Trial Outcomes & Findings for Study to Evaluate the Safety and Effectiveness of USL255 in Patients With Refractory Partial-onset Seizures (NCT NCT01142193)

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

249 participants

Primary outcome timeframe

11 weeks

Results posted on

2014-05-22

Participant Flow

This study was conducted in 16 countries (Argentina, Australia, Belgium, Canada, Chile, Germany, Greece, Hungary, India, Israel, New Zealand, Poland, Russia, South Africa, Spain, and United States). At least 1 subject was enrolled at 66 study centers, of which 60 study centers randomly assigned at least 1 subject to study drug.

Subject had to have a minimum of 8 partial-onset seizures and no more than 21 consecutive seizure free days during the 8-week baseline to be randomized into the trial.

Participant milestones

Participant milestones
Measure	USL255 Titration of 50 mg in weekly increments over 3 weeks to 200 mg	Placebo Placebo
Overall Study STARTED	124	125
Overall Study COMPLETED	103	114
Overall Study NOT COMPLETED	21	11

Reasons for withdrawal

Reasons for withdrawal
Measure	USL255 Titration of 50 mg in weekly increments over 3 weeks to 200 mg	Placebo Placebo
Overall Study Adverse Event	12	4
Overall Study Lack of Efficacy	2	1
Overall Study Physician Decision	1	1
Overall Study Withdrawal by Subject	4	3
Overall Study Protocol Discontinuation Criterion Met	1	0
Overall Study Other	1	2

Baseline Characteristics

Study to Evaluate the Safety and Effectiveness of USL255 in Patients With Refractory Partial-onset Seizures

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	USL255 n=124 Participants Titration of 50 mg in weekly increments over 3 weeks to 200 mg	Placebo n=125 Participants Placebo	Total n=249 Participants Total of all reporting groups
Age, Continuous	37.6 Years STANDARD_DEVIATION 10.97 • n=5 Participants	37.6 Years STANDARD_DEVIATION 11.11 • n=7 Participants	37.6 Years STANDARD_DEVIATION 11.02 • n=5 Participants
Sex: Female, Male Female	58 Participants n=5 Participants	59 Participants n=7 Participants	117 Participants n=5 Participants
Sex: Female, Male Male	66 Participants n=5 Participants	66 Participants n=7 Participants	132 Participants n=5 Participants

PRIMARY outcome

Timeframe: 11 weeks

Population: Intent-to-treat (ITT): all subjects who were randomized and received at least 1 dose of study drug

Outcome measures

Outcome measures
Measure	USL255 n=124 Participants Titration of 50 mg in weekly increments over 3 weeks to 200 mg	Placebo n=125 Participants Placebo
Percent Reduction From Baseline in Weekly (7 Day) Partial-onset Seizure Frequency During the Titration Plus Maintenance Phase Compared to Baseline.	39.5 Percent Reduction Interval -227.3 to 100.0	21.65 Percent Reduction Interval -531.2 to 100.0

SECONDARY outcome

Timeframe: 11 weeks

Population: Intent-to-treat (ITT): all subjects who were randomized and received at least 1 dose of study drug

Outcome measures

Outcome measures
Measure	USL255 n=124 Participants Titration of 50 mg in weekly increments over 3 weeks to 200 mg	Placebo n=125 Participants Placebo
Proportion of Subjects With ≥50% Reduction (Responder Rate) in Weekly (7 Day) Partial-onset Seizure Frequency During the Titration Plus Maintenance Phase Compared to Baseline.	37.9 Percentage of participants	23.2 Percentage of participants

SECONDARY outcome

Timeframe: 3 weeks (weeks 1-3)

Outcome measures

Outcome measures
Measure	USL255 n=124 Participants Titration of 50 mg in weekly increments over 3 weeks to 200 mg	Placebo n=125 Participants Placebo
Proportion of Subjects With ≥50% Reduction (Responder Rate) in Weekly (7 Day) Partial-onset Seizure Frequency During the Titration Phase Compared to Baseline.	33.9 Percentage of participants	17.6 Percentage of participants

SECONDARY outcome

Timeframe: 3 weeks (weeks 1-3)

Population: Intent-to-treat (ITT): all subjects who were randomized and received at least 1 dose of study drug

Outcome measures

Outcome measures
Measure	USL255 n=124 Participants Titration of 50 mg in weekly increments over 3 weeks to 200 mg	Placebo n=125 Participants Placebo
Percent Reductions From Baseline in Weekly (7 Day) Partial-onset Seizure Frequency During the Titration Phase Compared to Baseline.	33.93 Percent Reduction Interval -200.0 to 100.0	8.57 Percent Reduction Interval -158.3 to 100.0

SECONDARY outcome

Timeframe: 11 weeks

Population: Intent-to-treat (ITT): all subjects who were randomized and received at least 1 dose of study drug

Outcome measures

Outcome measures
Measure	USL255 n=124 Participants Titration of 50 mg in weekly increments over 3 weeks to 200 mg	Placebo n=125 Participants Placebo
Percent Reduction From Baseline in Weekly (7 Day) All Seizure Frequency During the Titration Plus Maintenance Phase.	39.50 Percent Reduction Interval -227.3 to 100.0	21.65 Percent Reduction Interval -531.2 to 100.0

SECONDARY outcome

Timeframe: 3 weeks (weeks 1-3)

Population: Intent-to-treat (ITT): all subjects who were randomized and received at least 1 dose of study drug

Outcome measures

Outcome measures
Measure	USL255 n=124 Participants Titration of 50 mg in weekly increments over 3 weeks to 200 mg	Placebo n=125 Participants Placebo
Proportion of Subjects With ≥25%, ≥75%, and 100% Reduction in Weekly (7 Day) Partial-onset Seizure Frequency During the Titration Phases Compared to Baseline. ≥25% reduction in seizure rate	56.5 Percentage of participants	34.4 Percentage of participants
Proportion of Subjects With ≥25%, ≥75%, and 100% Reduction in Weekly (7 Day) Partial-onset Seizure Frequency During the Titration Phases Compared to Baseline. ≥75% reduction in seizure rate	16.9 Percentage of participants	7.2 Percentage of participants
Proportion of Subjects With ≥25%, ≥75%, and 100% Reduction in Weekly (7 Day) Partial-onset Seizure Frequency During the Titration Phases Compared to Baseline. 100% reduction in seizure rate	12.1 Percentage of participants	3.2 Percentage of participants

SECONDARY outcome

Timeframe: 11 weeks

Population: Intent-to-treat (ITT): all subjects who were randomized and received at least 1 dose of study drug

Outcome measures

Outcome measures
Measure	USL255 n=124 Participants Titration of 50 mg in weekly increments over 3 weeks to 200 mg	Placebo n=125 Participants Placebo
Proportion of Subjects With ≥25%, ≥75%, and 100% Reduction in Weekly (7 Day) Partial-onset Seizure Frequency During the Titration Plus Maintenance Phase Compared to Baseline. ≥25% reduction in seizure rate	66.9 Percentage of participants	46.4 Percentage of participants
Proportion of Subjects With ≥25%, ≥75%, and 100% Reduction in Weekly (7 Day) Partial-onset Seizure Frequency During the Titration Plus Maintenance Phase Compared to Baseline. ≥75% reduction in seizure rate	15.3 Percentage of participants	4.8 Percentage of participants
Proportion of Subjects With ≥25%, ≥75%, and 100% Reduction in Weekly (7 Day) Partial-onset Seizure Frequency During the Titration Plus Maintenance Phase Compared to Baseline. 100% reduction in seizure rate	3.2 Percentage of participants	1.6 Percentage of participants

SECONDARY outcome

Timeframe: 8 weeks (weeks 4-11)

Population: Intent-to-treat (ITT): all subjects who were randomized and received at least 1 dose of study drug. Note: Sample size is less than for primary outcome because some subjects discontinued study prior to the maintenance phase.

Outcome measures

Outcome measures
Measure	USL255 n=113 Participants Titration of 50 mg in weekly increments over 3 weeks to 200 mg	Placebo n=120 Participants Placebo
Proportion of Subjects With ≥25%, ≥75%, and 100% Reduction in Weekly (7 Day) Partial-onset Seizure Frequency During the Maintenance Phase Compared to Baseline. ≥25% reduction in seizure rate	72.6 Percentage of participants	46.7 Percentage of participants
Proportion of Subjects With ≥25%, ≥75%, and 100% Reduction in Weekly (7 Day) Partial-onset Seizure Frequency During the Maintenance Phase Compared to Baseline. ≥75% reduction in seizure rate	26.5 Percentage of participants	9.2 Percentage of participants
Proportion of Subjects With ≥25%, ≥75%, and 100% Reduction in Weekly (7 Day) Partial-onset Seizure Frequency During the Maintenance Phase Compared to Baseline. 100% reduction in seizure rate	7.1 Percentage of participants	3.3 Percentage of participants

SECONDARY outcome

Timeframe: 8 weeks (weeks 4-11)

Population: Intent-to-treat (ITT): all subjects who were randomized and received at least 1 dose of study drug. Note: Sample size is less than for primary outcome because some subjects discontinued study prior to the maintenance phase.

Outcome measures

Outcome measures
Measure	USL255 n=113 Participants Titration of 50 mg in weekly increments over 3 weeks to 200 mg	Placebo n=120 Participants Placebo
Percent Reduction From Baseline in Weekly (7 Day) Partial-onset Seizure Frequency During the Maintenance Phase Compared to Baseline.	45.70 Percent Reduction Interval -237.5 to 100.0	22.09 Percent Reduction Interval -747.4 to 100.0

SECONDARY outcome

Timeframe: 8 weeks (weeks 4-11)

Population: Intent-to-treat (ITT): all subjects who were randomized and received at least 1 dose of study drug. Note: Sample size is less than for primary outcome because some subjects discontinued study prior to the maintenance phase.

Outcome measures

Outcome measures
Measure	USL255 n=113 Participants Titration of 50 mg in weekly increments over 3 weeks to 200 mg	Placebo n=120 Participants Placebo
Proportion of Subjects ≥50% Reduction (Responder Rate) in Weekly (7 Day) Partial-onset Seizure Frequency During the Maintenance Phase Compared to Baseline.	44.2 Percentage of participants	30.8 Percentage of participants

Adverse Events

USL255

Serious events: 2 serious events

Other events: 35 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	USL255 n=124 participants at risk Titration of 50 mg in weekly increments over 3 weeks to 200 mg	Placebo n=125 participants at risk Placebo
Infections and infestations Lobar Pneumonia	0.81% 1/124 • Adverse events with onset after the start of study medication and up to 30 days after the last dose of study drug are reported. If a subject experienced more than 1 of a given AE, the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class (SOC), the subject is counted only once for that SOC.	0.00% 0/125 • Adverse events with onset after the start of study medication and up to 30 days after the last dose of study drug are reported. If a subject experienced more than 1 of a given AE, the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class (SOC), the subject is counted only once for that SOC.
Social circumstances Physical Assault	0.81% 1/124 • Adverse events with onset after the start of study medication and up to 30 days after the last dose of study drug are reported. If a subject experienced more than 1 of a given AE, the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class (SOC), the subject is counted only once for that SOC.	0.00% 0/125 • Adverse events with onset after the start of study medication and up to 30 days after the last dose of study drug are reported. If a subject experienced more than 1 of a given AE, the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class (SOC), the subject is counted only once for that SOC.
Nervous system disorders Convulsion	0.00% 0/124 • Adverse events with onset after the start of study medication and up to 30 days after the last dose of study drug are reported. If a subject experienced more than 1 of a given AE, the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class (SOC), the subject is counted only once for that SOC.	0.80% 1/125 • Adverse events with onset after the start of study medication and up to 30 days after the last dose of study drug are reported. If a subject experienced more than 1 of a given AE, the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class (SOC), the subject is counted only once for that SOC.
Psychiatric disorders Epileptic Psychosis	0.00% 0/124 • Adverse events with onset after the start of study medication and up to 30 days after the last dose of study drug are reported. If a subject experienced more than 1 of a given AE, the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class (SOC), the subject is counted only once for that SOC.	0.80% 1/125 • Adverse events with onset after the start of study medication and up to 30 days after the last dose of study drug are reported. If a subject experienced more than 1 of a given AE, the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class (SOC), the subject is counted only once for that SOC.
Psychiatric disorders Suicidal Ideation	0.00% 0/124 • Adverse events with onset after the start of study medication and up to 30 days after the last dose of study drug are reported. If a subject experienced more than 1 of a given AE, the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class (SOC), the subject is counted only once for that SOC.	0.80% 1/125 • Adverse events with onset after the start of study medication and up to 30 days after the last dose of study drug are reported. If a subject experienced more than 1 of a given AE, the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class (SOC), the subject is counted only once for that SOC.

Other adverse events

Other adverse events
Measure	USL255 n=124 participants at risk Titration of 50 mg in weekly increments over 3 weeks to 200 mg	Placebo n=125 participants at risk Placebo
Nervous system disorders Somnolence	12.1% 15/124 • Adverse events with onset after the start of study medication and up to 30 days after the last dose of study drug are reported. If a subject experienced more than 1 of a given AE, the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class (SOC), the subject is counted only once for that SOC.	2.4% 3/125 • Adverse events with onset after the start of study medication and up to 30 days after the last dose of study drug are reported. If a subject experienced more than 1 of a given AE, the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class (SOC), the subject is counted only once for that SOC.
Nervous system disorders Dizziness	7.3% 9/124 • Adverse events with onset after the start of study medication and up to 30 days after the last dose of study drug are reported. If a subject experienced more than 1 of a given AE, the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class (SOC), the subject is counted only once for that SOC.	5.6% 7/125 • Adverse events with onset after the start of study medication and up to 30 days after the last dose of study drug are reported. If a subject experienced more than 1 of a given AE, the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class (SOC), the subject is counted only once for that SOC.
Nervous system disorders Paraesthesia	6.5% 8/124 • Adverse events with onset after the start of study medication and up to 30 days after the last dose of study drug are reported. If a subject experienced more than 1 of a given AE, the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class (SOC), the subject is counted only once for that SOC.	2.4% 3/125 • Adverse events with onset after the start of study medication and up to 30 days after the last dose of study drug are reported. If a subject experienced more than 1 of a given AE, the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class (SOC), the subject is counted only once for that SOC.
Investigations Weight Decreased	6.5% 8/124 • Adverse events with onset after the start of study medication and up to 30 days after the last dose of study drug are reported. If a subject experienced more than 1 of a given AE, the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class (SOC), the subject is counted only once for that SOC.	0.00% 0/125 • Adverse events with onset after the start of study medication and up to 30 days after the last dose of study drug are reported. If a subject experienced more than 1 of a given AE, the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class (SOC), the subject is counted only once for that SOC.
General disorders Fatigue	5.6% 7/124 • Adverse events with onset after the start of study medication and up to 30 days after the last dose of study drug are reported. If a subject experienced more than 1 of a given AE, the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class (SOC), the subject is counted only once for that SOC.	4.8% 6/125 • Adverse events with onset after the start of study medication and up to 30 days after the last dose of study drug are reported. If a subject experienced more than 1 of a given AE, the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class (SOC), the subject is counted only once for that SOC.
Nervous system disorders Headache	4.0% 5/124 • Adverse events with onset after the start of study medication and up to 30 days after the last dose of study drug are reported. If a subject experienced more than 1 of a given AE, the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class (SOC), the subject is counted only once for that SOC.	5.6% 7/125 • Adverse events with onset after the start of study medication and up to 30 days after the last dose of study drug are reported. If a subject experienced more than 1 of a given AE, the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class (SOC), the subject is counted only once for that SOC.

Additional Information

Bob Anders, Sr. Director of Clinical Operations

Upsher-Smith Laboratories, Inc.

Phone: 763-315-2000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place