A multicenter, randomized, double-blind, placebo-controlled, parallel study to evaluate the efficacy and safety of brivaracetam used as adjunctive treatment for 12 weeks in adolescent and adult patients (=16 years) with genetically ascertained Unverricht-Lundborg disease.

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2006-000169-12-SE
• Date of registration: 07/08/2006
• Prospective Registration: Yes
• Primary sponsor: UCB Pharma S.A.
• Public title: A multicenter, randomized, double-blind, placebo-controlled, parallel study to evaluate the efficacy and safety of brivaracetam used as adjunctive treatment for 12 weeks in adolescent and adult patients (=16 years) with genetically ascertained Unverricht-Lundborg disease.
• Scientific title: A multicenter, randomized, double-blind, placebo-controlled, parallel study to evaluate the efficacy and safety of brivaracetam used as adjunctive treatment for 12 weeks in adolescent and adult patients (=16 years) with genetically ascertained Unverricht-Lundborg disease.
• Date of first enrolment: 06/10/2006
• Target sample size: 45
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-000169-12
• 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: no Placebo: yes Other: no

Countries of recruitment

Finland, France, Italy, Netherlands, Sweden

Key inclusion & exclusion criteria

Inclusion criteria:
.) Subjects with diagnosed ULD ascertained by appropriate genetic testing for a
homozygous or compound heterozygous mutation in the CSTB gene.
.) Subjects with moderate to severe myoclonus documented by an Action Myoclonus
sum score of = 30 (evaluation by investigator).
.) Subjects currently being or having been treated with clonazepam up to the maximum recommended daily dose of 20 mg or up to their individual optimal dose as assessed by the investigator.
.) Subjects currently being or having been treated with valproate up to the maximum
recommended daily dose 60 mg/kg or serum levels of 100 mcg/ml or up to their individual optimal dose as specified by the investigator.
.)Female subjects without childbearing potential (premenarcheal; 2 years post-menopausal; bilateral oophorectomy or ovariectomy; bilateral salpingectomy, complete hysterectomy; congenital sterility) are eligible. Female subjects with childbearing potential are eligible if they use a medically accepted contraceptive method for the duration of the trial participation (Intra Uterine Device; diaphragm with spermicide; male or female condom with spermicide; oral hormonal contraceptive; non- oral hormonal contraceptive medication; bilateral tubal ligation; monogamous relationship with vasectomized partner).
In particular, oral or depot contraceptive treatment with at least 30 µg (or 50 µg if associated with a strong CYP450 inducer) ethinylestradiol per intake will be combined with double-barrier contraception method. The subject must understand the consequences and potential risks of inadequately protected sexual activity, be educated about and understand the proper use of contraceptive methods, and undertake to inform the Investigator of any potential change in status during the course of the study.

Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
.) Subjects currently on felbamate or having been on felbamate within less than 18
months prior to visit 1.
.) Subjects currently treated with phenytoin or having been on phenytoin in the last
month prior to visit 1.
.) Subjects currently on vigabatrine. Subjects having been on vigabatrine if no visual
fields examination report available including standard static (Humphrey or Octopus)
or cinetic perimetry (Goldman).
.) Subject taking any drug with possible CNS effects.
.) Subjects taking any drug that may significantly influence the metabolism of BRV
(CYP2C or CYP3A potent inducers/inhibitors).
.) Known clinically significant acute or chronic illness or illness which may impair
reliable participation in the trial, necessitate the use of medication not allowed by
protocol or represent a safety risk in the Investigator’s opinion.
.) Subjects with history of severe adverse hematological reaction to any drug.
.) Impaired hepatic function: ALAT/SGPT, ASAT/SGOT, alkaline phosphatase, GGT
value of more than three times the upper limit of the reference range.
.) History of suicide attempt during the last 5 years.
.) Subject with suicidal ideations within the last year or at risk of suicide attempt
unless cleared by written confirmation from a psychiatrist and approved by the UCB
physician.
.) Ongoing psychiatric disorder other than mild controlled disorder.


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

Health Condition(s) or Problem(s) studied

Patients with genetically ascertained Unverricht-Lundborg disease (ULD).
MedDRA version: 8.1 Level: LLT Classification code 10054894 Term: Unverricht-Lundborg disease

Intervention(s)

Product Name: Brivaracetam
Product Code: ucb 34714
Pharmaceutical Form: Tablet
INN or Proposed INN: brivaracetam
CAS Number: 357336-20-0
Current Sponsor code: ucb 34714
Other descriptive name: (2S)-2-[(4R)-2-oxo-4-propylpyrrolidin-1-yl] butanamide
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: Brivaracetam
Product Code: ucb 34714
Pharmaceutical Form: Tablet
INN or Proposed INN: brivaracetam
CAS Number: 357336-20-0
Current Sponsor code: ucb 34714
Other descriptive name: (2S)-2-[(4R)-2-oxo-4-propylpyrrolidin-1-yl] butanamide
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): The least-square means of the percent reduction from baseline on the Action Myoclonus will be estimated at every post-randomization visit in each treatment arm.
95% confidence limits on the difference between the least-square means of the Action Myoclonus score at the scheduled end of the treatment phase (V7) will be presented. Appropriate estimates will be calculated in order to compare placebo versus the average of the two brivaracetam doses.
The first hypothesis for the primary efficacy variable that will be tested compares placebo versus the average of the two brivaracetam doses. If this hypothesis is rejected (at 5%), both pairwise comparisons of Placebo versus each brivaracetam dose will be tested at 5% each.
The population for primary efficacy analysis is the ITT population.
The effect on the treatment difference because of concomitant use of Levetiracetam and/or Piracetam will be investigated through an interaction term with treatment and
randomization stratum in the model.
A descriptive analysis will be performed on the categorized percent reduction from
baseline at end of treatment on the action myoclonus. The defined categories are <- 25%, [-25% , 0[, [0 , 25%[ , [25% , 50%[ , [50% , 75%[ , [75% , 100%[ and 100%.

Main Objective: The primary objective of the study is to compare the efficacy of brivaracetam 50 and
150mg/d in b.i.d. administration with placebo, on the symptom relief of action myoclonus in patients with ULD.

Secondary Objective: The secondary objectives are to compare the efficacy of brivaracetam 50 and 150mg/d in b.i.d. administration with placebo on the functional disability, stimulus sensitivity and on the symptom relief as evaluated by the Myoclonus Patient Questionnaire in patients with ULD. The secondary objectives are also to evaluate the dose/clinical response relationship, to assess the safety and tolerability of Brivaracetam (BRV) in this patient population as well as to assess the effect of BRV on the global evaluation of the disease evolution (assessed by the investigator) of these ULD patients.
The exploratory objectives are to evaluate the effect of BRV on the mood, on the health related quality of life and on the global evaluation of the evolution of the disease (assessed by the patients) of these ULD patients.

Secondary ID(s)

N01187

2006-000169-12-FI