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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01142193
Recruitment Status : Completed
First Posted : June 11, 2010
Results First Posted : May 7, 2014
Last Update Posted : May 22, 2014
Sponsor:
Information provided by (Responsible Party):
Upsher-Smith Laboratories

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double;   Primary Purpose: Treatment
Condition Epilepsy
Interventions Drug: USL255
Drug: Placebo
Enrollment 249
Recruitment Details 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.
Pre-assignment Details 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.
Arm/Group Title USL255 Placebo
Hide Arm/Group Description Titration of 50 mg in weekly increments over 3 weeks to 200 mg Placebo
Period Title: Overall Study
Started 124 125
Completed 103 114
Not Completed 21 11
Reason Not Completed
Adverse Event             12             4
Lack of Efficacy             2             1
Physician Decision             1             1
Withdrawal by Subject             4             3
Protocol Discontinuation Criterion Met             1             0
Other             1             2
Arm/Group Title USL255 Placebo Total
Hide Arm/Group Description Titration of 50 mg in weekly increments over 3 weeks to 200 mg Placebo Total of all reporting groups
Overall Number of Baseline Participants 124 125 249
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 124 participants 125 participants 249 participants
37.6  (10.97) 37.6  (11.11) 37.6  (11.02)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 124 participants 125 participants 249 participants
Female
58
  46.8%
59
  47.2%
117
  47.0%
Male
66
  53.2%
66
  52.8%
132
  53.0%
1.Primary Outcome
Title Percent Reduction From Baseline in Weekly (7 Day) Partial-onset Seizure Frequency During the Titration Plus Maintenance Phase Compared to Baseline.
Hide Description [Not Specified]
Time Frame 11 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT): all subjects who were randomized and received at least 1 dose of study drug
Arm/Group Title USL255 Placebo
Hide Arm/Group Description:
Titration of 50 mg in weekly increments over 3 weeks to 200 mg
Placebo
Overall Number of Participants Analyzed 124 125
Median (Full Range)
Unit of Measure: Percent Reduction
39.5
(-227.3 to 100.0)
21.65
(-531.2 to 100.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection USL255, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value 17.85
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection USL255, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Hodges-Lehmann
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value 18.5
Confidence Interval (2-Sided) 95%
8.53 to 28.1
Estimation Comments [Not Specified]
2.Secondary Outcome
Title 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.
Hide Description [Not Specified]
Time Frame 11 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT): all subjects who were randomized and received at least 1 dose of study drug
Arm/Group Title USL255 Placebo
Hide Arm/Group Description:
Titration of 50 mg in weekly increments over 3 weeks to 200 mg
Placebo
Overall Number of Participants Analyzed 124 125
Measure Type: Number
Unit of Measure: Percentage of participants
37.9 23.2
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection USL255, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.013
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentages
Estimated Value 14.7
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Proportion of Subjects With ≥50% Reduction (Responder Rate) in Weekly (7 Day) Partial-onset Seizure Frequency During the Titration Phase Compared to Baseline.
Hide Description [Not Specified]
Time Frame 3 weeks (weeks 1-3)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title USL255 Placebo
Hide Arm/Group Description:
Titration of 50 mg in weekly increments over 3 weeks to 200 mg
Placebo
Overall Number of Participants Analyzed 124 125
Measure Type: Number
Unit of Measure: Percentage of participants
33.9 17.6
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection USL255, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.007
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Analysis was stratified by Geographic Region.
Method of Estimation Estimation Parameter Difference in Percentages
Estimated Value 16.3
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percent Reductions From Baseline in Weekly (7 Day) Partial-onset Seizure Frequency During the Titration Phase Compared to Baseline.
Hide Description [Not Specified]
Time Frame 3 weeks (weeks 1-3)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT): all subjects who were randomized and received at least 1 dose of study drug
Arm/Group Title USL255 Placebo
Hide Arm/Group Description:
Titration of 50 mg in weekly increments over 3 weeks to 200 mg
Placebo
Overall Number of Participants Analyzed 124 125
Median (Full Range)
Unit of Measure: Percent Reduction
33.93
(-200.00 to 100.0)
8.57
(-158.3 to 100.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection USL255, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value 25.36
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Percent Reduction From Baseline in Weekly (7 Day) All Seizure Frequency During the Titration Plus Maintenance Phase.
Hide Description [Not Specified]
Time Frame 11 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT): all subjects who were randomized and received at least 1 dose of study drug
Arm/Group Title USL255 Placebo
Hide Arm/Group Description:
Titration of 50 mg in weekly increments over 3 weeks to 200 mg
Placebo
Overall Number of Participants Analyzed 124 125
Median (Full Range)
Unit of Measure: Percent Reduction
39.50
(-227.3 to 100.0)
21.65
(-531.2 to 100.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection USL255, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value 17.85
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Proportion of Subjects With ≥25%, ≥75%, and 100% Reduction in Weekly (7 Day) Partial-onset Seizure Frequency During the Titration Phases Compared to Baseline.
Hide Description [Not Specified]
Time Frame 3 weeks (weeks 1-3)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT): all subjects who were randomized and received at least 1 dose of study drug
Arm/Group Title USL255 Placebo
Hide Arm/Group Description:
Titration of 50 mg in weekly increments over 3 weeks to 200 mg
Placebo
Overall Number of Participants Analyzed 124 125
Measure Type: Number
Unit of Measure: Percentage of participants
≥25% reduction in seizure rate 56.5 34.4
≥75% reduction in seizure rate 16.9 7.2
100% reduction in seizure rate 12.1 3.2
7.Secondary Outcome
Title 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.
Hide Description [Not Specified]
Time Frame 11 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT): all subjects who were randomized and received at least 1 dose of study drug
Arm/Group Title USL255 Placebo
Hide Arm/Group Description:
Titration of 50 mg in weekly increments over 3 weeks to 200 mg
Placebo
Overall Number of Participants Analyzed 124 125
Measure Type: Number
Unit of Measure: Percentage of participants
≥25% reduction in seizure rate 66.9 46.4
≥75% reduction in seizure rate 15.3 4.8
100% reduction in seizure rate 3.2 1.6
8.Secondary Outcome
Title Proportion of Subjects With ≥25%, ≥75%, and 100% Reduction in Weekly (7 Day) Partial-onset Seizure Frequency During the Maintenance Phase Compared to Baseline.
Hide Description [Not Specified]
Time Frame 8 weeks (weeks 4-11)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title USL255 Placebo
Hide Arm/Group Description:
Titration of 50 mg in weekly increments over 3 weeks to 200 mg
Placebo
Overall Number of Participants Analyzed 113 120
Measure Type: Number
Unit of Measure: Percentage of participants
≥25% reduction in seizure rate 72.6 46.7
≥75% reduction in seizure rate 26.5 9.2
100% reduction in seizure rate 7.1 3.3
9.Secondary Outcome
Title Percent Reduction From Baseline in Weekly (7 Day) Partial-onset Seizure Frequency During the Maintenance Phase Compared to Baseline.
Hide Description [Not Specified]
Time Frame 8 weeks (weeks 4-11)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title USL255 Placebo
Hide Arm/Group Description:
Titration of 50 mg in weekly increments over 3 weeks to 200 mg
Placebo
Overall Number of Participants Analyzed 113 120
Median (Full Range)
Unit of Measure: Percent Reduction
45.70
(-237.5 to 100.0)
22.09
(-747.4 to 100.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection USL255, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value 23.61
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Proportion of Subjects ≥50% Reduction (Responder Rate) in Weekly (7 Day) Partial-onset Seizure Frequency During the Maintenance Phase Compared to Baseline.
Hide Description [Not Specified]
Time Frame 8 weeks (weeks 4-11)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title USL255 Placebo
Hide Arm/Group Description:
Titration of 50 mg in weekly increments over 3 weeks to 200 mg
Placebo
Overall Number of Participants Analyzed 113 120
Measure Type: Number
Unit of Measure: Percentage of participants
44.2 30.8
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection USL255, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.048
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Analysis was stratified by Geographic Region.
Method of Estimation Estimation Parameter Difference in Percentages
Estimated Value 13.4
Estimation Comments [Not Specified]
Time Frame Adverse events with onset after the start of study medication and up to 30 days after the last dose of study drug are reported.
Adverse Event Reporting Description 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.
 
Arm/Group Title USL255 Placebo
Hide Arm/Group Description Titration of 50 mg in weekly increments over 3 weeks to 200 mg Placebo
All-Cause Mortality
USL255 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
USL255 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   2/124 (1.61%)   2/125 (1.60%) 
Infections and infestations     
Lobar Pneumonia * 1  1/124 (0.81%)  0/125 (0.00%) 
Nervous system disorders     
Convulsion * 1  0/124 (0.00%)  1/125 (0.80%) 
Psychiatric disorders     
Epileptic Psychosis * 1  0/124 (0.00%)  1/125 (0.80%) 
Suicidal Ideation * 1  0/124 (0.00%)  1/125 (0.80%) 
Social circumstances     
Physical Assault * 1  1/124 (0.81%)  0/125 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 11.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
USL255 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   35/124 (28.23%)   14/125 (11.20%) 
General disorders     
Fatigue * 1  7/124 (5.65%)  6/125 (4.80%) 
Investigations     
Weight Decreased * 1  8/124 (6.45%)  0/125 (0.00%) 
Nervous system disorders     
Somnolence * 1  15/124 (12.10%)  3/125 (2.40%) 
Dizziness * 1  9/124 (7.26%)  7/125 (5.60%) 
Paraesthesia * 1  8/124 (6.45%)  3/125 (2.40%) 
Headache * 1  5/124 (4.03%)  7/125 (5.60%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (11.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Bob Anders, Sr. Director of Clinical Operations
Organization: Upsher-Smith Laboratories, Inc.
Phone: 763-315-2000
EMail: Bob.Anders@upsher-smith.com
Layout table for additonal information
Responsible Party: Upsher-Smith Laboratories
ClinicalTrials.gov Identifier: NCT01142193    
Other Study ID Numbers: P09-004
2009-016996-31 ( EudraCT Number )
First Submitted: June 9, 2010
First Posted: June 11, 2010
Results First Submitted: April 3, 2014
Results First Posted: May 7, 2014
Last Update Posted: May 22, 2014