EpilepsyPhase 3NCT01405508
Safety and Tolerability of Intravenous Brivaracetam (Infusion or Bolus) as Adjunctive Antiepileptic Therapy
A Phase 3 study testing Brivaracetam tablets, Brivaracetam bolus and Brivaracetam infusion in people with Epilepsy, run by UCB Pharma at 17 sites in 4 countries.
Trial summary
This is a multicenter, open-label, 4-arm, randomized, parallel-group study to evaluate safety and tolerability of Brivaracetam Intravenous (BRV iv) as adjunctive treatment for adults with epilepsy according to an initiation or a conversion scheme, during repeated dosing (100 mg/administration twice daily for 4.5 days). Read more about this study
- Who is it for?
- Ages 16 to 70 years
- Conditions the study is for
- Epilepsy
- What is being tested?
- Brivaracetam tablets, Brivaracetam bolus and Brivaracetam infusion
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 105 participants
- Where
- 17 sitesin 4 countries
- Study dates
- Aug 2011to Jul 2012
- 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 to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- An Institutional Review Board/Independent Ethics Committee (IRB/IEC) approved written Informed Consent form signed and dated by the subject or by parent(s) or legal representative
- Subjects from 16 to 70 years
- Subjects with a body weight of >/= 40 kg
- Female subjects without childbearing potential or female subjects with childbearing potential if they use a medically accepted contraceptive method
- Subject/legal representative considered as reliable and capable of adhering to the protocol
- Subjects with well-characterized focal or generalized epilepsy or epileptic syndrome
Show all 9Show fewer
- Subjects with a history of partial-onset seizures whether or not secondarily generalized or primary generalized seizures
- Subjects being uncontrolled while treated with 1 to 2 permitted concomitant antiepileptic drugs (AEDs)
- Permitted concomitant antiepileptic drugs (AEDs) and vagus nerve stimulation (VNS) being stable and at optimal dosage for the subject from at least 1 month before Visit 1 and expected to be kept stable during the Run-In and Evaluation Periods
Who cannot join
- Mentally impaired subjects unable to understand the study purpose
- History or presence of status epilepticus during 1 year preceding Visit 1 or Baseline
- Subjects on felbamate with less than 18 months continuous exposure before Visit 1
- Subjects currently on vigabatrin
- Subject taking any drug with possible relevant central nervous system effects except is stable from at least 1 month before Visit 1 and expected to be kept stable during the trial
- Subjects taking any drug that may significantly influence the metabolism of Brivaracetam (BRV) except if the dose has been kept stable at least 1 month before Visit 1, and is expected to be kept stable during the trial
Show all 29Show fewer
- History of cerebrovascular accident in the last 6 months
- Subjects suffering from severe cardiovascular disease or peripheral vascular disease
- Presence of any sign suggesting rapidly progressing brain disorder or brain tumor
- Any clinical conditions which impair reliable participation in the study or necessitate the use of medication not allowed by protocol
- Presence of a terminal illness
- Presence of a serious infection
- Subjects with a history of sever adverse hematologic reaction to any drug
- Subjects suffering from severe disturbance of hemostasis
- Impaired hepatic function: alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT) values of more than 3 times the upper limit of the reference range
- Subjects having clinically significant deviations from reference range values for laboratory parameters: creatinine clearance calculated < 50 ml / min, platelets < 100,000 / µL, or neutrophil cells < 1,800 / µL
- Clinically significant electrocardiogram (ECG) abnormalities according to the Investigator
- History of suicide attempt
- In the Investigator's medical judgment, any current suicidal ideation or other serious psychiatric disorders requiring of having required hospitalization or medication
- Known allergic reaction or intolerance to pyrrolidone derivatives and / or investigational product excipients
- Known multiple drug allergies or severe drug allergy
- Pregnant or lactating women
- Known alcohol or drug addiction or abuse within the last 2 years
- Subject institutionalized under judicial decision
- Problems of venous accessibility
- Subject taking part in another clinical / pharmacological study in the month preceding enrollment (Visit 1)
- Investigators, coinvestigators, their spouses or children, or any study collaborators
- Subjects previously treated with Brivaracetam (BRV)
- Subject previously screened within this study
Trial locations and contacts
17 sites in 4 countries.
17 sites in 4 countries
United States8 sites
008
Bethesda, Maryland
036
Charlottesville, Virginia
778
Columbus, Ohio
777
Dallas, Texas
780
Lexington, Kentucky
775
Little Rock, Arkansas
776
Nashville, Tennessee
001
Phoenix, Arizona
About this study
Official title: A Multi-center, Open-label, Four-arm, Randomized Trial Evaluating the Safety and Tolerability of Brivaracetam Intravenous Infusion and Bolus, Administered in BID Regimen as an Adjunctive Antiepileptic Treatment in Subjects From 16 to 70 Years Suffering From Epilepsy
This is a multicenter, open-label, 4-arm, randomized, parallel-group study to evaluate safety and tolerability of Brivaracetam Intravenous (BRV iv) as adjunctive treatment for adults with epilepsy according to an initiation or a conversion scheme, during repeated dosing (100 mg/administration twice daily for 4.5 days).
Read the detailed description
Eligible subjects will be randomized in a 1:1:1:1 ratio to the 4 treatment arms
- Conditions
- Epilepsy
- Being tested
- Brivaracetam tablets, Brivaracetam bolus, Brivaracetam infusion, Placebo
- Keywords
- N01258, Brivaracetam, Epilepsy, IV, intravenous
- Medical subject headings
- Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Brivaracetam tabletsDrug
100 mg, intake twice daily (BID) for 7 days during Run-In Period
Brivaracetam bolusDrug
10 mL (= 100 mg) of Brivaracetam administered intravenously over 2 minutes twice daily (BID) during Evaluation Period
Brivaracetam infusionDrug
10 mL (= 100 mg) of Brivaracetam diluted in 90 mL 0.9 % isotonic saline sterile solution for intravenous administration infused over 15 minutes twice daily (BID) during Evaluation Period
PlaceboOther
100 mg twice daily (BID) for 7 days during Run-In Period
| Study group | Role | What they receive |
|---|---|---|
| Placebo tablets / Brivaracetam bolus | Experimental | Subjects will receive Placebo (PBO) tablets for one week followed by Brivaracetam (BRV) bolus for 4.5 days.
Down-Titration:
* If subject discontinues the study during the Run-In Period, then the subject will receive the treatment that he/she was assigned during Run-In
* If subject discontinues during the Evaluation Period or after Day 12, the subject will receive Placebo tablets during Down-Titration:
Tablets will be provided for 4 weeks; 75 mg / intake BID for the first week, 50 mg / intake BID for the second week, 25 mg / intake BID for the third week, 10 mg / intake BID for the fourth week Receives: Drug: Brivaracetam bolus; Other: Placebo |
| Brivaracetam (BRV) tablets / BRV bolus | Experimental | Subjects will receive Brivaracetam (BRV) tablets for one week followed by BRV bolus for 4.5 days.
Down-Titration:
* If subject discontinues the study during the Run-In Period, then the subject will receive the treatment that he/she was assigned during Run-In
* If subject discontinues during the Evaluation Period or after Day 12, the subject will receive BRV tablets during Down-Titration:
Tablets will be provided for 4 weeks; 75 mg / intake BID for the first week, 50 mg / intake BID for the second week, 25 mg / intake BID for the third week, 10 mg / intake bid for the fourth week Receives: Drug: Brivaracetam tablets; Drug: Brivaracetam bolus |
| Placebo tablets / Brivaracetam infusion | Experimental | Subjects will receive Placebo (PBO) tablets for one week followed by Brivaracetam (BRV) intravenous infusion for 4.5 days.
Down-Titration:
* If subject discontinues the study during the Run-In Period, then the subject will receive the treatment that he/she was assigned during Run-In
* If subject discontinues during the Evaluation Period or after Day 12, the subject will receive BRV tablets during Down-Titration:
Tablets will be provided for 4 weeks; 75 mg / intake BID for the first week, 50 mg / intake BID for the second week, 25 mg / intake BID for the third week, 10 mg / intake BID for the fourth week Receives: Drug: Brivaracetam infusion; Other: Placebo |
| Brivaracetam (BRV) tablets / BRV infusion | Experimental | Subjects will receive Brivaracetam (BRV) tablets for one week followed by Brivaracetam intravenous infusion for 4.5 days.
Down-Titration:
* If subject discontinues the study during the Run-In Period, then the subject will receive the treatment that he/she was assigned during Run-In
* If subject discontinues during the Evaluation Period or after Day 12, the subject will receive BRV tablets during Down-Titration:
Tablets will be provided for 4 weeks; 75 mg / intake BID for the first week, 50 mg / intake BID for the second week, 25 mg / intake BID for the third week, 10 mg / intake BID for the fourth week Receives: Drug: Brivaracetam tablets; Drug: Brivaracetam infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects With at Least One Treatment-emergent Adverse Event During the Study (Maximum 40 Days)
An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Measured: 40 days
Secondary outcomes (2)
Number of Subjects Who Withdrew Due to a Treatment-emergent Adverse Event During the Study (Maximum 40 Days)
An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Measured: 40 days
Number of Subjects With at Least One Injection-related Treatment-emergent Adverse Event (TEAE) During the Evaluation Period.
An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Measured: 4.5-day Evaluation Period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2011 (estimated)
- Study startAug 2011
- Primary completionJul 2012
- Study completionJul 2012
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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 105 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
- NCT01405508
- Sponsor's protocol ID
- N01258
- Other IDs
- 2008-004714-27, 2008
- Status last verified
- Jul 2016
- First submitted
- 27 Jul 2011
- Last updated
- 11 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Expanded access
- Available
Publications
Toledo M, Brandt C, Quarato PP, Schulz AL, Cleveland JM, Wagener G, Klein P. Long-term safety, efficacy, and quality of life during adjunctive brivaracetam treatment in patients with uncontrolled epilepsy: An open-label follow-up trial. Epilepsy Behav. 2021 May;118:107897. doi: 10.1016/j.yebeh.2021.107897. Epub 2021 Mar 27.
PubMed 33780735
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
- A Multi-center, Open-label, Four-arm, Randomized Trial Evaluating the Safety and Tolerability of Brivaracetam Intravenous Infusion and Bolus, Administered in BID Regimen as an Adjunctive Antiepileptic Treatment in Subjects From 16 to 70 Years Suffering From Epilepsy
- ClinicalTrials.gov ID
- NCT01405508
- Acronym / sponsor ID
- N01258
- Conditions
- Epilepsy
- Keywords
- N01258, Brivaracetam, Epilepsy, IV, intravenous
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 105 participants (actual)
- Lead sponsor
- UCB PharmaIndustry (pharma, biotech, devices)
- Study start
- Aug 2011
- Primary completion
- Jul 2012 (actual)
- Study completion
- Jul 2012 (actual)
- First posted
- 29 Jul 2011 (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.
This is a multicenter, open-label, 4-arm, randomized, parallel-group study to evaluate safety and tolerability of Brivaracetam Intravenous (BRV iv) as adjunctive treatment for adults with epilepsy according to an initiation or a conversion scheme, during repeated dosing (100 mg/administration twice daily for 4.5 days).
Detailed description
Eligible subjects will be randomized in a 1:1:1:1 ratio to the 4 treatment arms
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Placebo tablets / Brivaracetam bolus | Experimental | Drug: Brivaracetam bolus, Other: PlaceboSubjects will receive Placebo (PBO) tablets for one week followed by Brivaracetam (BRV) bolus for 4.5 days. Down-Titration: * If subject discontinues the study during the Run-In Period, then the subject will receive the treatment that he/she was assigned during Run-In * If subject discontinues during the Evaluation Period or after Day 12, the subject will receive Placebo tablets during Down-Titration: Tablets will be provided for 4 weeks; 75 mg / intake BID for the first week, 50 mg / intake BID for the second week, 25 mg / intake BID for the third week, 10 mg / intake BID for the fourth week |
| Brivaracetam (BRV) tablets / BRV bolus | Experimental | Drug: Brivaracetam tablets, Drug: Brivaracetam bolusSubjects will receive Brivaracetam (BRV) tablets for one week followed by BRV bolus for 4.5 days. Down-Titration: * If subject discontinues the study during the Run-In Period, then the subject will receive the treatment that he/she was assigned during Run-In * If subject discontinues during the Evaluation Period or after Day 12, the subject will receive BRV tablets during Down-Titration: Tablets will be provided for 4 weeks; 75 mg / intake BID for the first week, 50 mg / intake BID for the second week, 25 mg / intake BID for the third week, 10 mg / intake bid for the fourth week |
| Placebo tablets / Brivaracetam infusion | Experimental | Drug: Brivaracetam infusion, Other: PlaceboSubjects will receive Placebo (PBO) tablets for one week followed by Brivaracetam (BRV) intravenous infusion for 4.5 days. Down-Titration: * If subject discontinues the study during the Run-In Period, then the subject will receive the treatment that he/she was assigned during Run-In * If subject discontinues during the Evaluation Period or after Day 12, the subject will receive BRV tablets during Down-Titration: Tablets will be provided for 4 weeks; 75 mg / intake BID for the first week, 50 mg / intake BID for the second week, 25 mg / intake BID for the third week, 10 mg / intake BID for the fourth week |
| Brivaracetam (BRV) tablets / BRV infusion | Experimental | Drug: Brivaracetam tablets, Drug: Brivaracetam infusionSubjects will receive Brivaracetam (BRV) tablets for one week followed by Brivaracetam intravenous infusion for 4.5 days. Down-Titration: * If subject discontinues the study during the Run-In Period, then the subject will receive the treatment that he/she was assigned during Run-In * If subject discontinues during the Evaluation Period or after Day 12, the subject will receive BRV tablets during Down-Titration: Tablets will be provided for 4 weeks; 75 mg / intake BID for the first week, 50 mg / intake BID for the second week, 25 mg / intake BID for the third week, 10 mg / intake BID for the fourth week |
Who may qualify
- Ages
- 16 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- An Institutional Review Board/Independent Ethics Committee (IRB/IEC) approved written Informed Consent form signed and dated by the subject or by parent(s) or legal representative
- Subjects from 16 to 70 years
- Subjects with a body weight of >/= 40 kg
- Female subjects without childbearing potential or female subjects with childbearing potential if they use a medically accepted contraceptive method
- Subject/legal representative considered as reliable and capable of adhering to the protocol
Key exclusion criteria (29 listed)
- Mentally impaired subjects unable to understand the study purpose
- History or presence of status epilepticus during 1 year preceding Visit 1 or Baseline
- Subjects on felbamate with less than 18 months continuous exposure before Visit 1
- Subjects currently on vigabatrin
- Subject taking any drug with possible relevant central nervous system effects except is stable from at least 1 month before Visit 1 and expected to be kept stable during the trial
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 tablets100 mg, intake twice daily (BID) for 7 days during Run-In Period | Drug | Brivaracetam (BRV) tablets / BRV bolus, Brivaracetam (BRV) tablets / BRV infusion |
| Brivaracetam bolus10 mL (= 100 mg) of Brivaracetam administered intravenously over 2 minutes twice daily (BID) during Evaluation Period | Drug | Brivaracetam (BRV) tablets / BRV bolus, Placebo tablets / Brivaracetam bolus |
| Brivaracetam infusion10 mL (= 100 mg) of Brivaracetam diluted in 90 mL 0.9 % isotonic saline sterile solution for intravenous administration infused over 15 minutes twice daily (BID) during Evaluation Period | Drug | Brivaracetam (BRV) tablets / BRV infusion, Placebo tablets / Brivaracetam infusion |
| Placebo100 mg twice daily (BID) for 7 days during Run-In Period | Other | Placebo tablets / Brivaracetam bolus, Placebo tablets / Brivaracetam infusion |
Primary outcome
Number of Subjects With at Least One Treatment-emergent Adverse Event During the Study (Maximum 40 Days)
Time frame: 40 days
An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
2 secondary outcomes
Number of Subjects Who Withdrew Due to a Treatment-emergent Adverse Event During the Study (Maximum 40 Days)
Time frame: 40 days
Number of Subjects With at Least One Injection-related Treatment-emergent Adverse Event (TEAE) During the Evaluation Period.
Time frame: 4.5-day Evaluation Period
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 33780735Toledo M, Brandt C, Quarato PP, Schulz AL, Cleveland JM, Wagener G, Klein P. Long-term safety, efficacy, and quality of life during adjunctive brivaracetam treatment in patients with uncontrolled epilepsy: An open-label follow-up trial. Epilepsy Behav. 2021 May;118:107897. doi: 10.1016/j.yebeh.2021.107897. Epub 2021 Mar 27.
Related trials for Epilepsy
Not yet recruiting
Clinical Trial of SEEG for Drug-resistant Epilepsy
Drug-Resistant Epilepsy
RecruitingPhase 3
Investigate Efficacy and Safety of Carisbamate as Adjunctive Treatment for Seizures Associated With LGS in Children and Adults
Seizures, Lennox Gastaut Syndrome
RecruitingPhase 3
Study Evaluating the Efficacy and Safety of RAP-219 in Adult Participants With Focal Seizures
Focal Seizure, Epilepsy
Active, not recruitingObservational study
Transforming Research and Clinical Knowledge in Traumatic Brain Injury Epileptogenesis Project (TRACK-TBI EPI)
Traumatic Brain Injury, Post-traumatic Epilepsy
RecruitingPhase 3
Study Evaluating the Efficacy and Safety of RAP-219 in Adult Participants With Focal Seizures FOCUS-1
Focal Seizure, Epilepsy
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)
17 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Brivaracetam tablets, Brivaracetam bolus and Brivaracetam infusion in people with Epilepsy, run by UCB Pharma at 17 sites in 4 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 9 inclusion and 29 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 17 sites in United States, Czechia, Poland, Germany. 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 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?
Number of Subjects With at Least One Treatment-emergent Adverse Event During the Study (Maximum 40 Days) (time frame: 40 days). 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 NCT01405508, 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.