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CompletedNCT01142193Updated May 22, 2014Results posted

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

A Phase 3 interventional study of USL255 and Placebo in Epilepsy, sponsored by Upsher-Smith Laboratories. Completed at 69 sites in 16 countries. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2014-05-22.

Sponsored by Upsher-Smith Laboratories · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
249
Allocation
Randomized
Ages
18 Years to 75 Years
Sex
All
01

Study summary

The purpose of this study is to examine the safety and effectiveness of USL255 as adjunctive therapy in patients with refractory partial onset-seizures.

02

Conditions studied

  • Epilepsy

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Keywords

  • Epilepsy
  • partial onset seizure
  • adjunctive therapy
03

In context

Epilepsy

1,848 studies on the registry are indexed under Epilepsy; 422 are open to participants now.

This study's enrollment of 249 is above the median of 50 across 1,239 interventional studies indexed under Epilepsy.

Browse Epilepsy studies →

Lead sponsor

Upsher-Smith Laboratories is the lead sponsor of 6 studies on the registry; 1 is open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Subject has a confirmed diagnosis of partial-onset seizures with or without secondary generalization for at least 12 months prior to Visit 1.
  • Currently on a stable dosing regimen of 1 to 3 AEDs for at least 4-weeks prior to Visit 1 (12 weeks for phenobarbital and primidone).
  • Have a minimum of 8 partial-onset seizures and no more than 21 consecutive seizure free days, during the 8-week baseline.

Exclusion criteria

Exclusion Criteria:

  • Have a history of seizure episodes lasting less than 30 minutes in which several seizures occur with such frequency that the initiation and completion of each individual seizure cannot be distinguished, within 3 months prior to Visit 1.
  • Have a history of pseudoseizures, or status epilepticus, within 3 months prior to Visit 1.
  • Have a history of metabolic acidosis, nephrolithiasis, ureterolithiasis, or narrow angle glaucoma.
  • Have a history of suicidal attempts, suicidal ideation, or uncontrolled psychiatric illness within 2 years of Visit 1.
  • Currently taking, or have taken felbamate within the past 18 months, or have taken vigabatrin in the past.
  • Have taken topiramate within the past 6 months.
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double
Enrollment
249 participants (actual)

Study arms

  • Experimental
    USL255

    Drug: USL255

  • Placebo comparator
    Placebo

    Drug: Placebo

Interventions

06

What researchers measure

Primary outcomes

  1. Percent Reduction From Baseline in Weekly (7 Day) Partial-onset Seizure Frequency During the Titration Plus Maintenance Phase Compared to Baseline.

    Time frame: 11 weeks

Secondary outcomes

  1. 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.

    Time frame: 11 weeks

  2. Proportion of Subjects With ≥50% Reduction (Responder Rate) in Weekly (7 Day) Partial-onset Seizure Frequency During the Titration Phase Compared to Baseline.

    Time frame: 3 weeks (weeks 1-3)

  3. Percent Reductions From Baseline in Weekly (7 Day) Partial-onset Seizure Frequency During the Titration Phase Compared to Baseline.

    Time frame: 3 weeks (weeks 1-3)

  4. Percent Reduction From Baseline in Weekly (7 Day) All Seizure Frequency During the Titration Plus Maintenance Phase.

    Time frame: 11 weeks

  5. Proportion of Subjects With ≥25%, ≥75%, and 100% Reduction in Weekly (7 Day) Partial-onset Seizure Frequency During the Titration Phases Compared to Baseline.

    Time frame: 3 weeks (weeks 1-3)

  6. 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.

    Time frame: 11 weeks

  7. Proportion of Subjects With ≥25%, ≥75%, and 100% Reduction in Weekly (7 Day) Partial-onset Seizure Frequency During the Maintenance Phase Compared to Baseline.

    Time frame: 8 weeks (weeks 4-11)

  8. Percent Reduction From Baseline in Weekly (7 Day) Partial-onset Seizure Frequency During the Maintenance Phase Compared to Baseline.

    Time frame: 8 weeks (weeks 4-11)

  9. Proportion of Subjects ≥50% Reduction (Responder Rate) in Weekly (7 Day) Partial-onset Seizure Frequency During the Maintenance Phase Compared to Baseline.

    Time frame: 8 weeks (weeks 4-11)

07

Results

Posted May 7, 2014

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.

Participant flow — Overall Study
MilestoneUSL255Placebo
Started124125
Completed103114
Not completed2111
Withdrew: Adverse event124
Withdrew: Lack of efficacy21
Withdrew: Physician decision11
Withdrew: Withdrawal by subject43
Withdrew: Protocol discontinuation criterion met10
Withdrew: Other12

Outcome measures

PrimaryPercent Reduction From Baseline in Weekly (7 Day) Partial-onset Seizure Frequency During the Titration Plus Maintenance Phase Compared to Baseline.
Time frame:
11 weeks
Reported as:
Median · Percent Reduction
Percent Reduction From Baseline in Weekly (7 Day) Partial-onset Seizure Frequency During the Titration Plus Maintenance Phase Compared to Baseline.
Percent ReductionUSL255Placebo
Percent Reduction From Baseline in Weekly (7 Day) Partial-onset Seizure Frequency During the Titration Plus Maintenance Phase Compared to Baseline.39.5 (-227.3 to 100.0)21.65 (-531.2 to 100.0)
Statistical analysis
  • USL255 vs Placebo · Wilcoxon (Mann-Whitney) · p = <.001 · Median difference (net): 17.85
  • USL255 vs Placebo · Hodges-Lehmann · Median difference (net): 18.5 · 95% CI 8.53 to 28.1
SecondaryProportion of Subjects With ≥50% Reduction (Responder Rate) in Weekly (7 Day) Partial-onset Seizure Frequency During the Titration Plus Maintenance Phase Compared to Baseline.
Time frame:
11 weeks
Reported as:
Number · Percentage of participants
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.
Percentage of participantsUSL255Placebo
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.37.923.2
Statistical analysis
  • USL255 vs Placebo · Fisher Exact · p = 0.013 · Difference in percentages: 14.7
SecondaryProportion of Subjects With ≥50% Reduction (Responder Rate) in Weekly (7 Day) Partial-onset Seizure Frequency During the Titration Phase Compared to Baseline.
Time frame:
3 weeks (weeks 1-3)
Reported as:
Number · Percentage of participants
Proportion of Subjects With ≥50% Reduction (Responder Rate) in Weekly (7 Day) Partial-onset Seizure Frequency During the Titration Phase Compared to Baseline.
Percentage of participantsUSL255Placebo
Proportion of Subjects With ≥50% Reduction (Responder Rate) in Weekly (7 Day) Partial-onset Seizure Frequency During the Titration Phase Compared to Baseline.33.917.6
Statistical analysis
  • USL255 vs Placebo · Cochran-Mantel-Haenszel · p = 0.007 · Difference in percentages: 16.3Analysis was stratified by Geographic Region.
SecondaryPercent Reductions From Baseline in Weekly (7 Day) Partial-onset Seizure Frequency During the Titration Phase Compared to Baseline.
Time frame:
3 weeks (weeks 1-3)
Reported as:
Median · Percent Reduction
Percent Reductions From Baseline in Weekly (7 Day) Partial-onset Seizure Frequency During the Titration Phase Compared to Baseline.
Percent ReductionUSL255Placebo
Percent Reductions From Baseline in Weekly (7 Day) Partial-onset Seizure Frequency During the Titration Phase Compared to Baseline.33.93 (-200.00 to 100.0)8.57 (-158.3 to 100.0)
Statistical analysis
  • USL255 vs Placebo · Wilcoxon (Mann-Whitney) · p = <0.001 · Median difference (net): 25.36
SecondaryPercent Reduction From Baseline in Weekly (7 Day) All Seizure Frequency During the Titration Plus Maintenance Phase.
Time frame:
11 weeks
Reported as:
Median · Percent Reduction
Percent Reduction From Baseline in Weekly (7 Day) All Seizure Frequency During the Titration Plus Maintenance Phase.
Percent ReductionUSL255Placebo
Percent Reduction From Baseline in Weekly (7 Day) All Seizure Frequency During the Titration Plus Maintenance Phase.39.50 (-227.3 to 100.0)21.65 (-531.2 to 100.0)
Statistical analysis
  • USL255 vs Placebo · Wilcoxon (Mann-Whitney) · p = <0.001 · Median difference (net): 17.85
SecondaryProportion of Subjects With ≥25%, ≥75%, and 100% Reduction in Weekly (7 Day) Partial-onset Seizure Frequency During the Titration Phases Compared to Baseline.
Time frame:
3 weeks (weeks 1-3)
Reported as:
Number · 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.
Percentage of participantsUSL255Placebo
≥25% reduction in seizure rate56.534.4
≥75% reduction in seizure rate16.97.2
100% reduction in seizure rate12.13.2
SecondaryProportion 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.
Time frame:
11 weeks
Reported as:
Number · 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.
Percentage of participantsUSL255Placebo
≥25% reduction in seizure rate66.946.4
≥75% reduction in seizure rate15.34.8
100% reduction in seizure rate3.21.6
SecondaryProportion of Subjects With ≥25%, ≥75%, and 100% Reduction in Weekly (7 Day) Partial-onset Seizure Frequency During the Maintenance Phase Compared to Baseline.
Time frame:
8 weeks (weeks 4-11)
Reported as:
Number · 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.
Percentage of participantsUSL255Placebo
≥25% reduction in seizure rate72.646.7
≥75% reduction in seizure rate26.59.2
100% reduction in seizure rate7.13.3
SecondaryPercent Reduction From Baseline in Weekly (7 Day) Partial-onset Seizure Frequency During the Maintenance Phase Compared to Baseline.
Time frame:
8 weeks (weeks 4-11)
Reported as:
Median · Percent Reduction
Percent Reduction From Baseline in Weekly (7 Day) Partial-onset Seizure Frequency During the Maintenance Phase Compared to Baseline.
Percent ReductionUSL255Placebo
Percent Reduction From Baseline in Weekly (7 Day) Partial-onset Seizure Frequency During the Maintenance Phase Compared to Baseline.45.70 (-237.5 to 100.0)22.09 (-747.4 to 100.0)
Statistical analysis
  • USL255 vs Placebo · Wilcoxon (Mann-Whitney) · p = 0.001 · Median difference (net): 23.61
SecondaryProportion of Subjects ≥50% Reduction (Responder Rate) in Weekly (7 Day) Partial-onset Seizure Frequency During the Maintenance Phase Compared to Baseline.
Time frame:
8 weeks (weeks 4-11)
Reported as:
Number · Percentage of participants
Proportion of Subjects ≥50% Reduction (Responder Rate) in Weekly (7 Day) Partial-onset Seizure Frequency During the Maintenance Phase Compared to Baseline.
Percentage of participantsUSL255Placebo
Proportion of Subjects ≥50% Reduction (Responder Rate) in Weekly (7 Day) Partial-onset Seizure Frequency During the Maintenance Phase Compared to Baseline.44.230.8
Statistical analysis
  • USL255 vs Placebo · Cochran-Mantel-Haenszel · p = 0.048 · Difference in percentages: 13.4Analysis was stratified by Geographic Region.

Adverse events

Collected over Adverse events with onset after the start of study medication and up to 30 days after the last dose of study drug are reported.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
USL255—2/124 (1.6%)35/124 (28.2%)
Placebo—2/125 (1.6%)14/125 (11.2%)
Most frequent serious events
Most frequent serious events
EventUSL255Placebo
Lobar PneumoniaInfections and infestations1/1240/125
Physical AssaultSocial circumstances1/1240/125
ConvulsionNervous system disorders0/1241/125
Epileptic PsychosisPsychiatric disorders0/1241/125
Suicidal IdeationPsychiatric disorders0/1241/125
Most frequent other events
Most frequent other events
EventUSL255Placebo
SomnolenceNervous system disorders15/1243/125
DizzinessNervous system disorders9/1247/125
ParaesthesiaNervous system disorders8/1243/125
Weight DecreasedInvestigations8/1240/125
FatigueGeneral disorders7/1246/125
HeadacheNervous system disorders5/1247/125

Baseline characteristics

Age, Continuous
Age, Continuous(Years)USL255PlaceboTotal
Mean37.6 ± 10.9737.6 ± 11.1137.6 ± 11.02
Sex: Female, Male
Sex: Female, Male(Participants)USL255PlaceboTotal
Female5859117
Male6666132
08

Study locations

69 sites
  • Phoenix, Arizona, United States
  • Ventura, California, United States
  • Gainesville, Florida, United States
  • Gulf Breeze, Florida, United States
  • Jacksonville, Florida, United States
  • Pensacola, Florida, United States
  • Port Charlotte, Florida, United States
  • Boise, Idaho, United States
  • Lexington, Kentucky, United States
  • Waldorf, Maryland, United States
  • Chesterfield, Missouri, United States
  • St. Louis, Missouri, United States
  • New Brunswick, New Jersey, United States
  • New York, New York, United States
  • Charlotte, North Carolina, United States
  • Toledo, Ohio, United States
  • Dallas, Texas, United States
  • Temple, Texas, United States
  • Milwaukee, Wisconsin, United States
  • Buenos Aires, Argentina
  • Cordoba, Argentina
  • Guaymallen, Argentina
  • Salta, Argentina
  • Bedford Park, Australia
  • Clayton, Australia
  • Fitzory, Australia
  • Heidelberg West, Australia
  • Parkville, Australia
  • Randwick, Australia
  • Woodville, Australia
  • Brugge, Belgium
  • Duffel, Belgium
  • Leuven, Belgium
  • Greenfield Park, Canada
  • Santiago, Chile
  • Valdivia, Chile
  • Bonn, Germany
  • Munchen, Germany
  • Athens, Greece
  • Thessaloniki, Greece
  • Budapest, Hungary
  • Bangalore, India
  • Dehradun, India
  • Hyderabad, India
  • Mangalore, India
  • New Delhi, India
  • Ashkelon, Israel
  • Haifa, Israel
  • Holon, Israel
  • Nahariya, Israel
  • Petach Tikva, Israel
  • Ramat Gan, Israel
  • Auckland, New Zealand
  • Gdansk, Poland
  • Krakow, Poland
  • Lodz, Poland
  • Lublin, Poland
  • Warszawa, Poland
  • Kazan, Russian Federation
  • Moscow, Russian Federation
  • Samara, Russian Federation
  • St. Petersburg, Russian Federation
  • Tyumen, Russian Federation
  • Yaroslavi, Russian Federation
  • Cape Town, South Africa
  • Badalona, Spain
  • Baracaldo, Spain
  • Granada, Spain
  • Madrid, Spain
09

References and documents

Publications

  • Hogan RE, Blatt I, Lawson B, Nagaraddi V, Fakhoury TA, Anders B, Clark AM, Laine D, Halvorsen MB, Chung SS. Efficacy of once-daily extended-release topiramate (USL255): a subgroup analysis based on the level of treatment resistance. Epilepsy Behav. 2014 Dec;41:136-9. doi: 10.1016/j.yebeh.2014.09.061. Epub 2014 Oct 21. PubMed 25461205 ↗
  • Chung SS, Fakhoury TA, Hogan RE, Nagaraddi VN, Blatt I, Lawson B, Arnold S, Anders B, Clark AM, Laine D, Meadows RS, Halvorsen MB; PREVAIL Study Group. Once-daily USL255 as adjunctive treatment of partial-onset seizures: randomized phase III study. Epilepsia. 2014 Jul;55(7):1077-87. doi: 10.1111/epi.12660. Epub 2014 Jun 5. PubMed 24902983 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on May 22, 2014, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01142193
Lead sponsor
Upsher-Smith Laboratories
Responsible party
Sponsor
First posted
Jun 11, 2010
Start date
May 2010
Primary completion
Dec 2012
Completion
Jan 2013
Results posted
May 7, 2014
Last update
May 22, 2014
View the source record on ClinicalTrials.gov ↗

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