Clinical trial NCT02220114: Acceptability Study of a New Paediatric Form of Vigabatrin in Infants and Children With Infantile Spasms or Pharmacoresistant Partial Epilepsy
Official title: Acceptability Study of a New Paediatric Form of Vigabatrin in Infants and Children With Infantile Spasms or Pharmacoresistant Partial Epilepsy. Observational, Descriptive, Open-label, Multi-centric, Non-randomized Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Infantile Spasms
Keywords: Infantile spasms
vigabatrin
soluble tablets
acceptability
adherence
pharmacokinetics
Lead sponsor: Orphelia Pharma
Sponsor class: INDUSTRY
Collaborators: name: Institut National de la Santé Et de la Recherche Médicale, France
name: Hospices Civils de Lyon
name: National Research Agency, France
First posted: 2014-08-19
Enrollment: 38
Sex: ALL
Minimum age (years): 1
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The sponsor is developing a new paediatric formulation of vigabatrin to better adjust the dose to body weight and to limit waste of unused drug. The currently marketed vigabatrin (Sabril™) form only exists as 500 mg film coated tablets (for adults and children above 6 years) and 500 mg granules for oral solution sachets (for infants and children below 6 years). Sabril™ is not adapted for administration to infants when a fraction of the sachet is needed. Manual splitting of the sachet or lengthy and error-prone dilutions are often required.

This study is a descriptive, non-randomized, open label multi-centric acceptability study in infants and children affected with infantile spasms. The primary objective is to describe the adherence to the new formulation. Secondary objectives include:

* evaluation of the palatability and user-friendliness of the new treatment,
* evaluation of the pharmacokinetic parameters of the new formulation,
* PK parameters,
* evaluation of the tolerance,
* measurement of taurine plasma levels. This study will recruit up to 40 patients with infantile spasms and pharmacoresistant partial epilepsy aged 1 month to 6 years in 23 clinical sites in France.


Eligibility criteria: Inclusion Criteria:

* Patients with diagnosed infantile spasms (IS) or pharmacoresistant partial onset seizures (POS).
* Infants \> 1 month and \< 6 months; infants \> 6 months and \< 2 years; and children \> 2 years and \< 6 years.
* Patients under Sabril® or naive patients.
* Patients under a twice-a-day posology of Sabril® or patients for whom vigabatrin will be given twice daily.

Non inclusion Criteria:

* Use of more than 2 other antiepileptic drugs as concomitant treatment (including steroids). Ketogenic diet can be in addition to these 2 other antiepileptic drugs.
* Subjects receiving vigabatrin through a gastric tube.
* Weight \< 1.750 Kgs.
* Any planned major surgery within the duration of the trial.
* Participation in any other clinical trial within 3 months prior to V1.

Primary outcomes:
measure: Individual adherence to the new Soluble Tablets (ST) formulation of Vigabatrin (VGB) using Medication Event Monitoring System (MEMS)
timeFrame: from V1 (day 1) to V3 (day 84), continuous assessment.
Secondary outcomes:
measure: Adherence to the new ST formulation and to Sabril® granules for oral solution, by treatment unit accountability
timeFrame: VGB-ST: V1 (day 1) to V3 (day 84). Sabril®:V3 (day 85) to V4 (day 98)
measure: palatability of the new ST formulation and of Sabril® "granules for oral solution".
timeFrame: during 7 consecutive days: from D90 to D96 under Sabril® and from D29 to D35 under the new ST formulation
measure: Ease of use of the new ST formulation and of Sabril® "granules for oral solution".
timeFrame: during 7 consecutive days: from D90 to D96 under Sabril® and from D29 to D35 under the new ST formulation.
measure: Safety and tolerance
timeFrame: Results of electroretinogram: when available from D1 to D126; Blood assessment: at D1 & D84; Vital signs at D1, D28, D84, D98 & D126; Adverse events, serious adverse events: evaluated for the duration of study participation (at D1, D28, D84, D98 & D126)
measure: pharmacokinetic parameters for the new ST formulation (1 sample). Pharmacokinetic parameters for the new ST formulation (population PK) : Area under the curve (AUC), Tmax, Cmax, T½, Ka, V/F, Cl/F
timeFrame: PK D84: 1 sample before treatment.
measure: Evaluation of the taurine plasma levels in children treated by vigabatrin. Taurine plasma concentration will be measured and a relationship between vigabatrin exposition and taurine plasma levels will be sought.
timeFrame: 1 sample will be drawn at V3 (day 84): just before treatment when patient is fasting.
Other outcomes:
Locations:
city: Amiens
country: France
facility: Service de neurologie pédiatrique - CHU
city: Angers
country: France
facility: Service de neurologie pédiatrique - CHU
city: Bordeaux
country: France
facility: Service de neuropédiatrie - CHU Pellegrin Enfants
city: Lille
country: France
facility: Service de neurologie infantile - Hôpital Salengro
city: Lyon
country: France
facility: Service de nuerologie pédiatrique - Hôpital Femme Mère Enfant
city: Marseille
country: France
facility: Service de neurologie pédiatrique - Hôpital de la Timone
city: Paris
country: France
facility: Service de neurologie pédiatrique - Hôpital Necker Enfants Malades
city: Paris
country: France
facility: Service de neuropédiatrie - Hôpital Robert Debré
city: Rennes
country: France
facility: Service de neurologie pédiatrique - Hôpital Sud
city: Strasbourg
country: France
facility: Centre référent des épilepsies rares pédiatrique associé - Hôpital de Hautepierre
city: Toulouse
country: France
facility: Service de neuropédiatrie - Hôpital Purpan
city: Tours
country: France
facility: Service de neuropédiatrie - Hôpital de Clocheville
Study officials:
affiliation: Hôpital Necker Enfants Malades - APHP
name: Rima NABBOUT
role: PRINCIPAL_INVESTIGATOR
References: