Partial Onset Seizures
Conditions
Keywords
Seizures, oxcarbazepine, child
Brief summary
This study is designed to provide short term efficacy and safety data of TRI476 in children with inadequately-controlled partial seizures. Patients will be randomized into either drug treatment or placebo group at 1:1 ratio, and receive their respective treatment for 8 weeks. The purpose of study is to confirm that TRI476 as adjunctive therapy is effective and safe.
Interventions
DRUGTRI476
TRI476 oral suspension doses, based on body weight twice daily
DRUGPlacebo to TRI476
Placebo oral suspension, taken twice daily
DRUGBenzodiazepines
Benzodiazepines could be used as needed as rescue medication during the duration of the study.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
4 Years to 14 Years
Healthy volunteers
No
Inclusion criteria
* Male and female outpatients, aged 4 to 14 years (inclusive), with a minimum body weight of 15 kg. * A diagnosis of partial onset seizures, which include the seizure subtypes of simple, complex, and secondarily generalized seizures (based on the International League Against Epilepsy (ILAE) Classification, as modified in 1981).
Exclusion criteria
* A document history of generalized status epileptics in the past 6 months. * Seizures having a metabolic, neoplastic, or active infectious origin. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Double-blind Phase, by Treatment Group | screening and 28 days | Percent change in partial onset seizure frequency per 28 days during the double-blind phase from the screening phase, was calculated according to the following formula: Percent change in partial onset seizure frequency per 28 days from the screening phase = (partial onset seizure frequency per 28 days during the double-blind phase - partial onset seizure frequency per 28 days during the screening phase) / partial onset seizure frequency per 28 days during the double-blind phase x 100 Partial onset seizure frequency per 28 days = Number of partial onset seizures during each phase (screening phase or double-blind phase) / number of days during the screening or double-blind phase × 28. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Partial Seizure Frequency Per 28 Days, by Study Period (Every 28 Days) and Treatment Group | baseline, 28 days and 56 days | Partial onset seizure frequency per 28 days during a period between baseline and Week 4 was measured. Partial onset seizure frequency per 28 days (count/28 days) = Number of partial onset seizures during each phase (screening phase or double-blind phase) / Number of days during the phase x 28. |
| Percent of Participants With Response During Double-blind Phase, by Treatment Group | screening to 28 days | Responder rate was defined as the percent of participants with an at least 50% reduction in partial onset seizure frequency per 28 days from the screening phase. |
| Percent Change in Partial Onset Seizure Frequency During the Double-blind Phase by Seizure Type | 28 days | Percent change in seizure frequency from baseline = 100 (T-B)/B, B=Seizure frequency per 28 days during baseline phase, T=Seizure frequency per 28 days during the double-blind phase. Seizure frequency per 28 days is calculated as: (seizure frequency during the double-blind phase / the number of days the seizure information were provided) x 28. Only patients with both baseline and corresponding post-baseline values are included. |
| Number of Participants With Clinical Global Impression of Change (CGIC) at Final Assessment, by Treatment Group | 56 days | Clinical Global Impression of Change (CGI) is rated on a 7-point scale, with the severity of illness scale using a range of responses from 1 (normal) through to 7 (amongst the most severely ill patients). CGI-C scores range from 1 (very much improved) through to 7 (very much worse). |
Countries
Japan
Participant flow
Recruitment details
A total of 99 patients were randomized, one patient who did not receive study drug was excluded. A total of 48 participants were randomized to TRI476 and 51 to placebo. 7 participants discontinued during the titration period and 3 discontinued during the maintenance period. A total of 89 participants completed the study.
Pre-assignment details
Participants kept same dosage of their traditional antiepileptics prior to screening and throughout the study. They received TRI476 or placebo in a 1:1 ratio. TRI476 dose was increased gradually, based on body weight during the titration period (day 0- 14). The tolerated dose was given during the maintenance period (up to day 56).
Participants by arm
| Arm | Count |
|---|---|
| TRI476 Participants received TRI476 based on body weight with titration up to the maintenance dose, in addition to their traditional antiepileptics dosage. | 48 |
| Placebo Participants received placebo to TRI476 without any adjustment to the dosing regimen, in addition to their traditional antiepileptics dosage. | 51 |
| Total | 99 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Maintenance Period | Adverse Event | 2 | 1 |
| Titration Period | Adverse Event | 6 | 0 |
| Titration Period | Protocol Violation | 1 | 0 |
Baseline characteristics
| Characteristic | TRI476 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 9.8 years STANDARD_DEVIATION 2.91 | 9.2 years STANDARD_DEVIATION 2.83 | 9.5 years STANDARD_DEVIATION 2.87 |
| Sex: Female, Male Female | 22 Participants | 24 Participants | 46 Participants |
| Sex: Female, Male Male | 26 Participants | 27 Participants | 53 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 38 / 47 | 27 / 51 |
| serious Total, serious adverse events | 1 / 47 | 1 / 51 |
Outcome results
Primary
Percent Change in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Double-blind Phase, by Treatment Group
Percent change in partial onset seizure frequency per 28 days during the double-blind phase from the screening phase, was calculated according to the following formula: Percent change in partial onset seizure frequency per 28 days from the screening phase = (partial onset seizure frequency per 28 days during the double-blind phase - partial onset seizure frequency per 28 days during the screening phase) / partial onset seizure frequency per 28 days during the double-blind phase x 100 Partial onset seizure frequency per 28 days = Number of partial onset seizures during each phase (screening phase or double-blind phase) / number of days during the screening or double-blind phase × 28.
Time frame: screening and 28 days
Population: The Full Analysis set included all participants who received study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TRI476 | Percent Change in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Double-blind Phase, by Treatment Group | -2.85 percentage change per 28 days | Standard Deviation 63.546 |
| Placebo | Percent Change in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Double-blind Phase, by Treatment Group | 14.82 percentage change per 28 days | Standard Deviation 73.333 |
Secondary
Number of Participants With Clinical Global Impression of Change (CGIC) at Final Assessment, by Treatment Group
Clinical Global Impression of Change (CGI) is rated on a 7-point scale, with the severity of illness scale using a range of responses from 1 (normal) through to 7 (amongst the most severely ill patients). CGI-C scores range from 1 (very much improved) through to 7 (very much worse).
Time frame: 56 days
Population: The Analysis set included all participants who received study drug and had data available for analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TRI476 | Number of Participants With Clinical Global Impression of Change (CGIC) at Final Assessment, by Treatment Group | No change | 21 participants |
| TRI476 | Number of Participants With Clinical Global Impression of Change (CGIC) at Final Assessment, by Treatment Group | Moderate aggravation | 0 participants |
| TRI476 | Number of Participants With Clinical Global Impression of Change (CGIC) at Final Assessment, by Treatment Group | Slight improvement | 8 participants |
| TRI476 | Number of Participants With Clinical Global Impression of Change (CGIC) at Final Assessment, by Treatment Group | Moderate improvement | 8 participants |
| TRI476 | Number of Participants With Clinical Global Impression of Change (CGIC) at Final Assessment, by Treatment Group | Slight aggravation | 1 participants |
| TRI476 | Number of Participants With Clinical Global Impression of Change (CGIC) at Final Assessment, by Treatment Group | Marked aggravation | 0 participants |
| TRI476 | Number of Participants With Clinical Global Impression of Change (CGIC) at Final Assessment, by Treatment Group | Marked improvement | 9 participants |
| Placebo | Number of Participants With Clinical Global Impression of Change (CGIC) at Final Assessment, by Treatment Group | Marked aggravation | 0 participants |
| Placebo | Number of Participants With Clinical Global Impression of Change (CGIC) at Final Assessment, by Treatment Group | Marked improvement | 2 participants |
| Placebo | Number of Participants With Clinical Global Impression of Change (CGIC) at Final Assessment, by Treatment Group | Slight improvement | 6 participants |
| Placebo | Number of Participants With Clinical Global Impression of Change (CGIC) at Final Assessment, by Treatment Group | No change | 38 participants |
| Placebo | Number of Participants With Clinical Global Impression of Change (CGIC) at Final Assessment, by Treatment Group | Slight aggravation | 3 participants |
| Placebo | Number of Participants With Clinical Global Impression of Change (CGIC) at Final Assessment, by Treatment Group | Moderate aggravation | 0 participants |
| Placebo | Number of Participants With Clinical Global Impression of Change (CGIC) at Final Assessment, by Treatment Group | Moderate improvement | 2 participants |
Secondary
Partial Seizure Frequency Per 28 Days, by Study Period (Every 28 Days) and Treatment Group
Partial onset seizure frequency per 28 days during a period between baseline and Week 4 was measured. Partial onset seizure frequency per 28 days (count/28 days) = Number of partial onset seizures during each phase (screening phase or double-blind phase) / Number of days during the phase x 28.
Time frame: baseline, 28 days and 56 days
Population: The Full Analysis set included all participants who received study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TRI476 | Partial Seizure Frequency Per 28 Days, by Study Period (Every 28 Days) and Treatment Group | Baseline to Week 4 (day 0 to day 28) | 65.58 seizures per 28 days | Standard Deviation 109.457 |
| TRI476 | Partial Seizure Frequency Per 28 Days, by Study Period (Every 28 Days) and Treatment Group | Week 4 to Week 8 (day 28 to day 56) | 45.40 seizures per 28 days | Standard Deviation 70.209 |
| Placebo | Partial Seizure Frequency Per 28 Days, by Study Period (Every 28 Days) and Treatment Group | Week 4 to Week 8 (day 28 to day 56) | 98.73 seizures per 28 days | Standard Deviation 291.781 |
| Placebo | Partial Seizure Frequency Per 28 Days, by Study Period (Every 28 Days) and Treatment Group | Baseline to Week 4 (day 0 to day 28) | 90.61 seizures per 28 days | Standard Deviation 283.187 |
Secondary
Percent Change in Partial Onset Seizure Frequency During the Double-blind Phase by Seizure Type
Percent change in seizure frequency from baseline = 100 (T-B)/B, B=Seizure frequency per 28 days during baseline phase, T=Seizure frequency per 28 days during the double-blind phase. Seizure frequency per 28 days is calculated as: (seizure frequency during the double-blind phase / the number of days the seizure information were provided) x 28. Only patients with both baseline and corresponding post-baseline values are included.
Time frame: 28 days
Population: Analyzed set includes all participants who received study drug and had both baseline and post baseline data available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TRI476 | Percent Change in Partial Onset Seizure Frequency During the Double-blind Phase by Seizure Type | Simple partial seizures | -9.73 percentage change in seizure frequency | Standard Deviation 51.329 |
| TRI476 | Percent Change in Partial Onset Seizure Frequency During the Double-blind Phase by Seizure Type | Complex partial seizures | -6.86 percentage change in seizure frequency | Standard Deviation 78.583 |
| TRI476 | Percent Change in Partial Onset Seizure Frequency During the Double-blind Phase by Seizure Type | Secondarily generalized seizures | -29.54 percentage change in seizure frequency | Standard Deviation 64.66 |
| Placebo | Percent Change in Partial Onset Seizure Frequency During the Double-blind Phase by Seizure Type | Simple partial seizures | -16.89 percentage change in seizure frequency | Standard Deviation 45.822 |
| Placebo | Percent Change in Partial Onset Seizure Frequency During the Double-blind Phase by Seizure Type | Complex partial seizures | 30.59 percentage change in seizure frequency | Standard Deviation 91.551 |
| Placebo | Percent Change in Partial Onset Seizure Frequency During the Double-blind Phase by Seizure Type | Secondarily generalized seizures | 12.11 percentage change in seizure frequency | Standard Deviation 82.879 |
Secondary
Percent of Participants With Response During Double-blind Phase, by Treatment Group
Responder rate was defined as the percent of participants with an at least 50% reduction in partial onset seizure frequency per 28 days from the screening phase.
Time frame: screening to 28 days
Population: The Full Analysis set included all participants who received study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TRI476 | Percent of Participants With Response During Double-blind Phase, by Treatment Group | 23.4 percentage of participants |
| Placebo | Percent of Participants With Response During Double-blind Phase, by Treatment Group | 3.9 percentage of participants |