Trial Outcomes & Findings for Efficacy, Safety and Tolerability of TRI476 (Oxcarbazepine) in Children With Inadequately Controlled Partial Onset Seizures (NCT NCT00975715)

Last Updated: 2014-07-16

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

99 participants

Primary outcome timeframe

screening and 28 days

Results posted on

2014-07-16

Participant Flow

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.

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).

Participant milestones

Participant milestones
Measure	TRI476 Participants received TRI476 based on body weight with titration up to the maintenance dose, in addition to their traditional antiepileptics dosage.	Placebo Participants received placebo to TRI476 without any adjustment to the dosing regimen, in addition to their traditional antiepileptics dosage.
Titration Period STARTED	48	51
Titration Period COMPLETED	41	51
Titration Period NOT COMPLETED	7	0
Maintenance Period STARTED	41	51
Maintenance Period COMPLETED	39	50
Maintenance Period NOT COMPLETED	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	TRI476 Participants received TRI476 based on body weight with titration up to the maintenance dose, in addition to their traditional antiepileptics dosage.	Placebo Participants received placebo to TRI476 without any adjustment to the dosing regimen, in addition to their traditional antiepileptics dosage.
Titration Period Adverse Event	6	0
Titration Period Protocol Violation	1	0
Maintenance Period Adverse Event	2	1

Baseline Characteristics

Efficacy, Safety and Tolerability of TRI476 (Oxcarbazepine) in Children With Inadequately Controlled Partial Onset Seizures

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TRI476 n=48 Participants Participants received TRI476 based on body weight with titration up to the maintenance dose, in addition to their traditional antiepileptics dosage.	Placebo n=51 Participants Participants received placebo to TRI476 without any adjustment to the dosing regimen, in addition to their traditional antiepileptics dosage.	Total n=99 Participants Total of all reporting groups
Age, Continuous	9.8 years STANDARD_DEVIATION 2.91 • n=93 Participants	9.2 years STANDARD_DEVIATION 2.83 • n=4 Participants	9.5 years STANDARD_DEVIATION 2.87 • n=27 Participants
Sex: Female, Male Female	22 Participants n=93 Participants	24 Participants n=4 Participants	46 Participants n=27 Participants
Sex: Female, Male Male	26 Participants n=93 Participants	27 Participants n=4 Participants	53 Participants n=27 Participants

PRIMARY outcome

Timeframe: screening and 28 days

Population: The Full Analysis set included all participants who received study drug.

Outcome measures

Outcome measures
Measure	TRI476 n=47 Participants Participants received TRI476 based on body weight with titration up to the maintenance dose, in addition to their traditional antiepileptics dosage.	Placebo n=51 Participants Participants received placebo to TRI476 without any adjustment to the dosing regimen, in addition to their traditional antiepileptics dosage.
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	14.82 percentage change per 28 days Standard Deviation 73.333

SECONDARY outcome

Timeframe: baseline, 28 days and 56 days

Population: The Full Analysis set included all participants who received study drug.

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.

Outcome measures

Outcome measures
Measure	TRI476 n=47 Participants Participants received TRI476 based on body weight with titration up to the maintenance dose, in addition to their traditional antiepileptics dosage.	Placebo n=51 Participants Participants received placebo to TRI476 without any adjustment to the dosing regimen, in addition to their traditional antiepileptics dosage.
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	90.61 seizures per 28 days Standard Deviation 283.187
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	98.73 seizures per 28 days Standard Deviation 291.781

SECONDARY outcome

Timeframe: screening to 28 days

Population: The Full Analysis set included all participants who received study drug.

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.

Outcome measures

Outcome measures
Measure	TRI476 n=47 Participants Participants received TRI476 based on body weight with titration up to the maintenance dose, in addition to their traditional antiepileptics dosage.	Placebo n=51 Participants Participants received placebo to TRI476 without any adjustment to the dosing regimen, in addition to their traditional antiepileptics dosage.
Percent of Participants With Response During Double-blind Phase, by Treatment Group	23.4 percentage of participants	3.9 percentage of participants

SECONDARY outcome

Timeframe: 28 days

Population: Analyzed set includes all participants who received study drug and had both baseline and post baseline data available.

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.

Outcome measures

Outcome measures
Measure	TRI476 n=47 Participants Participants received TRI476 based on body weight with titration up to the maintenance dose, in addition to their traditional antiepileptics dosage.	Placebo n=51 Participants Participants received placebo to TRI476 without any adjustment to the dosing regimen, in addition to their traditional antiepileptics dosage.
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	-16.89 percentage change in seizure frequency Standard Deviation 45.822
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	30.59 percentage change in seizure frequency Standard Deviation 91.551
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 64.660	12.11 percentage change in seizure frequency Standard Deviation 82.879

SECONDARY outcome

Timeframe: 56 days

Population: The Analysis set included all participants who received study drug and had data available for analysis.

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).

Outcome measures

Outcome measures
Measure	TRI476 n=47 Participants Participants received TRI476 based on body weight with titration up to the maintenance dose, in addition to their traditional antiepileptics dosage.	Placebo n=51 Participants Participants received placebo to TRI476 without any adjustment to the dosing regimen, in addition to their traditional antiepileptics dosage.
Number of Participants With Clinical Global Impression of Change (CGIC) at Final Assessment, by Treatment Group Marked improvement	9 participants	2 participants
Number of Participants With Clinical Global Impression of Change (CGIC) at Final Assessment, by Treatment Group Moderate improvement	8 participants	2 participants
Number of Participants With Clinical Global Impression of Change (CGIC) at Final Assessment, by Treatment Group Slight improvement	8 participants	6 participants
Number of Participants With Clinical Global Impression of Change (CGIC) at Final Assessment, by Treatment Group No change	21 participants	38 participants
Number of Participants With Clinical Global Impression of Change (CGIC) at Final Assessment, by Treatment Group Slight aggravation	1 participants	3 participants
Number of Participants With Clinical Global Impression of Change (CGIC) at Final Assessment, by Treatment Group Moderate aggravation	0 participants	0 participants
Number of Participants With Clinical Global Impression of Change (CGIC) at Final Assessment, by Treatment Group Marked aggravation	0 participants	0 participants

Adverse Events

TRI476

Serious events: 1 serious events

Other events: 38 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 27 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	TRI476 n=47 participants at risk Participants received TRI476 based on body weight with titration up to the maintenance dose, in addition to their traditional antiepileptics dosage.	Placebo n=51 participants at risk Participants received placebo to TRI476 without any adjustment to the dosing regimen, in addition to their traditional antiepileptics dosage.
Infections and infestations Bronchopneumonia	0.00% 0/47 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set	2.0% 1/51 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set
Nervous system disorders Somnolence	2.1% 1/47 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set	0.00% 0/51 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set

Other adverse events

Additional Information

Study Director

Novartis

Phone: 41 61 324 1111

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	TRI476 n=47 participants at risk Participants received TRI476 based on body weight with titration up to the maintenance dose, in addition to their traditional antiepileptics dosage.	Placebo n=51 participants at risk Participants received placebo to TRI476 without any adjustment to the dosing regimen, in addition to their traditional antiepileptics dosage.
Blood and lymphatic system disorders Leukopenia	4.3% 2/47 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set	0.00% 0/51 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set
Ear and labyrinth disorders Vertigo	4.3% 2/47 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set	0.00% 0/51 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set
Eye disorders Conjunctivitis	4.3% 2/47 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set	3.9% 2/51 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set
Eye disorders Diplopia	4.3% 2/47 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set	0.00% 0/51 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set
Gastrointestinal disorders Constipation	6.4% 3/47 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set	0.00% 0/51 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set
Gastrointestinal disorders Nausea	4.3% 2/47 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set	5.9% 3/51 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set
Gastrointestinal disorders Vomiting	10.6% 5/47 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set	5.9% 3/51 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set
General disorders Pyrexia	4.3% 2/47 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set	3.9% 2/51 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set
Infections and infestations Gastroenteritis	2.1% 1/47 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set	3.9% 2/51 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set
Infections and infestations Influenza	4.3% 2/47 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set	5.9% 3/51 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set
Infections and infestations Nasopharyngitis	10.6% 5/47 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set	17.6% 9/51 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set
Infections and infestations Otitis media	4.3% 2/47 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set	0.00% 0/51 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set
Infections and infestations Upper respiratory tract infection	8.5% 4/47 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set	9.8% 5/51 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set
Injury, poisoning and procedural complications Contusion	4.3% 2/47 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set	0.00% 0/51 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set
Injury, poisoning and procedural complications Head injury	4.3% 2/47 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set	0.00% 0/51 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set
Metabolism and nutrition disorders Hyponatraemia	4.3% 2/47 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set	0.00% 0/51 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set
Nervous system disorders Ataxia	4.3% 2/47 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set	0.00% 0/51 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set
Nervous system disorders Somnolence	42.6% 20/47 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set	9.8% 5/51 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set
Respiratory, thoracic and mediastinal disorders Upper respiratory tract inflammation	4.3% 2/47 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set	3.9% 2/51 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set
Skin and subcutaneous tissue disorders Drug eruption	4.3% 2/47 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set	2.0% 1/51 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set
Skin and subcutaneous tissue disorders Eczema	4.3% 2/47 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set	3.9% 2/51 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set
Skin and subcutaneous tissue disorders Rash	8.5% 4/47 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set	3.9% 2/51 A total of 99 patients were randomized, one patient who did not receive study drug was excluded from the safety analysis set