Pharmacokinetic Study of Deferiprone in Paediatric Patients

Chronic Iron Overload Clinical Trial

— DEEP-1  

Official title:

Multi-centre, Oral Single Dose Experimental and Modelling Study to Evaluate the Pharmacokinetics of Deferiprone in Patients Aged From 1 Month to Less Than 6 Years of Age Affected by Transfusion-dependent Haemoglobinopathies.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01740713
• Other study ID #: DEEP-1
• Status: Completed
• Phase: Phase 2
• First received: November 28, 2012
• Last updated: November 17, 2014
• Start date: December 2012
• Est. completion date: February 2014

Study information

• Verified date: November 2014
• Source: Consorzio per Valutazioni Biologiche e Farmacologiche
• Contact: n/a
• Is FDA regulated: No
• Health authority: European Union: European Medicines AgencyItaly: The Italian Medicines AgencyEgypt: Ministry of Health, Drug Policy and Planning Center
• Study type: Interventional

Clinical Trial Summary

Deferiprone (DFP) is the most extensively studied oral iron chelator to date. It has been authorised in Europe in 1999 for the treatment of iron overload in patients with beta-thalassaemia major when DFO is contraindicated or inadequate. Despite a wide experience of DFP there are limited experimental data available on DFP in children and no pharmacokinetic data in children under 6 years of age. On the basis of the existing data in adults and adolescent, in the DEEP-1 trial a pharmacokinetic bridging model will be developed to support the dose selection in children aged less than 6 years. The study will consist of two phases, namely an experimental phase, during which patients will receive a single dose and a modeling phase, during which PK data obtained after single dose in patients < 6 years of age will be analysed in conjunction with historical PK data in adults and older children and adolescents. The model-based analysis of the data obtained after single dose will enable the assessment of the dosing regimen required for the purpose of accurate pharmacokinetic bridging. The ratio between the predicted systemic exposure parameters (AUC and Cmax) in the target population and reference group will be used as basis for recommendation of the dose in the target population.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: February 2014
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Month to 6 Years

Eligibility

Inclusion Criteria:

• Patients in a chronic transfusional program who have received at least 150 ml/kg/year of packed red blood cells (corresponding approximately to 12 transfusions) and on current treatment with DFO, DFX, DFP; aged from 1 month to less than 6 years; or

• Patients naïve to any chelation treatment who have received not less than 150 ml/kg of packed red blood cells (corresponding to approximately 12 transfusions) and have ferritin levels > 800 ng/mL, aged from 1 month to less than 6 years; or

• Patients who meet the transfusion criteria (150 ml/kg/year corresponding approximately to 12 transfusions) and have known intolerance or contraindication to DFO

And if all of the following criteria apply:

• Patients affected by any hereditary haemoglobinopathies requiring chronic transfusion therapy including but not limited to thalassaemia and sickle cell disease

• Written informed consent obtained from their legal guardian on the patient's behalf in accordance with the national legislations. According to his/her capability, patient's informed assent will be collected

Exclusion Criteria:

• Patient with known intolerance or contraindication to the trial treatment

• Patient with Hb levels less than 8g/dl (entry may be delayed until values return to normal)

• Patient with platelet count <100.000/mm3 or absolute neutrophil count <1.500/mm3 (entry may be delayed until values return to normal)

• Patient with evidence of abnormal liver function (ALT level >5 times the upper normal limit during six months preceding enrolment; entry may be delayed until values return to normal)

• iron overload from causes other than transfusional haemosiderosis

• severe heart dysfunction secondary to iron overload defined as the occurrence of heart failure or severe arrhythmia or as indicated by cardiac T2* lower than 10 ms, if recent MRI data is available,

• Patient with serum creatinine level above the upper normal limit at screening; entry may be delayed until values return to normal.

• Serological evidence of chronic hepatitis B (presence of HBe Ag, HBsAg, HBcAb-IgM, in the absence of HBsAb).

• History of significant medical or psychiatric disorder that may impair compliance with the requirements of the protocol.

• The patient has received another investigational drug within 30 days prior to this study.

• Patient with a pre-existing condition or any other surgical or medical condition which might significantly interfere with normal gastrointestinal and hepatic function that could alter the absorption, metabolism, and/or excretion of the study drug.

• Patient with a known history of HIV seropositivity.

• Fever and other signs/symptoms of infection in the 10 days before drug administration(treatment day)

• Concomitant use of other iron chelators or trivalent cation-dependent medicinal products such as aluminium-based antacids.

• Patient with a chronic condition that does not allow suspension of related treatment from starting of washout until drug is administered.

Study Design

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Chronic Iron Overload
• Hemoglobinopathies
• Iron Overload

Intervention

Drug:
• Deferiprone
deferiprone liquid oral solution (80 mg/ml)

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Consorzio per Valutazioni Biologiche e Farmacologiche	European Commission

Countries where clinical trial is conducted

Cyprus,  Egypt,  Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PK parameters	CL/F, Vd/F, Ka, AUC, Cmax, Tmax, Css and Cmin	Baseline, day 6	No
Secondary	Safety	Clinical safety and tolerability data including ferritin levels, spontaneous AE reporting, ECGs, vital signs, nursing/physician observation and clinical laboratory values (haematology and biochemistry).	Baseline, day 6	Yes