Unverricht-Lundborg DiseasePhase 3NCT00368251
Brivaracetam as add-on Treatment of Unverricht-Lundborg Disease (ULD) in Adolescents and Adults
A Phase 3 study testing BRV 2.5 mg, BRV 25 mg and BRV 50 mg in people with Unverricht-Lundborg Disease, run by UCB Pharma at 18 sites in 8 countries.
Trial summary
The study will compare the efficacy and safety of Brivaracetam with placebo in patients with Unverricht- Lundborg Disease (ULD). Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Unverricht-Lundborg Disease
- What is being tested?
- BRV 2.5 mg, BRV 25 mg and BRV 50 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 56 participants
- Where
- 18 sitesin 8 countries
- Study dates
- Nov 2006to Jan 2008
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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 locations and contacts
18 sites in 8 countries.
18 sites in 8 countries
United States4 sites
131
Charlottesville, Virginia
133
Gainesville, Florida
132
New York, New York
135
San Francisco, California
Canada3 sites
150
Montreal, Quebec
152
Québec, Quebec
151
Vancouver, British Columbia
About this study
Official 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
The study will compare the efficacy and safety of Brivaracetam with placebo in patients with Unverricht- Lundborg Disease (ULD).
- Conditions
- Unverricht-Lundborg Disease
- Being tested
- Placebo, BRV 2.5 mg, BRV 25 mg, BRV 50 mg
- Keywords
- Unverricht-Lundborg Disease, Baltic Myoclonus, Progressive Myoclonic Epilepsies, Myoclonus, Brivaracetam
- Medical subject headings
- Unverricht-Lundborg Syndrome, Myoclonic Epilepsies, Progressive, Myoclonus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboOther
- Pharmaceutical Form: Tablet
- Concentration: 2.5 mg, 25 mg and 50 mg
- Route of Administration: Oral use
BRV 2.5 mgDrug
Also called ucb34714
- Pharmaceutical Form: Tablet
- Concentration: 2.5 mg
- Route of Administration: Oral use
BRV 25 mgDrug
- Pharmaceutical Form: Tablet
- Concentration: 25 mg
- Route of Administration: Oral use
BRV 50 mgDrug
- Pharmaceutical Form: Tablet
- Concentration: 50 mg
- Route of Administration: Oral use
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Placebo Placebo twice a day (bid), 14 weeks (2 week Up-Titration Period + 12 week Maintenance Period) Receives: Other: Placebo |
| Brivaracetam 5 mg/day | Experimental | 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) Receives: Drug: BRV 2.5 mg |
| Brivaracetam 150 mg/day | Experimental | 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) Receives: Drug: BRV 25 mg; Drug: BRV 50 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change From Baseline to the End of Treatment Period on the Action Myoclonus Score (Unified Myoclonus Rating Scale (UMRS) Section 4)
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.
Measured: From Baseline to End of Treatment Period (Week 14 or Early Discontinuation Visit)
Secondary outcomes (4)
Percent Change From Baseline to the End of Treatment Period on the Functional Disability Score (Unified Myoclonus Rating Scale (UMRS) Section 5)
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.
Measured: Baseline to End of Treatment Period (Week 14 or Early Discontinuation Visit)
Percent Change From Baseline to the End of Treatment Period on the Stimulus Sensitivity Score (Unified Myoclonus Rating Scale (UMRS) Section 3)
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.
Measured: Baseline to End of Treatment Period (Week 14 or Early Discontinuation Visit)
Percent Change From Baseline to the End of Treatment Period on the Myoclonus Patient Questionnaire (Unified Myoclonus Rating Scale (UMRS) Section 1)
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.
Measured: Baseline to End of Treatment Period (Week 14 or Early Discontinuation Visit)
Global Evaluation Score (Investigator) at the End of Treatment Period
The Global Evaluation Scale Score (Investigator) ranges from 1 (Marked worsening) to 7 (Marked improvement).
Measured: End of Treatment Period (Week 14 or Early Discontinuation Visit)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2006 (estimated)
- Study startNov 2006
- Primary completionJan 2008
- Study completionJan 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Unverricht-Lundborg DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- UCB Pharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- UCB Clinical Trial Call Center, Study director, +1 877 822 9493 (UCB)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00368251
- Sponsor's protocol ID
- N01236
- Other IDs
- 2006-001536-46
- Status last verified
- May 2023
- First submitted
- 23 Aug 2006
- Last updated
- 31 May 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Expanded access
- Available
Publications
Ben-Menachem E, Baulac M, Hong SB, Cleveland JM, Reichel C, Schulz AL, Wagener G, Brandt C. Safety, tolerability, and efficacy of brivaracetam as adjunctive therapy in patients with focal seizures, generalized onset seizures, or Unverricht-Lundborg disease: An open-label, long-term follow-up trial. Epilepsy Res. 2021 Feb;170:106526. doi: 10.1016/j.eplepsyres.2020.106526. Epub 2020 Dec 4.
PubMed 33461041Kalviainen R, Genton P, Andermann E, Andermann F, Magaudda A, Frucht SJ, Schlit AF, Gerard D, de la Loge C, von Rosenstiel P. Brivaracetam in Unverricht-Lundborg disease (EPM1): Results from two randomized, double-blind, placebo-controlled studies. Epilepsia. 2016 Feb;57(2):210-21. doi: 10.1111/epi.13275. Epub 2015 Dec 15.
PubMed 26666500
Study at a glance
From the registry record, last updated by the sponsor on 31 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT00368251
- Acronym / sponsor ID
- N01236
- Conditions
- Unverricht-Lundborg Disease
- Keywords
- Unverricht-Lundborg Disease, Baltic Myoclonus, Progressive Myoclonic Epilepsies, Myoclonus, Brivaracetam
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- UCB PharmaIndustry (pharma, biotech, devices)
- Study start
- Nov 2006
- Primary completion
- Jan 2008 (actual)
- Study completion
- Jan 2008 (actual)
- First posted
- 24 Aug 2006 (estimated)
- Results
- Posted 13 Apr 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study will compare the efficacy and safety of Brivaracetam with placebo in patients with Unverricht- Lundborg Disease (ULD).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Other: PlaceboPlacebo Placebo twice a day (bid), 14 weeks (2 week Up-Titration Period + 12 week Maintenance Period) |
| Brivaracetam 5 mg/day | Experimental | Drug: BRV 2.5 mgBrivaracetam (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 | Experimental | Drug: BRV 25 mg, Drug: BRV 50 mgBrivaracetam (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) |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- 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
Key exclusion criteria (1 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Placebo* Pharmaceutical Form: Tablet * Concentration: 2.5 mg, 25 mg and 50 mg * Route of Administration: Oral use | Other | Placebo |
| BRV 2.5 mgAlso: ucb34714* Pharmaceutical Form: Tablet * Concentration: 2.5 mg * Route of Administration: Oral use | Drug | Brivaracetam 5 mg/day |
| BRV 25 mg* Pharmaceutical Form: Tablet * Concentration: 25 mg * Route of Administration: Oral use | Drug | Brivaracetam 150 mg/day |
| BRV 50 mg* Pharmaceutical Form: Tablet * Concentration: 50 mg * Route of Administration: Oral use | Drug | Brivaracetam 150 mg/day |
Primary outcome
Percent Change From Baseline to the End of Treatment Period on the Action Myoclonus Score (Unified Myoclonus Rating Scale (UMRS) Section 4)
Time frame: 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.
4 secondary outcomes
Percent Change From Baseline to the End of Treatment Period on the Functional Disability Score (Unified Myoclonus Rating Scale (UMRS) Section 5)
Time frame: Baseline to End of Treatment Period (Week 14 or Early Discontinuation Visit)
Percent Change From Baseline to the End of Treatment Period on the Stimulus Sensitivity Score (Unified Myoclonus Rating Scale (UMRS) Section 3)
Time frame: Baseline to End of Treatment Period (Week 14 or Early Discontinuation Visit)
Percent Change From Baseline to the End of Treatment Period on the Myoclonus Patient Questionnaire (Unified Myoclonus Rating Scale (UMRS) Section 1)
Time frame: Baseline to End of Treatment Period (Week 14 or Early Discontinuation Visit)
Global Evaluation Score (Investigator) at the End of Treatment Period
Time frame: End of Treatment Period (Week 14 or Early Discontinuation Visit)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 May 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33461041Ben-Menachem E, Baulac M, Hong SB, Cleveland JM, Reichel C, Schulz AL, Wagener G, Brandt C. Safety, tolerability, and efficacy of brivaracetam as adjunctive therapy in patients with focal seizures, generalized onset seizures, or Unverricht-Lundborg disease: An open-label, long-term follow-up trial. Epilepsy Res. 2021 Feb;170:106526. doi: 10.1016/j.eplepsyres.2020.106526. Epub 2020 Dec 4.
- Derived from this study: PubMed 26666500Kalviainen R, Genton P, Andermann E, Andermann F, Magaudda A, Frucht SJ, Schlit AF, Gerard D, de la Loge C, von Rosenstiel P. Brivaracetam in Unverricht-Lundborg disease (EPM1): Results from two randomized, double-blind, placebo-controlled studies. Epilepsia. 2016 Feb;57(2):210-21. doi: 10.1111/epi.13275. Epub 2015 Dec 15.
- Product InformationLink provided by the sponsor.
- FDA Safety Alerts and RecallsLink provided by the sponsor.
Related trials for Unverricht-Lundborg Disease
RecruitingObservational study
Registry and Natural History Study for Progressive Myoclonus Epilepsy Type 1 (EPM1)
Progressive Myoclonus Epilepsy Type 1, EPM1
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
UCB Clinical Trial Call Center study director
+1 877 822 9493 (UCB)
18 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing BRV 2.5 mg, BRV 25 mg and BRV 50 mg in people with Unverricht-Lundborg Disease, run by UCB Pharma at 18 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in United States, Canada, France, Russia, Serbia and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Apr 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change From Baseline to the End of Treatment Period on the Action Myoclonus Score (Unified Myoclonus Rating Scale (UMRS) Section 4) (time frame: From Baseline to End of Treatment Period (Week 14 or Early Discontinuation Visit)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00368251, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 May 2023.