Brivaracetam as add-on Treatment of Unverricht-Lundborg Disease (ULD) in Adolescents and Adults

UCB

Status and phase: Completed; Phase 3

Conditions: Unverricht-Lundborg Disease

Treatments: Drug: BRV 50 mg; Other: Placebo; Drug: BRV 25 mg; Drug: BRV 2.5 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT00368251

N01236

2006-001536-46 (EudraCT Number)

Details and patient eligibility

About

The study will compare the efficacy and safety of Brivaracetam with placebo in patients with Unverricht- Lundborg Disease (ULD).

Enrollment: 56 patients

Sex: All

Ages: 16+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Subjects with diagnosed Unverricht-Lundborg disease (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 Myoclonussum 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- Male/female subjects from 16 years onwards. Subjects under 18 years may only be included where legally permitted and ethically accepted

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 central nervous system (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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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56 participants in 3 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Placebo Placebo twice a day (bid), 14 weeks (2 week Up-Titration Period + 12 week Maintenance Period)

Treatment:

Other: Placebo

Brivaracetam 5 mg/day

Experimental group

Description:

Brivaracetam (BRV) 5 mg/day 5 mg twice a day (bid) using 2.5 mg tablets for 12 weeks (after 2 week Up- Titration Period)

Treatment:

Drug: BRV 2.5 mg

Brivaracetam 150 mg/day

Experimental group

Description:

Brivaracetam (BRV) 150 mg/day 150 mg twice a day (bid) using 25 mg and 50 mg tablets for 12 weeks (after 2 week Up-Titration Period)

Treatment:

Drug: BRV 25 mg

Drug: BRV 50 mg