Partial Epilepsy
Conditions
Keywords
partial onset seizures, treatment resistant, partial epilepsy
Brief summary
This study is to evaluate the efficacy of YKP3089 in reducing seizure frequency when compared to baseline in subjects with partial onset seizures not fully controlled despite their treatment with 1 to 3 concomitant anti-epileptic drugs. Also to evaluate the safety and tolerability of YKP3089.
Interventions
DRUGYKP3089
Capsule, dose to be titrated Tablet, dose to be titrated
DRUGPlacebo
Placebo capsule Placebo tablet
Sponsors
SK Life Science, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of treatment resistant partial epilepsy; * History of epilepsy for at least 2 years; * Have at least 3 simple partial with motor component, complex partial or secondarily generalized seizures per month with no consecutive 21 day seizure free period. * Currently treated on a stable dose of : * 1 - 3 AED's for at least 12 weeks prior to randomization. * VNS will not be counted as AED; however the parameters must remain stable for at least 4 weeks prior to baseline. * Benzodiazepines taken at least once per week for epilepsy, or for anxiety or sleep disorder, will be counted as 1 AED. Therefore only a maximum of two additional approved AEDs will be allowed.
Exclusion criteria
1. A history of alcoholism, drug abuse, or drug addiction within the past 2 years. 2. Subject has had status epilepticus within past 1 year. 3. Subject has had greater than 2 allergic reactions to an AED or one serious hypersensitivity reaction to an AED. 4. Subjects taking felbamate with less than 18 months continuous exposure. 5. Subjects receiving phenytoin, phenobarbitone or metabolites of these drugs. 6. No active suicidal plan/intent or active suicidal thoughts in the past 6 months. 7. History of suicide attempt in the last 2 years; not more than 1 lifetime suicide attempt. 8. Subject meets criteria for current major depressive episode (within 6 months). 9. Use of intermittent rescue benzodiazepines more than once/month (1-2 doses in a 24-hour period is considered one rescue) in the one month period prior to Visit 1.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Partial-onset Seizure Frequency Per 28 Days | assessed per 28 days during 12 week period; change from baseline and 12 weeks reported | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 50% Responder Rate | 12 weeks | 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. |
Countries
India, Poland, South Korea, United States
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.
Participants by arm
| Arm | Count |
|---|---|
| YKP3089 YKP3089: Capsule, dose to be titrated to a target dose of 200mg/day | 113 |
| Placebo Placebo: capsule, dose to be titrated to a target dose of 200mg/day | 109 |
| Total | 222 |
Baseline characteristics
| Characteristic | Total | Placebo | YKP3089 |
|---|---|---|---|
| 28-day partial-onset seizure frequency | 6.5 seizures/28 days | 5.5 seizures/28 days | 7.5 seizures/28 days |
| Age, Continuous | 37 Years | 38 Years | 36 Years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 3 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 206 Participants | 101 Participants | 105 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 9 Participants | 5 Participants | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 94 Participants | 45 Participants | 49 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 8 Participants | 4 Participants | 4 Participants |
| Race (NIH/OMB) White | 115 Participants | 58 Participants | 57 Participants |
| Region of Enrollment India | 51 participants | 25 participants | 26 participants |
| Region of Enrollment Poland | 44 participants | 22 participants | 22 participants |
| Region of Enrollment South Korea | 41 participants | 19 participants | 22 participants |
| Region of Enrollment United States | 86 participants | 43 participants | 43 participants |
| Sex: Female, Male Female | 109 Participants | 51 Participants | 58 Participants |
| Sex: Female, Male Male | 113 Participants | 58 Participants | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 113 | 0 / 109 |
| other Total, other adverse events | 86 / 113 | 69 / 109 |
| serious Total, serious adverse events | 3 / 113 | 4 / 109 |
Outcome results
Primary
Percent Change From Baseline in Partial-onset Seizure Frequency Per 28 Days
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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| YKP3089 | Percent Change From Baseline in Partial-onset Seizure Frequency Per 28 Days | 55.6 percent seizure reduction |
| Placebo | Percent Change From Baseline in Partial-onset Seizure Frequency Per 28 Days | 21.5 percent seizure reduction |
p-value: <0.0001Wilcoxon rank sum
Secondary
50% Responder Rate
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| YKP3089 | 50% Responder Rate | 57 Participants |
| Placebo | 50% Responder Rate | 24 Participants |
p-value: <0.0001Regression, Logistic