Dear Partners,
WELCOME
to the first Newsletter
of the GAPP project

Before enrolling children <2 years of age in the GABA-1 and GABA-2 clinical trials, the Paediatric Committee (PDCO) at the European Medicines Agency (EMA) requested to perform a complete evaluation of the possible neurotoxic effects of gabapentin in the youngsters, as described in the WP6 “Juvenile animal study” of the GAPP project. These studies are intended to provide a rational basis for the toxicological risk assessment in paediatric patients. Studies have been performed, in juvenile rats from post-natal day 4 under Dompè coordination and include both toxicological and neurological tests. Studies are now completed and did not indicate any direct toxicity of gabapentin, up to the highest dose level tested. The only abnormal finding was an increased incidence of kidney hydronephrosis in treated rat females. Since a relationship with the treatment could not be ruled out, although a spontaneous occurrence could has been possible, a standard renal ultrasound scan has been included in the GABA-1 and GABA-2 protocols at screening and at the end of the study for participating children < 3 years of age.

A lot of efforts have been put into the resolution of the challenges imposed by such an ambition clinical development plan.
Thanks to the contribution of many of you, the protocols of the two clinical studies, included in the GAPP project, named GABA-1 and GABA-2, have been agreed and finalised. The two studies are aimed to evaluate gabapentin for the treatment of paediatric patients (3 months - <18 years), affected by chronic neuropathic or mixed pain both as monotherapy and adjunctive therapy to morphine.
The GABA-1 is a randomised, double-blind, double-dummy, active controlled, multi-centre, non-inferiority, phase-III study to compare the pharmacokinetic, efficacy and safety of gabapentin liquid formulation to tramadol in children experiencing moderate to severe chronic neuropathic or mixed pain. The protocol involves the enrolment of at least 94 patients.
The GABA-2 study, is a randomised, double-blind, placebo controlled, multi-centre study to evaluate the safety, pharmacokinetic, efficacy of gabapentin liquid formulation as add-on to morphine in children experiencing severe chronic neuropathic or mixed pain. This protocol involves 66 patients that will be randomised to either the morphine + gabapentin (intervention) group or morphine + placebo (control) group.
The doses to be used in this paediatric population were selected based on a model-based approach.
Patients participating to either GABA-1 or GABA-2 will be invited, on voluntary basis, to participate to three additional exploratory studies, that will assess the metabolomics and genetic polymorphisms profiles that may affect the drug therapy, and the validation of the diagnostic neurological pain questionnaire DN4 in children.