Epilepsies, Partial
Conditions
Brief summary
Examine the efficacy, safety and pharmacokinetics of gabapentin as adjunctive therapy in Japanese pediatric patients with partial seizures
Interventions
DRUGgabapentin
Orally administered gabapentin
Sponsors
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 15 Years
Healthy volunteers
No
Inclusion criteria
* Japanese male or females, ages 3-15 years old at acquisition of informed consent, 15 years old or less at the baseline visit * Seizures are classified as simple partial, complex partial or partial becoming secondarily generalized (defined according to the International League Against Epilepsy) * Have not been able to achieve adequate seizure control with antiepileptic drugs
Exclusion criteria
* Seizures related to drugs or acute medical illness * History of any serious medical or psychiatric disorder * Diagnosis or history of a structural CNS lesion or an encephalopathy shown to be progressive
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Ratio of Gabapentin in Japanese Pediatric Patients With Partial Seizures | 12 weeks | The Response Ratio calculated by the following equation was assessed as the primary endpoint: R Ratio = (T-B) / (T+B) where T is seizure frequency per 28 days (i.e., the number of seizures per 28 days) calculated from the total number of seizures for the 12-week treatment period, and B is seizure frequency per 28 days (i.e., the number of seizures per 28 days) calculated from the total number of seizures for the 6-week baseline period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Responder Rate | 12 weeks | Responder Rate was defined as the percentage of subjects with a 50% or greater reduction in the seizure frequency per 28 days for the 12-week treatment period in comparison with the frequency per 28 days for the 6-week baseline period. |
| Percent Change in Seizure Frequency (PCH) | 12 weeks | PCH calculated by the following equation was assessed as secondary endpoint: PCH = 100 (T-B) / B where T is seizure frequency per 28 days (i.e., the number of seizures per 28 days) calculated from the total number of seizures for the 12-week treatment period, and B is seizure frequency per 28 days (i.e., the number of seizures per 28 days) calculated from the total number of seizures for the 6-week baseline period. |
Countries
Japan
Participant flow
Recruitment details
Participants were screened at 27 centers in Japan.
Pre-assignment details
Ninety subjects were enrolled in the study. Of them, 89 received the study treatment, while 1 withdrew consent.
Participants by arm
| Arm | Count |
|---|---|
| Gabapentin The dosage of oral solution for subjects aged 3 to 12 years was calculated based on their body weight. The dose was titrated for the first 3 days of the treatment period. Subjects aged 3 to 4 years received gabapentin 10 mg/kg/day on Day 1, 20 mg/kg/day on Day 2 and 40 mg/kg/day from Day 3. Subjects aged 5 to 12 years received gabapentin 10 mg/kg/day on Day 1, 20 mg/kg/day on Day 2 and 25 to 35 mg/kg/day from Day 3. Subjects aged 13 to 15 years received gabapentin 600 mg/day on Day 1, 1200 mg/day on Day 2 and 1200 or 1800 mg/day from Day 3. After Day 3, the dose was adjusted if necessary within the range of maintenance doses. The maximum daily dose was 600 mg for Day 1, 1200 mg for Day 2, and 1800 mg for Day 3 and thereafter. | 89 |
| Total | 89 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
| Overall Study | Lack of Efficacy | 4 |
| Overall Study | Protocol Violation | 1 |
Baseline characteristics
| Characteristic | Gabapentin |
|---|---|
| Age, Customized >= 13 years and =< 15 years | 15 Subjects |
| Age, Customized >= 3 years and < 5 years | 11 Subjects |
| Age, Customized >= 5 years and < 13 years | 63 Subjects |
| Sex: Female, Male Female | 40 Participants |
| Sex: Female, Male Male | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 73 / 89 |
| serious Total, serious adverse events | 1 / 89 |
Outcome results
Primary
Response Ratio of Gabapentin in Japanese Pediatric Patients With Partial Seizures
The Response Ratio calculated by the following equation was assessed as the primary endpoint: R Ratio = (T-B) / (T+B) where T is seizure frequency per 28 days (i.e., the number of seizures per 28 days) calculated from the total number of seizures for the 12-week treatment period, and B is seizure frequency per 28 days (i.e., the number of seizures per 28 days) calculated from the total number of seizures for the 6-week baseline period.
Time frame: 12 weeks
Population: Modified intent-to-treat (MITT) population: Subjects who have received the study medication for at least 28 days and in whom the number of epileptic seizures used for efficacy assessment has been counted for at least 28 days in both the baseline and treatment periods.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Gabapentin | Response Ratio of Gabapentin in Japanese Pediatric Patients With Partial Seizures | -0.158 ratio |
Secondary
Percent Change in Seizure Frequency (PCH)
PCH calculated by the following equation was assessed as secondary endpoint: PCH = 100 (T-B) / B where T is seizure frequency per 28 days (i.e., the number of seizures per 28 days) calculated from the total number of seizures for the 12-week treatment period, and B is seizure frequency per 28 days (i.e., the number of seizures per 28 days) calculated from the total number of seizures for the 6-week baseline period.
Time frame: 12 weeks
Population: Modified intent-to-treat (MITT) population: Subjects who have received the study medication for at least 28 days and in whom the number of epileptic seizures used for efficacy assessment has been counted for at least 28 days in both the baseline and treatment periods.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Gabapentin | Percent Change in Seizure Frequency (PCH) | -24.4 Percent Change |
Secondary
Responder Rate
Responder Rate was defined as the percentage of subjects with a 50% or greater reduction in the seizure frequency per 28 days for the 12-week treatment period in comparison with the frequency per 28 days for the 6-week baseline period.
Time frame: 12 weeks
Population: Modified intent-to-treat (MITT) population: Subjects who have received the study medication for at least 28 days and in whom the number of epileptic seizures used for efficacy assessment has been counted for at least 28 days in both the baseline and treatment periods.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Gabapentin | Responder Rate | 19.8 Percentage of Subjects |