microM
	1.5; (0.92 to 2.6)	1.9; (0.79 to 5.5)	6.8; (3.1 to 13.9)

9. Secondary Outcome

Title	Adverse Events
Description	All the medical occurrences that started after the administration of the drug
Time Frame	from drug administration up to 8 days post treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Safety Population
Arm/Group Description:	patients who may experience adverse events occurred before or after treatment
Overall Number of Participants Analyzed	21
Measure Type: Number; Unit of Measure: participants
	3

Adverse Events

Time Frame	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.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Deferiprone 25mg/kg/Day		Deferiprone 50 mg/kg/Day		Deferiprone 100 mg/kg/Day
Arm/Group Description	Deferiprone will be administered at 25 mg/kg/day Deferiprone, dose level 1: deferiprone liquid oral solution (80 mg/ml)		Deferiprone will be administered at 50 mg/kg/day Deferiprone, dose level 2: deferiprone liquid oral solution (80 mg/ml)		Deferiprone will be administered at 100 mg/kg/day Deferiprone, dose level 3: deferiprone liquid oral solution (80 mg/ml)
All-Cause Mortality
	Deferiprone 25mg/kg/Day		Deferiprone 50 mg/kg/Day		Deferiprone 100 mg/kg/Day
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--		--/--
Serious Adverse Events
	Deferiprone 25mg/kg/Day		Deferiprone 50 mg/kg/Day		Deferiprone 100 mg/kg/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0.00%)		0/8 (0.00%)		0/7 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Deferiprone 25mg/kg/Day		Deferiprone 50 mg/kg/Day		Deferiprone 100 mg/kg/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/6 (16.67%)		0/8 (0.00%)		2/7 (28.57%)
Pregnancy, puerperium and perinatal conditions
Infantile spitting up † 1	0/6 (0.00%)	0	0/8 (0.00%)	0	2/7 (28.57%)	2
Skin and subcutaneous tissue disorders
Rash trunk † 1	1/6 (16.67%)	1	0/8 (0.00%)	0	0/7 (0.00%)	0
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (Unspecified)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Clinical Research Coordinator
• Organization: Consorzio per Valutazioni Biologiche e Farmacologiche
• Phone: 0039 0382 25075
• EMail: mariagraziafelisi@cvbf.net

• Responsible Party: Consorzio per Valutazioni Biologiche e Farmacologiche
• ClinicalTrials.gov Identifier: NCT01740713
• Other Study ID Numbers: DEEP-1
• First Submitted: November 28, 2012
• First Posted: December 4, 2012
• Results First Submitted: March 4, 2016
• Results First Posted: January 11, 2017
• Last Update Posted: January 11, 2017