Epilepsies, Partial
Conditions
Brief summary
Examine the safety and efficacy 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 No maximum
Healthy volunteers
No
Inclusion criteria
* Completion of study A9451162 (NCT00603473)
Exclusion criteria
* Seizures related to drugs or acute medical illness * History of any serious medical or psychiatric disorder
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (All Causalities and Treatment-Related) | up to 53 weeks | Any untoward medical occurrence in a participant who received study drug was considered an adverse event (AE), without regard to possibility of causal relationship. Treatment-emergent adverse events: those which occurred or worsened after baseline. Severe AEs: those which interferes significantly with participant's usual function. An AE resulting in any of the following outcomes, was considered to be a serious adverse event: death; life-threatening; initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Ratio | Up to 52 weeks | The Response Ratio calculated by the following equation : Response Ratio = (T minus B) divided by (T plus 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 52-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 of the previous study A9451162 (NCT00603473). |
| Responder Rate | Up to 52 weeks | Responder Rate was defined as the percentage of subjects with a 50 percent or greater reduction in the seizure frequency per 28 days for the 52-week treatment period in comparison with the frequency per 28 days for the 6-week baseline period of the previous study A9451162 (NCT00603473). |
| Percent Change in Seizure Frequency | Up to 52 weeks | Percent change in seizure frequency (PCH) was calculated as follows: PCH = 100\*(T minus B) divided by 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 52-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 of the previous study A9451162 (NCT00603473). |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Gabapentin Pediatric participants received gabapentin three times daily for 52 weeks. Participants aged 3 to 12 years received oral solution (250 mg/5 mL) at the dose calculated based on their body weight; 40 mg/kg/day for 3 to 4 years old and 25 to 35 mg/kg/day for 5 to 12 years old but not exceeding 1800 mg per day. Participants aged 13 to 15 years received gabapentin tablet at the dose of 1200 or 1800 mg/day. The dose was adjusted within the range of maintenance doses. Gabapentin could be increased if necessary with the maximum dose of 50 mg/kg/day for participants aged 3 to 12 years; All participants could receive gabapentin tablet not exceeding 2400 mg per day. | 65 |
| Total | 65 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
| Overall Study | Choice of other treatment | 1 |
| Overall Study | Lack of Efficacy | 12 |
| Overall Study | Protocol Violation | 2 |
| Overall Study | Visit failure against planned | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Gabapentin |
|---|---|
| Age, Customized 13-16 years | 15 Participants |
| Age, Customized 3-4 years | 8 Participants |
| Age, Customized 5-12 years | 42 Participants |
| Sex: Female, Male Female | 27 Participants |
| Sex: Female, Male Male | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 48 / 65 |
| serious Total, serious adverse events | 2 / 65 |
Outcome results
Primary
Number of Participants With Treatment-Emergent Adverse Events (All Causalities and Treatment-Related)
Any untoward medical occurrence in a participant who received study drug was considered an adverse event (AE), without regard to possibility of causal relationship. Treatment-emergent adverse events: those which occurred or worsened after baseline. Severe AEs: those which interferes significantly with participant's usual function. An AE resulting in any of the following outcomes, was considered to be a serious adverse event: death; life-threatening; initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect.
Time frame: up to 53 weeks
Population: Safety analysis set: All paticipants who have received at least one dose of the study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Gabapentin | Number of Participants With Treatment-Emergent Adverse Events (All Causalities and Treatment-Related) | Treatment-related severe AEs | 0 Participants |
| Gabapentin | Number of Participants With Treatment-Emergent Adverse Events (All Causalities and Treatment-Related) | All-causality adverse events (AEs) | 58 Participants |
| Gabapentin | Number of Participants With Treatment-Emergent Adverse Events (All Causalities and Treatment-Related) | Treatment-related AEs | 13 Participants |
| Gabapentin | Number of Participants With Treatment-Emergent Adverse Events (All Causalities and Treatment-Related) | All-causality serious AEs | 2 Participants |
| Gabapentin | Number of Participants With Treatment-Emergent Adverse Events (All Causalities and Treatment-Related) | Treatment-related serious AEs | 0 Participants |
| Gabapentin | Number of Participants With Treatment-Emergent Adverse Events (All Causalities and Treatment-Related) | All-causality severe AEs | 1 Participants |
| Gabapentin | Number of Participants With Treatment-Emergent Adverse Events (All Causalities and Treatment-Related) | Discontinuation due to all-causality AEs | 4 Participants |
| Gabapentin | Number of Participants With Treatment-Emergent Adverse Events (All Causalities and Treatment-Related) | Discontinuation due to treatment-related AEs | 2 Participants |
| Gabapentin | Number of Participants With Treatment-Emergent Adverse Events (All Causalities and Treatment-Related) | Dose reduction due to all-causality AEs | 2 Participants |
| Gabapentin | Number of Participants With Treatment-Emergent Adverse Events (All Causalities and Treatment-Related) | Dose reduction due to treatment-related AEs | 2 Participants |
Secondary
Percent Change in Seizure Frequency
Percent change in seizure frequency (PCH) was calculated as follows: PCH = 100\*(T minus B) divided by 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 52-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 of the previous study A9451162 (NCT00603473).
Time frame: Up to 52 weeks
Population: Intent to treat (ITT): Subjects who have received at least one dose of the study drug and in whom the number of epileptic seizures used for efficacy assessment has been counted in both the baseline and treatment periods.~n = number of participants who have total number of seizures at each assessment time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Gabapentin | Percent Change in Seizure Frequency | Week 9 to 16 (n=60) | -33.0 Percent change |
| Gabapentin | Percent Change in Seizure Frequency | Week 17 to 24 (n=58) | -42.0 Percent change |
| Gabapentin | Percent Change in Seizure Frequency | Week 1 to 8 (n=65) | -34.2 Percent change |
| Gabapentin | Percent Change in Seizure Frequency | Week 25 to 36 (n=54) | -41.6 Percent change |
| Gabapentin | Percent Change in Seizure Frequency | Week 37 to 52 (n=47) | -49.2 Percent change |
Secondary
Responder Rate
Responder Rate was defined as the percentage of subjects with a 50 percent or greater reduction in the seizure frequency per 28 days for the 52-week treatment period in comparison with the frequency per 28 days for the 6-week baseline period of the previous study A9451162 (NCT00603473).
Time frame: Up to 52 weeks
Population: Intent to treat (ITT): Subjects who have received at least one dose of the study drug and in whom the number of epileptic seizures used for efficacy assessment has been counted in both the baseline and treatment periods.~n = number of participants who have total number of seizures at each assessment time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Gabapentin | Responder Rate | Week 1 to 8 (n=65) | 35.4 Percentage of participants |
| Gabapentin | Responder Rate | Week 9 to 16 (n=60) | 40.0 Percentage of participants |
| Gabapentin | Responder Rate | Week 17 to 24 (n=58) | 39.7 Percentage of participants |
| Gabapentin | Responder Rate | Week 25 to 36 (n=54) | 40.7 Percentage of participants |
| Gabapentin | Responder Rate | Week 37 to 52 (n=47) | 46.8 Percentage of participants |
Secondary
Response Ratio
The Response Ratio calculated by the following equation : Response Ratio = (T minus B) divided by (T plus 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 52-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 of the previous study A9451162 (NCT00603473).
Time frame: Up to 52 weeks
Population: Intent to treat (ITT): Subjects who have received at least one dose of the study drug and in whom the number of epileptic seizures used for efficacy assessment has been counted in both the baseline and treatment periods.~n = number of participants who have total number of seizures at each assessment time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Gabapentin | Response Ratio | Week 1 to 8 (n=65) | -0.263 Ratio | Standard Deviation 0.3141 |
| Gabapentin | Response Ratio | Week 9 to 16 (n=60) | -0.256 Ratio | Standard Deviation 0.3513 |
| Gabapentin | Response Ratio | Week 17 to 24 (n=58) | -0.300 Ratio | Standard Deviation 0.3671 |
| Gabapentin | Response Ratio | Week 25 to 36 (n=54) | -0.280 Ratio | Standard Deviation 0.3753 |
| Gabapentin | Response Ratio | Week 37 to 52 (n=47) | -0.327 Ratio | Standard Deviation 0.3712 |