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A Double-Blind, Randomized, Placebo-Controlled, Phase 2 Trial of YKP3089 as Adjunctive Therapy in Subjects With 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: NCT01866111
Recruitment Status : Completed
First Posted : May 31, 2013
Results First Posted : April 29, 2022
Last Update Posted : April 29, 2022
Sponsor:
Information provided by (Responsible Party):
SK Life Science, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Partial Epilepsy
Interventions Drug: YKP3089
Drug: Placebo
Enrollment 437
Recruitment Details  
Pre-assignment Details 533 subjects were screened and 96 were excluded for the following reasons: did not meet eligibility criteria (n=83) and withdrew consent (n=13).
Arm/Group Title Placebo Cenobamate 100 mg/Day Cenobamate 200 mg/Day Cenobamate 400 mg/Day
Hide Arm/Group Description Subjects treated with identical appearing study drug. Subjects titrated to a target dose of 100 mg/day Subjects titrated to a target dose of 200 mg/day Subjects titrated to a target dose of 400 mg/day
Period Title: Double-blind Period of Study YKP3089C017
Started 108 108 110 111
Completed 94 95 90 81
Not Completed 14 13 20 30
Reason Not Completed
Not all subjects from double-blind rolled over to open-label             14             13             20             30
Period Title: Open-label Extension Study YKP3089C017
Started [1] 91 [2] 95 90 80 [2]
Completed [3] 26 28 27 28
Not Completed 65 67 63 52
Reason Not Completed
Not all subjects completed open-label             65             67             63             52
[1]
Study is ongoing
[2]
Not all patients from double-blind rolled over to open-label
[3]
OLE terminated in US
Arm/Group Title Placebo Cenobamate 100 mg/Day Cenobamate 200 mg/Day Cenobamate 400 mg/Day Total
Hide Arm/Group Description Subjects treated with identical appearing study drug. Subjects titrated to a target dose of 100 mg/day Subjects titrated to a target dose of 200 mg/day Subjects titrated to a target dose of 400 mg/day Total of all reporting groups
Overall Number of Baseline Participants 108 108 110 111 437
Hide Baseline Analysis Population Description
Overall number of baseline participants includes all randomized pts, 437. Baseline analysis population includes all randomized pts who took at least 1 dose of study drug with any post-baseline seizure data (434): Pbo (n=106), Cnb: 100mg (n=108), 200mg (n=109), 400mg (n=111). Baseline seizure frequency and enrollment region used analysis population.
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 108 participants 108 participants 110 participants 111 participants 437 participants
38
(19 to 70)
37.5
(19 to 66)
40.5
(19 to 69)
38.0
(21 to 66)
38
(19 to 70)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 108 participants 108 participants 110 participants 111 participants 437 participants
Female
50
  46.3%
51
  47.2%
56
  50.9%
59
  53.2%
216
  49.4%
Male
58
  53.7%
57
  52.8%
54
  49.1%
52
  46.8%
221
  50.6%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 108 participants 108 participants 110 participants 111 participants 437 participants
Hispanic or Latino
9
   8.3%
8
   7.4%
7
   6.4%
13
  11.7%
37
   8.5%
Not Hispanic or Latino
99
  91.7%
100
  92.6%
103
  93.6%
98
  88.3%
400
  91.5%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 108 participants 108 participants 110 participants 111 participants 437 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
9
   8.3%
10
   9.3%
11
  10.0%
11
   9.9%
41
   9.4%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
4
   3.7%
4
   3.7%
3
   2.7%
1
   0.9%
12
   2.7%
White
93
  86.1%
89
  82.4%
94
  85.5%
96
  86.5%
372
  85.1%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
2
   1.9%
5
   4.6%
2
   1.8%
3
   2.7%
12
   2.7%
28-day partial-onset seizure frequency   [1] [2] 
Median (Full Range)
Unit of measure:  Seizures/28 days
Number Analyzed 106 participants 108 participants 109 participants 111 participants 434 participants
8.4
(4 to 704)
9.5
(3.5 to 202)
11.0
(4 to 418)
9.0
(4 to 638)
9.4
(3.5 to 704)
[1]
Measure Description: Baseline measures were reported in the randomized population, with the exception of baseline seizure frequency/28 days, which was reported for all randomized subjects who took at least one dose of study drug and had any post-baseline seizure data.
[2]
Measure Analysis Population Description: Baseline seizure frequency was analyzed
1.Primary Outcome
Title Percent Change From Baseline in Partial-onset Seizure Frequency Per 28 Days
Hide Description Percent change in complex partial and/or secondarily generalized and/or simple partial motor seizure frequency per 28 days (average 28-day seizure rate) in each treatment group during the double-blind period relative to the pretreatment baseline.
Time Frame baseline and 18 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomly assigned patients who took at least one dose of study drug and had any post-baseline seizure data.
Arm/Group Title Placebo Cenobamate 100 mg/Day Cenobamate 200 mg/Day Cenobamate 400 mg/Day
Hide Arm/Group Description:
Subjects treated with identical appearing study drug.
Subjects titrated to a target dose of 100 mg/day
Subjects titrated to a target dose of 200 mg/day
Subjects titrated to a target dose of 400 mg/day
Overall Number of Participants Analyzed 106 108 109 111
Median (Full Range)
Unit of Measure: percent change
-24.0
(-91 to 198)
-35.5
(-100 to 206)
-55.0
(-100 to 191)
-55.0
(-100 to 167)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Cenobamate 200 mg/Day
Comments A step down procedure was used for the primary efficacy analyses to ensure the type one error rate for multiple comparisons was controlled at the 5% level using the following hierarchy: 200 mg vs placebo, 400 mg vs placebo, 100 mg vs placebo, in which a statistically significant difference had to be detected in this order for each subsequent comparison to occur.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Cenobamate 400 mg/Day
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Cenobamate 100 mg/Day
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.007
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
2.Secondary Outcome
Title 50% Responder Rate
Hide Description Percentage of patients achieving a 50% or more reduction from baseline in partial seizure frequency during the double-blind treatment period
Time Frame 18 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomly assigned patients who had taken at least one dose of study drug and had any post-baseline seizure data
Arm/Group Title Placebo Cenobamate 100 mg/Day Cenobamate 200 mg/Day Cenobamate 400 mg/Day
Hide Arm/Group Description:
Subjects treated with identical appearing study drug.
Subjects titrated to a target dose of 100 mg/day
Subjects titrated to a target dose of 200 mg/day
Subjects titrated to a target dose of 400 mg/day
Overall Number of Participants Analyzed 106 108 109 111
Measure Type: Count of Participants
Unit of Measure: Participants
23
  21.7%
44
  40.7%
63
  57.8%
67
  60.4%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Cenobamate 200 mg/Day
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Cenobamate 400 mg/Day
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Cenobamate 100 mg/Day
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Time Frame 18 weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo Cenobamate 100 mg/Day Cenobamate 200 mg/Day Cenobamate 400 mg/Day
Hide Arm/Group Description Subjects treated with identical appearing study drug. Subjects titrated to a target dose of 100 mg/day Subjects titrated to a target dose of 200 mg/day Subjects titrated to a target dose of 400 mg/day
All-Cause Mortality
Placebo Cenobamate 100 mg/Day Cenobamate 200 mg/Day Cenobamate 400 mg/Day
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/108 (0.00%)      0/108 (0.00%)      0/110 (0.00%)      0/111 (0.00%)    
Hide Serious Adverse Events
Placebo Cenobamate 100 mg/Day Cenobamate 200 mg/Day Cenobamate 400 mg/Day
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/108 (5.56%)      10/108 (9.26%)      4/110 (3.64%)      8/111 (7.21%)    
Ear and labyrinth disorders         
Vertigo * 1  0/108 (0.00%)  0/108 (0.00%)  0/110 (0.00%)  1/111 (0.90%) 
Gastrointestinal disorders         
Gastrooesophageal reflux disease * 1  1/108 (0.93%)  0/108 (0.00%)  0/110 (0.00%)  0/111 (0.00%) 
General disorders         
Chest pain * 1  0/108 (0.00%)  1/108 (0.93%)  0/110 (0.00%)  0/111 (0.00%) 
Infections and infestations         
Abscess jaw * 1  1/108 (0.93%)  0/108 (0.00%)  0/110 (0.00%)  0/111 (0.00%) 
Infectious colitis * 1  1/108 (0.93%)  0/108 (0.00%)  0/110 (0.00%)  0/111 (0.00%) 
Injury, poisoning and procedural complications         
Fall * 1  0/108 (0.00%)  0/108 (0.00%)  1/110 (0.91%)  1/111 (0.90%) 
Concussion * 1  1/108 (0.93%)  0/108 (0.00%)  0/110 (0.00%)  0/111 (0.00%) 
Facial bones fracture * 1  0/108 (0.00%)  0/108 (0.00%)  0/110 (0.00%)  1/111 (0.90%) 
Femur fracture * 1  0/108 (0.00%)  0/108 (0.00%)  1/110 (0.91%)  0/111 (0.00%) 
Hand fracture * 1  0/108 (0.00%)  1/108 (0.93%)  0/110 (0.00%)  0 0/111 (0.00%) 
Jaw fracture * 1  1/108 (0.93%)  0/108 (0.00%)  0/110 (0.00%)  0/111 (0.00%) 
Laceration * 1  0/108 (0.00%)  1/108 (0.93%)  0/110 (0.00%)  0/111 (0.00%) 
Limb injury * 1  0/108 (0.00%)  1/108 (0.93%)  0/110 (0.00%)  0/111 (0.00%) 
Thermal burn * 1  0/108 (0.00%)  1/108 (0.93%)  0/110 (0.00%)  0/111 (0.00%) 
Investigations         
ALT increased * 1  0/108 (0.00%)  0/108 (0.00%)  0/110 (0.00%)  1/111 (0.90%) 
AST increased * 1  0/108 (0.00%)  0/108 (0.00%)  0/110 (0.00%)  1/111 (0.90%) 
Immunoglobulins decreased * 1  0/108 (0.00%)  0/108 (0.00%)  0/110 (0.00%)  1/111 (0.90%) 
Nervous system disorders         
Seizure * 1  0/108 (0.00%)  2/108 (1.85%)  1/110 (0.91%)  1/111 (0.90%) 
Ataxia * 1  0/108 (0.00%)  0/108 (0.00%)  0/110 (0.00%)  2/111 (1.80%) 
Dizziness * 1  0/108 (0.00%)  0/108 (0.00%)  0/110 (0.00%)  2/111 (1.80%) 
Nystagmus * 1  0/108 (0.00%)  0/108 (0.00%)  0/110 (0.00%)  2/111 (1.80%) 
Hemiparesis * 1  0/108 (0.00%)  1/108 (0.93%)  0/110 (0.00%)  0/111 (0.00%) 
Lethargy * 1  0/108 (0.00%)  1/108 (0.93%)  0/110 (0.00%)  0/111 (0.00%) 
Somnolence * 1  0/108 (0.00%)  0/108 (0.00%)  0/110 (0.00%)  1/111 (0.90%) 
Status epilepticus * 1  1/108 (0.93%)  0/108 (0.00%)  0/110 (0.00%)  0/111 (0.00%) 
Psychiatric disorders         
Suicidal ideation * 1  0/108 (0.00%)  2/108 (1.85%)  0/110 (0.00%)  0/111 (0.00%) 
Suicide attempt * 1  0/108 (0.00%)  1/108 (0.93%)  0/110 (0.00%)  0/111 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Pulmonary embolism * 1  0/108 (0.00%)  1/108 (0.93%)  0/110 (0.00%)  0/111 (0.00%) 
Skin and subcutaneous tissue disorders         
DRESS * 1  0/108 (0.00%)  0/108 (0.00%)  1/110 (0.91%)  0/111 (0.00%) 
1
Term from vocabulary, MedDRA (18.1)
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 4%
Placebo Cenobamate 100 mg/Day Cenobamate 200 mg/Day Cenobamate 400 mg/Day
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   76/108 (70.37%)      70/108 (64.81%)      84/110 (76.36%)      100/111 (90.09%)    
Ear and labyrinth disorders         
Vertigo * 1  3/108 (2.78%)  1/108 (0.93%)  3/110 (2.73%)  6/111 (5.41%) 
Eye disorders         
Diplopia * 1  2/108 (1.85%)  8/108 (7.41%)  11/110 (10.00%)  17/111 (15.32%) 
Gastrointestinal disorders         
Constipation * 1  1/108 (0.93%)  2/108 (1.85%)  3/110 (2.73%)  10/111 (9.01%) 
Nausea * 1  1/108 (0.93%)  7/108 (6.48%)  1/110 (0.91%)  10/111 (9.01%) 
Vomiting * 1  0/108 (0.00%)  2/108 (1.85%)  3/110 (2.73%)  6/111 (5.41%) 
Diarrhea * 1  1/108 (0.93%)  1/108 (0.93%)  1/110 (0.91%)  5/111 (4.50%) 
General disorders         
Fatigue * 1  9/108 (8.33%)  13/108 (12.04%)  19/110 (17.27%)  27/111 (24.32%) 
Gait disturbance * 1  3/108 (2.78%)  1/108 (0.93%)  6/110 (5.45%)  9/111 (8.11%) 
Infections and infestations         
Upper respiratory tract infection * 1  6/108 (5.56%)  3/108 (2.78%)  4/110 (3.64%)  3/111 (2.70%) 
Nasopharyngitis * 1  5/108 (4.63%)  2/108 (1.85%)  2/110 (1.82%)  5/111 (4.50%) 
Injury, poisoning and procedural complications         
Fall * 1  6/108 (5.56%)  2/108 (1.85%)  4/110 (3.64%)  4/111 (3.60%) 
Laceration * 1  5/108 (4.63%)  1/108 (0.93%)  1/110 (0.91%)  1/111 (0.90%) 
Metabolism and nutrition disorders         
Decreased appetite * 1  1/108 (0.93%)  3/108 (2.78%)  1/110 (0.91%)  6/111 (5.41%) 
Musculoskeletal and connective tissue disorders         
Back pain * 1  3/108 (2.78%)  4/108 (3.70%)  1/110 (0.91%)  6/111 (5.41%) 
Nervous system disorders         
Somnolence * 1  9/108 (8.33%)  20/108 (18.52%)  23/110 (20.91%)  41/111 (36.94%) 
Dizziness * 1  15/108 (13.89%)  19/108 (17.59%)  22/110 (20.00%)  37/111 (33.33%) 
Headache * 1  6/108 (5.56%)  11/108 (10.19%)  12/110 (10.91%)  12/111 (10.81%) 
Balance disorder * 1  0/108 (0.00%)  3/108 (2.78%)  2/110 (1.82%)  10/111 (9.01%) 
Nystagmus * 1  1/108 (0.93%)  3/108 (2.78%)  4/110 (3.64%)  7/111 (6.31%) 
Ataxia * 1  1/108 (0.93%)  2/108 (1.85%)  4/110 (3.64%)  7/111 (6.31%) 
Dysarthria * 1  0/108 (0.00%)  2/108 (1.85%)  3/110 (2.73%)  7/111 (6.31%) 
1
Term from vocabulary, MedDRA (18.1)
*
Indicates events were collected by non-systematic assessment
[Not Specified]
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: Chief Medical Officer
Organization: SK Life Science
Phone: 201-421-3830
EMail: mkamin@sklsi.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: SK Life Science, Inc.
ClinicalTrials.gov Identifier: NCT01866111    
Other Study ID Numbers: YKP3089C017
First Submitted: May 28, 2013
First Posted: May 31, 2013
Results First Submitted: August 20, 2020
Results First Posted: April 29, 2022
Last Update Posted: April 29, 2022