Trial Outcomes & Findings for A Dose-ranging Study With Brivaracetam in Patients From 16 to 65 Years With Refractory Partial Onset Seizures. (NCT NCT00175825)

NCT ID: NCT00175825

Last Updated: 2018-10-02

Results Overview

Calculated as 7-day partial onset seizure frequency.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 210 participants
• Primary outcome timeframe: During the 7-week Treatment Period
• Results posted on: 2018-10-02

Participant Flow

The study started to enroll patients in November 2005 and concluded in June 2006.

Participant Flow refers to the Intention-to-treat (ITT) Set. 210 subjects were initially randomized, 2 subjects discontinued due to Lost to Follow-Up before first study drug intake.

Participant milestones

Measure	Placebo Matching Placebo tablets administered twice a day	Brivaracetam 5 mg/Day Brivaracetam 5 mg/day, 2.5 mg administered twice a day	Brivaracetam 20 mg/Day Brivaracetam 20 mg/day, 10 mg administered twice a day	Brivaracetam 50 mg/Day Brivaracetam 50 mg/day, 25 mg administered twice a day
Overall Study STARTED	54	50	52	52
Overall Study COMPLETED	49	46	51	51
Overall Study NOT COMPLETED	5	4	1	1

Reasons for withdrawal

Measure	Placebo Matching Placebo tablets administered twice a day	Brivaracetam 5 mg/Day Brivaracetam 5 mg/day, 2.5 mg administered twice a day	Brivaracetam 20 mg/Day Brivaracetam 20 mg/day, 10 mg administered twice a day	Brivaracetam 50 mg/Day Brivaracetam 50 mg/day, 25 mg administered twice a day
Overall Study Adverse Event	3	2	1	1
Overall Study Lost to Follow-up	1	2	0	0
Overall Study Withdrawal by Subject	1	0	0	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Placebo n=54 Participants Matching Placebo tablets administered twice a day	Brivaracetam 5 mg/Day n=50 Participants Brivaracetam 5 mg/day, 2.5 mg administered twice a day	Brivaracetam 20 mg/Day n=52 Participants Brivaracetam 20 mg/day, 10 mg administered twice a day	Brivaracetam 50 mg/Day n=52 Participants Brivaracetam 50 mg/day, 25 mg administered twice a day	Total Title n=208 Participants
Age, Categorical <=18 years	3 Participants n=5 Participants	4 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants	13 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	51 Participants n=5 Participants	46 Participants n=7 Participants	50 Participants n=5 Participants	47 Participants n=4 Participants	194 Participants n=21 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Age, Continuous	33.59 years STANDARD_DEVIATION 11.26 • n=5 Participants	32.72 years STANDARD_DEVIATION 12.16 • n=7 Participants	35.31 years STANDARD_DEVIATION 13.66 • n=5 Participants	30.92 years STANDARD_DEVIATION 11.57 • n=4 Participants	33.15 years STANDARD_DEVIATION 12.20 • n=21 Participants
Sex: Female, Male Female	30 Participants n=5 Participants	20 Participants n=7 Participants	24 Participants n=5 Participants	24 Participants n=4 Participants	98 Participants n=21 Participants
Sex: Female, Male Male	24 Participants n=5 Participants	30 Participants n=7 Participants	28 Participants n=5 Participants	28 Participants n=4 Participants	110 Participants n=21 Participants

PRIMARY outcome

Timeframe: During the 7-week Treatment Period

Calculated as 7-day partial onset seizure frequency.

Outcome measures

Measure	Placebo n=54 Participants Matching Placebo tablets administered twice a day	Brivaracetam 5 mg/Day n=50 Participants Brivaracetam 5 mg/day, 2.5 mg administered twice a day	Brivaracetam 20 mg/Day n=52 Participants Brivaracetam 20 mg/day, 10 mg administered twice a day	Brivaracetam 50 mg/Day n=52 Participants Brivaracetam 50 mg/day, 25 mg administered twice a day
Partial Onset Seizure Frequency Per Week During the 7-week Treatment Period	1.81 Seizures per week Interval 0.88 to 3.5	1.61 Seizures per week Interval 0.75 to 4.34	1.55 Seizures per week Interval 0.57 to 3.83	0.92 Seizures per week Interval 0.69 to 2.05

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo n=54 Participants Matching Placebo tablets administered twice a day	Brivaracetam 5 mg/Day n=50 Participants Brivaracetam 5 mg/day, 2.5 mg administered twice a day	Brivaracetam 20 mg/Day n=52 Participants Brivaracetam 20 mg/day, 10 mg administered twice a day	Brivaracetam 50 mg/Day n=52 Participants Brivaracetam 50 mg/day, 25 mg administered twice a day
Percentage Change From Baseline in Partial Onset Seizure Frequency Per Week (Type I) Over the 7-week Treatment Period	-21.7 percentage of change Interval -42.99 to 12.04	-29.91 percentage of change Interval -53.33 to -3.83	-42.56 percentage of change Interval -67.92 to 0.44	-53.04 percentage of change Interval -69.33 to -19.56

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo n=54 Participants Matching Placebo tablets administered twice a day	Brivaracetam 5 mg/Day n=50 Participants Brivaracetam 5 mg/day, 2.5 mg administered twice a day	Brivaracetam 20 mg/Day n=52 Participants Brivaracetam 20 mg/day, 10 mg administered twice a day	Brivaracetam 50 mg/Day n=52 Participants Brivaracetam 50 mg/day, 25 mg administered twice a day
Seizure Frequency Per Week for All Seizures (Types I +II +III) Over the Treatment Period Baseline	2.23 seizures per week Interval 1.3 to 4.22	2.21 seizures per week Interval 1.38 to 5.0	2.50 seizures per week Interval 1.5 to 6.06	1.99 seizures per week Interval 1.36 to 3.97
Seizure Frequency Per Week for All Seizures (Types I +II +III) Over the Treatment Period Treatment	1.81 seizures per week Interval 0.88 to 3.5	1.61 seizures per week Interval 0.75 to 4.34	1.70 seizures per week Interval 0.59 to 3.97	0.92 seizures per week Interval 0.69 to 2.05

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo n=54 Participants Matching Placebo tablets administered twice a day	Brivaracetam 5 mg/Day n=50 Participants Brivaracetam 5 mg/day, 2.5 mg administered twice a day	Brivaracetam 20 mg/Day n=52 Participants Brivaracetam 20 mg/day, 10 mg administered twice a day	Brivaracetam 50 mg/Day n=52 Participants Brivaracetam 50 mg/day, 25 mg administered twice a day
Absolute Change From Baseline in Seizure Frequency Per Week for Partial Onset Seizures (Type I) Over the Treatment Period	-0.37 seizures per week Interval -1.18 to 0.19	-0.66 seizures per week Interval -1.19 to -0.07	-0.84 seizures per week Interval -2.21 to -0.08	-0.92 seizures per week Interval -2.44 to -0.24

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo n=54 Participants Matching Placebo tablets administered twice a day	Brivaracetam 5 mg/Day n=50 Participants Brivaracetam 5 mg/day, 2.5 mg administered twice a day	Brivaracetam 20 mg/Day n=52 Participants Brivaracetam 20 mg/day, 10 mg administered twice a day	Brivaracetam 50 mg/Day n=52 Participants Brivaracetam 50 mg/day, 25 mg administered twice a day
Absolute Change From Baseline in Seizure Frequency Per Week for All Seizures (Types I + II + III) Over the Treatment Period	-0.40 seizures per week Interval -1.18 to 0.19	-0.66 seizures per week Interval -1.19 to -0.07	-0.80 seizures per week Interval -2.21 to -0.08	-0.92 seizures per week Interval -2.44 to -0.37

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo n=54 Participants Matching Placebo tablets administered twice a day	Brivaracetam 5 mg/Day n=50 Participants Brivaracetam 5 mg/day, 2.5 mg administered twice a day	Brivaracetam 20 mg/Day n=52 Participants Brivaracetam 20 mg/day, 10 mg administered twice a day	Brivaracetam 50 mg/Day n=52 Participants Brivaracetam 50 mg/day, 25 mg administered twice a day
Percentage Change From Baseline in Seizure Frequency Per Week for All Seizures (Types I + II + III) Over the Treatment Period	-24.35 percentage of change Interval -43.61 to 12.0	-29.91 percentage of change Interval -53.33 to -3.83	-41.57 percentage of change Interval -65.31 to 0.44	-53.05 percentage of change Interval -69.33 to -22.82

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo n=54 Participants Matching Placebo tablets administered twice a day	Brivaracetam 5 mg/Day n=50 Participants Brivaracetam 5 mg/day, 2.5 mg administered twice a day	Brivaracetam 20 mg/Day n=52 Participants Brivaracetam 20 mg/day, 10 mg administered twice a day	Brivaracetam 50 mg/Day n=52 Participants Brivaracetam 50 mg/day, 25 mg administered twice a day
Responder Rate in Partial Onset Seizures (Type I) Over the Treatment Period	16.7 percentage of participants	32.0 percentage of participants	44.2 percentage of participants	55.8 percentage of participants

SECONDARY outcome

Timeframe: 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 %.

Outcome measures

Measure	Placebo n=54 Participants Matching Placebo tablets administered twice a day	Brivaracetam 5 mg/Day n=50 Participants Brivaracetam 5 mg/day, 2.5 mg administered twice a day	Brivaracetam 20 mg/Day n=52 Participants Brivaracetam 20 mg/day, 10 mg administered twice a day	Brivaracetam 50 mg/Day n=52 Participants Brivaracetam 50 mg/day, 25 mg administered twice a day
Percentage of Subjects With Categorized Response to the Treatment in Partial Onset Seizures (Type I) Over the Treatment Period < -25%	18.5 percentage of participants	8.0 percentage of participants	9.6 percentage of participants	13.5 percentage of participants
Percentage of Subjects With Categorized Response to the Treatment in Partial Onset Seizures (Type I) Over the Treatment Period -25% to <25%	35.2 percentage of participants	38.0 percentage of participants	30.8 percentage of participants	13.5 percentage of participants
Percentage of Subjects With Categorized Response to the Treatment in Partial Onset Seizures (Type I) Over the Treatment Period 25% to <75%	40.7 percentage of participants	42.0 percentage of participants	40.4 percentage of participants	55.8 percentage of participants
Percentage of Subjects With Categorized Response to the Treatment in Partial Onset Seizures (Type I) Over the Treatment Period 75% to <100%	1.9 percentage of participants	4.0 percentage of participants	11.5 percentage of participants	9.6 percentage of participants
Percentage of Subjects With Categorized Response to the Treatment in Partial Onset Seizures (Type I) Over the Treatment Period 100%	3.7 percentage of participants	8.0 percentage of participants	7.7 percentage of participants	7.7 percentage of participants

SECONDARY outcome

Timeframe: During the 7-week Treatment Period

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

Outcome measures

Measure	Placebo n=54 Participants Matching Placebo tablets administered twice a day	Brivaracetam 5 mg/Day n=50 Participants Brivaracetam 5 mg/day, 2.5 mg administered twice a day	Brivaracetam 20 mg/Day n=52 Participants Brivaracetam 20 mg/day, 10 mg administered twice a day	Brivaracetam 50 mg/Day n=52 Participants Brivaracetam 50 mg/day, 25 mg administered twice a day
Percentage of Subjects Who Are Seizure Free During the 7-week Treatment Period Completed the Period	1.9 percentage of participants	8.0 percentage of participants	7.7 percentage of participants	5.8 percentage of participants
Percentage of Subjects Who Are Seizure Free During the 7-week Treatment Period Discontinued from the Period	1.9 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Baseline, during the 7-week Treatment Period

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

Outcome measures

Measure	Placebo n=54 Participants Matching Placebo tablets administered twice a day	Brivaracetam 5 mg/Day n=50 Participants Brivaracetam 5 mg/day, 2.5 mg administered twice a day	Brivaracetam 20 mg/Day n=52 Participants Brivaracetam 20 mg/day, 10 mg administered twice a day	Brivaracetam 50 mg/Day n=52 Participants Brivaracetam 50 mg/day, 25 mg administered twice a day
Number of Seizure-free Days Per 4 Weeks	22.66 Days/4 Weeks Interval 16.57 to 24.57	22.86 Days/4 Weeks Interval 15.43 to 25.14	22.84 Days/4 Weeks Interval 18.57 to 25.71	24.65 Days/4 Weeks Interval 21.14 to 25.86

SECONDARY outcome

Timeframe: During the 7-week Treatment Period

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

Outcome measures

Measure	Placebo n=54 Participants Matching Placebo tablets administered twice a day	Brivaracetam 5 mg/Day n=50 Participants Brivaracetam 5 mg/day, 2.5 mg administered twice a day	Brivaracetam 20 mg/Day n=52 Participants Brivaracetam 20 mg/day, 10 mg administered twice a day	Brivaracetam 50 mg/Day n=52 Participants Brivaracetam 50 mg/day, 25 mg administered twice a day
Time to Nth (n= 1, 5, 10) Seizure During the 7-week Treatment Period Number of days to first seizure after baseline	4.0 days Interval 3.0 to 6.0	4.0 days Interval 3.0 to 7.0	4.5 days Interval 2.0 to 8.0	7.0 days Interval 4.0 to 13.0
Time to Nth (n= 1, 5, 10) Seizure During the 7-week Treatment Period Number of days to fifth seizure after baseline	17.0 days Interval 13.0 to 22.0	20.0 days Interval 17.0 to 27.0	18.5 days Interval 14.0 to 29.0	32.5 days Interval 23.0 to 42.0
Time to Nth (n= 1, 5, 10) Seizure During the 7-week Treatment Period Number of days to tenth seizure after baseline	32.0 days Interval 23.0 to 45.0	38.0 days Interval 27.0 to upper limit is not available	39.0 days Interval 23.0 to upper limit is not available	57.0 days Interval 49.0 to upper limit is not available

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

Brivaracetam 5 mg/Day

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Brivaracetam 20 mg/Day

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Brivaracetam 50 mg/Day

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=54 participants at risk Matching Placebo tablets administered twice a day	Brivaracetam 5 mg/Day n=50 participants at risk Brivaracetam 5 mg/day, 2.5 mg administered twice a day	Brivaracetam 20 mg/Day n=52 participants at risk Brivaracetam 20 mg/day, 10 mg administered twice a day	Brivaracetam 50 mg/Day n=52 participants at risk Brivaracetam 50 mg/day, 25 mg administered twice a day
Nervous system disorders Neurotoxicity	0.00% 0/54 • Adverse events were collected from Baseline until Safety Visit (up to 3 months). Adverse Events refer to the Safety Population consisting of all subjects who were dispensed medication.	0.00% 0/50 • Adverse events were collected from Baseline until Safety Visit (up to 3 months). Adverse Events refer to the Safety Population consisting of all subjects who were dispensed medication.	1.9% 1/52 • Adverse events were collected from Baseline until Safety Visit (up to 3 months). Adverse Events refer to the Safety Population consisting of all subjects who were dispensed medication.	0.00% 0/52 • Adverse events were collected from Baseline until Safety Visit (up to 3 months). Adverse Events refer to the Safety Population consisting of all subjects who were dispensed medication.

Other adverse events

Measure	Placebo n=54 participants at risk Matching Placebo tablets administered twice a day	Brivaracetam 5 mg/Day n=50 participants at risk Brivaracetam 5 mg/day, 2.5 mg administered twice a day	Brivaracetam 20 mg/Day n=52 participants at risk Brivaracetam 20 mg/day, 10 mg administered twice a day	Brivaracetam 50 mg/Day n=52 participants at risk Brivaracetam 50 mg/day, 25 mg administered twice a day
Blood and lymphatic system disorders Neutropenia	1.9% 1/54 • Adverse events were collected from Baseline until Safety Visit (up to 3 months). Adverse Events refer to the Safety Population consisting of all subjects who were dispensed medication.	8.0% 4/50 • Adverse events were collected from Baseline until Safety Visit (up to 3 months). Adverse Events refer to the Safety Population consisting of all subjects who were dispensed medication.	3.8% 2/52 • Adverse events were collected from Baseline until Safety Visit (up to 3 months). Adverse Events refer to the Safety Population consisting of all subjects who were dispensed medication.	1.9% 1/52 • Adverse events were collected from Baseline until Safety Visit (up to 3 months). Adverse Events refer to the Safety Population consisting of all subjects who were dispensed medication.
General disorders Fatigue	3.7% 2/54 • Adverse events were collected from Baseline until Safety Visit (up to 3 months). Adverse Events refer to the Safety Population consisting of all subjects who were dispensed medication.	0.00% 0/50 • Adverse events were collected from Baseline until Safety Visit (up to 3 months). Adverse Events refer to the Safety Population consisting of all subjects who were dispensed medication.	3.8% 2/52 • Adverse events were collected from Baseline until Safety Visit (up to 3 months). Adverse Events refer to the Safety Population consisting of all subjects who were dispensed medication.	5.8% 3/52 • Adverse events were collected from Baseline until Safety Visit (up to 3 months). Adverse Events refer to the Safety Population consisting of all subjects who were dispensed medication.
Infections and infestations Influenza	7.4% 4/54 • Adverse events were collected from Baseline until Safety Visit (up to 3 months). Adverse Events refer to the Safety Population consisting of all subjects who were dispensed medication.	8.0% 4/50 • Adverse events were collected from Baseline until Safety Visit (up to 3 months). Adverse Events refer to the Safety Population consisting of all subjects who were dispensed medication.	0.00% 0/52 • Adverse events were collected from Baseline until Safety Visit (up to 3 months). Adverse Events refer to the Safety Population consisting of all subjects who were dispensed medication.	1.9% 1/52 • Adverse events were collected from Baseline until Safety Visit (up to 3 months). Adverse Events refer to the Safety Population consisting of all subjects who were dispensed medication.
Nervous system disorders Dizziness	5.6% 3/54 • Adverse events were collected from Baseline until Safety Visit (up to 3 months). Adverse Events refer to the Safety Population consisting of all subjects who were dispensed medication.	2.0% 1/50 • Adverse events were collected from Baseline until Safety Visit (up to 3 months). Adverse Events refer to the Safety Population consisting of all subjects who were dispensed medication.	0.00% 0/52 • Adverse events were collected from Baseline until Safety Visit (up to 3 months). Adverse Events refer to the Safety Population consisting of all subjects who were dispensed medication.	7.7% 4/52 • Adverse events were collected from Baseline until Safety Visit (up to 3 months). Adverse Events refer to the Safety Population consisting of all subjects who were dispensed medication.
Nervous system disorders Headache	7.4% 4/54 • Adverse events were collected from Baseline until Safety Visit (up to 3 months). Adverse Events refer to the Safety Population consisting of all subjects who were dispensed medication.	8.0% 4/50 • Adverse events were collected from Baseline until Safety Visit (up to 3 months). Adverse Events refer to the Safety Population consisting of all subjects who were dispensed medication.	3.8% 2/52 • Adverse events were collected from Baseline until Safety Visit (up to 3 months). Adverse Events refer to the Safety Population consisting of all subjects who were dispensed medication.	1.9% 1/52 • Adverse events were collected from Baseline until Safety Visit (up to 3 months). Adverse Events refer to the Safety Population consisting of all subjects who were dispensed medication.
Nervous system disorders Somnolence	7.4% 4/54 • Adverse events were collected from Baseline until Safety Visit (up to 3 months). Adverse Events refer to the Safety Population consisting of all subjects who were dispensed medication.	2.0% 1/50 • Adverse events were collected from Baseline until Safety Visit (up to 3 months). Adverse Events refer to the Safety Population consisting of all subjects who were dispensed medication.	5.8% 3/52 • Adverse events were collected from Baseline until Safety Visit (up to 3 months). Adverse Events refer to the Safety Population consisting of all subjects who were dispensed medication.	5.8% 3/52 • Adverse events were collected from Baseline until Safety Visit (up to 3 months). Adverse Events refer to the Safety Population consisting of all subjects who were dispensed medication.

Additional Information

UCB

Cares

Phone: +1844 599

Email: UCBCares@ucb.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60