DEEP-1 Performing a pharmacokinetics trial of deferiprone in children up to 6 years

The study – DEEP-1 is a multi-centre, oral single dose experimental and modelling study to evaluate the pharmacokinetics of the systemic exposure of deferiprone 80 mg/ml (DFP) in paediatric patients aged from 1 month to < 6 years (for which PK profile of deferiprone is unknown) affected by transfusion-dependent haemoglobinopathies.

The study consists of two phases: an experimental phase, during which patients received a single dose and a modelling phase, during which PK data obtained after single dose in patients < 6 years of age were analysed in conjunction with historical PK data in adults and older children and adolescents. The ratio between the predicted systemic exposure parameters (AUC and Cmax) in the target population and reference group was used as base for recommendation of the dose in the target population.

Objectives – In a scenario characterised by the lack of information in the paediatric subset ranged from 1 month to < 6 years, which implies an empirical calculation of DFP based on adult data, the primary objective of this study is to provide supporting evidence for the dose rationale for the use of DFP in paediatric patients aged from 1 month to less than 6 years.

Secondary objectives of this study include the identification of dose levels yielding DFP exposures comparable to adults and definition of the dose rationale; the evaluation of safety and tolerability of DFP after single dose administration, and the evaluation of the effect of demographic covariates on DFP disposition and estimate the clearance distribution across the population, in children aged from 1 month to less than 6 years.

Centres Involved – The DEEP-1 study involved a total of 7 recruiting centres: Cyprus (1), Egypt (1), Italy (5).The coordinating centre was the Unit of Paediatrics “Federico Vecchio” at the University Hospital Consortium “Policlinico di Bari”, and study sites were located in Bari (Italy), Palermo (Italy), Padova (Italy), Napoli (Italy), Sassari (Italy), Nicosia (Cyprus), Cairo (Egypt). Unfortunately at Cairo site the authorization was denied due to the unaffordable necessity to export biological samples from the country, while at Nicosia site it was received when it was too  late and no more needed to include other patients, being the effort registered at the Italian sites enough to reach the study objectives.

Results – The study has enrolled a total of 23 paediatric patients, of which 18 completed the study receiving one of the three dose levels of deferiprone. The investigational product was well tolerated and no clinically relevant safety findings were detected during the study or at the follow-up visit. Simulation scenarios showed that comparable exposure levels are achieved in children and adults based on a dosing regimen in mg/kg.

Conclusions: The DEEP-1 PK-study, was concluded on February 2014, providing scientific evidence that the dosage of deferiprone used in adults can provide sufficient exposure to ensure efficacy also in small children and allowing children aged under 6 years of age to start to be recruited in DEEP-2 safety/efficacy study.