Efficacy and Safety of YKP3089 in Subjects With Treatment Resistant Partial Onset Seizures

• ClinicalTrials.gov Identifier: NCT01397968
• Recruitment Status: Completed
• First Posted: July 20, 2011
• Results First Posted: April 11, 2022
• Last Update Posted: April 11, 2022
• Sponsor: SK Life Science, Inc.
• Information provided by (Responsible Party): SK Life Science, Inc.

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Partial Epilepsy
• Interventions: Drug: YKP3089; Drug: Placebo
• Enrollment: 222

Participant Flow

Recruitment Details	Enrollment occurred in 4 countries (United States, Poland, Korea, India) between 06 July 2011 and 15 June 2013 when the last subject completed the double-blind period.
Pre-assignment Details	There were 285 patients screened; 63 were excluded before assignment to study group for reasons as follows: inclusion/exclusion criteria, withdrew by patient, other, lost to follow-up.

Arm/Group Title	YKP3089	Placebo
Arm/Group Description	YKP3089: Capsule, dose to be titrated to a target dose of 200mg/day	Placebo: capsule, dose to be titrated to a target dose of 200mg/day
Period Title: Double-blind Period of Study YKP3089C013
Started	113	109
Completed	102	99
Not Completed	11	10
Period Title: Open-label Extension Study YKP3089C013
Started [1]	76 [2]	73 [2]
Completed	40	37
Not Completed	36	36
[1] Not all subjects moved from double-blind to open-label extension.; [2] Not all subjects from double-blind rolled over to open-label.

Baseline Characteristics

Arm/Group Title		YKP3089	Placebo	Total
Arm/Group Description		YKP3089: Capsule, dose to be titrated to a target dose of 200mg/day	Placebo: capsule, dose to be titrated to a target dose of 200mg/day	Total of all reporting groups
Overall Number of Baseline Participants		113	109	222
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Median (Full Range); Unit of measure: Years
	Number Analyzed	113 participants	109 participants	222 participants
		36; (18 to 61)	38; (18 to 59)	37; (18 to 61)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	113 participants	109 participants	222 participants
	Female	58 51.3%	51 46.8%	109 49.1%
	Male	55 48.7%	58 53.2%	113 50.9%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	113 participants	109 participants	222 participants
	Hispanic or Latino	4 3.5%	3 2.8%	7 3.2%
	Not Hispanic or Latino	105 92.9%	101 92.7%	206 92.8%
	Unknown or Not Reported	4 3.5%	5 4.6%	9 4.1%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	113 participants	109 participants	222 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	49 43.4%	45 41.3%	94 42.3%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	3 2.7%	2 1.8%	5 2.3%
	White	57 50.4%	58 53.2%	115 51.8%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	4 3.5%	4 3.7%	8 3.6%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants	Number Analyzed	113 participants	109 participants	222 participants
South Korea		22	19	41
United States		43	43	86
Poland		22	22	44
India		26	25	51
28-day partial-onset seizure frequency; Median (Full Range); Unit of measure: Seizures/28 days
	Number Analyzed	113 participants	109 participants	222 participants
		7.5; (0 to 187)	5.5; (2 to 237)	6.5; (0 to 237)

Outcome Measures

1. Primary Outcome

Title	Percent Change From Baseline in Partial-onset Seizure Frequency Per 28 Days
Description	Percent change in 28-day frequency of simple partial motor, and/or complex partial, and/or secondarily generalized tonic-clonic seizures during the 12 week treatment period relative to baseline
Time Frame	assessed per 28 days during 12 week period; change from baseline and 12 weeks reported

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	YKP3089	Placebo
Arm/Group Description:	YKP3089: Capsule, dose to be titrated Tablet, dose to be titrated	Placebo: Placebo capsule Placebo tablet
Overall Number of Participants Analyzed	113	108
Median (Full Range); Unit of Measure: percent seizure reduction
	55.6; (-417.3 to 100.0)	21.5; (-588.0 to 100.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	YKP3089, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Wilcoxon rank sum
	Comments	[Not Specified]

2. Secondary Outcome

Title	50% Responder Rate
Description	Greater than or equal to 50% reduction in 28-day frequency of simple partial motor, and/or complex partial, and/or secondarily generalized tonic-clonic seizures during the 12 week treatment period relative to baseline.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	YKP3089	Placebo
Arm/Group Description:	YKP3089: Capsule, dose to be titrated to a target dose of 200mg/day	Placebo: capsule, dose to be titrated to a target dose of 200mg/day
Overall Number of Participants Analyzed	113	108
Measure Type: Count of Participants; Unit of Measure: Participants
	57 50.4%	24 22.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	YKP3089, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]

Adverse Events

Time Frame	12 week double-blind treatment period plus taper period (2-3 weeks)
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	YKP3089	Placebo
Arm/Group Description	YKP3089: Capsule, dose to be titrated to a target dose of 200mg/day	Placebo: capsule, dose to be titrated to a target dose of 200mg/day
All-Cause Mortality
	YKP3089	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/113 (0.00%)	0/109 (0.00%)
Serious Adverse Events
	YKP3089	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	3/113 (2.65%)	4/109 (3.67%)
Immune system disorders
Drug hypersensitivity reaction * 1	1/113 (0.88%)	0/109 (0.00%)
Infections and infestations
Urinary tract infection * 1	1/113 (0.88%)	0/109 (0.00%)
Investigations
Arteriogram coronary normal * 1	0/113 (0.00%)	1/109 (0.92%)
Nervous system disorders
Status epilepticus * 1	1/113 (0.88%)	2/109 (1.83%)
Convulsion * 1	0/113 (0.00%)	1/109 (0.92%)
1 Term from vocabulary, MedDRA (16.0); * Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	YKP3089	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	86/113 (76.11%)	69/109 (63.30%)
Gastrointestinal disorders
Nausea * 1	13/113 (11.50%)	5/109 (4.59%)
Constipation * 1	6/113 (5.31%)	0/109 (0.00%)
Diarrhea * 1	6/113 (5.31%)	0/109 (0.00%)
Vomiting * 1	6/113 (5.31%)	2/109 (1.83%)
General disorders
Fatigue * 1	12/113 (10.62%)	7/109 (6.42%)
Infections and infestations
Urinary tract infection * 1	9/113 (7.96%)	2/109 (1.83%)
Upper respiratory tract infection * 1	8/113 (7.08%)	5/109 (4.59%)
Nasopharyngitis * 1	7/113 (6.19%)	1/109 (0.92%)
Nervous system disorders
Somnolence * 1	25/113 (22.12%)	13/109 (11.93%)
Dizziness * 1	25/113 (22.12%)	18/109 (16.51%)
Headache * 1	14/113 (12.39%)	14/109 (12.84%)
Nystagmus * 1	11/113 (9.73%)	0/109 (0.00%)
Balance disorder * 1	9/113 (7.96%)	1/109 (0.92%)
Tremor * 1	7/113 (6.19%)	3/109 (2.75%)
Psychiatric disorders
Anxiety * 1	1/113 (0.88%)	6/109 (5.50%)
1 Term from vocabulary, MedDRA (16.0); * Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

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

• 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):

French JA, Chung SS, Krauss GL, Lee SK, Maciejowski M, Rosenfeld WE, Sperling MR, Kamin M. Long-term safety of adjunctive cenobamate in patients with uncontrolled focal seizures: Open-label extension of a randomized clinical study. Epilepsia. 2021 Sep;62(9):2142-2150. doi: 10.1111/epi.17007. Epub 2021 Jul 13.

Chung SS, French JA, Kowalski J, Krauss GL, Lee SK, Maciejowski M, Rosenfeld WE, Sperling MR, Mizne S, Kamin M. Randomized phase 2 study of adjunctive cenobamate in patients with uncontrolled focal seizures. Neurology. 2020 Jun 2;94(22):e2311-e2322. doi: 10.1212/WNL.0000000000009530. Epub 2020 May 14.

Bialer M, Johannessen SI, Levy RH, Perucca E, Tomson T, White HS. Progress report on new antiepileptic drugs: a summary of the Eleventh Eilat Conference (EILAT XI). Epilepsy Res. 2013 Jan;103(1):2-30. doi: 10.1016/j.eplepsyres.2012.10.001. Epub 2012 Dec 4.

• Responsible Party: SK Life Science, Inc.
• ClinicalTrials.gov Identifier: NCT01397968
• Other Study ID Numbers: YKP3089C013
• First Submitted: July 18, 2011
• First Posted: July 20, 2011
• Results First Submitted: August 20, 2020
• Results First Posted: April 11, 2022
• Last Update Posted: April 11, 2022