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

Phase 3

Completed

• Conditions: Unverricht-Lundborg Disease
• Interventions: Drug: BRV 25 mg; Drug: BRV 2.5 mg; Other: Placebo; Drug: BRV 50 mg

• Registration Number: NCT00368251
• Lead Sponsor: UCB Pharma

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2006-08-23
• Study First Submitted QC: 2006-08-23
• Study First Posted: 2006-08-24
• Study Start: 2006-11
• Primary Completion: 2008-01
• Study Completion: 2008-01
• Disposition First Submitted: 2009-09-09
• Disposition First Submitted QC: 2009-11-05
• Disposition First Posted: 2009-11-09
• Results First Submitted: 2016-03-14
• Results First Submitted QC: 2016-03-14
• Results First Posted: 2016-04-13
• Status Verified: 2023-05
• Last Update Submitted: 2023-05-03
• Last Update Posted: 2023-05-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 56

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Brivaracetam 150 mg/day	BRV 25 mg	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)
Brivaracetam 5 mg/day	BRV 2.5 mg	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)
Brivaracetam 150 mg/day	BRV 50 mg	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)
Placebo	Placebo	Placebo Placebo twice a day (bid), 14 weeks (2 week Up-Titration Period + 12 week Maintenance Period)

Primary Outcome Measures

Name	Time	Method
Percent Change From Baseline to the End of Treatment Period on the Action Myoclonus Score (Unified Myoclonus Rating Scale (UMRS) Section 4)	From Baseline to End of Treatment Period (Week 14 or Early Discontinuation Visit)	The range for Action Myoclonus Score (centrally read) is 0 (best) - 160 (worst). Percent change from Baseline = 100 X ((Baseline UMRS4 - Treatment UMRS4) / Baseline UMRS4). Baseline is defined as the last non-missing value prior to or on Randomization Visit.

Secondary Outcome Measures

Name	Time	Method
Percent Change From Baseline to the End of Treatment Period on the Functional Disability Score (Unified Myoclonus Rating Scale (UMRS) Section 5)	Baseline to End of Treatment Period (Week 14 or Early Discontinuation Visit)	The range for Functional Disability Score is 0 (best) to 28 (worst). Percent change from Baseline = 100 X ((Baseline UMRS5 - Treatment UMRS5) / Baseline UMRS5). Baseline is defined as the last non-missing value prior to or on Randomization Visit.
Global Evaluation Score (Investigator) at the End of Treatment Period	End of Treatment Period (Week 14 or Early Discontinuation Visit)	The Global Evaluation Scale Score (Investigator) ranges from 1 (Marked worsening) to 7 (Marked improvement).
Percent Change From Baseline to the End of Treatment Period on the Stimulus Sensitivity Score (Unified Myoclonus Rating Scale (UMRS) Section 3)	Baseline to End of Treatment Period (Week 14 or Early Discontinuation Visit)	The range for Stimulus Sensitivity Score is 0 (best) to 17 (worst). Percent change from Baseline = 100 X ((Baseline UMRS3 - Treatment UMRS3) / Baseline UMRS3). Baseline is defined as the last non-missing value prior to or on Randomization Visit.
Percent Change From Baseline to the End of Treatment Period on the Myoclonus Patient Questionnaire (Unified Myoclonus Rating Scale (UMRS) Section 1)	Baseline to End of Treatment Period (Week 14 or Early Discontinuation Visit)	The range for Myoclonus Patient Questionnaire is 0 (best) to 44 (worst). Percent change from Baseline = 100 X ((Baseline UMRS1 - Treatment UMRS1) / Baseline UMRS1). Baseline is defined as the last non-missing value prior to or on Randomization Visit.

Trial Locations

Locations (18)

121; 🇫🇷 Lille, France

122; 🇫🇷 Bron, France

170; 🇮🇱 Tel Aviv, Israel

143; 🇷🇺 Samara, Russian Federation

162; 🇷🇸 Belgrade, Serbia

180; 🇹🇳 La Manouba, Tunisia

150; 🇨🇦 Montreal, Quebec, Canada

161; 🇷🇸 Belgrade, Serbia

142; 🇷🇺 Saint Petersburg, Russian Federation

135; 🇺🇸 San Francisco, California, United States

132; 🇺🇸 New York, New York, United States

133; 🇺🇸 Gainesville, Florida, United States

151; 🇨🇦 Vancouver, British Columbia, Canada

131; 🇺🇸 Charlottesville, Virginia, United States

152; 🇨🇦 Quebec, Canada

120; 🇫🇷 Paris, France

100; 🇫🇮 Helsinki, Finland

141; 🇷🇺 Moscow, Russian Federation