Acceptability Study of a New Paediatric Form of Vigabatrin in Infants and Children With Infantile Spasms or Pharmacoresistant Partial Epilepsy

NCT02220114 | Completed DMC

• 1 other identifier: TGO-VGB-III-01
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 12

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.

Conditions

Infantile Spasms

Keywords

Infantile spasms; vigabatrin; soluble tablets; acceptability; adherence; pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• Individual adherence to the new Soluble Tablets (ST) formulation of Vigabatrin (VGB) using Medication Event Monitoring System (MEMS)

  Adherence will be assessed by measurement of the dosing history of patients using an electronic Medication Event Monitoring System (MEMS).The date and time of each opening will be recorded

  from V1 (day 1) to V3 (day 84), continuous assessment.

Secondary Outcomes (6)

• Adherence to the new ST formulation and to Sabril® granules for oral solution, by treatment unit accountability

  VGB-ST: V1 (day 1) to V3 (day 84). Sabril®:V3 (day 85) to V4 (day 98)

• palatability of the new ST formulation and of Sabril® "granules for oral solution".

  during 7 consecutive days: from D90 to D96 under Sabril® and from D29 to D35 under the new ST formulation

• Ease of use of the new ST formulation and of Sabril® "granules for oral solution".

  during 7 consecutive days: from D90 to D96 under Sabril® and from D29 to D35 under the new ST formulation.

• Safety and tolerance

  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)

• 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

  PK D84: 1 sample before treatment.

Study Arms (1)

Vigabatrin: Vigabatrin new ST formulation then Sabril®

OTHER

Sabril®: sachet for oral solution 500 mg, 50 to 100mg/Kg/day, twice a day, 14 days. Vigabatrin new ST formulation: Soluble tablets 100 or 500 mg, 50 to 100mg/Kg/day, twice a day, 12 weeks.

Drug: Vigabatrin: Vigabatrin new ST formulation then Sabril®

Interventions

Vigabatrin: Vigabatrin new ST formulation then Sabril® DRUG

* first "treatment" phase (V1/D1-V3/D84), in which patients already under Sabril® "granules for oral solution" and naive patients start the new ST formulation; patients already under Sabril® will start at the same dose and regimen as their usual Sabril®. Dose and regimen for naive patients will be chosen according to SPC. * second "treatment" phase (V3/D84-V4/D98) in which the patient is switched to Sabril® "granules for oral solution" (supplied by sponsor) for 15 days at the same dose as under the new ST formulation. Dose and treatment regimen should be maintained as in first treatment phase. \- At V4/D98, patients who received Sabril® "granules for oral solution" (supplied by sponsor) continue with marketed Sabril® treatment (or switches to another AED, according to the natural evolution of the patient's condition and upon investigator decision).

Vigabatrin: Vigabatrin new ST formulation then Sabril®

Eligibility Criteria

• Age: 1 Month - 6 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Orphelia Pharma: lead
• Institut National de la Santé Et de la Recherche Médicale, France: collaborator
• Hospices Civils de Lyon: collaborator
• National Research Agency, France: collaborator

Study Sites (12)

Service de neurologie pédiatrique - CHU

Amiens, 80054, France

Location

Service de neurologie pédiatrique - CHU

Angers, 49033², France

Location

Service de neuropédiatrie - CHU Pellegrin Enfants

Bordeaux, 33076, France

Location

Service de neurologie infantile - Hôpital Salengro

Lille, 59037, France

Location

Service de nuerologie pédiatrique - Hôpital Femme Mère Enfant

Lyon, 69677, France

Location

Service de neurologie pédiatrique - Hôpital de la Timone

Marseille, 13385, France

Location

Service de neurologie pédiatrique - Hôpital Necker Enfants Malades

Paris, 75015, France

Location

Service de neuropédiatrie - Hôpital Robert Debré

Paris, 75019, France

Location

Service de neurologie pédiatrique - Hôpital Sud

Rennes, 35203, France

Location

Centre référent des épilepsies rares pédiatrique associé - Hôpital de Hautepierre

Strasbourg, 67098, France

Location

Service de neuropédiatrie - Hôpital Purpan

Toulouse, 331059, France

Location

Service de neuropédiatrie - Hôpital de Clocheville

Tours, 37044, France

Location

MeSH Terms

Conditions

Spasms, Infantile

Condition Hierarchy (Ancestors)

Epilepsy, Generalized; Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epileptic Syndromes

Study Officials

• Rima NABBOUT

  Hôpital Necker Enfants Malades - APHP

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2014
• First Posted: August 19, 2014
• Study Start: May 1, 2014
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: April 24, 2018

Record last verified: 2018-04

Locations

FR (12)