EpilepsyPhase 3NCT01653262
Effect of Brivaracetam (BRV) on Nonpsychotic Behavioral Side Effects in Subjects Treated Previously With Levetiracetam (LEV)
A Phase 3 study testing Brivaracetam in people with Epilepsy, run by UCB Pharma SA at 12 sites in 5 countries.
Trial summary
Trial N01395 is to evaluate the reduction of nonpsychotic behavioral side effects in subjects with Epilepsy who switched to BRV 200 mg/day after discontinuing LEV due to such side effects; as well as the efficacy, safety and tolerability of BRV. No statistical hypothesis testing will be performed. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Epilepsy
- What is being tested?
- Brivaracetam
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 12 sitesin 5 countries
- Study dates
- Jul 2012to Nov 2013
- 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
- Subject with well-characterized Epilepsy according to the 1989 International League Against Epilepsy (ILAE) classification
- Subject with Epilepsy who the investigator expects will benefit from Levetiracetam (LEV) but for whom the investigator has decided to discontinue due to nonpsychotic behavioral side effects following the introduction of LEV
- Subject is currently receiving LEV at the recommended therapeutic dose (dose ranging from 1 g/day to 3 g/day)
- Subject currently treated with minimum 2 and maximum 3 Anti-Epileptic Drugs (AEDs) including LEV. Vagal Nerve Stimulation (VNS) is allowed and will be counted as a concomitant AED
- Female subjects without childbearing potential (postmenopausal for at least 2 years, bilateral oophorectomy or tubal ligation, complete hysterectomy) are eligible. Female subjects with childbearing potential are eligible if they use a medically accepted contraceptive method
Who cannot join
- Subject has a lifetime history of suicide attempt (including an actual, interrupted or aborted attempt), or has had suicidal ideation in the past 6 months as indicated by a positive response ("Yes") to either Question 4 or Question 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) at Visit 1
- Subject whose seizures could not be reliably counted on a regular basis due to their fast and repetitive occurrence (clusters or flurries)
- Subject has history or presence of status epilepticus during the year preceding Visit 1 or during Baseline
- Subject has history or presence of known psychogenic nonepileptic seizures
- Subject has any clinical conditions (eg, bone marrow depression, chronic hepatic disease, and/or severe renal impairment) which impair reliable participation in the study or necessitate the use of medication not allowed by protocol
- Subject is pregnant or lactating
Trial locations and contacts
12 sites in 5 countries.
12 sites in 5 countries
United States6 sites
106
Akron, Ohio
110
Dallas, Texas
108
Lexington, Kentucky
103
Little Rock, Arkansas
109
New York, New York
102
Salt Lake City, Utah
About this study
Official title: An Open-label, Multicenter, Single-arm Study to Evaluate the Reduction in Nonpsychotic Behavioral Side Effects in Subjects With Epilepsy Switching From Levetiracetam to Brivaracetam Due to Nonpsychotic Behavioral Side Effects Phase 3b
Trial N01395 is to evaluate the reduction of nonpsychotic behavioral side effects in subjects with Epilepsy who switched to BRV 200 mg/day after discontinuing LEV due to such side effects; as well as the efficacy, safety and tolerability of BRV. No statistical hypothesis testing will be performed.
- Conditions
- Epilepsy
- Being tested
- Brivaracetam
- Keywords
- Brivaracetam, Levetiracetam, Epilepsy, Nonpsychotic behavior
- Medical subject headings
- Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BrivaracetamDrug
| Study group | Role | What they receive |
|---|---|---|
| Brivaracetam | Experimental | The subjects will be treated with Brivaracetam (BRV) tablets 200 mg/day during 12 weeks: four 25 mg tablets, twice daily.
Based on the Investigator's judgement, at any time, the dose can be decreased to BRV 150 mg/day, 100 mg/day, or 50 mg/day. Flexible dosing, can be up- and down-titrated as needed.
At the end of the Treatment Period, the subject will either enter the N01372 long-term follow-up study or down-titrate during 4 weeks. Receives: Drug: Brivaracetam |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Subjects Who Achieved a Clinically Meaningful Reduction of Nonpsychotic Behavioral Side Effects Based on the Investigator's Overall Assessment From Study Entry to the End of the Treatment Period
Nonpsychotic behavioral side effects include (but are not limited to) such symptoms as aggression, agitation, anger, anxiety, apathy, depersonalization, depression, emotional lability, hostility, irritability, etc.
The Investigator completed the assessment by answering the following:
"Has there been a clinically meaningful reduction of nonpsychotic behavioral side effects since the start of BRV?"
- Yes/No
Measured: From Study Entry (Visit1, Week -1) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit
Secondary outcomes (9)
Shift in the Maximum Intensity From Baseline to the End of the Treatment Period for Side Effects Primarily Associated With Discontinuation of Levetiracetam (LEV) as Determined by the Investigator
Nonpsychotic behavioral side effects include (but are not limited to) such symptoms as aggression, agitation, anger, anxiety, apathy, depersonalization, depression, emotional lability, hostility, irritability, etc.
Measured: From Baseline (maximum of 12 weeks prior to Study Entry at Week -1) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit
Change From Study Entry in Nonpsychotic Behavioral Side Effects to the End of the Treatment Period/Early Discontinuation Visit, Measured by Means of the Investigator Global Evaluation of Nonpsychotic Behavioral Side Effects (I-GEBSE) Scale
There are seven levels for the I-GEBSE:
- Marked improvement
- Moderate improvement
- Slight improvement
- No change
- Slight worsening
- Moderate worsening
- Marked worsening
Measured: From Study Entry (Visit1, Week -1) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit
Number of Subjects Who Have a Complete Abatement of Nonpsychotic Behavioral Side Effects for the Last Assessment During the Treatment Period, Based on the Investigator's Overall Assessment
Nonpsychotic behavioral side effects include (but are not limited to) such symptoms as aggression, agitation, anger, anxiety, apathy, depersonalization, depression, emotional lability, hostility, irritability, etc.
Measured: From Baseline (maximum of 12 weeks prior to Study Entry at Week -1) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit
Number of Subjects Who Are Free From Nonpsychotic Behavioral Side Effects Over the Entire Treatment Period
Nonpsychotic behavioral side effects (NBSE) include (but are not limited to) such symptoms as aggression, agitation, anger, anxiety, apathy, depersonalization, depression, emotional lability, hostility, irritability, etc.
Measured: From Visit 2 (Week 0) to Visit 6 (Week 12)
Incidence of Treatment Emergent Adverse Events During the Study Period
An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. A treatment emergent AE is any event that emerges during treatment having been absent pre-treatment, or worsens relative to the pre-treatment state.
Measured: From Study Entry (Visit1, Week -1) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit
Withdrawal Due to an Adverse Event (AE) During the Study Period
An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment.
Measured: From Study Entry (Visit1, Week -1) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit
Occurrence of Serious Adverse Events During the Study Period
A serious adverse event is any untoward medical occurrences in a subject administered study treatment, whether or not the event is related to treatment, with at least one of the follow outcomes: death, life-threatening, initial inpatient hospitalization or prolongation of hospitalization, significant or persistent disability/incapacity, congenital anomaly/birth defect, or an important medical event that may jeopardize the subject and require a medical/surgical intervention.
Measured: From Study Entry (Visit1, Week -1) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit
Partial Onset Seizure (POS) Frequency Over the Treatment Period for Subjects With Focal Epilepsy
The POS frequency is standardized to a 28-day duration and changes in POS frequency are measured relative to the reported seizure counts for the 4 weeks prior to Visit 2 (Week 0).
Partial seizures can be classified into one of the following three groups:
- Simple partial seizures (IA)
- Complex partial seizures (IB)
- Partial seizures evolving to secondarily generalized seizures (IC)
Measured: From 4 weeks prior to Visit 2 (Week 0) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit
Generalized Seizure Days Over the Treatment Period for Subjects With Idiopathic Generalized Epilepsy
Generalized seizure days are standardized to a 28-day duration and changes in generalized seizure days are measured relative to the reported seizure counts for the 4 weeks prior to Visit 2 (Week 0).
Generalized seizures (Type II) include the following seizure types:
- Absence (IIA1)
- Atypical absence (IIA2)
- Myoclonic (IIB)
- Clonic (IIC)
- Tonic (IID)
- Tonic-clonic (IIE)
- Atonic (IIF)
A specific effect of BRV on the occurrence of generalized seizures was not assessed.
Measured: From 4 weeks prior to Visit 2 (Week 0) to the end of the Treatment Period (Visit 6, Week 12) 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 posted30 Jul 2012 (estimated)
- Study startJul 2012
- Primary completionNov 2013
- Study completionNov 2013
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 (1)Papers the sponsor has linked to this study.
- Other trials for EpilepsyStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- UCB Pharma SA
- 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
- NCT01653262
- Sponsor's protocol ID
- N01395
- Other IDs
- 2011-005177-23
- Status last verified
- Jul 2016
- First submitted
- 26 Jul 2012
- Last updated
- 11 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Expanded access
- Available
Publications
Yates SL, Fakhoury T, Liang W, Eckhardt K, Borghs S, D'Souza J. An open-label, prospective, exploratory study of patients with epilepsy switching from levetiracetam to brivaracetam. Epilepsy Behav. 2015 Nov;52(Pt A):165-8. doi: 10.1016/j.yebeh.2015.09.005. Epub 2015 Sep 29.
PubMed 26432008
Study at a glance
From the registry record, last updated by the sponsor on 11 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Multicenter, Single-arm Study to Evaluate the Reduction in Nonpsychotic Behavioral Side Effects in Subjects With Epilepsy Switching From Levetiracetam to Brivaracetam Due to Nonpsychotic Behavioral Side Effects Phase 3b
- ClinicalTrials.gov ID
- NCT01653262
- Acronym / sponsor ID
- N01395
- Conditions
- Epilepsy
- Keywords
- Brivaracetam, Levetiracetam, Epilepsy, Nonpsychotic behavior
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- UCB Pharma SAIndustry (pharma, biotech, devices)
- Study start
- Jul 2012
- Primary completion
- Nov 2013 (actual)
- Study completion
- Nov 2013 (actual)
- First posted
- 30 Jul 2012 (estimated)
- Results
- Posted 15 Aug 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Trial N01395 is to evaluate the reduction of nonpsychotic behavioral side effects in subjects with Epilepsy who switched to BRV 200 mg/day after discontinuing LEV due to such side effects; as well as the efficacy, safety and tolerability of BRV. No statistical hypothesis testing will be performed.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Brivaracetam | Experimental | Drug: BrivaracetamThe subjects will be treated with Brivaracetam (BRV) tablets 200 mg/day during 12 weeks: four 25 mg tablets, twice daily. Based on the Investigator's judgement, at any time, the dose can be decreased to BRV 150 mg/day, 100 mg/day, or 50 mg/day. Flexible dosing, can be up- and down-titrated as needed. At the end of the Treatment Period, the subject will either enter the N01372 long-term follow-up study or down-titrate during 4 weeks. |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Subject with well-characterized Epilepsy according to the 1989 International League Against Epilepsy (ILAE) classification
- Subject with Epilepsy who the investigator expects will benefit from Levetiracetam (LEV) but for whom the investigator has decided to discontinue due to nonpsychotic behavioral side effects following the introduction of LEV
- Subject is currently receiving LEV at the recommended therapeutic dose (dose ranging from 1 g/day to 3 g/day)
- Subject currently treated with minimum 2 and maximum 3 Anti-Epileptic Drugs (AEDs) including LEV. Vagal Nerve Stimulation (VNS) is allowed and will be counted as a concomitant AED
- Female subjects without childbearing potential (postmenopausal for at least 2 years, bilateral oophorectomy or tubal ligation, complete hysterectomy) are eligible. Female subjects with childbearing potential are eligible if they use a medically accepted contraceptive method
Key exclusion criteria (6 listed)
- Subject has a lifetime history of suicide attempt (including an actual, interrupted or aborted attempt), or has had suicidal ideation in the past 6 months as indicated by a positive response ("Yes") to either Question 4 or Question 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) at Visit 1
- Subject whose seizures could not be reliably counted on a regular basis due to their fast and repetitive occurrence (clusters or flurries)
- Subject has history or presence of status epilepticus during the year preceding Visit 1 or during Baseline
- Subject has history or presence of known psychogenic nonepileptic seizures
- Subject has any clinical conditions (eg, bone marrow depression, chronic hepatic disease, and/or severe renal impairment) which impair reliable participation in the study or necessitate the use of medication not allowed by protocol
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 |
|---|---|---|
| Brivaracetam | Drug | Brivaracetam |
Primary outcome
Percentage of Subjects Who Achieved a Clinically Meaningful Reduction of Nonpsychotic Behavioral Side Effects Based on the Investigator's Overall Assessment From Study Entry to the End of the Treatment Period
Time frame: From Study Entry (Visit1, Week -1) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit
Nonpsychotic behavioral side effects include (but are not limited to) such symptoms as aggression, agitation, anger, anxiety, apathy, depersonalization, depression, emotional lability, hostility, irritability, etc. The Investigator completed the assessment by answering the following: "Has there been a clinically meaningful reduction of nonpsychotic behavioral side effects since the start of BRV?" - Yes/No
9 secondary outcomes
Shift in the Maximum Intensity From Baseline to the End of the Treatment Period for Side Effects Primarily Associated With Discontinuation of Levetiracetam (LEV) as Determined by the Investigator
Time frame: From Baseline (maximum of 12 weeks prior to Study Entry at Week -1) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit
Change From Study Entry in Nonpsychotic Behavioral Side Effects to the End of the Treatment Period/Early Discontinuation Visit, Measured by Means of the Investigator Global Evaluation of Nonpsychotic Behavioral Side Effects (I-GEBSE) Scale
Time frame: From Study Entry (Visit1, Week -1) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit
Number of Subjects Who Have a Complete Abatement of Nonpsychotic Behavioral Side Effects for the Last Assessment During the Treatment Period, Based on the Investigator's Overall Assessment
Time frame: From Baseline (maximum of 12 weeks prior to Study Entry at Week -1) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit
Number of Subjects Who Are Free From Nonpsychotic Behavioral Side Effects Over the Entire Treatment Period
Time frame: From Visit 2 (Week 0) to Visit 6 (Week 12)
Incidence of Treatment Emergent Adverse Events During the Study Period
Time frame: From Study Entry (Visit1, Week -1) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit
Withdrawal Due to an Adverse Event (AE) During the Study Period
Time frame: From Study Entry (Visit1, Week -1) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit
Occurrence of Serious Adverse Events During the Study Period
Time frame: From Study Entry (Visit1, Week -1) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit
Partial Onset Seizure (POS) Frequency Over the Treatment Period for Subjects With Focal Epilepsy
Time frame: From 4 weeks prior to Visit 2 (Week 0) to the end of the Treatment Period (Visit 6, Week 12) or Early Discontinuation Visit
Generalized Seizure Days Over the Treatment Period for Subjects With Idiopathic Generalized Epilepsy
Time frame: From 4 weeks prior to Visit 2 (Week 0) to the end of the Treatment Period (Visit 6, Week 12) 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 11 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26432008Yates SL, Fakhoury T, Liang W, Eckhardt K, Borghs S, D'Souza J. An open-label, prospective, exploratory study of patients with epilepsy switching from levetiracetam to brivaracetam. Epilepsy Behav. 2015 Nov;52(Pt A):165-8. doi: 10.1016/j.yebeh.2015.09.005. Epub 2015 Sep 29.
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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)
12 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Brivaracetam in people with Epilepsy, run by UCB Pharma SA at 12 sites in 5 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 5 inclusion and 6 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 11 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States, France, Germany, Spain, United Kingdom. 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. 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 15 Aug 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?
Percentage of Subjects Who Achieved a Clinically Meaningful Reduction of Nonpsychotic Behavioral Side Effects Based on the Investigator's Overall Assessment From Study Entry to the End of the Treatment Period (time frame: From Study Entry (Visit1, Week -1) to the end of the Treatment Period (Visit 6, Week 12) 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 NCT01653262, which also lists 1 linked publication.
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 11 Jul 2018.