Epilepsy, Partial Seizures
Conditions
Keywords
Levetiracetam, Keppra, Monotherapy, China, Epilepsy, Partial-onset Seizures
Brief summary
To demonstrate the non-inferiority of Levetiracetam (1000 mg/day) versus Carbamazepine Immediate-Release (400 mg/day) used as monotherapy for at least 6 months in a Chinese population with newly or recently diagnosed Epilepsy who are experiencing Partial-Onset Seizures (POS).
Interventions
DRUGLevetiracetam
Immediate release film-coated tablets at strengths of 250 mg and 500 mg. * Up-titration Period (Week 1 to Week 3): Levetiracetam (LEV) 250 mg twice daily (bid) * Stabilization Period and Evaluation Period (Week 3 to Week 30): LEV 500 mg bid * Down-titration Period (Week 30 up to Week 33)
DRUGCarbamazepine
Immediate release tablets at a strength of 200 mg. * Up-titration Period (Week 1 to Week 3): Carbamazepine- Immediate Release (CBZ-IR) 200 mg once daily (qd) * Stabilization Period and Evaluation Period (Week 3 to Week 30): CBZ-IR 200 mg bid * Down-titration Period (Week 30 up to Week 33)
Sponsors
UCB Pharma SA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject is of Chinese origin and ≥ 16 years of age * Subject is newly or recently diagnosed with Epilepsy, having experienced unprovoked Partial-Onset Seizures (POS) * Subject has experienced at least 2 unprovoked seizures in the year preceding randomization, of which at least 1 unprovoked seizure occurred in the 3 months preceding randomization * Subject has had an Electroencephalogram (EEG) and a brain Computed Tomography (CT) scan or brain Magnetic Resonance Imaging (MRI) scan consistent with a diagnosis of Epilepsy with POS
Exclusion criteria
* Subject tests positive for human leukocyte antigen major histocompatibility complex, class I,B (HLA-B)\* 1502 allele * Subject has a history or presence of seizures of other types than Partial-Onset Seizures (POS) * Subject has only experienced type IA nonmotor seizures * Subject has a history or presence of seizures occurring only in clustered patterns * Subject has a history of clinical or Electroencephalogram (EEG) findings suggestive of Idiopathic Generalized Epilepsy prior to randomization * Subject has current or previous diagnosis of pseudoseizures, conversion disorders, or other nonepileptic ictal events that could be confused with seizures * Subject has a history of Status Epilepticus
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of Subjects Remaining Seizure Free During the 6-months Evaluation Period | 6-months Evaluation Period (From Week 4 to Week 30) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects Retained in the Study for the Duration of the Period Covering the Up Titration Period, Stabilization Period, and Evaluation Period | From Week 1 to Week 30 | — |
| Time to First Seizure or Discontinuation Due to an Adverse Event (AE) / Lack of Efficacy (LOE) During the Evaluation Period | From first day in the Evaluation Period (Week 4) up to end of the Evaluation Period (Week 30) | Number of qualifying events is reported because it is the only descriptive measure available from the proportional hazards model, that was applied. |
| Time to First Seizure During the Evaluation Period | From first day in the Evaluation Period (Week 4) up to end of the Evaluation Period (Week 30) | Number of qualifying events is reported because it is the only descriptive measure available from the proportional hazards model, that was applied. |
| Time to First Seizure During the Period Covering the Up Titration Period, Stabilization Period, and Evaluation Period From the First Dose of Study Drug | From Randomization (Week 1) up to Evaluation Visit (Week 30) | Number of qualifying events is reported because it is the only descriptive measure available from the proportional hazards model, that was applied. |
Countries
China
Participant flow
Recruitment details
This study started to enroll subjects in China in September 2013.
Pre-assignment details
Participant Flow refers to the Randomized Set which consists of all subjects who were randomized in this study.
Participants by arm
| Arm | Count |
|---|---|
| Levetiracetam (Safety Set) During the Up-Titration period (2 weeks), subjects initiated treatment at half the randomized target dose with Levetiracetam (LEV) 250 mg bid. During Stabilization and Evaluation Period (27 weeks) LEV was taken bid 500 mg. | 218 |
| Carbamazepine-IR (Safety Set) During the Up-Titration period (2 weeks), subjects initiated treatment at half the randomized target dose with Carbamazepine immediate-release (CBZ-IR) 200 mg qd. During Stabilization and Evaluation (27 weeks) Period CBZ-IR was taken bid 200 mg. | 215 |
| Total Title | 433 |
| Total | 866 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | AE, non-serious non-fatal | 5 | 22 |
| Overall Study | AE, serious fatal | 1 | 0 |
| Overall Study | Lack of Efficacy | 94 | 41 |
| Overall Study | Lost to Follow-up | 5 | 6 |
| Overall Study | Non-compliant patient | 1 | 1 |
| Overall Study | Non-compliant with study procedures | 1 | 0 |
| Overall Study | Pregnancy | 1 | 1 |
| Overall Study | Protocol Violation | 0 | 2 |
| Overall Study | SAE, non-fatal | 1 | 4 |
| Overall Study | Subject did not follow instructions | 0 | 2 |
| Overall Study | Withdrawal by Subject | 18 | 12 |
Baseline characteristics
| Characteristic | Levetiracetam (Safety Set) | Carbamazepine-IR (Safety Set) | Total Title |
|---|---|---|---|
| Age, Categorical <=18 years | 20 Participants | 22 Participants | 42 Participants |
| Age, Categorical >=65 years | 14 Participants | 7 Participants | 21 Participants |
| Age, Categorical Between 18 and 65 years | 184 Participants | 186 Participants | 370 Participants |
| Age, Continuous mean (standard deviation) | 37.8 years STANDARD_DEVIATION 16.2 | 33.3 years STANDARD_DEVIATION 14.3 | 35.6 years STANDARD_DEVIATION 15.4 |
| Sex: Female, Male Female | 106 Participants | 94 Participants | 200 Participants |
| Sex: Female, Male Male | 112 Participants | 121 Participants | 233 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 92 / 218 | 93 / 215 |
| serious Total, serious adverse events | 9 / 218 | 11 / 215 |
Outcome results
Primary
Proportion of Subjects Remaining Seizure Free During the 6-months Evaluation Period
Time frame: 6-months Evaluation Period (From Week 4 to Week 30)
Population: The Per Protocol Set consisted of all subjects in the Full Analysis Set who entered the Evaluation Period and who did not have any important protocol deviations determined to impact the interpretation of efficacy. Criteria that might impact the assessment of efficacy was determined during a Data Review Meeting before the database lock.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Levetiracetam (Per Protocol Set) | Proportion of Subjects Remaining Seizure Free During the 6-months Evaluation Period | 47.3 percentage of subjects |
| Carbamazepine-IR (Per Protocol Set) | Proportion of Subjects Remaining Seizure Free During the 6-months Evaluation Period | 68.4 percentage of subjects |
Comparison: The adjusted absolute difference in treatment group seizure-free proportions (referenced as 'Adjusted difference in proportions' in 'Method of Estimation' below) was derived from the adjusted treatment group proportions of seizure-free subjects. The adjusted proportions were derived from a logistic regression model of seizure freedom using treatment and the categories for the number of seizures in the 3-month period prior to Visit 1 (≤2 seizures and \>2 seizures) as covariates.95% CI: [-33.1, -12.6]
Secondary
Proportion of Subjects Retained in the Study for the Duration of the Period Covering the Up Titration Period, Stabilization Period, and Evaluation Period
Time frame: From Week 1 to Week 30
Population: The Per Protocol Set consisted of all subjects in the Full Analysis Set who entered the Evaluation Period and who did not have any important protocol deviations determined to impact the interpretation of efficacy. Criteria that might impact the assessment of efficacy was determined during a Data Review Meeting before the database lock.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Levetiracetam (Per Protocol Set) | Proportion of Subjects Retained in the Study for the Duration of the Period Covering the Up Titration Period, Stabilization Period, and Evaluation Period | 48.4 percentage of subjects |
| Carbamazepine-IR (Per Protocol Set) | Proportion of Subjects Retained in the Study for the Duration of the Period Covering the Up Titration Period, Stabilization Period, and Evaluation Period | 70.2 percentage of subjects |
Secondary
Time to First Seizure During the Evaluation Period
Number of qualifying events is reported because it is the only descriptive measure available from the proportional hazards model, that was applied.
Time frame: From first day in the Evaluation Period (Week 4) up to end of the Evaluation Period (Week 30)
Population: The Per Protocol Set consisted of all subjects in the Full Analysis Set who entered the Evaluation Period and who did not have any important protocol deviations determined to impact the interpretation of efficacy. Criteria that might impact the assessment of efficacy was determined during a Data Review Meeting before the database lock.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Levetiracetam (Per Protocol Set) | Time to First Seizure During the Evaluation Period | 87 events |
| Carbamazepine-IR (Per Protocol Set) | Time to First Seizure During the Evaluation Period | 39 events |
Secondary
Time to First Seizure During the Period Covering the Up Titration Period, Stabilization Period, and Evaluation Period From the First Dose of Study Drug
Number of qualifying events is reported because it is the only descriptive measure available from the proportional hazards model, that was applied.
Time frame: From Randomization (Week 1) up to Evaluation Visit (Week 30)
Population: The Per Protocol Set consisted of all subjects in the Full Analysis Set who entered the Evaluation Period and who did not have any important protocol deviations determined to impact the interpretation of efficacy. Criteria that might impact the assessment of efficacy was determined during a Data Review Meeting before the database lock.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Levetiracetam (Per Protocol Set) | Time to First Seizure During the Period Covering the Up Titration Period, Stabilization Period, and Evaluation Period From the First Dose of Study Drug | 97 events |
| Carbamazepine-IR (Per Protocol Set) | Time to First Seizure During the Period Covering the Up Titration Period, Stabilization Period, and Evaluation Period From the First Dose of Study Drug | 57 events |
Secondary
Time to First Seizure or Discontinuation Due to an Adverse Event (AE) / Lack of Efficacy (LOE) During the Evaluation Period
Number of qualifying events is reported because it is the only descriptive measure available from the proportional hazards model, that was applied.
Time frame: From first day in the Evaluation Period (Week 4) up to end of the Evaluation Period (Week 30)
Population: The Per Protocol Set consisted of all subjects in the Full Analysis Set who entered the Evaluation Period and who did not have any important protocol deviations determined to impact the interpretation of efficacy. Criteria that might impact the assessment of efficacy was determined during a Data Review Meeting before the database lock.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Levetiracetam (Per Protocol Set) | Time to First Seizure or Discontinuation Due to an Adverse Event (AE) / Lack of Efficacy (LOE) During the Evaluation Period | 88 events |
| Carbamazepine-IR (Per Protocol Set) | Time to First Seizure or Discontinuation Due to an Adverse Event (AE) / Lack of Efficacy (LOE) During the Evaluation Period | 45 events |