E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Infantile spasms and pharmaco-resistant partial epilepsy |
spasmes infantiles et épilepsie partielle pharmacorésistante |
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E.1.1.1 | Medical condition in easily understood language |
Infantile spasms and pharmaco-resistant partial epilepsy |
spasmes infantiles et épilepsie partielle pharmacorésistante |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10021750 |
E.1.2 | Term | Infantile spasms |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065336 |
E.1.2 | Term | Partial epilepsy |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To describe the adherence to a new vigabatrin formulation (soluble tablets). |
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E.2.2 | Secondary objectives of the trial |
1)Evaluate the palatability and the ease of use of the new vigabatrin formulation.
2)Describe the adherence to Sabril and the new formulation (by treatments accountability)
3)Evaluate the pharmacokinetic parameters of the new vigabatrin formulation.
4)Evaluate the treatment safety, including the visual safety (by electroretinogram).
5)Evaluate the taurine plasma concentrations in children treated with vigabatrin.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Boys and girls.
- Patients with diagnosed infantile spasms (IS) or pharmaco-resistant partial onset seizures (POS).
- Infants > 1 month and < 6 months; infants > 6 months and < 2 years; and children > 2 years and < 6 years.
- Patients stabilized under Sabril® for at least 2 weeks prior to V1: patients with no spasms/POS or with a stable frequency of spasms/POS (i.e. with no more than 50% variation in the number of spasms/POS) within 2 weeks prior to V1.
- Patients under a twice-a-day posology of Sabril®.
- Subjects covered by or having the rights to social security.
- Signed informed consent and/or child assent.
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E.4 | Principal exclusion criteria |
- Change in anti-epileptic treatment and/or Sabril® dose within 7 days before V1.
- 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 < 4 Kgs.
- Any planned major surgery within the duration of the trial.
- Participation in any other clinical trial within 3 months prior to V1.
- Lack of ability or willingness to give informed consent.
- Anticipated non-availability for study visits / procedures.
- Lack of willingness or inability to co-operate adequately. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the proportion of adherent patients for the new VGB formulation. Adherence will be assessed by measurement of the dosing history of patients using an electronic Medication Event Monitoring System (MEMS). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Continuous endpoint between D15 and D98, 12 weeks under VGB-ST. |
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E.5.2 | Secondary end point(s) |
- Adherence by accountability of Treatment units for the new ST formulation (number of tablets) and to Sabril® “granules for oral solution” (number of sachets).
- Palatability evaluated using a two face visual hedonic scale filled in by the parents and/or by the child, if feasible, on a daily basis. Each “face” of the scale will be assigned a score (1 to 2), and the average score will be calculated for the group. Palatability will be considered good if the average score for the group is at least 1.5 out of a maximum of 2.
- Ease of use will be evaluated for Sabril® « granules for oral solution » and for the new ST formulation using two diaries filled by the parents or care-givers during 7 consecutive days. Time required for preparation of both VGB ST and Sabril® administrations will be averaged and compared, together with the global use satisfaction .
- Safety measures include:
o Results of electroretinogram (when available).
o General safety, including:
• blood cells count, blood electrolytes, blood ionogram, serum creatinine, liver function assessment
• vital signs (cardiac frequency and blood pressure)
• adverse events and serious adverse events.
- Pharmacokinetic parameters for the new ST formulation (population PK) : AUC, T max, Cmax, T½, Ka, V/F, Cl/F .
- Taurine plasma concentration. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Accountability : D1 to D14 under Sabril ; D15 to D98 under VGB-ST.
- Palatability and ease of use, 7 consecutive days :D8 to D14 for Sabril® ; D22 to D28 under VGB-ST.
- Safety measures :
• blood assessment at V1 and V4,
• vital signs at V1, V2, V4 and V5.
• AE and SAE at each study visit.
- Pharmacokinetic:
• After V3, the same day, 1 sample just before treatment and 1 sample 1h after treatment.
• At least 1 week before V4, the same day, 1 sample 3 to 5h after treatment and 1 sample 6 to 9 h after treatment.
• At V4, 1 sample just before treatment and 1 sample 2h after treatment.
- Taurine concentration at V4 fasting. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
palatability study, adherence |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 12 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 12 |
E.8.9.1 | In the Member State concerned days | 0 |