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Anticonvulsants

Brivaracetam

Subjects in this arm will receive open-label Brivaracetam.

* Pharmaceutical form: Solution for injection
* Concentration: 10 mg/ml
* Route of administration: Intravenous injection

UCB Cares

The purpose of the study is to evaluate the safety and tolerability of intravenous (iv) brivaracetam (BRV) as adjunctive therapy administered as a replacement for oral BRV at doses ranging from BRV 50 mg/day to 200 mg/day in Japanese subjects \>=16 years of age with partial seizures with or without secondary generalization and to evaluate the partial seizure frequency after switching from oral administration to iv BRV.

A Study to Evaluate the Safety and Tolerability of Intravenous Brivaracetam (BRV) as Replacement for Oral Brivaracetam in Japanese Subjects >=16 Years of Age With Partial Seizures With or Without Secondary Generalization

A Multicenter, Open-Label Study to Evaluate the Safety and Tolerability of Intravenous Brivaracetam as Replacement for Oral Brivaracetam in Japanese Subjects >=16 Years of Age With Partial Seizures With or Without Secondary Generalization

An 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 SAE must meet 1 or more of the following criteria:

* Death
* Life-threatening
* Significant or persistent disability/incapacity
* Congenital anomaly/birth defect
* Initial inpatient hospitalization or prolongation of hospitalization
* Important medical event that, based upon appropriate medical judgment, may jeopardize the patient or subject and may require medical or surgical intervention to prevent 1 of the other outcomes listed in the definition of serious

Partial Seizures can be classified into one of the following three groups: Simple Partial Seizures, Complex Partial Seizures, Partial Seizures evolving to Secondarily Generalized Seizures. The partial seizure frequency will be assessed using the seizure count information recorded on the daily record card (DRC). The written information will be discussed with the subject in order to ensure completeness and accuracy. As a result of the discussion, the Investigator will assess the seizures according to the International League Against Epilepsy (ILAE) codes and record the seizure types and frequency on the DRC.

The plasma concentration level of brivaracetam 5 minutes postdose on Day 1.

The plasma concentration level of brivaracetam 5 minutes postdose on Day 2.

The plasma concentration level of brivaracetam 5 minutes postdose on Day 5.

UCB Biopharma S.P.R.L.

* 12 weeks Treatment Period: Subjects will receive Placebo
* 4 weeks Down-Titration Period: Subjects will receive Placebo

12 weeks Treatment Period: Subjects will receive BRV 50 mg/day

- Subjects entering into the Long term follow up (LTFU) study or managed access program (MAP): 2 weeks Transition Period: Subjects will receive BRV 50 mg/day followed by LTFU or MAP: Subjects will receive BRV 100 mg/day

- Subjects not entering into the LTFU study or MAP: 4 weeks Down-Titration Period: Subjects will receive BRV 25 mg/day for 1 week followed by Placebo for 3 weeks, followed by a Study Drug-Free Period

12 weeks Treatment Period: Subjects will receive BRV 200 mg/day

- Subjects entering into the Long term follow up (LTFU) study or managed access program (MAP): 2 weeks Transition Period: Subjects will receive BRV 150 mg/day followed by LTFU or MAP: Subjects will receive BRV 100 mg/day

- Subjects not entering into the LTFU study or MAP: 4 weeks Down-Titration Period: Subjects will receive BRV 150 mg/day for 1 week followed by BRV 100 mg/day for 1 week, followed by BRV 50 mg/day for 1 week, followed by BRV 25 mg/day for 1 week followed by a Study Drug-Free Period

* Pharmaceutical form: Film-coated tablets
* Route of administration: Oral use

Placebo

* Pharmaceutical form: Film-coated tablets
* Concentration: 25 mg tablets and 50 mg tablets
* Route of administration: Oral use

The purpose of the study is to evaluate the efficacy of brivaracetam (BRV) compared to placebo (PBO) as adjunctive treatment in subjects (\>=16 to 80 years of age) with partial seizures with or without secondary generalization despite current treatment with 1 or 2 concomitant antiepileptic drugs (AEDs) and to assess the safety and tolerability of BRV in subjects \>= 16 years to 80 years of age.

A Study to Evaluate the Efficacy and Safety of Brivaracetam in Study Participants (>=16 to 80 Years of Age) With Epilepsy

A Randomized, Double-blind, Placebo-controlled, Multicenter, Parallel-group Study to Evaluate the Efficacy and Safety of Adjunctive Brivaracetam in Subjects (>=16 to 80 Years of Age) With Partial Seizures With or Without Secondary Generalization

Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe, or global development is discontinued, and 18 months after trial completion. Investigators may request access to anonymized individual patient-level data and redacted trial documents which may include: analysis-ready datasets, study protocol, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a prespecified time, typically 12 months, on a password protected portal. This plan may change if the risk of re-identifying trial participants is determined to be too high after the trial is completed; in this case and to protect participants, individual patient-level data would not be made available.

An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. Treatment-Emergent AEs were defined as AEs which had onset on or after the first dose of IMP. As per planned analysis, safety data for all study periods was combined excluding Open-Label Temporary period.

Serious Adverse event (SAE) was defined as any events which: • results in death, • is life-threatening threatening (note that this did not include a reaction that might have caused death had it occurred in a more severe form.), •results in significant or persistent disability/incapacity, • results in a congenital anomaly/birth defect (including that occurring in a fetus), • results in Important medical event that, based upon appropriate medical judgment, may jeopardize the participant and might require medical or surgical intervention to prevent 1 of the other outcomes listed here, and • results in initial inpatient hospitalization or prolongation of hospitalization. As per planned analysis, safety data for all study periods was combined excluding Open-Label Temporary period.

According to International League Against Epilepsy (ILAE) classification (1981), seizures were classified as type IA (IA1, IA2, IA3, and IA4), IB, IC, II (IIA, IIB, IIC, IID, IIE, and IIF) or III. 28 day adjusted seizure frequency for partial seizures (seizure types IA+IB+IC) was calculated for treatment period by dividing the number of partial seizures by the number of days for which the DRC was completed for treatment period and multiplying the resulting value by 28.

Responders were those participants with at least 50% reduction from Baseline to the 12-week Treatment Period in partial seizure frequency per 28 days. 50% Responder rate was calculated for treatment period by dividing the number of 50% responders by the number of participants in the analysis set and multiplying the resulting value by 100.

Percent change from Baseline to the Treatment Period in partial seizure frequency was calculated by subtracting 28-day adjusted Treatment Period partial seizure frequency from 28-day adjusted Baseline Period partial seizure frequency, and multiplying the resulting quantity by 100 and dividing by the Baseline Period 28-day adjusted partial seizure frequency. A negative value in percent change from Baseline indicates a decrease in partial seizure frequency from Baseline to the Treatment Period.

The percentage of participants within each of the following categories of percent change in partial seizure frequency from Baseline to the Treatment Period were summarized for each treatment group: 100%, 75% to less than 100%, 50% to less than 75%, 25% to less than 50%, -25% to less than 25%, and less than -25%. Percent change from Baseline to the Treatment Period in partial seizure frequency was calculated by subtracting 28-day adjusted Treatment Period partial seizure frequency from 28-day adjusted Baseline Period partial seizure frequency and multiplying the resulting quantity by 100 and dividing by the Baseline Period 28-day adjusted partial seizure frequency.

There were three types of epileptic seizures: Partial epileptic seizures (Type I), Generalized epileptic seizures (Type II) and unclassified epileptic seizures (Type III). 28 day adjusted seizure frequency for all seizure types was calculated for treatment period by dividing the number of targeted seizures by the number of days for which the DRC was completed for treatment period and multiplying the resulting value by 28.

Participants were defined as seizure free, if they did not have missing diary days and no reported seizures during the Treatment Period.

The evaluation of time to 1st partial seizure was based on the relative day of occurrence of the 1st partial seizure during the Treatment Period.

The evaluation of time to 5th partial seizure was based on the relative day of occurrence of the 5th partial seizure during the Treatment Period.

The evaluation of time to 10th partial seizure was based on the relative day of occurrence of the 10th partial seizure during the Treatment Period.

Blood samples were collected at indicated time points to determine the brivaracetam plasma concentration. Participants of arm 'BRV 200 mg/day' received BRV 200 mg/day until Week 12 only and 150 mg/day during the Transition Period at Week 14. Therefore, the data is reported according to the dosage information at specified time point. As per planned analysis, one blood sample was collected for BRV plasma levels during each dosing interval between 0 to 4 hours, 4 to 8 hours, and 8 to 12 hours postdose.

UCB Biopharma SRL

TEAEs were defined as AEs which had onset on or after the first dose of investigational medicinal product (IMP). The Safety Set (SS) included all randomized participants who took at least 1 dose of study medication. As per planned analysis, safety data for all study periods was combined excluding Open-Label Temporary period.

Participants received matching Placebo as film-coated tablets, administered orally, twice daily (bid), during 12 weeks of Treatment Period. At the end of the Treatment Period, participants who entered long-term follow-up (LTFU) study (EP0085 (NCT03250377)) or managed access program (MAP), the same matching Placebo dose was kept during 2 weeks of Transition Period and brivaracetam (BRV) 100 milligrams/day (mg/day) in LTFU study or MAP. Participants who did not enter the LTFU study or MAP had 4 weeks Down-Titration Period followed by a Study Drug-Free Period (no drug for 2 weeks). During Down-Titration Period, participants received the same Placebo dose for 4 weeks.

Participants received BRV 50 mg/day as film-coated tablets, administered orally, bid, during 12 weeks of Treatment Period. At the end of the Treatment Period, participants who entered the LTFU study or MAP received BRV 50 mg/day during 2 weeks of Transition Period and BRV 100 mg/day in LTFU study or MAP. Participants who did not enter the LTFU study or MAP had 4 weeks Down-Titration Period followed by a Study Drug-Free Period (no drug for 2 weeks). During Down-Titration Period, participants received BRV 25 mg/day for 1 week followed by Placebo for 3 weeks.

BRV 50 mg/Day

Participants received BRV 200 mg/day as film-coated tablets, administered orally, bid, during 12 weeks of Treatment Period. At the end of the Treatment Period, participants who entered LTFU study or MAP received BRV 150 mg/day during 2 weeks of Transition Period and BRV 100 mg/day in LTFU study or MAP. Participants who did not enter the LTFU study or MAP had 4 weeks Down-Titration Period followed by a Study Drug-Free Period (no drug for 2 weeks). During Down-Titration Period, participants received BRV 150 mg/day for 1 week followed by BRV 100 mg/day for 1 week, followed by BRV 50 mg/day for 1 week, followed by BRV 25 mg/day for 1 week.

BRV 200 mg/Day

Participants who received Placebo during Treatment Period and were eligible to enter MAP received BRV 100 mg/day due to delayed importation of medication during OLTP. BRV dose might be adjusted for an individual participant (between 50 mg/day to 200 mg/day) during the OLTP. The period was defined from immediately after the last visit of the Transition Period (Week 14) and until a visit when the participant could convert to MAP.

Placebo to OLTP BRV

Participants who received BRV 50 mg/day during Treatment Period and were eligible to enter MAP received BRV 100 mg/day due to delayed importation of medication during Open-Label Temporary Period (OLTP). BRV dose might be adjusted for an individual participant (between 50 mg/day to 200 mg/day) during the OLTP. The period was defined from immediately after the last visit of the Transition Period (Week 14) and until a visit when the participant could convert to MAP.

BRV 50 mg/Day to OLTP BRV

Participants who received BRV 200 mg/day during Treatment Period and were eligible to enter MAP received BRV 100 mg/day due to delayed importation of medication during Open-Label Temporary Period (OLTP). BRV dose might be adjusted for an individual participant (between 50 mg/day to 200 mg/day) during the OLTP. The period was defined from immediately after the last visit of the Transition Period (Week 14) and until a visit when the participant could convert to MAP.

BRV 200 mg/Day to OLTP BRV

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Race/Ethnicity, Customized

Baseline Characteristics refer to the Randomized Set (RS) which consisted of all study participants who were randomized to investigational medicinal product (IMP).

The Safety Set (SS) included all randomized study participants who received at least 1 dose of IMP.

Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)

The SS included all randomized study participants who received at least 1 dose of IMP.

Percentage of Participants With Treatment-Emergent AEs (TEAEs) Leading to Study Withdrawal

Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs)

The Full Analysis Set (FAS) consisted of all randomized study participants who received at least 1 dose of IMP and had at least 1 post Baseline seizure daily record card (DRC) data during the Treatment Period.

Partial Seizure Frequency Per 28 Days During the 12-week Treatment Period

The FAS consisted of all randomized study participants who received at least 1 dose of IMP and had at least 1 post Baseline seizure DRC data during the Treatment Period.

50% Responder Rate Based on Percent Change in Partial Seizure Frequency Per 28 Days From Baseline to the 12-week Treatment Period

Percent Change in Partial Seizure Frequency Per 28 Days From Baseline to the 12-week Treatment Period

100%

75% to less than 100%

50% to less than 75%

25% to less than 50%

-25% to less than 25%

less than-25%

Percentage of Participants With Categorized Percent Change in Partial Seizure Frequency Per 28 Days From Baseline to the 12-week Treatment Period

All Seizure Frequency (Partial, Generalized, and Unclassified Epileptic Seizures) Per 28 Days During the 12-week Treatment Period

All epileptic seizures

Partial onset seizures

Percentage of Participants Who Are Seizure Free (Partial, All Epileptic Seizures) During the 12-week Treatment Period

Time to 1st Partial Seizure During the 12-week Treatment Period

Time to 5th Partial Seizure During the 12-week Treatment Period

Time to 10th Partial Seizure During the 12-week Treatment Period

Week 2: > 0 - 4 hours

Week 2: > 4 - 8 hours

Week 2: > 8 hours

Week 4: > 0 - 4 hours

Week 4: > 4 - 8 hours

Week 4: > 8 hours

Week 8: > 0 - 4 hours

Week 8: > 4 - 8 hours

Week 8: > 8 hours

Week 12: > 0 - 4 hours

Week 12: > 4 - 8 hours

Week 12: > 8 hours

Week 14 (Transition): > 0 - 4 hours

Week 14 (Transition): > 4 - 8 hours

Week 14 (Transition): > 8 hours

At the end of the Treatment Period, participants of arm BRV 200 mg/day who entered LTFU study or MAP received BRV 150 mg/day during 2 weeks of Transition Period. The number of participants for BRV 150 mg/day group are those who had BRV 200 mg/day and valid PK data in Transition Period.

BRV 150 mg/Day

The Pharmacokinetic Per-Protocol Set (PK-PPS) consisted of all study participants who took at least 1 dose of BRV and for whom at least 1 valid BRV plasma concentration time and dosing information were available. Here, 'n' (Number analyzed) signifies participants who were evaluable at specified time points.

Brivaracetam Plasma Concentration

Double-Blind Period

Open-Label Temporary Period (OLTP)

SPM 927

UCB Clinical Trial Call Center

Male and female patients between 16 and 70 years of age who are diagnosed with epilepsy with partial seizures and are taking up to 3 medications for this medical condition will take part in this research study at approximately 80 different locations in Australia and Europe.

The purpose of this study is to evaluate the effectiveness, safety and tolerability of consistent dosages of study drug (lacosamide) taken orally twice a day for about 4 months.

Each patient who qualifies and chooses to participate in the study will receive placebo (inactive drug) or gradually increasing doses of lacosamide (SPM 927) up to the target dose of 200mg/day or 400mg/day. The target dose or placebo will be maintained for 12 weeks.

The study clinic visits will include a medical history and physical exam, ECG, blood and urine sample collection, and completion of a seizure diary.

Patients who complete the study may enroll in an extension trial and receive active study drug.

A Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel Group Trial to Investigate the Efficacy and Safety of SPM 927 (200mg/Day and 400mg/Day) as Adjunctive Therapy in Subjects With Partial Seizures With or Without Secondary Generalization

UCB Pharma

Subjects randomized to this arm will receive open-label Brivaracetam

* Pharmaceutical form: Film-coated tablet
* Concentration: 25 mg and 50 mg
* Route of administration: Oral use

The purpose of the study is to evaluate the long-term safety and tolerability of Brivaracetam (BRV) in focal epilepsy subjects with partial seizures and to evaluate the maintenance of efficacy of BRV over time.

A Study to Test the Safety/ Efficacy of Brivaracetam (BRV) Used as Adjunctive Treatment in Subjects >=16 Years of Age With Partial Seizures With or Without Secondary Generalization

An Open-Label, Multicenter, Follow-up Study to Evaluate the Long-Term Safety and Efficacy of Brivaracetam Used as Adjunctive Treatment in Subjects >=16 Years of Age With Partial Seizures With or Without Secondary Generalization

The seizure frequency is calculated as number of seizures per 28 days. This evaluation will be done every 3 months of the Evaluation Period (by 3-month periods). Change in seizure frequency from Baseline of EP0083 (NCT03083665) or N01358 (NCT01261325) is calculated as the seizure frequency at the evaluation time point minus the seizure frequency at Baseline of EP0083 or N01358.

The seizure frequency is calculated as number of seizures per 28 days. This evaluation will be done every 3 months of the Evaluation Period (by 3-month periods). A responder is defined as a subject with a \>= 50% reduction in seizure frequency from the Baseline Period of EP0083 or N01358.

A study participant was considered seizure free, if no seizure occurred during 6 consecutive months in the Evaluation Period.

A study participant was considered seizure free, if no seizure occurred during 12 consecutive months in the Evaluation Period.

A study participant was considered seizure free (partial, all epileptic seizure), if no seizure occurred during the Evaluation Period.

The seizure frequency for directly enrolled participants is calculated as number of seizures per 28 days from 8 weeks prior to BRV administration.

Change in seizure frequency is calculated as the seizure frequency at the evaluation time point minus the seizure frequency at Baseline of directly enrolled participants.

The seizure frequency for directly enrolled participants is calculated as number of seizures per 28 days from 8 weeks prior to BRV administration.

A responder is defined as a study participant with a \>= 50% reduction in seizure frequency from the Baseline Period.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study to Evaluate the Safety and Tolerability of Intravenous Brivaracetam (BRV) as Replacement for Oral Brivaracetam in Japanese Subjects >=16 Years of Age With Partial Seizures With or Without Secondary Generalization	NCT03685630	Partial Seizure... Epilepsy	Brivaracetam	16 Years -	UCB Pharma
A Study to Evaluate the Efficacy and Safety of Brivaracetam in Study Participants (>=16 to 80 Years of Age) With Epilepsy	NCT03083665	Partial Seizure... Epilepsy	Placebo Brivaracetam	16 Years - 80 Years	UCB Pharma
A Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel Group Trial to Investigate the Efficacy and Safety of SPM 927 (200mg/Day and 400mg/Day) as Adjunctive Therapy in Subjects With Partial Seizures With or Without Secondary Generalization	NCT00220415	Partial Seizure...	SPM 927	16 Years - 70 Years	UCB Pharma
A Study to Evaluate the Safety and Tolerability of Intravenous Brivaracetam (BRV) as Replacement for Oral Brivaracetam in Japanese Subjects >=16 Years of Age With Partial Seizures With or Without Secondary Generalization	NCT03685630	Partial Seizure... Epilepsy	Brivaracetam	16 Years -	UCB Pharma
A Study to Test the Safety/ Efficacy of Brivaracetam (BRV) Used as Adjunctive Treatment in Subjects >=16 Years of Age With Partial Seizures With or Without Secondary Generalization	NCT03250377	Partial Seizure... Epilepsy	Brivaracetam	16 Years -	UCB Pharma

Spots Global Cancer Trial Database for partial seizures with or without secondary generalization