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Trial record 1 of 1 for:    NCT03373383
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Study to Test the Efficacy and Safety of Padsevonil as Adjunctive Treatment of Focal-onset Seizures in Adults With Drug-resistant Epilepsy (ARISE)

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ClinicalTrials.gov Identifier: NCT03373383
Recruitment Status : Completed
First Posted : December 14, 2017
Results First Posted : April 9, 2021
Last Update Posted : April 9, 2021
Sponsor:
Information provided by (Responsible Party):
UCB Pharma ( UCB Biopharma S.P.R.L. )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Drug-resistant Epilepsy
Focal-Onset Seizures
Interventions Drug: Padsevonil
Other: Placebo
Enrollment 411
Recruitment Details The study started to enroll patients in February 2018 and concluded in January 2020.
Pre-assignment Details

The study included: a 4-week Baseline Period, a 16-week Treatment Period, a 4-week Taper Period (for participants who discontinued or choose not to enroll in the open-label extension study) and a Safety Follow-up Period. Participants continuing to the OLE study had a 3-week Conversion Period.

Participant Flow refers to the Randomized Set.

Arm/Group Title Placebo Padsevonil 50mg BID Padsevonil 100mg BID Padsevonil 200mg BID Padsevonil 400mg BID
Hide Arm/Group Description Participants randomized to the placebo group received 5-6 placebo tablets to maintain the blinding up to week 19. Participants were randomized to receive a combination of tablets of padsevonil 50 milligrams (mg) and placebo (as appropriate) to maintain the blinding, twice daily (bid) up to week 19 Participants were randomized to receive a combination of tablets of padsevonil 100 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants were randomized to receive a combination of tablets of padsevonil 200 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants were randomized to receive a combination of tablets of padsevonil 400 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19.
Period Title: Treatment Period: Wk0-16
Started 83 81 83 82 82
Completed Titration and Stabilization 78 72 71 68 65
Completed Maintenance Period 70 66 68 61 58
Had Taper and Safety Follow-up 6 11 8 18 21
Completed 70 66 68 61 58
Not Completed 13 15 15 21 24
Reason Not Completed
Adverse Event             7             6             11             15             21
Lack of Efficacy             2             1             0             0             0
Protocol Violation             0             4             2             1             0
Lost to Follow-up             2             0             0             0             0
Withdrawal by Subject             2             3             2             3             3
As advised by the sponsor             0             1             0             0             0
By opinion of investigator             0             0             0             1             0
Sponsor decision             0             0             0             1             0
Period Title: Post-Treatment Period: Wk16-23
Started 70 66 68 61 58
Started Conversion Period 69 64 66 55 57
Completed Conversion Period 68 64 66 55 57
Had Taper and Safety Follow-up 3 3 3 6 1
Enrolled in EP0093 67 63 65 55 57
Completed 69 66 68 61 58
Not Completed 1 0 0 0 0
Reason Not Completed
Participant decided not to roll over             1             0             0             0             0
Arm/Group Title Placebo Padsevonil 50mg BID Padsevonil 100mg BID Padsevonil 200mg BID Padsevonil 400mg BID Total Title
Hide Arm/Group Description Participants randomized to the placebo group received 5-6 placebo tablets to maintain the blinding up to week 19. Participants were randomized to receive a combination of tablets of padsevonil 50 milligrams (mg) and placebo (as appropriate) to maintain the blinding, twice daily (bid) up to week 19 Participants were randomized to receive a combination of tablets of padsevonil 100 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants were randomized to receive a combination of tablets of padsevonil 200 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants were randomized to receive a combination of tablets of padsevonil 400 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. [Not Specified]
Overall Number of Baseline Participants 83 81 83 82 82 411
Hide Baseline Analysis Population Description
Baseline characteristics refer to the Randomized Set (RS) consisting of all participants randomized into the study.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 83 participants 81 participants 83 participants 82 participants 82 participants 411 participants
<=18 years
0
   0.0%
0
   0.0%
2
   2.4%
1
   1.2%
1
   1.2%
4
   1.0%
Between 18 and 65 years
82
  98.8%
76
  93.8%
80
  96.4%
79
  96.3%
80
  97.6%
397
  96.6%
>=65 years
1
   1.2%
5
   6.2%
1
   1.2%
2
   2.4%
1
   1.2%
10
   2.4%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 83 participants 81 participants 83 participants 82 participants 82 participants 411 participants
40.0  (12.9) 42.5  (11.6) 36.9  (13.1) 40.9  (12.0) 38.8  (12.1) 39.8  (12.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 83 participants 81 participants 83 participants 82 participants 82 participants 411 participants
Female
48
  57.8%
46
  56.8%
47
  56.6%
51
  62.2%
43
  52.4%
235
  57.2%
Male
35
  42.2%
35
  43.2%
36
  43.4%
31
  37.8%
39
  47.6%
176
  42.8%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 83 participants 81 participants 83 participants 82 participants 82 participants 411 participants
American Indian or Alaska Native
1
   1.2%
1
   1.2%
1
   1.2%
2
   2.4%
0
   0.0%
5
   1.2%
Asian
7
   8.4%
7
   8.6%
5
   6.0%
7
   8.5%
7
   8.5%
33
   8.0%
Black or African American
2
   2.4%
1
   1.2%
1
   1.2%
2
   2.4%
2
   2.4%
8
   1.9%
Native Hawaiian or Other Pacific Islander
1
   1.2%
1
   1.2%
1
   1.2%
1
   1.2%
1
   1.2%
5
   1.2%
White
69
  83.1%
69
  85.2%
73
  88.0%
69
  84.1%
71
  86.6%
351
  85.4%
Other/mixed
3
   3.6%
2
   2.5%
2
   2.4%
1
   1.2%
1
   1.2%
9
   2.2%
1.Primary Outcome
Title Change in Log-transformed Observable Focal Onset Seizure Frequency From Baseline Over the 12 Week Maintenance Period
Hide Description During the study, participants kept diaries to record daily seizure activity. Seizure frequency refers to 28-day adjusted frequency. Seizure frequency was based on investigator assessment of participants' reports of daily seizure type and frequency. Observable focal-onset seizures refer to Type IA1, IB, and IC (ILAE Classification of Epileptic Seizures, 1981). Based on ANCOVA on change in log-transformed, 28-day adjusted seizure frequency from Baseline with treatment group as the main factor, Baseline log-transformed seizure frequency as a continuous covariate, Baseline SV2A use (yes or no) and Region (Europe, Non-Europe) as categorical factors.
Time Frame From Baseline over the 12 Week Maintenance Period
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consisted of all study participants in the RS who were administered at least 1 dose or a partial dose of IMP and had Baseline and at least 1 post-Baseline seizure frequency data during the 16-week Treatment Period.
Arm/Group Title Placebo (FAS) Padsevonil 50mg BID (FAS) Padsevonil 100mg BID (FAS) Padsevonil 200mg BID (FAS) Padsevonil 400mg BID (FAS)
Hide Arm/Group Description:
Participants randomized to the placebo group received 5-6 placebo tablets to maintain the blinding up to week 19. Participants formed the Full Analysis Set (FAS).
Participants were randomized to receive a combination of tablets of padsevonil 50 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the FAS.
Participants were randomized to receive a combination of tablets of padsevonil 100 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the FAS.
Participants were randomized to receive a combination of tablets of padsevonil 200 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the FAS.
Participants were randomized to receive a combination of tablets of padsevonil 400 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the FAS.
Overall Number of Participants Analyzed 81 80 82 81 81
Least Squares Mean (95% Confidence Interval)
Unit of Measure: loge seizures per 28 days
-0.27585
(-0.44311 to -0.10858)
-0.46424
(-0.63276 to -0.29573)
-0.48804
(-0.65436 to -0.32172)
-0.48960
(-0.65734 to -0.32187)
-0.40831
(-0.57485 to -0.24177)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (FAS), Padsevonil 50mg BID (FAS)
Comments Percent reduction over placebo was calculated as 100*(1-exp(diff)), where diff was the model estimate of the log ratio between each PSL group and placebo group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.102
Comments Adjusted p-values were from the Hochberg step-up procedure within SAS® Proc Multtest to control Type I error.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Percent reduction
Estimated Value 17.2
Confidence Interval (2-Sided) 95%
-3.8 to 33.9
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo (FAS), Padsevonil 100mg BID (FAS)
Comments Percent reduction over placebo was calculated as 100*(1-exp(diff)), where diff was the model estimate of the log ratio between each PSL group and placebo group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.064
Comments Adjusted p-values were from the Hochberg step-up procedure within SAS® Proc Multtest to control Type I error.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Percent reduction
Estimated Value 19.1
Confidence Interval (2-Sided) 95%
-1.2 to 35.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo (FAS), Padsevonil 200mg BID (FAS)
Comments Percent reduction over placebo was calculated as 100*(1-exp(diff)), where diff was the model estimate of the log ratio between each PSL group and placebo group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.063
Comments Adjusted p-values were from the Hochberg step-up procedure within SAS® Proc Multtest to control Type I error.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Percent reduction
Estimated Value 19.2
Confidence Interval (2-Sided) 95%
-1.2 to 35.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo (FAS), Padsevonil 400mg BID (FAS)
Comments Percent reduction over placebo was calculated as 100*(1-exp[diff]), where diff was the model estimate of the log ratio between each PSL group and placebo group.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.248
Comments Adjusted p-values were from the Hochberg step-up procedure within SAS® Proc Multtest to control Type I error.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Percent reduction
Estimated Value 12.4
Confidence Interval (2-Sided) 95%
-9.7 to 30.1
Estimation Comments [Not Specified]
2.Primary Outcome
Title Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Reported by the Subject and/or Caregiver or Observed by the Investigator During the Entire Study
Hide Description An Adverse Event is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment.
Time Frame From Baseline until Safety Follow-Up (up to Week 23)
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Set consisted of all study participants who were administered at least 1 dose or a partial dose of IMP.
Arm/Group Title Placebo (SS) Padsevonil 50mg BID (SS) Padsevonil 100mg BID (SS) Padsevonil 200mg BID (SS) Padsevonil 400mg BID (SS)
Hide Arm/Group Description:
Participants randomized to the placebo group received 5-6 placebo tablets to maintain the blinding up to week 19. Participants formed the Safety Set (SS).
Participants were randomized to receive a combination of tablets of padsevonil 50 mg and Placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the SS.
Participants were randomized to receive a combination of tablets of padsevonil 100 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the SS.
Participants were randomized to receive a combination of tablets of padsevonil 200 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the SS.
Participants were randomized to receive tablets of padsevonil 400 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the SS.
Overall Number of Participants Analyzed 83 81 83 82 81
Measure Type: Number
Unit of Measure: percentage of participants
78.3 84.0 80.7 75.6 92.6
3.Primary Outcome
Title Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Leading to Study Withdrawal
Hide Description An Adverse Event is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment.
Time Frame From Baseline until Safety Follow-Up (up to Week 23)
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Set consisted of all study participants who were administered at least 1 dose or a partial dose of IMP.
Arm/Group Title Placebo (SS) Padsevonil 50mg BID (SS) Padsevonil 100mg BID (SS) Padsevonil 200mg BID (SS) Padsevonil 400mg BID (SS)
Hide Arm/Group Description:
Participants randomized to the placebo group received 5-6 placebo tablets to maintain the blinding up to week 19. Participants formed the Safety Set (SS).
Participants were randomized to receive a combination of tablets of padsevonil 50 mg and Placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the SS.
Participants were randomized to receive a combination of tablets of padsevonil 100 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the SS.
Participants were randomized to receive a combination of tablets of padsevonil 200 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the SS.
Participants were randomized to receive tablets of padsevonil 400 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the SS.
Overall Number of Participants Analyzed 83 81 83 82 81
Measure Type: Number
Unit of Measure: percentage of participants
8.4 7.4 12.0 18.3 25.9
4.Primary Outcome
Title Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs) During the Entire Study
Hide Description

A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose:

  • Results in death
  • Is life-threatening
  • Requires in patient hospitalization or prolongation of existing hospitalization
  • Is a congenital anomaly or birth defect
  • Is an infection that requires treatment parenteral antibiotics
  • Other important medical events which based on medical or scientific judgement may jeopardize the patients, or may require medical or surgical intervention to prevent any of the above.
Time Frame From Baseline until Safety Follow-Up (up to Week 23)
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Set consisted of all study participants who were administered at least 1 dose or a partial dose of IMP.
Arm/Group Title Placebo (SS) Padsevonil 50mg BID (SS) Padsevonil 100mg BID (SS) Padsevonil 200mg BID (SS) Padsevonil 400mg BID (SS)
Hide Arm/Group Description:
Participants randomized to the placebo group received 5-6 placebo tablets to maintain the blinding up to week 19. Participants formed the Safety Set (SS).
Participants were randomized to receive a combination of tablets of padsevonil 50 mg and Placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the SS.
Participants were randomized to receive a combination of tablets of padsevonil 100 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the SS.
Participants were randomized to receive a combination of tablets of padsevonil 200 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the SS.
Participants were randomized to receive tablets of padsevonil 400 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the SS.
Overall Number of Participants Analyzed 83 81 83 82 81
Measure Type: Number
Unit of Measure: percentage of participants
4.8 7.4 4.8 6.1 6.2
5.Secondary Outcome
Title 75 % Responder Rate Over the 12 Week Maintenance Period
Hide Description The 75% responder rate, where a responder is a participant experiencing a ≥75% reduction in observable focal-onset seizure frequency from Baseline, over the 12-Week Maintenance Period.
Time Frame End of Maintenance Period (Week 16) following 3 Weeks of titration and 1 Week stabilization
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consisted of all study participants in the RS who were administered at least 1 dose or a partial dose of IMP and had Baseline and at least 1 post-Baseline seizure frequency data during the 16-week Treatment Period.
Arm/Group Title Placebo (FAS) Padsevonil 50mg BID (FAS) Padsevonil 100mg BID (FAS) Padsevonil 200mg BID (FAS) Padsevonil 400mg BID (FAS)
Hide Arm/Group Description:
Participants randomized to the placebo group received 5-6 placebo tablets to maintain the blinding up to week 19. Participants formed the Full Analysis Set (FAS).
Participants were randomized to receive a combination of tablets of padsevonil 50 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the FAS.
Participants were randomized to receive a combination of tablets of padsevonil 100 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the FAS.
Participants were randomized to receive a combination of tablets of padsevonil 200 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the FAS.
Participants were randomized to receive a combination of tablets of padsevonil 400 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the FAS.
Overall Number of Participants Analyzed 81 80 82 81 81
Measure Type: Number
Unit of Measure: percentage of participants
6.2 13.8 12.2 11.1 16.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (FAS), Padsevonil 50mg BID (FAS)
Comments PSL dose/Placebo was calculated using logistic regression with categorical factors for treatment group, Region (Europe, Non-Europe), Baseline SV2A use (0, 1) and log-transformed Baseline seizure frequency as a continuous covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.081
Comments Nominal p-values were not adjusted for multiplicity.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.72
Confidence Interval (2-Sided) 95%
0.88 to 8.39
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo (FAS), Padsevonil 100mg BID (FAS)
Comments PSL dose/Placebo was calculated using logistic regression with categorical factors for treatment group, Region (Europe, Non-Europe), Baseline SV2A use (0, 1) and log-transformed Baseline seizure frequency as a continuous covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.137
Comments Nominal p-values were not adjusted for multiplicity.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.37
Confidence Interval (2-Sided) 95%
0.76 to 7.41
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo (FAS), Padsevonil 200mg BID (FAS)
Comments PSL dose/Placebo was calculated using logistic regression with categorical factors for treatment group, Region (Europe, Non-Europe), Baseline SV2A use (0, 1) and log-transformed Baseline seizure frequency as a continuous covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.192
Comments Nominal p-values were not adjusted for multiplicity.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.16
Confidence Interval (2-Sided) 95%
0.68 to 6.89
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo (FAS), Padsevonil 400mg BID (FAS)
Comments PSL dose/Placebo was calculated using logistic regression with categorical factors for treatment group, Region (Europe, Non-Europe), Baseline SV2A use (0, 1) and log-transformed Baseline seizure frequency as a continuous covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.041
Comments Nominal p-values were not adjusted for multiplicity.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.14
Confidence Interval (2-Sided) 95%
1.05 to 9.42
Estimation Comments [Not Specified]
6.Secondary Outcome
Title 50 % Responder Rate Over the 12 Week Maintenance Period
Hide Description The 50% responder rate, where a responder was a participant experiencing a ≥50% reduction in observable focal-onset seizure frequency from Baseline, over the 12-Week Maintenance Period.
Time Frame End of Maintenance Period (Week 16) following 3 Weeks of titration and 1 Week stabilization
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consisted of all study participants in the RS who were administered at least 1 dose or a partial dose of IMP and had Baseline and at least 1 post-Baseline seizure frequency data during the 16-week Treatment Period.
Arm/Group Title Placebo (FAS) Padsevonil 50mg BID (FAS) Padsevonil 100mg BID (FAS) Padsevonil 200mg BID (FAS) Padsevonil 400mg BID (FAS)
Hide Arm/Group Description:
Participants randomized to the placebo group received 5-6 placebo tablets to maintain the blinding up to week 19. Participants formed the Full Analysis Set (FAS).
Participants were randomized to receive a combination of tablets of padsevonil 50 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the FAS.
Participants were randomized to receive a combination of tablets of padsevonil 100 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the FAS.
Participants were randomized to receive a combination of tablets of padsevonil 200 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the FAS.
Participants were randomized to receive a combination of tablets of padsevonil 400 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the FAS.
Overall Number of Participants Analyzed 81 80 82 81 81
Measure Type: Number
Unit of Measure: percentage of participants
21.0 33.8 31.7 25.9 32.1
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (FAS), Padsevonil 50mg BID (FAS)
Comments PSL dose/placebo calculated using logistic regression with categorical factors for treatment group (each PSL dose group referenced to the placebo group), region (Europe, Non-Europe), Baseline SV2A use (0, 1) and log-transformed Baseline seizure frequency as a continuous covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.045
Comments Nominal p-values were not adjusted for multiplicity.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.09
Confidence Interval (2-Sided) 95%
1.02 to 4.30
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo (FAS), Padsevonil 100mg BID (FAS)
Comments PSL dose/placebo calculated using logistic regression with categorical factors for treatment group (each PSL dose group referenced to the placebo group), region (Europe, Non-Europe), Baseline SV2A use (0, 1) and log-transformed Baseline seizure frequency as a continuous covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.079
Comments Nominal p-values were not adjusted for multiplicity.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.91
Confidence Interval (2-Sided) 95%
0.93 to 3.93
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo (FAS), Padsevonil 200mg BID (FAS)
Comments PSL dose/placebo calculated using logistic regression with categorical factors for treatment group (each PSL dose group referenced to the placebo group), region (Europe, Non-Europe), Baseline SV2A use (0, 1) and log-transformed Baseline seizure frequency as a continuous covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.338
Comments Nominal p-values were not adjusted for multiplicity.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.44
Confidence Interval (2-Sided) 95%
0.68 to 3.02
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo (FAS), Padsevonil 400mg BID (FAS)
Comments PSL dose/Placebo calculated using logistic regression with categorical factors for treatment group, Region (Europe, Non-Europe), Baseline SV2A use (0, 1) and log-transformed Baseline seizure frequency as a continuous covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.087
Comments Nominal p-values were not adjusted for multiplicity.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.88
Confidence Interval (2-Sided) 95%
0.91 to 3.87
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Percent Change in Observable Focal-onset Seizure Frequency From Baseline Over the 12 Week Maintenance Period
Hide Description During the study, participants kept diaries to record daily seizure activity. The percentage of participants who experienced a 50 % or greater reduction in seizure frequency per 28 days relative to Baseline (responders) was assessed.
Time Frame End of Maintenance Period (Week 16) following 3 Weeks of titration and 1 Week stabilization
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consisted of all study participants in the RS who were administered at least 1 dose or a partial dose of IMP and had Baseline and at least 1 post-Baseline seizure frequency data during the 16-week Treatment Period.
Arm/Group Title Placebo (FAS) Padsevonil 50mg BID (FAS) Padsevonil 100mg BID (FAS) Padsevonil 200mg BID (FAS) Padsevonil 400mg BID (FAS)
Hide Arm/Group Description:
Participants randomized to the placebo group received 5-6 placebo tablets to maintain the blinding up to week 19. Participants formed the Full Analysis Set (FAS).
Participants were randomized to receive a combination of tablets of padsevonil 50 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the FAS.
Participants were randomized to receive a combination of tablets of padsevonil 100 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the FAS.
Participants were randomized to receive a combination of tablets of padsevonil 200 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the FAS.
Participants were randomized to receive a combination of tablets of padsevonil 400 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the FAS.
Overall Number of Participants Analyzed 81 80 82 81 81
Mean (Standard Deviation)
Unit of Measure: percent change
12.49  (58.26) 24.70  (46.62) 25.25  (51.73) 20.79  (66.54) 15.79  (67.55)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (FAS), Padsevonil 50mg BID (FAS)
Comments Dose group comparisons to Placebo p-value were based on the Wilcoxon-Mann-Whitney test. The Hodges-Lehmann nonparametric estimator was used to estimate the median difference between each PSL dose group versus placebo, along with the corresponding 95% CI of the estimate.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.316
Comments Nominal p-values were not adjusted for multiplicity.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value 7.40
Confidence Interval (2-Sided) 95%
-6.59 to 21.89
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo (FAS), Padsevonil 100mg BID (FAS)
Comments Dose group comparisons to Placebo p-value were based on the Wilcoxon-Mann-Whitney test. The Hodges-Lehmann nonparametric estimator was used to estimate the median difference between each PSL dose group versus placebo, along with the corresponding 95% CI of the estimate.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.133
Comments Nominal p-values were not adjusted for multiplicity.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value 9.99
Confidence Interval (2-Sided) 95%
-3.15 to 23.26
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo (FAS), Padsevonil 200mg BID (FAS)
Comments Dose group comparisons to Placebo p-value were based on the Wilcoxon-Mann-Whitney test. The Hodges-Lehmann nonparametric estimator was used to estimate the median difference between each PSL dose group versus placebo, along with the corresponding 95% CI of the estimate.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.203
Comments Nominal p-values were not adjusted for multiplicity.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value 8.19
Confidence Interval (2-Sided) 95%
-3.95 to 21.37
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo (FAS), Padsevonil 400mg BID (FAS)
Comments Dose group comparisons to Placebo p-value were based on the Wilcoxon-Mann-Whitney test. The Hodges-Lehmann nonparametric estimator was used to estimate the median difference between each PSL dose group versus placebo, along with the corresponding 95% CI of the estimate.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.784
Comments Nominal p-values were not adjusted for multiplicity.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value 2.39
Confidence Interval (2-Sided) 95%
-13.65 to 17.79
Estimation Comments [Not Specified]
Time Frame Treatment-emergent AEs were collected from Baseline to Safety Follow-Up (up to Week 23)
Adverse Event Reporting Description

Adverse events refer to the SS which consisted of all participants who were administered at least 1 dose or a partial dose of IMP.

TEAEs counts are for each study period: Treatment Period, Conversion Period for participants who entered the OLE study and Taper Period followed by SFU for participants not entering OLE study.

 
Arm/Group Title Placebo Treatment Period (SS) Padsevonil 50mg BID Treatment Period (SS) Padsevonil 100mg BID Treatment Period (SS) Padsevonil 200mg BID Treatment Period (SS) Padsevonil 400mg BID Treatment Period (SS) Placebo Conversion Period (SS) Padsevonil 50mg BID Conversion Period (SS) Padsevonil 100mg BID Conversion Period (SS) Padsevonil 200mg BID Conversion Period (SS) Padsevonil 400mg BID Conversion Period (SS) Placebo Taper and SFU Period (SS) Padsevonil 50mg BID Taper and SFU Period (SS) Padsevonil 100mg BID Taper and SFU Period (SS) Padsevonil 200mg BID Taper and SFU Period (SS) Padsevonil 400mg BID Taper and SFU Period (SS)
Hide Arm/Group Description Participants randomized to the placebo group received 5-6 placebo tablets to maintain the blinding up to week 19. Participants formed the Safety Set (SS). Participants were randomized to receive a combination of tablets of padsevonil 50 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the SS. Participants were randomized to receive a combination of tablets of padsevonil 100 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the SS. Participants were randomized to receive a combination of tablets of padsevonil 200 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the SS. Participants were randomized to receive a combination of tablets of padsevonil 400 mg and placebo (as appropriate) to maintain the blinding, bid up to week 19. Participants formed the SS. A 3-week Conversion Period was required for study participants who chose to enroll in the open-label extension (OLE) study at the end of the 12-week Maintenance Period. Participants initially randomized to placebo progressively received padsevonil in a blinded way to reach the entry dose of 400mg/day for the OLE. Participants formed the Safety Set (SS). A 3-week Conversion Period was required for study participants who chose to enroll in the OLE study at the end of the 12-week Maintenance Period. The dose for participants initially randomized to padsevonil 50mg bid was gradually adapted (increased or decreased) in a blinded way to reach the entry dose of 400mg/day for the OLE. Participants formed the SS. A 3-week Conversion Period was required for study participants who chose to enroll in the OLE study at the end of the 12-week Maintenance Period. The dose for participants initially randomized to padsevonil 100mg bid was gradually adapted (increased or decreased) in a blinded way to reach the entry dose of 400mg/day for the OLE. Participants formed the SS. A 3-week Conversion Period was required for study participants who chose to enroll in the OLE study at the end of the 12-week Maintenance Period. The dose for participants initially randomized to padsevonil 200mg bid was gradually adapted (increased or decreased) in a blinded way to reach the entry dose of 400mg/day for the OLE. Participants formed the SS. A 3-week Conversion Period was required for study participants who chose to enroll in the OLE study at the end of the 12-week Maintenance Period. The dose for participants initially randomized to padsevonil 400mg bid was gradually adapted (increased or decreased) in a blinded way to reach the entry dose of 400mg/day for the OLE. Participants formed the SS.

A 4-week Taper Period was required for participants who chose not to enroll in the OLE study or who discontinued prior to the end of the 12-week Maintenance Period. Participants initially randomized to placebo group received 5-6 placebo tablets to maintain the blinding and have been gradually tapered off the IMP over a 3-week period followed by 1-week drug-free period.

Afterwards, participants had a Safety Follow-Up visit 30 days after the last IMP intake. Participants formed the Safety Set (SS).

A 4-week Taper Period was required for participants who chose not to enroll in the OLE study or who discontinued prior to the end of the 12-week Maintenance Period. Participants initially randomized to padsevonil 50 mg bid have been gradually tapered off the IMP over a 3-week period followed by 1-week drug-free period. Afterwards, participants had a Safety Follow-Up visit 30 days after the last IMP intake. Participants formed the SS. A 4-week Taper Period was required for participants who chose not to enroll in the OLE study or who discontinued prior to the end of the 12-week Maintenance Period. Participants initially randomized to padsevonil 100 mg bid have been gradually tapered off the IMP over a 3-week period followed by 1-week drug-free period. Afterwards, participants had a Safety Follow-Up visit 30 days after the last IMP intake. Participants formed the SS. A 4-week Taper Period was required for participants who chose not to enroll in the OLE study or who discontinued prior to the end of the 12-week Maintenance Period. Participants initially randomized to padsevonil 200 mg bid have been gradually tapered off the IMP over a 3-week period followed by 1-week drug-free period. Afterwards, participants had a Safety Follow-Up visit 30 days after the last IMP intake. Participants formed the SS. A 4-week Taper Period was required for participants who chose not to enroll in the OLE study or who discontinued prior to the end of the 12-week Maintenance Period. Participants initially randomized to padsevonil 400 mg bid have been gradually tapered off the IMP over a 3-week period followed by 1-week drug-free period. Afterwards, participants had a Safety Follow-Up visit 30 days after the last IMP intake. Participants formed the SS.
All-Cause Mortality
Placebo Treatment Period (SS) Padsevonil 50mg BID Treatment Period (SS) Padsevonil 100mg BID Treatment Period (SS) Padsevonil 200mg BID Treatment Period (SS) Padsevonil 400mg BID Treatment Period (SS) Placebo Conversion Period (SS) Padsevonil 50mg BID Conversion Period (SS) Padsevonil 100mg BID Conversion Period (SS) Padsevonil 200mg BID Conversion Period (SS) Padsevonil 400mg BID Conversion Period (SS) Placebo Taper and SFU Period (SS) Padsevonil 50mg BID Taper and SFU Period (SS) Padsevonil 100mg BID Taper and SFU Period (SS) Padsevonil 200mg BID Taper and SFU Period (SS) Padsevonil 400mg BID Taper and SFU Period (SS)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/83 (0.00%)      0/81 (0.00%)      0/83 (0.00%)      0/82 (0.00%)      0/81 (0.00%)      0/69 (0.00%)      0/64 (0.00%)      0/66 (0.00%)      0/55 (0.00%)      0/57 (0.00%)      0/9 (0.00%)      0/14 (0.00%)      0/11 (0.00%)      0/24 (0.00%)      0/22 (0.00%)    
Hide Serious Adverse Events
Placebo Treatment Period (SS) Padsevonil 50mg BID Treatment Period (SS) Padsevonil 100mg BID Treatment Period (SS) Padsevonil 200mg BID Treatment Period (SS) Padsevonil 400mg BID Treatment Period (SS) Placebo Conversion Period (SS) Padsevonil 50mg BID Conversion Period (SS) Padsevonil 100mg BID Conversion Period (SS) Padsevonil 200mg BID Conversion Period (SS) Padsevonil 400mg BID Conversion Period (SS) Placebo Taper and SFU Period (SS) Padsevonil 50mg BID Taper and SFU Period (SS) Padsevonil 100mg BID Taper and SFU Period (SS) Padsevonil 200mg BID Taper and SFU Period (SS) Padsevonil 400mg BID Taper and SFU Period (SS)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/83 (3.61%)      5/81 (6.17%)      4/83 (4.82%)      3/82 (3.66%)      5/81 (6.17%)      0/69 (0.00%)      0/64 (0.00%)      0/66 (0.00%)      2/55 (3.64%)      0/57 (0.00%)      1/9 (11.11%)      1/14 (7.14%)      0/11 (0.00%)      0/24 (0.00%)      0/22 (0.00%)    
Cardiac disorders                               
Atrial flutter * 1  0/83 (0.00%)  0 1/81 (1.23%)  1 0/83 (0.00%)  0 0/82 (0.00%)  0 0/81 (0.00%)  0 0/69 (0.00%)  0 0/64 (0.00%)  0 0/66 (0.00%)  0 0/55 (0.00%)  0 0/57 (0.00%)  0 0/9 (0.00%)  0 0/14 (0.00%)  0 0/11 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0
Infections and infestations                               
Diverticulitis * 1  0/83 (0.00%)  0 1/81 (1.23%)  1 0/83 (0.00%)  0 0/82 (0.00%)  0 0/81 (0.00%)  0 0/69 (0.00%)  0 0/64 (0.00%)  0 0/66 (0.00%)  0 0/55 (0.00%)  0 0/57 (0.00%)  0 0/9 (0.00%)  0 0/14 (0.00%)  0 0/11 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0
Injury, poisoning and procedural complications                               
Concussion * 1  0/83 (0.00%)  0 0/81 (0.00%)  0 1/83 (1.20%)  1 0/82 (0.00%)  0 0/81 (0.00%)  0 0/69 (0.00%)  0 0/64 (0.00%)  0 0/66 (0.00%)  0 0/55 (0.00%)  0 0/57 (0.00%)  0 0/9 (0.00%)  0 0/14 (0.00%)  0 0/11 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0
Fall * 1  0/83 (0.00%)  0 0/81 (0.00%)  0 0/83 (0.00%)  0 1/82 (1.22%)  1 0/81 (0.00%)  0 0/69 (0.00%)  0 0/64 (0.00%)  0 0/66 (0.00%)  0 0/55 (0.00%)  0 0/57 (0.00%)  0 0/9 (0.00%)  0 0/14 (0.00%)  0 0/11 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0
Head injury * 1  0/83 (0.00%)  0 0/81 (0.00%)  0 1/83 (1.20%)  1 0/82 (0.00%)  0 1/81 (1.23%)  1 0/69 (0.00%)  0 0/64 (0.00%)  0 0/66 (0.00%)  0 0/55 (0.00%)  0 0/57 (0.00%)  0 0/9 (0.00%)  0 1/14 (7.14%)  1 0/11 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0
Toxicity to various agents * 1  0/83 (0.00%)  0 0/81 (0.00%)  0 0/83 (0.00%)  0 1/82 (1.22%)  1 0/81 (0.00%)  0 0/69 (0.00%)  0 0/64 (0.00%)  0 0/66 (0.00%)  0 0/55 (0.00%)  0 0/57 (0.00%)  0 0/9 (0.00%)  0 0/14 (0.00%)  0 0/11 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0
Traumatic haemothorax * 1  1/83 (1.20%)  1 0/81 (0.00%)  0 0/83 (0.00%)  0 0/82 (0.00%)  0 0/81 (0.00%)  0 0/69 (0.00%)  0 0/64 (0.00%)  0 0/66 (0.00%)  0 0/55 (0.00%)  0 0/57 (0.00%)  0 0/9 (0.00%)  0 0/14 (0.00%)  0 0/11 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0
Metabolism and nutrition disorders                               
Hyperkalaemia * 1  0/83 (0.00%)  0 0/81 (0.00%)  0 1/83 (1.20%)  1 0/82 (0.00%)  0 0/81 (0.00%)  0 0/69 (0.00%)  0 0/64 (0.00%)  0 0/66 (0.00%)  0 0/55 (0.00%)  0 0/57 (0.00%)  0 0/9 (0.00%)  0 0/14 (0.00%)  0 0/11 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0
Nervous system disorders                               
Altered state of consciousness * 1  0/83 (0.00%)  0 0/81 (0.00%)  0 0/83 (0.00%)  0 0/82 (0.00%)  0 1/81 (1.23%)  1 0/69 (0.00%)  0 0/64 (0.00%)  0 0/66 (0.00%)  0 0/55 (0.00%)  0 0/57 (0.00%)  0 0/9 (0.00%)  0 0/14 (0.00%)  0 0/11 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0
Encephalopathy * 1  0/83 (0.00%)  0 0/81 (0.00%)  0 0/83 (0.00%)  0 0/82 (0.00%)  0 1/81 (1.23%)  1 0/69 (0.00%)  0 0/64 (0.00%)  0 0/66 (0.00%)  0 0/55 (0.00%)  0 0/57 (0.00%)  0 0/9 (0.00%)  0 0/14 (0.00%)  0 0/11 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0
Focal dyscognitive seizures * 1  0/83 (0.00%)  0 1/81 (1.23%)  1 0/83 (0.00%)  0 0/82 (0.00%)  0 0/81 (0.00%)  0 0/69 (0.00%)  0 0/64 (0.00%)  0 0/66 (0.00%)  0 0/55 (0.00%)  0 0/57 (0.00%)  0 0/9 (0.00%)  0 0/14 (0.00%)  0 0/11 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0
Partial seizures * 1  0/83 (0.00%)  0 1/81 (1.23%)  1 0/83 (0.00%)  0 0/82 (0.00%)  0 0/81 (0.00%)  0 0/69 (0.00%)  0 0/64 (0.00%)  0 0/66 (0.00%)  0 0/55 (0.00%)  0 0/57 (0.00%)  0 0/9 (0.00%)  0 0/14 (0.00%)  0 0/11 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0
Seizure cluster * 1  1/83 (1.20%)  1 0/81 (0.00%)  0 0/83 (0.00%)  0 0/82 (0.00%)  0 0/81 (0.00%)  0 0/69 (0.00%)  0 0/64 (0.00%)  0 0/66 (0.00%)  0 0/55 (0.00%)  0 0/57 (0.00%)  0 0/9 (0.00%)  0 0/14 (0.00%)  0 0/11 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0
Status epilepticus * 1  1/83 (1.20%)  1 1/81 (1.23%)  1 1/83 (1.20%)  1 1/82 (1.22%)  1 1/81 (1.23%)  1 0/69 (0.00%)  0 0/64 (0.00%)  0 0/66 (0.00%)  0 1/55 (1.82%)  1 0/57 (0.00%)  0 0/9 (0.00%)  0 0/14 (0.00%)  0 0/11 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0
Syncope * 1  0/83 (0.00%)  0 0/81 (0.00%)  0 0/83 (0.00%)  0 0/82 (0.00%)  0 1/81 (1.23%)  1 0/69 (0.00%)  0 0/64 (0.00%)  0 0/66 (0.00%)  0 0/55 (0.00%)  0 0/57 (0.00%)  0 0/9 (0.00%)  0 0/14 (0.00%)  0 0/11 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0
Psychiatric disorders                               
Depression * 1  0/83 (0.00%)  0 0/81 (0.00%)  0 0/83 (0.00%)  0 0/82 (0.00%)  0 0/81 (0.00%)  0 0/69 (0.00%)  0 0/64 (0.00%)  0 0/66 (0.00%)  0 1/55 (1.82%)  1 0/57 (0.00%)  0 0/9 (0.00%)  0 0/14 (0.00%)  0 0/11 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0
Acute psychosis * 1  0/83 (0.00%)  0 0/81 (0.00%)  0 0/83 (0.00%)  0 0/82 (0.00%)  0 0/81 (0.00%)  0 0/69 (0.00%)  0 0/64 (0.00%)  0 0/66 (0.00%)  0 0/55 (0.00%)  0 0/57 (0.00%)  0 1/9 (11.11%)  1 0/14 (0.00%)  0 0/11 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0
Renal and urinary disorders                               
Renal disorder * 1  0/83 (0.00%)  0 0/81 (0.00%)  0 1/83 (1.20%)  1 0/82 (0.00%)  0 0/81 (0.00%)  0 0/69 (0.00%)  0 0/64 (0.00%)  0 0/66 (0.00%)  0 0/55 (0.00%)  0 0/57 (0.00%)  0 0/9 (0.00%)  0 0/14 (0.00%)  0 0/11 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0
Respiratory, thoracic and mediastinal disorders                               
Pneumonia aspiration * 1  0/83 (0.00%)  0 0/81 (0.00%)  0 1/83 (1.20%)  1 0/82 (0.00%)  0 0/81 (0.00%)  0 0/69 (0.00%)  0 0/64 (0.00%)  0 0/66 (0.00%)  0 0/55 (0.00%)  0 0/57 (0.00%)  0 0/9 (0.00%)  0 0/14 (0.00%)  0 0/11 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0
Surgical and medical procedures                               
Medical device battery replacement * 1  0/83 (0.00%)  0 0/81 (0.00%)  0 1/83 (1.20%)  1 0/82 (0.00%)  0 1/81 (1.23%)  1 0/69 (0.00%)  0 0/64 (0.00%)  0 0/66 (0.00%)  0 0/55 (0.00%)  0 0/57 (0.00%)  0 0/9 (0.00%)  0 0/14 (0.00%)  0 0/11 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0
1
Term from vocabulary, MedDRA22.1
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Treatment Period (SS) Padsevonil 50mg BID Treatment Period (SS) Padsevonil 100mg BID Treatment Period (SS) Padsevonil 200mg BID Treatment Period (SS) Padsevonil 400mg BID Treatment Period (SS) Placebo Conversion Period (SS) Padsevonil 50mg BID Conversion Period (SS) Padsevonil 100mg BID Conversion Period (SS) Padsevonil 200mg BID Conversion Period (SS) Padsevonil 400mg BID Conversion Period (SS) Placebo Taper and SFU Period (SS) Padsevonil 50mg BID Taper and SFU Period (SS) Padsevonil 100mg BID Taper and SFU Period (SS) Padsevonil 200mg BID Taper and SFU Period (SS) Padsevonil 400mg BID Taper and SFU Period (SS)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   45/83 (54.22%)      54/81 (66.67%)      60/83 (72.29%)      53/82 (64.63%)      65/81 (80.25%)      11/69 (15.94%)      18/64 (28.13%)      10/66 (15.15%)      5/55 (9.09%)      5/57 (8.77%)      3/9 (33.33%)      3/14 (21.43%)      0/11 (0.00%)      3/24 (12.50%)      4/22 (18.18%)    
Ear and labyrinth disorders                               
Vertigo * 1  7/83 (8.43%)  7 3/81 (3.70%)  3 2/83 (2.41%)  2 3/82 (3.66%)  3 4/81 (4.94%)  5 1/69 (1.45%)  1 0/64 (0.00%)  0 0/66 (0.00%)  0 0/55 (0.00%)  0 0/57 (0.00%)  0 0/9 (0.00%)  0 0/14 (0.00%)  0 0/11 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0
Gastrointestinal disorders                               
Nausea * 1  7/83 (8.43%)  7 4/81 (4.94%)  4 7/83 (8.43%)  7 2/82 (2.44%)  3 7/81 (8.64%)  13 1/69 (1.45%)  1 0/64 (0.00%)  0 1/66 (1.52%)  1 0/55 (0.00%)  0 0/57 (0.00%)  0 0/9 (0.00%)  0 0/14 (0.00%)  0 0/11 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0
Diarrhoea * 1  3/83 (3.61%)  3 6/81 (7.41%)  8 3/83 (3.61%)  4 5/82 (6.10%)  7 4/81 (4.94%)  5 1/69 (1.45%)  1 1/64 (1.56%)  1 1/66 (1.52%)  1 0/55 (0.00%)  0 1/57 (1.75%)  1 0/9 (0.00%)  0 0/14 (0.00%)  0 0/11 (0.00%)  0 1/24 (4.17%)  1 0/22 (0.00%)  0
General disorders                               
Fatigue * 1  10/83 (12.05%)  10 20/81 (24.69%)  27 12/83 (14.46%)  17 14/82 (17.07%)  22 20/81 (24.69%)  21 3/69 (4.35%)  3 5/64 (7.81%)  5 2/66 (3.03%)  2 1/55 (1.82%)  1 0/57 (0.00%)  0 0/9 (0.00%)  0 0/14 (0.00%)  0 0/11 (0.00%)  0 1/24 (4.17%)  2 0/22 (0.00%)  0
Gait disturbance * 1  1/83 (1.20%)  1 2/81 (2.47%)  2 0/83 (0.00%)  0 1/82 (1.22%)  1 5/81 (6.17%)  5 0/69 (0.00%)  0 0/64 (0.00%)  0 0/66 (0.00%)  0 0/55 (0.00%)  0 0/57 (0.00%)  0 0/9 (0.00%)  0 0/14 (0.00%)  0 0/11 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0
Infections and infestations                               
Nasopharyngitis * 1  5/83 (6.02%)  5 5/81 (6.17%)  5 9/83 (10.84%)  13 7/82 (8.54%)  11 5/81 (6.17%)  5 1/69 (1.45%)  1 1/64 (1.56%)  1 0/66 (0.00%)  0 1/55 (1.82%)  1 0/57 (0.00%)  0 0/9 (0.00%)  0 0/14 (0.00%)  0 0/11 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0
Upper respiratory tract infection * 1  1/83 (1.20%)  3 5/81 (6.17%)  5 0/83 (0.00%)  0 0/82 (0.00%)  0 2/81 (2.47%)  3 0/69 (0.00%)  0 1/64 (1.56%)  1 0/66 (0.00%)  0 0/55 (0.00%)  0 0/57 (0.00%)  0 0/9 (0.00%)  0 1/14 (7.14%)  1 0/11 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0
Urinary tract infection * 1  2/83 (2.41%)  2 1/81 (1.23%)  1 1/83 (1.20%)  1 0/82 (0.00%)  0 2/81 (2.47%)  2 1/69 (1.45%)  1 0/64 (0.00%)  0 1/66 (1.52%)  1 0/55 (0.00%)  0 0/57 (0.00%)  0 1/9 (11.11%)  1 0/14 (0.00%)  0 0/11 (0.00%)  0 0/24 (0.00%)  0 1/22 (4.55%)  1
Injury, poisoning and procedural complications                               
Fall * 1  4/83 (4.82%)  4 2/81 (2.47%)  2 1/83 (1.20%)  1 1/82 (1.22%)  2 7/81 (8.64%)  7 0/69 (0.00%)  0 0/64 (0.00%)  0 1/66 (1.52%)  2 1/55 (1.82%)  1 0/57 (0.00%)  0 0/9 (0.00%)  0 0/14 (0.00%)  0 0/11 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0
Ligament sprain * 1  0/83 (0.00%)  0 2/81 (2.47%)  2 0/83 (0.00%)  0 0/82 (0.00%)  0 0/81 (0.00%)  0 0/69 (0.00%)  0 2/64 (3.13%)  2 0/66 (0.00%)  0 0/55 (0.00%)  0 0/57 (0.00%)  0 1/9 (11.11%)  1 0/14 (0.00%)  0 0/11 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0
Burns second degree * 1  0/83 (0.00%)  0 0/81 (0.00%)  0 0/83 (0.00%)  0 0/82 (0.00%)  0 0/81 (0.00%)  0 0/69 (0.00%)  0 0/64 (0.00%)  0 0/66 (0.00%)  0 0/55 (0.00%)  0 0/57 (0.00%)  0 0/9 (0.00%)  0 1/14 (7.14%)  1 0/11 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0
Investigations                               
Platelet count decreased * 1  0/83 (0.00%)  0 0/81 (0.00%)  0 1/83 (1.20%)  1 0/82 (0.00%)  0 0/81 (0.00%)  0 0/69 (0.00%)  0 0/64 (0.00%)  0 0/66 (0.00%)  0 0/55 (0.00%)  0 0/57 (0.00%)  0 1/9 (11.11%)  1 0/14 (0.00%)  0 0/11 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0
Anticonvulsant drug level increased * 1  0/83 (0.00%)  0 0/81 (0.00%)  0 0/83 (0.00%)  0 0/82 (0.00%)  0 0/81 (0.00%)  0 0/69 (0.00%)  0 0/64 (0.00%)  0 0/66 (0.00%)  0 0/55 (0.00%)  0 0/57 (0.00%)  0 1/9 (11.11%)  1 0/14 (0.00%)  0 0/11 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0
Musculoskeletal and connective tissue disorders                               
Back pain * 1  0/83 (0.00%)  0 1/81 (1.23%)  1 2/83 (2.41%)  2 2/82 (2.44%)  2 5/81 (6.17%)  5 0/69 (0.00%)  0 0/64 (0.00%)  0 0/66 (0.00%)  0 0/55 (0.00%)  0 0/57 (0.00%)  0 1/9 (11.11%)  1 0/14 (0.00%)  0 0/11 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0
Nervous system disorders                               
Dizziness * 1  9/83 (10.84%)  9 18/81 (22.22%)  19 23/83 (27.71%)  31 19/82 (23.17%)  25 28/81 (34.57%)  55 3/69 (4.35%)  3 2/64 (3.13%)  2 1/66 (1.52%)  1 2/55 (3.64%)  2 2/57 (3.51%)  6 0/9 (0.00%)  0 0/14 (0.00%)  0 0/11 (0.00%)  0 1/24 (4.17%)  1 1/22 (4.55%)  1
Somnolence * 1  10/83 (12.05%)  11 19/81 (23.46%)  24 24/83 (28.92%)  29 25/82 (30.49%)  26 30/81 (37.04%)  35 1/69 (1.45%)  1 4/64 (6.25%)  5 1/66 (1.52%)  1 1/55 (1.82%)  1 2/57 (3.51%)  2 0/9 (0.00%)  0 0/14 (0.00%)  0 0/11 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0
Headache * 1  10/83 (12.05%)  14 17/81 (20.99%)  29 9/83 (10.84%)  16 15/82 (18.29%)  21 9/81 (11.11%)  31 0/69 (0.00%)  0 3/64 (4.69%)  3 2/66 (3.03%)  3 0/55 (0.00%)  0 1/57 (1.75%)  5 1/9 (11.11%)  1 0/14 (0.00%)  0 0/11 (0.00%)  0 2/24 (8.33%)  2 1/22 (4.55%)  1
Memory impairment * 1  1/83 (1.20%)  1 3/81 (3.70%)  3 1/83 (1.20%)  1 8/82 (9.76%)  9 14/81 (17.28%)  14 1/69 (1.45%)  1 0/64 (0.00%)  0 1/66 (1.52%)  1 0/55 (0.00%)  0 0/57 (0.00%)  0 0/9 (0.00%)  0 0/14 (0.00%)  0 0/11 (0.00%)  0 0/24 (0.00%)  0 1/22 (4.55%)  1
Tremor * 1  0/83 (0.00%)  0 5/81 (6.17%)  5 2/83 (2.41%)  2 6/82 (7.32%)  6 5/81 (6.17%)  5 1/69 (1.45%)  1 0/64 (0.00%)  0 0/66 (0.00%)  0 0/55 (0.00%)  0 0/57 (0.00%)  0 0/9 (0.00%)  0 0/14 (0.00%)  0 0/11 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0
Balance disorder * 1  1/83 (1.20%)  2 3/81 (3.70%)  3 3/83 (3.61%)  3 5/82 (6.10%)  5 3/81 (3.70%)  3 0/69 (0.00%)  0 0/64 (0.00%)  0 0/66 (0.00%)  0 0/55 (0.00%)  0 0/57 (0.00%)  0 0/9 (0.00%)  0 0/14 (0.00%)  0 0/11 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0
Nystagmus * 1  0/83 (0.00%)  0 0/81 (0.00%)  0 0/83 (0.00%)  0 0/82 (0.00%)  0 0/81 (0.00%)  0 1/69 (1.45%)  1 0/64 (0.00%)  0 0/66 (0.00%)  0 0/55 (0.00%)  0 0/57 (0.00%)  0 0/9 (0.00%)  0 1/14 (7.14%)  1 0/11 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0
Psychiatric disorders                               
Irritability * 1  8/83 (9.64%)  8 4/81 (4.94%)  4 7/83 (8.43%)  7 1/82 (1.22%)  1 5/81 (6.17%)  6 0/69 (0.00%)  0 1/64 (1.56%)  1 1/66 (1.52%)  1 0/55 (0.00%)  0 0/57 (0.00%)  0 0/9 (0.00%)  0 0/14 (0.00%)  0 0/11 (0.00%)  0 0/24 (0.00%)  0 1/22 (4.55%)  1
Anxiety * 1  3/83 (3.61%)  3 1/81 (1.23%)  1 1/83 (1.20%)  2 7/82 (8.54%)  9 0/81 (0.00%)  0 1/69 (1.45%)  1 0/64 (0.00%)  0 0/66 (0.00%)  0 0/55 (0.00%)  0 0/57 (0.00%)  0 0/9 (0.00%)  0 0/14 (0.00%)  0 0/11 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0
Paranoia * 1  0/83 (0.00%)  0 0/81 (0.00%)  0 0/83 (0.00%)  0 0/82 (0.00%)  0 0/81 (0.00%)  0 0/69 (0.00%)  0 0/64 (0.00%)  0 0/66 (0.00%)  0 0/55 (0.00%)  0 0/57 (0.00%)  0 0/9 (0.00%)  0 1/14 (7.14%)  1 0/11 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0
1
Term from vocabulary, MedDRA22.1
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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: UCB
Organization: Cares
Phone: +1844 599 ext 2273
EMail: UCBCares@ucb.com
Layout table for additonal information
Responsible Party: UCB Pharma ( UCB Biopharma S.P.R.L. )
ClinicalTrials.gov Identifier: NCT03373383    
Other Study ID Numbers: EP0091
2017-003200-48 ( EudraCT Number )
First Submitted: December 7, 2017
First Posted: December 14, 2017
Results First Submitted: January 28, 2021
Results First Posted: April 9, 2021
Last Update Posted: April 9, 2021