Epilepsy, Monotherapy
Conditions
Keywords
Lacosamide
Brief summary
Compare safety of Lacosamide (LCM) to Carbamazepine Controlled-Release (CBZ-CR) as monotherapy in newly or recently newly diagnosed subjects with primary safety variables including spontaneous reports of Adverse Events (AEs), withdrawal of subjects due to AEs, reporting of Serious AEs (SAEs).
Interventions
DRUGLacosamide
50 and 100 mg tablets of Lacosamide given as 100 mg/day, 200 mg/day, 300 mg/day, 400 mg/day, 500 mg/day or 600 mg/day throughout the Treatment Period (Maximum 3.5 Years)
DRUGCarbamazepine-Controlled Release (CBZ-CR)
200 mg tablets of Carbamazepine-CR given as 200 mg/day, 400 mg/day, 600 mg/day, 800 mg/day, 1000 mg/day or 1200 mg/day throughout the Treatment Period (Maximum 3.5 Years)
Sponsors
Eden Sarl
UCB BIOSCIENCES GmbH
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Subject/legal representative is considered reliable and capable of adhering to the protocol * Subject has remained seizure free and completed the Maintenance Phase of the SP0993; or subject has experienced 1 or more seizures on the first or second target dose during the SP0993 Maintenance Phase * Subject is expected to benefit from participation in SP0994 in the opinion of the investigator
Exclusion criteria
* Subject is receiving any investigational drugs or using any experimental devices in addition to LCM or CBZ-CR * Subject experienced a seizure at the third target dose during the Evaluation Phase or Maintenance Phase of the SP0993 study * Subject is taking benzodiazepines for a non-epilepsy indication * Subject meets a withdrawal criterion from the previous study SP0993 * Subject is experiencing an ongoing SAE from the previous study SP0993 * Subject has a lifetime history of suicide attempt (including an active attempt, interrupted attempt, or aborted attempt), or has suicidal ideation in the past 6 months as indicated by a positive response (Yes) to either Question 4 or Question 5 of the Columbia Suicide Severity Rating Scale (C-SSRS) at Screening. Or subject has a positive response (Yes) to either Question 4 or Question 5 of the C-SSRS at Screening in the Since Last Visit version
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With at Least One Treatment-emergent Adverse Event (AE) During the Treatment Phase (Maximum of 3.5 Years) | Up to 3.5 Years (Duration of the Treatment Phase) | Treatment-emergent AEs were defined as those events which started on or after the date of first dose of SP0994 study medication, or events in which severity worsened on or after the date of first dose of SP0994 study medication. AEs which occurred within 30 days after last dose of study medication were considered treatment emergent. |
| Number of Subjects Who Withdrew From the Study Due to a Treatment-emergent Adverse Event (AE) During the Treatment Phase (Maximum 3.5 Years) | Up to 3.5 Years (Duration of the Treatment Phase) | Treatment-emergent AEs were defined as those events which started on or after the date of first dose of SP0994 study medication, or events in which severity worsened on or after the date of first dose of SP0994 study medication. AEs which occurred within 30 days after last dose of study medication were considered treatment emergent. |
| Number of Subjects With at Least One Treatment-emergent Serious Adverse Event (SAE) During the Treatment Phase (Maximum of 3.5 Years) | Up to 3.5 Years (Duration of the Treatment Phase) | A Serious Adverse Event is any untoward medical occurrence that at any dose results in death, is life threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity is a congenital anomaly/birth defect. |
Countries
Australia, Belgium, Bulgaria, Canada, Czechia, Finland, France, Germany, Greece, Hungary, Italy, Japan, Latvia, Lithuania, Mexico, Philippines, Poland, Portugal, Romania, Russia, Slovakia, South Korea, Spain, Sweden, Switzerland, Thailand, Ukraine, United Kingdom, United States
Participant flow
Recruitment details
Enrollment started in May 2012 and concluded in January 2017 - 551 patients. Due to the political and civil unrest in Luhansk PAREXEL was not able to conduct further site visits to one site in Ukraine and to collect further data for 2 subjects,they were excluded from SP0994, leaving 549 patients in the Enrolled Set out of 551 initially enrolled.
Pre-assignment details
A total of 549 subjects gave informed consent in SP0994 and were included in the Enrolled Set, 548 subjects received at least 1 dose of study medication and were included in the Safety Set (SS). Participant Flow refers to the Safety Population including all enrolled subjects who received at least 1 dose of study medication in the current study.
Participants by arm
| Arm | Count |
|---|---|
| Lacosamide 50 and 100 mg tablets of Lacosamide given as 200 mg/day, 300 mg/day, 400 mg/day, 500 mg/day or 600 mg/day throughout the Treatment Period (Maximum 3.5 Years). CBZ-CR placebo capsules were administered to maintain the blinding. | 279 |
| Carbamazepine-Controlled Release (CBZ-CR) 200 mg tablets of Carbamazepine-CR given as 400 mg/day, 600 mg/day, 800 mg/day, 1000 mg/day or 1200 mg/day throughout the Treatment Period (Maximum of 3.5 Years). Lacosamide placebo capsules were administered to maintain the blinding. | 269 |
| Total Title | 548 |
| Total | 1,096 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 12 | 22 |
| Overall Study | Death | 0 | 1 |
| Overall Study | decision by site staff | 0 | 1 |
| Overall Study | investigator's decision | 1 | 1 |
| Overall Study | Lack of Efficacy | 13 | 1 |
| Overall Study | local lab unblinded site | 1 | 0 |
| Overall Study | Lost to Follow-up | 6 | 9 |
| Overall Study | Protocol Violation | 1 | 4 |
| Overall Study | sponsor's decision | 1 | 1 |
| Overall Study | subject left participation SP0993 | 0 | 1 |
| Overall Study | subject withdrew consent | 1 | 0 |
| Overall Study | Withdrawal by Subject | 32 | 35 |
| Overall Study | withdrew before follow-up | 0 | 13 |
Baseline characteristics
| Characteristic | Total Title | Lacosamide | Carbamazepine-Controlled Release (CBZ-CR) |
|---|---|---|---|
| Age, Categorical <=18 years | 16 Participants | 8 Participants | 8 Participants |
| Age, Categorical >=65 years | 77 Participants | 41 Participants | 36 Participants |
| Age, Categorical Between 18 and 65 years | 455 Participants | 230 Participants | 225 Participants |
| Age, Continuous | 42.9 years STANDARD_DEVIATION 17 | 43.2 years STANDARD_DEVIATION 17.2 | 42.7 years STANDARD_DEVIATION 16.7 |
| Sex: Female, Male Female | 250 Participants | 125 Participants | 125 Participants |
| Sex: Female, Male Male | 298 Participants | 154 Participants | 144 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 45 / 279 | 42 / 269 |
| serious Total, serious adverse events | 32 / 279 | 22 / 269 |
Outcome results
Primary
Number of Subjects Who Withdrew From the Study Due to a Treatment-emergent Adverse Event (AE) During the Treatment Phase (Maximum 3.5 Years)
Treatment-emergent AEs were defined as those events which started on or after the date of first dose of SP0994 study medication, or events in which severity worsened on or after the date of first dose of SP0994 study medication. AEs which occurred within 30 days after last dose of study medication were considered treatment emergent.
Time frame: Up to 3.5 Years (Duration of the Treatment Phase)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lacosamide (SS) | Number of Subjects Who Withdrew From the Study Due to a Treatment-emergent Adverse Event (AE) During the Treatment Phase (Maximum 3.5 Years) | 12 Participants |
| Carbamazepine-Controlled Release (CBZ-CR) (SS) | Number of Subjects Who Withdrew From the Study Due to a Treatment-emergent Adverse Event (AE) During the Treatment Phase (Maximum 3.5 Years) | 21 Participants |
Primary
Number of Subjects With at Least One Treatment-emergent Adverse Event (AE) During the Treatment Phase (Maximum of 3.5 Years)
Treatment-emergent AEs were defined as those events which started on or after the date of first dose of SP0994 study medication, or events in which severity worsened on or after the date of first dose of SP0994 study medication. AEs which occurred within 30 days after last dose of study medication were considered treatment emergent.
Time frame: Up to 3.5 Years (Duration of the Treatment Phase)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lacosamide (SS) | Number of Subjects With at Least One Treatment-emergent Adverse Event (AE) During the Treatment Phase (Maximum of 3.5 Years) | 181 Participants |
| Carbamazepine-Controlled Release (CBZ-CR) (SS) | Number of Subjects With at Least One Treatment-emergent Adverse Event (AE) During the Treatment Phase (Maximum of 3.5 Years) | 182 Participants |
Primary
Number of Subjects With at Least One Treatment-emergent Serious Adverse Event (SAE) During the Treatment Phase (Maximum of 3.5 Years)
A Serious Adverse Event is any untoward medical occurrence that at any dose results in death, is life threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity is a congenital anomaly/birth defect.
Time frame: Up to 3.5 Years (Duration of the Treatment Phase)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lacosamide (SS) | Number of Subjects With at Least One Treatment-emergent Serious Adverse Event (SAE) During the Treatment Phase (Maximum of 3.5 Years) | 32 Participants |
| Carbamazepine-Controlled Release (CBZ-CR) (SS) | Number of Subjects With at Least One Treatment-emergent Serious Adverse Event (SAE) During the Treatment Phase (Maximum of 3.5 Years) | 22 Participants |