A MULTICENTRE RANDOMIZED CONTROLLED TRIAL COMPARING TOPIRAMATE, STIRIPENTOL AND CLOBAZAM AT THE MAXIMAL TOLERATED DOSAGE, AS ADJUNCTIVE THERAPY TO VALPROATE AND CLOBAZAM IN PAEDIATRIC PATIENTS WITH DRAVET`S SYNDROME (SMEI), AND AUXILIARY PHARMACOGENETIC STUDY

• Register: EUCTR
• Last refreshed on: 17 February 2014
• Main ID: EUCTR2007-002198-30-IT
• Date of registration: 17/01/2012
• Prospective Registration: No
• Primary sponsor: Inserm-ISP Pole Recherches cliniques et thérapeutiques
• Public title: A MULTICENTRE RANDOMIZED CONTROLLED TRIAL COMPARING TOPIRAMATE, STIRIPENTOL AND CLOBAZAM AT THE MAXIMAL TOLERATED DOSAGE, AS ADJUNCTIVE THERAPY TO VALPROATE AND CLOBAZAM IN PAEDIATRIC PATIENTS WITH DRAVET`S SYNDROME (SMEI), AND AUXILIARY PHARMACOGENETIC STUDY
• Scientific title: A MULTICENTRE RANDOMIZED CONTROLLED TRIAL COMPARING TOPIRAMATE, STIRIPENTOL AND CLOBAZAM AT THE MAXIMAL TOLERATED DOSAGE, AS ADJUNCTIVE THERAPY TO VALPROATE AND CLOBAZAM IN PAEDIATRIC PATIENTS WITH DRAVET`S SYNDROME (SMEI), AND AUXILIARY PHARMACOGENETIC STUDY
• Date of first enrolment: 03/07/2007
• Target sample size: 90
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-002198-30
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 3

Countries of recruitment

Italy

Key inclusion & exclusion criteria

Inclusion criteria:
- Aged between 6 months and 15 years. - A signed Consent Form collection from parents or legal guardian. - Proven diagnosis of Dravet`s syndrome *. - Treated with VPA and CLB at usual dosages (at the appreciation of the investigator). - Clonic or tonic-clonic seizures not adequately controlled with VPA and CLB at usual dosages (at the appreciation of the investigator). * Criteria for Â?confirmed diagnosis of Dravet syndromeÂ? - First seizure before the age of 1 year - Seizure types: convulsive seizures (clonic or tonic-clonic) - generalized or hemibody seizures - usually prolonged ((> 15 minutes), - febrile and afebrile - Later on (from the age fo1year to 2 years) seizure types possible: myoclonia, absences, partial seizures - Normal psychomotor development before the first seizure - Later on, severe mental retardation - EEG usually normal before the first seizure - Later on, abnormalities usually present *Diagnostic criteria for DravetÂ?s syndrome in patients between 6 months and 1 year - At least two clonic or tonic-clonic seizures, either generalized or unilateral or followed by a unilateral deficit - At least one afebrile seizure - At least one prolonged seizure (> 15 minutes), - In case of unilateral seizures or seizures followed by a unilateral deficit, both sides having been involved at least once - Normal psychomotor development - No pathological perinatal antecedent
Are the trial subjects under 18? yes
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
- Patients currently treated or history of treatment [in the past] with STP or TPM, - Patients treated with any other AED than VPA and CLB within one month before screening visit, with the exception of diazepam [(VALIUM)], midazolam, lorazepam and clonazepam [(RIVOTRIL)] if used [only] occasionally as emergency treatment for epileptic seizures, - Patients treated with medications known as inhibitors of the CYP3A4 (macrolides, azol antifungal agents, theophylline) or with oral anti-coagulants, - Parents or legal guardian unable to follow the study protocol and or complete the subjectâ??s seizures diary, - Contra indications to study treatments : o Hypersensitivity to the active substance or to any of the excipients. o History of psychoses in the form of episodes of delirium o Renal and/or hepatic function disorder o Glucose and galactose malabsorption o Congenital intolerance to fructose o patients with myasthenia gravis o severe respiratory insufficiency o sleep apnoea syndrome - ongoing pregnancy or breastfeeding female, - childbearing potential female not willing to use an effective mean of contraception, - parents or legual guardians unable to give their consent.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Dravet Syndrome
MedDRA version: 14.1 Level: PT Classification code 10054859 Term: Myoclonic epilepsy System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Trade Name: stiripentolo
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Other antiepileptics
Concentration unit: mg milligram(s)
Concentration number: 250-

Trade Name: TOPAMAX
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Topiramate
Concentration unit: mg milligram(s)
Concentration number: 25-

Trade Name: FRISIUM*30CPS 10MG
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Clobazam
Concentration unit: mg milligram(s)
Concentration number: 10-

Primary Outcome(s)

Primary end point(s): Absolute variation of the monthly number of clonic or tonic-clonic seizures and status epilepticus (defined as clonic or tonic-clonic seizures > 15 minutes), formulated for 30 days in the double blind comparison period (total number of seizures over the three months divided by 3) compared to the screening period ( total number of seizures over the 5 weeks * 4/5).

Secondary Objective: - Evaluate the efficacy of STP and TPM, used as an add-on therapy in addition to VPA and CLB used at usual dosages, on convulsive status epilepticus (a status epilepticus is defined as a clonic or tonic-clonic seizure lasting more than 15 minutes) in Dravet`s syndrome, compared to CLB used at the maximal tolerated dosage. - Compare the efficacy of STP to that of TPM, used as an add-on therapy in addition to VPA and CLB used at usual dosages, on the clonic or tonic-clonic seizures and convulsive status epilepticus in Dravet`s syndrome. - Evaluate the efficacy of STP and TPM, used as an add-on therapy in addition to VPA and CLB used at usual dosages in other seizure types other than clonic or tonic-clonic, compared to CLB used at the maximal tolerated dosage. - Evaluate the safety of STP and TPM (defined as their toxicity), used as an add-on therapy in addition to VPA and CLB used at usual dosages, in Dravet`s syndrome, compared to CLB used at the maximal tolerated dosage.

Main Objective: evaluate the efficacy of STP and TPM, used as an add-on therapy in addition to VPA and CLB used at usual dosages, on the clonic or tonic-clonic seizures in paediatric patients with DravetÂ?s syndrome not adequately controlled with clobazam and valproate, compared to CLB used at the maximal tolerated dosage

Secondary ID(s)

EPICURESUB05T02