NCT00175825

A Dose-ranging Study With Brivaracetam in Patients From 16 to 65 Years With Refractory Partial Onset Seizures.

Completed Phase 2 Results posted Last updated 2 October 2018

What this trial tests

Phase 2 trial testing Placebo in Epilepsy in 210 participants. Completed in 29 June 2006.

Timeline

7 November 2005

Primary endpoint
29 June 2006

29 June 2006

Quick facts

Lead sponsor	UCB Pharma
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	210
Start date	7 November 2005
Primary completion	29 June 2006
Estimated completion	29 June 2006
Sites	42 locations across United States, Mexico, Brazil, India

Drugs / interventions tested

• Placebo
• Brivaracetam (BRIVARACETAM) — full drug profile →

Conditions studied

• Epilepsy — all drugs for Epilepsy →

Sponsor

UCB Pharma — full company profile →

Who can join

Adults 16 to 65, any sex, with Epilepsy. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage Change From Baseline in Partial Onset Seizure Frequency Per Week (Type I) Over the 7-week Treatment Period Secondary · Baseline, during the 7-week Treatment Period

Calculated as 7-day seizure frequency during the 7-week Treatment Period - 7-day seizure frequency during the Baseline Period, divided by the 7-day seizure frequency during the Baseline Period with this quantity multiplied by 100. A negative value in percent change from Baseline indicates a decrease in partial seizure frequency from Baseline.

Group	Value	95% CI
Placebo	-21.7	-42.99 – 12.04
Brivaracetam 5 mg/Day	-29.91	-53.33 – -3.83
Brivaracetam 20 mg/Day	-42.56	-67.92 – 0.44
Brivaracetam 50 mg/Day	-53.04	-69.33 – -19.56

Seizure Frequency Per Week for All Seizures (Types I +II +III) Over the Treatment Period Secondary · During the 7-week Treatment Period

Types I+II+III seizure frequency (Type I: Partial (focal, local), Type II: Generalized (convulsive or nonconvulsive), Type III: Unclassified) per week will be derived from the seizure count information recorded on the daily record card (e.g. date, number, type of epileptic seizures) and is defined as the number of seizures standardized to a 7-day period.

Baseline

Group	Value	95% CI
Placebo	2.23	1.30 – 4.22
Brivaracetam 5 mg/Day	2.21	1.38 – 5.00
Brivaracetam 20 mg/Day	2.50	1.50 – 6.06
Brivaracetam 50 mg/Day	1.99	1.36 – 3.97

Treatment

Group	Value	95% CI
Placebo	1.81	0.88 – 3.50
Brivaracetam 5 mg/Day	1.61	0.75 – 4.34
Brivaracetam 20 mg/Day	1.70	0.59 – 3.97
Brivaracetam 50 mg/Day	0.92	0.69 – 2.05

Absolute Change From Baseline in Seizure Frequency Per Week for Partial Onset Seizures (Type I) Over the Treatment Period Secondary · During the 7-week Treatment Period

Calculated as 7-day Partial Onset Seizures (Type I) frequency during the 7-week Treatment Period 7-day seizure frequency during the Baseline Period. A negative value from Baseline indicates a decrease in partial seizure frequency from Baseline.

Group	Value	95% CI
Placebo	-0.37	-1.18 – 0.19
Brivaracetam 5 mg/Day	-0.66	-1.19 – -0.07
Brivaracetam 20 mg/Day	-0.84	-2.21 – -0.08
Brivaracetam 50 mg/Day	-0.92	-2.44 – -0.24

Absolute Change From Baseline in Seizure Frequency Per Week for All Seizures (Types I + II + III) Over the Treatment Period Secondary · During the 7-week Treatment Period

Calculated as 7-day seizure frequency during the 7-week Treatment Period 7-day seizure (Types I + II + III) frequency during the Baseline Period. A negative value from Baseline indicates a decrease in partial seizure frequency from Baseline.

Group	Value	95% CI
Placebo	-0.40	-1.18 – 0.19
Brivaracetam 5 mg/Day	-0.66	-1.19 – -0.07
Brivaracetam 20 mg/Day	-0.80	-2.21 – -0.08
Brivaracetam 50 mg/Day	-0.92	-2.44 – -0.37

Percentage Change From Baseline in Seizure Frequency Per Week for All Seizures (Types I + II + III) Over the Treatment Period Secondary · During the 7-week Treatment Period

Calculated as 7-day seizure frequency during the 7-week Treatment Period - 7-day seizure frequency during the Baseline Period, divided by the 7-day seizure frequency during the Baseline Period with this quantity multiplied by 100. A negative value in percent change from Baseline indicates a decrease in partial seizure frequency from Baseline.

Group	Value	95% CI
Placebo	-24.35	-43.61 – 12.00
Brivaracetam 5 mg/Day	-29.91	-53.33 – -3.83
Brivaracetam 20 mg/Day	-41.57	-65.31 – 0.44
Brivaracetam 50 mg/Day	-53.05	-69.33 – -22.82

Responder Rate in Partial Onset Seizures (Type I) Over the Treatment Period Secondary · During the 7-week Treatment Period

A responder was defined as a subject with a \>= 50 % reduction in seizure frequency per week from the Baseline Period to the end of the Treatment Period.

Group	Value	95% CI
Placebo	16.7
Brivaracetam 5 mg/Day	32.0
Brivaracetam 20 mg/Day	44.2
Brivaracetam 50 mg/Day	55.8

Percentage of Subjects With Categorized Response to the Treatment in Partial Onset Seizures (Type I) Over the Treatment Period Secondary · During the 7-week Treatment Period

Categories of percentage reductions in seizures from baseline were as following: \< -25 %; -25 % to \<25 %; 25 % to \<75 %; 75 % to \<100 %; 100 %.

< -25%

Group	Value	95% CI
Placebo	18.5
Brivaracetam 5 mg/Day	8.0
Brivaracetam 20 mg/Day	9.6
Brivaracetam 50 mg/Day	13.5

-25% to <25%

Group	Value	95% CI
Placebo	35.2
Brivaracetam 5 mg/Day	38.0
Brivaracetam 20 mg/Day	30.8
Brivaracetam 50 mg/Day	13.5

25% to <75%

Group	Value	95% CI
Placebo	40.7
Brivaracetam 5 mg/Day	42.0
Brivaracetam 20 mg/Day	40.4
Brivaracetam 50 mg/Day	55.8

75% to <100%

Group	Value	95% CI
Placebo	1.9
Brivaracetam 5 mg/Day	4.0
Brivaracetam 20 mg/Day	11.5
Brivaracetam 50 mg/Day	9.6

100%

Group	Value	95% CI
Placebo	3.7
Brivaracetam 5 mg/Day	8.0
Brivaracetam 20 mg/Day	7.7
Brivaracetam 50 mg/Day	7.7

Percentage of Subjects Who Are Seizure Free During the 7-week Treatment Period Secondary · During the 7-week Treatment Period

A subject was considered seizure free, if no seizure was reported during the 7-week Treatment Period.

Completed the Period

Group	Value	95% CI
Placebo	1.9
Brivaracetam 5 mg/Day	8.0
Brivaracetam 20 mg/Day	7.7
Brivaracetam 50 mg/Day	5.8

Discontinued from the Period

Group	Value	95% CI
Placebo	1.9
Brivaracetam 5 mg/Day	0
Brivaracetam 20 mg/Day	0
Brivaracetam 50 mg/Day	0

Number of Seizure-free Days Per 4 Weeks Secondary · Baseline, during the 7-week Treatment Period

A day was considered seizure-free, if no seizure was reported during 24 hours.

Group	Value	95% CI
Placebo	22.66	16.57 – 24.57
Brivaracetam 5 mg/Day	22.86	15.43 – 25.14
Brivaracetam 20 mg/Day	22.84	18.57 – 25.71
Brivaracetam 50 mg/Day	24.65	21.14 – 25.86

Time to Nth (n= 1, 5, 10) Seizure During the 7-week Treatment Period Secondary · During the 7-week Treatment Period

Number of days to first, fifth, and tenth seizure after baseline.

Number of days to first seizure after baseline

Group	Value	95% CI
Placebo	4.0	3.0 – 6.0
Brivaracetam 5 mg/Day	4.0	3.0 – 7.0
Brivaracetam 20 mg/Day	4.5	2.0 – 8.0
Brivaracetam 50 mg/Day	7.0	4.0 – 13.0

Number of days to fifth seizure after baseline

Group	Value	95% CI
Placebo	17.0	13.0 – 22.0
Brivaracetam 5 mg/Day	20.0	17.0 – 27.0
Brivaracetam 20 mg/Day	18.5	14.0 – 29.0
Brivaracetam 50 mg/Day	32.5	23.0 – 42.0

Number of days to tenth seizure after baseline

Group	Value	95% CI
Placebo	32.0	23.0 – 45.0
Brivaracetam 5 mg/Day	38.0	27.0 – NA
Brivaracetam 20 mg/Day	39.0	23.0 – NA
Brivaracetam 50 mg/Day	57.0	49.0 – NA

Partial Onset Seizure Frequency Per Week During the 7-week Treatment Period Primary · During the 7-week Treatment Period

Calculated as 7-day partial onset seizure frequency.

Group	Value	95% CI
Placebo	1.81	0.88 – 3.50
Brivaracetam 5 mg/Day	1.61	0.75 – 4.34
Brivaracetam 20 mg/Day	1.55	0.57 – 3.83
Brivaracetam 50 mg/Day	0.92	0.69 – 2.05

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were collected from Baseline until Safety Visit (up to 3 months).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo

Serious: 0/54 (0%)

Deaths: 0/54

Brivaracetam 5 mg/Day

Serious: 0/50 (0%)

Deaths: 0/50

Brivaracetam 20 mg/Day

Serious: 1/52 (2%)

Deaths: 0/52

Brivaracetam 50 mg/Day

Serious: 0/52 (0%)

Deaths: 0/52

Serious adverse events (1 terms)

Reaction	System	Placebo	Brivaracetam 5 mg/Day	Brivaracetam 20 mg/Day	Brivaracetam 50 mg/Day
Neurotoxicity	Nervous system disorders	—	—	—	—

Other adverse events (6 terms — click to expand)

Reaction	System	Placebo	Brivaracetam 5 mg/Day	Brivaracetam 20 mg/Day	Brivaracetam 50 mg/Day
Neutropenia	Blood and lymphatic system disorders	—	—	—	—
Influenza	Infections and infestations	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—
Headache	Nervous system disorders	—	—	—	—
Somnolence	Nervous system disorders	—	—	—	—
Fatigue	General disorders	—	—	—	—

Most-reported serious reactions: Neurotoxicity.

Data from ClinicalTrials.gov NCT00175825 adverse events section.

Sponsor's own description

This trial will evaluate the efficacy and safety of brivaracetam (at doses of 5, 20 and 50 mg/day in twice a day administration) as add-on therapy in subjects with focal epilepsy.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Efficacy and safety of brivaracetam for partial-onset seizures in 3 pooled clinical studies.
   Ben-Menachem E, Mameniškienė R, Quarato PP, Klein P, et al · · 2016 · cited 91× · PMID 27335114 · DOI 10.1212/wnl.0000000000002864
2. A review of the pharmacology and clinical efficacy of brivaracetam.
   Klein P, Diaz A, Gasalla T, Whitesides J. · · 2018 · cited 67× · PMID 29403319 · DOI 10.2147/cpaa.s114072
3. Safety, tolerability, and seizure control during long-term treatment with adjunctive brivaracetam for partial-onset seizures.
   Toledo M, Whitesides J, Schiemann J, Johnson ME, et al · · 2016 · cited 56× · PMID 27265725 · DOI 10.1111/epi.13416
4. Safety and tolerability of adjunctive brivaracetam in epilepsy: In-depth pooled analysis.
   Brandt C, Klein P, Badalamenti V, Gasalla T, et al · · 2020 · cited 30× · PMID 31937513 · DOI 10.1016/j.yebeh.2019.106864
5. Long-term safety, efficacy, and quality of life outcomes with adjunctive brivaracetam treatment at individualized doses in patients with epilepsy: An up to 11-year, open-label, follow-up trial.
   O'Brien TJ, Borghs S, He QJ, Schulz AL, et al · · 2020 · cited 26× · PMID 32221987 · DOI 10.1111/epi.16484
6. Pharmacokinetic interaction of brivaracetam on other antiepileptic drugs in adults with focal seizures: Pooled analysis of data from randomized clinical trials.
   Moseley BD, Otoul C, Staelens L, Stockis A. · · 2019 · cited 10× · PMID 31675621 · DOI 10.1016/j.eplepsyres.2019.106218
7. Brivaracetam add-on therapy for drug-resistant epilepsy.
   Bresnahan R, Panebianco M, Marson AG. · · 2019 · cited 8× · PMID 30920649 · DOI 10.1002/14651858.cd011501.pub2
8. Brivaracetam add-on therapy for drug-resistant epilepsy.
   Bresnahan R, Panebianco M, Marson AG. · · 2022 · cited 7× · PMID 35285519 · DOI 10.1002/14651858.cd011501.pub3