Trial Outcomes & Findings for An Open Label Study of Levetiracetam in Japanese Pediatric Patients With Partial Seizures (NCT NCT01063764)
NCT ID: NCT01063764
Last Updated: 2015-03-05
Results Overview
The change in partial seizure frequency from Baseline (B) over the Treatment Period (T) is given as a percentage reduction computed as: (B values- T values) / B values x 100. Positive values in percent reduction mean that the value decreased from Baseline during the first 14-week Period. Frequency per week of partial seizures = (Total number of partial seizures in a certain Period/number of observation days in the Period) x 7. Partial seizures can be classified into: * Simple partial seizures * Complex partial seizures * Partial seizures evolving to secondarily generalized seizures.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
73 participants
Primary outcome timeframe
From Baseline (Week 0-8) to the 14-weeks Treatment Period (First Period: 4 weeks Up-titration (Week 8-12) and 10 weeks Evaluation (Week 12-22)); Week 0-22
Results posted on
2015-03-05
Participant Flow
Full Analysis Set (FAS) includes all subjects taking at least one dose of study medication. Per-Protocol Set (PPS) is a subset of the FAS, consisting of subjects without major protocol violations affecting the primary efficacy variable.
Participant Flow refers to the Full Analysis Set. First Period started after Baseline (Week 0 to Week 8).
Participant milestones
| Measure |
Levetiracetam
* First Period (4 weeks Up-titration and 10 weeks Evaluation): Dry syrup 50 %, 20 mg/kg/day or 1000 mg/day, 40 mg/kg/day or 2000 mg/day, 60 mg/kg/day or 3000 mg/day, twice daily administration Per Os (PO) for 14 weeks.
* Second Period: Dry syrup 50 % or tablets (250 mg and 500 mg strengths), 20 to 60 mg/kg/day or 1000 to 3000 mg/day, twice daily administration Per Os (PO) until indication granted.
* Withdrawal Period (6 weeks): Patients on the dose at 60 mg/kg/day or 3000 mg/day will be decreased to 40 mg/kg/day or 2000 mg/day for first 2 weeks and then to 20 mg/kg/day or 1000 mg/day for 2 additional weeks. For patients on the dose at 40 mg/kg/day or 2000 mg/day, the dosage will be decreased to 20 mg/kg/day or 1000 mg/day for 2 weeks and then the treatment with LEV will be stopped.
|
|---|---|
|
1st Period (From Week 8 to Week 22)
STARTED
|
73
|
|
1st Period (From Week 8 to Week 22)
COMPLETED
|
62
|
|
1st Period (From Week 8 to Week 22)
NOT COMPLETED
|
11
|
|
2nd Period (Week 22 to the End of Study)
STARTED
|
55
|
|
2nd Period (Week 22 to the End of Study)
COMPLETED
|
35
|
|
2nd Period (Week 22 to the End of Study)
NOT COMPLETED
|
20
|
Reasons for withdrawal
| Measure |
Levetiracetam
* First Period (4 weeks Up-titration and 10 weeks Evaluation): Dry syrup 50 %, 20 mg/kg/day or 1000 mg/day, 40 mg/kg/day or 2000 mg/day, 60 mg/kg/day or 3000 mg/day, twice daily administration Per Os (PO) for 14 weeks.
* Second Period: Dry syrup 50 % or tablets (250 mg and 500 mg strengths), 20 to 60 mg/kg/day or 1000 to 3000 mg/day, twice daily administration Per Os (PO) until indication granted.
* Withdrawal Period (6 weeks): Patients on the dose at 60 mg/kg/day or 3000 mg/day will be decreased to 40 mg/kg/day or 2000 mg/day for first 2 weeks and then to 20 mg/kg/day or 1000 mg/day for 2 additional weeks. For patients on the dose at 40 mg/kg/day or 2000 mg/day, the dosage will be decreased to 20 mg/kg/day or 1000 mg/day for 2 weeks and then the treatment with LEV will be stopped.
|
|---|---|
|
1st Period (From Week 8 to Week 22)
Adverse Event
|
4
|
|
1st Period (From Week 8 to Week 22)
Lack of Efficacy
|
6
|
|
1st Period (From Week 8 to Week 22)
Withdrawal by Subject
|
1
|
|
2nd Period (Week 22 to the End of Study)
Adverse Event
|
3
|
|
2nd Period (Week 22 to the End of Study)
Lack of Efficacy
|
9
|
|
2nd Period (Week 22 to the End of Study)
Withdrawal by Subject
|
7
|
|
2nd Period (Week 22 to the End of Study)
Protocol Violation
|
1
|
Baseline Characteristics
An Open Label Study of Levetiracetam in Japanese Pediatric Patients With Partial Seizures
Baseline characteristics by cohort
| Measure |
Levetiracetam
n=73 Participants
* First Period (4 weeks Up-titration and 10 weeks Evaluation): Dry syrup 50 %, 20 mg/kg/day or 1000 mg/day, 40 mg/kg/day or 2000 mg/day, 60 mg/kg/day or 3000 mg/day, twice daily administration Per Os (PO) for 14 weeks.
* Second Period: Dry syrup 50 % or tablets (250 mg and 500 mg strengths), 20 to 60 mg/kg/day or 1000 to 3000 mg/day, twice daily administration Per Os (PO) until indication granted.
* Withdrawal Period (6 weeks): Patients on the dose at 60 mg/kg/day or 3000 mg/day will be decreased to 40 mg/kg/day or 2000 mg/day for first 2 weeks and then to 20 mg/kg/day or 1000 mg/day for 2 additional weeks. For patients on the dose at 40 mg/kg/day or 2000 mg/day, the dosage will be decreased to 20 mg/kg/day or 1000 mg/day for 2 weeks and then the treatment with LEV will be stopped.
|
|---|---|
|
Age, Continuous
|
10.1 years
STANDARD_DEVIATION 3.4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
32 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
41 Participants
n=5 Participants
|
|
Region of Enrollment
Japan
|
73 participants
n=5 Participants
|
|
Age Categorical
>=4 - <8 years
|
22 participants
n=5 Participants
|
|
Age Categorical
>=8 - <12 years
|
22 participants
n=5 Participants
|
|
Age Categorical
>=12 - <16 years
|
29 participants
n=5 Participants
|
|
Body Weight
|
32.43 kilogram (kg)
STANDARD_DEVIATION 13.20 • n=5 Participants
|
|
Height
|
134.55 centimeter (cm)
STANDARD_DEVIATION 20.69 • n=5 Participants
|
|
Body Mass Index (BMI)
|
17.15 kilogram / meter^2 (kg/m^2)
STANDARD_DEVIATION 2.99 • n=5 Participants
|
|
Hospitalization Status
Yes
|
0 participants
n=5 Participants
|
|
Hospitalization Status
No
|
73 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From Baseline (Week 0-8) to the 14-weeks Treatment Period (First Period: 4 weeks Up-titration (Week 8-12) and 10 weeks Evaluation (Week 12-22)); Week 0-22Population: Full Analysis Set (FAS).
The change in partial seizure frequency from Baseline (B) over the Treatment Period (T) is given as a percentage reduction computed as: (B values- T values) / B values x 100. Positive values in percent reduction mean that the value decreased from Baseline during the first 14-week Period. Frequency per week of partial seizures = (Total number of partial seizures in a certain Period/number of observation days in the Period) x 7. Partial seizures can be classified into: * Simple partial seizures * Complex partial seizures * Partial seizures evolving to secondarily generalized seizures.
Outcome measures
| Measure |
Levetiracetam
n=73 Participants
* First Period (4 weeks Up-titration and 10 weeks Evaluation): Dry syrup 50 %, 20 mg/kg/day or 1000 mg/day, 40 mg/kg/day or 2000 mg/day, 60 mg/kg/day or 3000 mg/day, twice daily administration Per Os (PO) for 14 weeks.
* Second Period: Dry syrup 50 % or tablets (250 mg and 500 mg strengths), 20 to 60 mg/kg/day or 1000 to 3000 mg/day, twice daily administration Per Os (PO) until indication granted.
* Withdrawal Period (6 weeks): Patients on the dose at 60 mg/kg/day or 3000 mg/day will be decreased to 40 mg/kg/day or 2000 mg/day for first 2 weeks and then to 20 mg/kg/day or 1000 mg/day for 2 additional weeks. For patients on the dose at 40 mg/kg/day or 2000 mg/day, the dosage will be decreased to 20 mg/kg/day or 1000 mg/day for 2 weeks and then the treatment with LEV will be stopped.
|
|---|---|
|
Change From Baseline in Partial Seizure Frequency Per Week Over the 14-weeks Treatment Period
|
43.21 Percent reduction
Interval 26.19 to 52.14
|
PRIMARY outcome
Timeframe: During the second Period from Visit 8 (Week 22) to the end of the Follow-up Period (up to three years until the time of approval granted)Population: Full Analysis Set (FAS).
An Adverse Event (AE) is any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product which does not necessarily have a causal relationship with the pharmaceutical product. Incidence of treatment-emergent AEs is reported by the percentage of subjects with at least one treatment-emergent AE.
Outcome measures
| Measure |
Levetiracetam
n=55 Participants
* First Period (4 weeks Up-titration and 10 weeks Evaluation): Dry syrup 50 %, 20 mg/kg/day or 1000 mg/day, 40 mg/kg/day or 2000 mg/day, 60 mg/kg/day or 3000 mg/day, twice daily administration Per Os (PO) for 14 weeks.
* Second Period: Dry syrup 50 % or tablets (250 mg and 500 mg strengths), 20 to 60 mg/kg/day or 1000 to 3000 mg/day, twice daily administration Per Os (PO) until indication granted.
* Withdrawal Period (6 weeks): Patients on the dose at 60 mg/kg/day or 3000 mg/day will be decreased to 40 mg/kg/day or 2000 mg/day for first 2 weeks and then to 20 mg/kg/day or 1000 mg/day for 2 additional weeks. For patients on the dose at 40 mg/kg/day or 2000 mg/day, the dosage will be decreased to 20 mg/kg/day or 1000 mg/day for 2 weeks and then the treatment with LEV will be stopped.
|
|---|---|
|
Incidence of Treatment-Emergent Adverse Events (TEAEs) During the Second Period (up to Three Years Until the Time of Approval Granted)
|
98.2 percentage of participants
|
SECONDARY outcome
Timeframe: From Baseline (Week 0-8) to the 10-weeks Evaluation Period (Part of the first Period: Week 12 to Week 22)Population: Of the 73 subjects in the FAS, 68 subjects had available data at Baseline and during the Evaluation Period.
The change in partial seizure frequency from Baseline (B) over the Evaluation Period (E) is given as a percentage reduction computed as: (B values- E values) / B values x 100. Positive values in percent reduction mean that the value decreased from Baseline to the 10-week Evaluation Period. Frequency per week of partial seizures = (Total number of partial seizures in a certain Period/number of observation days in the Period) x 7. Partial seizures can be classified into: * Simple partial seizures * Complex partial seizures * Partial seizures evolving to secondarily generalized seizures.
Outcome measures
| Measure |
Levetiracetam
n=68 Participants
* First Period (4 weeks Up-titration and 10 weeks Evaluation): Dry syrup 50 %, 20 mg/kg/day or 1000 mg/day, 40 mg/kg/day or 2000 mg/day, 60 mg/kg/day or 3000 mg/day, twice daily administration Per Os (PO) for 14 weeks.
* Second Period: Dry syrup 50 % or tablets (250 mg and 500 mg strengths), 20 to 60 mg/kg/day or 1000 to 3000 mg/day, twice daily administration Per Os (PO) until indication granted.
* Withdrawal Period (6 weeks): Patients on the dose at 60 mg/kg/day or 3000 mg/day will be decreased to 40 mg/kg/day or 2000 mg/day for first 2 weeks and then to 20 mg/kg/day or 1000 mg/day for 2 additional weeks. For patients on the dose at 40 mg/kg/day or 2000 mg/day, the dosage will be decreased to 20 mg/kg/day or 1000 mg/day for 2 weeks and then the treatment with LEV will be stopped.
|
|---|---|
|
Change From Baseline in Partial Seizure Frequency Per Week Over the 10-week Evaluation Period
|
39.02 Percent reduction
Interval 26.67 to 52.07
|
SECONDARY outcome
Timeframe: 14-weeks Treatment Period (First Period: 4 weeks Up-titration (Week 8-12) and 10 weeks Evaluation (Week 12-22))Population: Full Analysis Set (FAS). Only subjects having values unequal to zero over Baseline and values equal to or greater than zero over Treatment Period are included.
The seizure frequency per week was calculated as: Frequency per week of partial seizures = (Total number of partial seizures in the Treatment Period/number of days for observation in the Treatment Period) x 7. Partial seizures can be classified into one of the following three groups: * Simple partial seizures * Complex partial seizures * Partial seizures evolving to secondarily generalized seizures.
Outcome measures
| Measure |
Levetiracetam
n=73 Participants
* First Period (4 weeks Up-titration and 10 weeks Evaluation): Dry syrup 50 %, 20 mg/kg/day or 1000 mg/day, 40 mg/kg/day or 2000 mg/day, 60 mg/kg/day or 3000 mg/day, twice daily administration Per Os (PO) for 14 weeks.
* Second Period: Dry syrup 50 % or tablets (250 mg and 500 mg strengths), 20 to 60 mg/kg/day or 1000 to 3000 mg/day, twice daily administration Per Os (PO) until indication granted.
* Withdrawal Period (6 weeks): Patients on the dose at 60 mg/kg/day or 3000 mg/day will be decreased to 40 mg/kg/day or 2000 mg/day for first 2 weeks and then to 20 mg/kg/day or 1000 mg/day for 2 additional weeks. For patients on the dose at 40 mg/kg/day or 2000 mg/day, the dosage will be decreased to 20 mg/kg/day or 1000 mg/day for 2 weeks and then the treatment with LEV will be stopped.
|
|---|---|
|
Partial Seizure Frequency Per Week Over the 14-weeks Treatment Period
|
3.92 Seizures per week
Interval 0.93 to 17.08
|
SECONDARY outcome
Timeframe: 10-weeks Evaluation Period (Part of the first Period: Week 12 to Week 22)Population: Full Analysis Set (FAS). Only subjects having values unequal to zero over Baseline and values equal to or greater than zero over Treatment Period are included.
The seizure frequency per week was calculated as: Frequency per week of partial seizures = (Total number of partial seizures in the Evaluation Period/number of days for observation in the Evaluation Period) x 7. Partial seizures can be classified into one of the following three groups: * Simple partial seizures * Complex partial seizures * Partial seizures evolving to secondarily generalized seizures.
Outcome measures
| Measure |
Levetiracetam
n=68 Participants
* First Period (4 weeks Up-titration and 10 weeks Evaluation): Dry syrup 50 %, 20 mg/kg/day or 1000 mg/day, 40 mg/kg/day or 2000 mg/day, 60 mg/kg/day or 3000 mg/day, twice daily administration Per Os (PO) for 14 weeks.
* Second Period: Dry syrup 50 % or tablets (250 mg and 500 mg strengths), 20 to 60 mg/kg/day or 1000 to 3000 mg/day, twice daily administration Per Os (PO) until indication granted.
* Withdrawal Period (6 weeks): Patients on the dose at 60 mg/kg/day or 3000 mg/day will be decreased to 40 mg/kg/day or 2000 mg/day for first 2 weeks and then to 20 mg/kg/day or 1000 mg/day for 2 additional weeks. For patients on the dose at 40 mg/kg/day or 2000 mg/day, the dosage will be decreased to 20 mg/kg/day or 1000 mg/day for 2 weeks and then the treatment with LEV will be stopped.
|
|---|---|
|
Partial Seizure Frequency Per Week Over the 10-weeks Evaluation Period
|
3.90 Seizures per week
Interval 0.86 to 17.26
|
SECONDARY outcome
Timeframe: 14-weeks Treatment Period (First Period: 4 weeks Up-titration (Week 8-12) and 10 weeks Evaluation (Week 12-22))Population: Full Analysis Set (FAS).
50 % responders are those subjects which have a 50 % or more reduction in the frequency of partial seizures from Baseline to the Treatment Period. The results show the percentage of participants that are 50 % responders. Partial seizures can be classified into one of the following three groups: * Simple partial seizures * Complex partial seizures * Partial seizures evolving to secondarily generalized seizures.
Outcome measures
| Measure |
Levetiracetam
n=73 Participants
* First Period (4 weeks Up-titration and 10 weeks Evaluation): Dry syrup 50 %, 20 mg/kg/day or 1000 mg/day, 40 mg/kg/day or 2000 mg/day, 60 mg/kg/day or 3000 mg/day, twice daily administration Per Os (PO) for 14 weeks.
* Second Period: Dry syrup 50 % or tablets (250 mg and 500 mg strengths), 20 to 60 mg/kg/day or 1000 to 3000 mg/day, twice daily administration Per Os (PO) until indication granted.
* Withdrawal Period (6 weeks): Patients on the dose at 60 mg/kg/day or 3000 mg/day will be decreased to 40 mg/kg/day or 2000 mg/day for first 2 weeks and then to 20 mg/kg/day or 1000 mg/day for 2 additional weeks. For patients on the dose at 40 mg/kg/day or 2000 mg/day, the dosage will be decreased to 20 mg/kg/day or 1000 mg/day for 2 weeks and then the treatment with LEV will be stopped.
|
|---|---|
|
Percentage of Partial Seizures 50 % Responders Over the 14-weeks Treatment Period
|
38.4 percentage of participants
Interval 27.2 to 50.5
|
SECONDARY outcome
Timeframe: 10-weeks Evaluation Period (Part of the first Period: Week 12 to Week 22)Population: Of the 73 subjects in the FAS, 68 subjects had available data over the Evaluation Period.
50 % responders are those subjects which have a 50 % or more reduction in the frequency of partial seizures from Baseline to the Evaluation Period. The results show the percentage of participants that are 50 % responders. Partial seizures can be classified into one of the following three groups: * Simple partial seizures * Complex partial seizures * Partial seizures evolving to secondarily generalized seizures.
Outcome measures
| Measure |
Levetiracetam
n=68 Participants
* First Period (4 weeks Up-titration and 10 weeks Evaluation): Dry syrup 50 %, 20 mg/kg/day or 1000 mg/day, 40 mg/kg/day or 2000 mg/day, 60 mg/kg/day or 3000 mg/day, twice daily administration Per Os (PO) for 14 weeks.
* Second Period: Dry syrup 50 % or tablets (250 mg and 500 mg strengths), 20 to 60 mg/kg/day or 1000 to 3000 mg/day, twice daily administration Per Os (PO) until indication granted.
* Withdrawal Period (6 weeks): Patients on the dose at 60 mg/kg/day or 3000 mg/day will be decreased to 40 mg/kg/day or 2000 mg/day for first 2 weeks and then to 20 mg/kg/day or 1000 mg/day for 2 additional weeks. For patients on the dose at 40 mg/kg/day or 2000 mg/day, the dosage will be decreased to 20 mg/kg/day or 1000 mg/day for 2 weeks and then the treatment with LEV will be stopped.
|
|---|---|
|
Percentage of Partial Seizures 50 % Responders Over the 10-weeks Evaluation Period
|
38.2 percentage of participants
Interval 26.7 to 50.8
|
SECONDARY outcome
Timeframe: 14-weeks Treatment Period (First Period: 4 weeks Up-titration (Week 8-12) and 10 weeks Evaluation (Week 12-22))Population: Full Analysis Set (FAS).
Seizure-free means not having a seizure of type I (Partial seizure). Partial seizures can be classified into one of the following three groups: * Simple partial seizures * Complex partial seizures * Partial seizures evolving to secondarily generalized seizures.
Outcome measures
| Measure |
Levetiracetam
n=73 Participants
* First Period (4 weeks Up-titration and 10 weeks Evaluation): Dry syrup 50 %, 20 mg/kg/day or 1000 mg/day, 40 mg/kg/day or 2000 mg/day, 60 mg/kg/day or 3000 mg/day, twice daily administration Per Os (PO) for 14 weeks.
* Second Period: Dry syrup 50 % or tablets (250 mg and 500 mg strengths), 20 to 60 mg/kg/day or 1000 to 3000 mg/day, twice daily administration Per Os (PO) until indication granted.
* Withdrawal Period (6 weeks): Patients on the dose at 60 mg/kg/day or 3000 mg/day will be decreased to 40 mg/kg/day or 2000 mg/day for first 2 weeks and then to 20 mg/kg/day or 1000 mg/day for 2 additional weeks. For patients on the dose at 40 mg/kg/day or 2000 mg/day, the dosage will be decreased to 20 mg/kg/day or 1000 mg/day for 2 weeks and then the treatment with LEV will be stopped.
|
|---|---|
|
Number of Seizure-free Subjects Over the 14-weeks Treatment Period
|
2 participants
|
SECONDARY outcome
Timeframe: 10-weeks Evaluation Period (Part of the first Period: Week 12 to Week 22)Population: Of the 73 subjects in the FAS, 68 subjects had available data over the Evaluation Period.
Seizure-free means not having a seizure of type I (Partial seizure). Partial seizures can be classified into one of the following three groups: * Simple partial seizures * Complex partial seizures * Partial seizures evolving to secondarily generalized seizures.
Outcome measures
| Measure |
Levetiracetam
n=68 Participants
* First Period (4 weeks Up-titration and 10 weeks Evaluation): Dry syrup 50 %, 20 mg/kg/day or 1000 mg/day, 40 mg/kg/day or 2000 mg/day, 60 mg/kg/day or 3000 mg/day, twice daily administration Per Os (PO) for 14 weeks.
* Second Period: Dry syrup 50 % or tablets (250 mg and 500 mg strengths), 20 to 60 mg/kg/day or 1000 to 3000 mg/day, twice daily administration Per Os (PO) until indication granted.
* Withdrawal Period (6 weeks): Patients on the dose at 60 mg/kg/day or 3000 mg/day will be decreased to 40 mg/kg/day or 2000 mg/day for first 2 weeks and then to 20 mg/kg/day or 1000 mg/day for 2 additional weeks. For patients on the dose at 40 mg/kg/day or 2000 mg/day, the dosage will be decreased to 20 mg/kg/day or 1000 mg/day for 2 weeks and then the treatment with LEV will be stopped.
|
|---|---|
|
Number of Seizure-free Subjects Over the 10-weeks Evaluation Period
|
3 participants
|
SECONDARY outcome
Timeframe: During the second Period from Visit 8 (Week 22) to the end of the Follow-up Period (up to three years until the time of approval granted)Population: Full Analysis Set (FAS).
An Adverse Drug Reaction (ADR) is an Adverse Event for which a causal relationship between the product and the occurrence is suspected. Incidence of ADRs is reported by the number of subjects with at least one ADR.
Outcome measures
| Measure |
Levetiracetam
n=55 Participants
* First Period (4 weeks Up-titration and 10 weeks Evaluation): Dry syrup 50 %, 20 mg/kg/day or 1000 mg/day, 40 mg/kg/day or 2000 mg/day, 60 mg/kg/day or 3000 mg/day, twice daily administration Per Os (PO) for 14 weeks.
* Second Period: Dry syrup 50 % or tablets (250 mg and 500 mg strengths), 20 to 60 mg/kg/day or 1000 to 3000 mg/day, twice daily administration Per Os (PO) until indication granted.
* Withdrawal Period (6 weeks): Patients on the dose at 60 mg/kg/day or 3000 mg/day will be decreased to 40 mg/kg/day or 2000 mg/day for first 2 weeks and then to 20 mg/kg/day or 1000 mg/day for 2 additional weeks. For patients on the dose at 40 mg/kg/day or 2000 mg/day, the dosage will be decreased to 20 mg/kg/day or 1000 mg/day for 2 weeks and then the treatment with LEV will be stopped.
|
|---|---|
|
Incidence of Treatment-emergent Adverse Drug Reactions (ADRs) During the Second Period (up to Three Years Until the Time of Approval Granted)
|
15 participants
|
SECONDARY outcome
Timeframe: From Baseline (Week 0-8) until the time of approval granted (up to three years from date of informed consent (Week 0); without 6-weeks Withdrawal Period)Population: Full Analysis Set (FAS).
The outcome was also calculated for each 3-month Period but here only the result for the total Second Evaluation Period (Second Period without following 6-weeks Withdrawal Period for withdrawers) is presented. Change in partial seizure frequency from Baseline (B) over Second Evaluation Period (E) is given as a percentage reduction computed as: (B values- E values) / B values x 100. Positive values in percent reduction show a decrease from Baseline. Frequency per week of partial seizures = (Total number of partial seizures in a certain Period/number of observation days in the Period) x 7.
Outcome measures
| Measure |
Levetiracetam
n=55 Participants
* First Period (4 weeks Up-titration and 10 weeks Evaluation): Dry syrup 50 %, 20 mg/kg/day or 1000 mg/day, 40 mg/kg/day or 2000 mg/day, 60 mg/kg/day or 3000 mg/day, twice daily administration Per Os (PO) for 14 weeks.
* Second Period: Dry syrup 50 % or tablets (250 mg and 500 mg strengths), 20 to 60 mg/kg/day or 1000 to 3000 mg/day, twice daily administration Per Os (PO) until indication granted.
* Withdrawal Period (6 weeks): Patients on the dose at 60 mg/kg/day or 3000 mg/day will be decreased to 40 mg/kg/day or 2000 mg/day for first 2 weeks and then to 20 mg/kg/day or 1000 mg/day for 2 additional weeks. For patients on the dose at 40 mg/kg/day or 2000 mg/day, the dosage will be decreased to 20 mg/kg/day or 1000 mg/day for 2 weeks and then the treatment with LEV will be stopped.
|
|---|---|
|
Change From Baseline in Partial Seizure Frequency Per Week for the Second Period (up to Three Years From Informed Consent Until the Time of Approval Granted)
|
41.32 Percent reduction
Interval 15.37 to 82.4
|
Adverse Events
Levetiracetam
Serious events: 8 serious events
Other events: 66 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Levetiracetam
n=73 participants at risk
* First Period (4 weeks Up-titration and 10 weeks Evaluation): Dry syrup 50 %, 20 mg/kg/day or 1000 mg/day, 40 mg/kg/day or 2000 mg/day, 60 mg/kg/day or 3000 mg/day, twice daily administration Per Os (PO) for 14 weeks.
* Second Period: Dry syrup 50 % or tablets (250 mg and 500 mg strengths), 20 to 60 mg/kg/day or 1000 to 3000 mg/day, twice daily administration Per Os (PO) until indication granted.
* Withdrawal Period (6 weeks): Patients on the dose at 60 mg/kg/day or 3000 mg/day will be decreased to 40 mg/kg/day or 2000 mg/day for first 2 weeks and then to 20 mg/kg/day or 1000 mg/day for 2 additional weeks. For patients on the dose at 40 mg/kg/day or 2000 mg/day, the dosage will be decreased to 20 mg/kg/day or 1000 mg/day for 2 weeks and then the treatment with LEV will be stopped.
|
|---|---|
|
Eye disorders
Strabismus
|
1.4%
1/73 • Number of events 1 • Adverse Events (AEs) were collected over the whole study from Baseline (Visit 2) over the complete First Period (14 weeks plus up to 6-week Down-titration and Follow-up) and the Second Period (Week 22 to the end of study).
AEs refer to the Full Analysis Set (FAS). FAS includes all subjects which received at least one dose of study medication.
|
|
Gastrointestinal disorders
Abdominal pain lower
|
1.4%
1/73 • Number of events 1 • Adverse Events (AEs) were collected over the whole study from Baseline (Visit 2) over the complete First Period (14 weeks plus up to 6-week Down-titration and Follow-up) and the Second Period (Week 22 to the end of study).
AEs refer to the Full Analysis Set (FAS). FAS includes all subjects which received at least one dose of study medication.
|
|
Gastrointestinal disorders
Acetonaemic vomiting
|
1.4%
1/73 • Number of events 2 • Adverse Events (AEs) were collected over the whole study from Baseline (Visit 2) over the complete First Period (14 weeks plus up to 6-week Down-titration and Follow-up) and the Second Period (Week 22 to the end of study).
AEs refer to the Full Analysis Set (FAS). FAS includes all subjects which received at least one dose of study medication.
|
|
Gastrointestinal disorders
Dental caries
|
1.4%
1/73 • Number of events 1 • Adverse Events (AEs) were collected over the whole study from Baseline (Visit 2) over the complete First Period (14 weeks plus up to 6-week Down-titration and Follow-up) and the Second Period (Week 22 to the end of study).
AEs refer to the Full Analysis Set (FAS). FAS includes all subjects which received at least one dose of study medication.
|
|
Infections and infestations
Gastroenteritis
|
2.7%
2/73 • Number of events 2 • Adverse Events (AEs) were collected over the whole study from Baseline (Visit 2) over the complete First Period (14 weeks plus up to 6-week Down-titration and Follow-up) and the Second Period (Week 22 to the end of study).
AEs refer to the Full Analysis Set (FAS). FAS includes all subjects which received at least one dose of study medication.
|
|
Infections and infestations
Pneumonia
|
1.4%
1/73 • Number of events 1 • Adverse Events (AEs) were collected over the whole study from Baseline (Visit 2) over the complete First Period (14 weeks plus up to 6-week Down-titration and Follow-up) and the Second Period (Week 22 to the end of study).
AEs refer to the Full Analysis Set (FAS). FAS includes all subjects which received at least one dose of study medication.
|
|
Injury, poisoning and procedural complications
Near drowning
|
1.4%
1/73 • Number of events 1 • Adverse Events (AEs) were collected over the whole study from Baseline (Visit 2) over the complete First Period (14 weeks plus up to 6-week Down-titration and Follow-up) and the Second Period (Week 22 to the end of study).
AEs refer to the Full Analysis Set (FAS). FAS includes all subjects which received at least one dose of study medication.
|
|
Nervous system disorders
Convulsion
|
2.7%
2/73 • Number of events 2 • Adverse Events (AEs) were collected over the whole study from Baseline (Visit 2) over the complete First Period (14 weeks plus up to 6-week Down-titration and Follow-up) and the Second Period (Week 22 to the end of study).
AEs refer to the Full Analysis Set (FAS). FAS includes all subjects which received at least one dose of study medication.
|
|
Nervous system disorders
Status epilepticus
|
1.4%
1/73 • Number of events 1 • Adverse Events (AEs) were collected over the whole study from Baseline (Visit 2) over the complete First Period (14 weeks plus up to 6-week Down-titration and Follow-up) and the Second Period (Week 22 to the end of study).
AEs refer to the Full Analysis Set (FAS). FAS includes all subjects which received at least one dose of study medication.
|
|
Psychiatric disorders
Conversion disorder
|
1.4%
1/73 • Number of events 2 • Adverse Events (AEs) were collected over the whole study from Baseline (Visit 2) over the complete First Period (14 weeks plus up to 6-week Down-titration and Follow-up) and the Second Period (Week 22 to the end of study).
AEs refer to the Full Analysis Set (FAS). FAS includes all subjects which received at least one dose of study medication.
|
Other adverse events
| Measure |
Levetiracetam
n=73 participants at risk
* First Period (4 weeks Up-titration and 10 weeks Evaluation): Dry syrup 50 %, 20 mg/kg/day or 1000 mg/day, 40 mg/kg/day or 2000 mg/day, 60 mg/kg/day or 3000 mg/day, twice daily administration Per Os (PO) for 14 weeks.
* Second Period: Dry syrup 50 % or tablets (250 mg and 500 mg strengths), 20 to 60 mg/kg/day or 1000 to 3000 mg/day, twice daily administration Per Os (PO) until indication granted.
* Withdrawal Period (6 weeks): Patients on the dose at 60 mg/kg/day or 3000 mg/day will be decreased to 40 mg/kg/day or 2000 mg/day for first 2 weeks and then to 20 mg/kg/day or 1000 mg/day for 2 additional weeks. For patients on the dose at 40 mg/kg/day or 2000 mg/day, the dosage will be decreased to 20 mg/kg/day or 1000 mg/day for 2 weeks and then the treatment with LEV will be stopped.
|
|---|---|
|
Eye disorders
Conjunctivitis
|
5.5%
4/73 • Number of events 5 • Adverse Events (AEs) were collected over the whole study from Baseline (Visit 2) over the complete First Period (14 weeks plus up to 6-week Down-titration and Follow-up) and the Second Period (Week 22 to the end of study).
AEs refer to the Full Analysis Set (FAS). FAS includes all subjects which received at least one dose of study medication.
|
|
Gastrointestinal disorders
Diarrhoea
|
12.3%
9/73 • Number of events 16 • Adverse Events (AEs) were collected over the whole study from Baseline (Visit 2) over the complete First Period (14 weeks plus up to 6-week Down-titration and Follow-up) and the Second Period (Week 22 to the end of study).
AEs refer to the Full Analysis Set (FAS). FAS includes all subjects which received at least one dose of study medication.
|
|
Gastrointestinal disorders
Nausea
|
6.8%
5/73 • Number of events 5 • Adverse Events (AEs) were collected over the whole study from Baseline (Visit 2) over the complete First Period (14 weeks plus up to 6-week Down-titration and Follow-up) and the Second Period (Week 22 to the end of study).
AEs refer to the Full Analysis Set (FAS). FAS includes all subjects which received at least one dose of study medication.
|
|
Gastrointestinal disorders
Abdominal Pain
|
6.8%
5/73 • Number of events 7 • Adverse Events (AEs) were collected over the whole study from Baseline (Visit 2) over the complete First Period (14 weeks plus up to 6-week Down-titration and Follow-up) and the Second Period (Week 22 to the end of study).
AEs refer to the Full Analysis Set (FAS). FAS includes all subjects which received at least one dose of study medication.
|
|
Gastrointestinal disorders
Constipation
|
8.2%
6/73 • Number of events 7 • Adverse Events (AEs) were collected over the whole study from Baseline (Visit 2) over the complete First Period (14 weeks plus up to 6-week Down-titration and Follow-up) and the Second Period (Week 22 to the end of study).
AEs refer to the Full Analysis Set (FAS). FAS includes all subjects which received at least one dose of study medication.
|
|
Gastrointestinal disorders
Dental Caries
|
6.8%
5/73 • Number of events 11 • Adverse Events (AEs) were collected over the whole study from Baseline (Visit 2) over the complete First Period (14 weeks plus up to 6-week Down-titration and Follow-up) and the Second Period (Week 22 to the end of study).
AEs refer to the Full Analysis Set (FAS). FAS includes all subjects which received at least one dose of study medication.
|
|
General disorders
Pyrexia
|
23.3%
17/73 • Number of events 32 • Adverse Events (AEs) were collected over the whole study from Baseline (Visit 2) over the complete First Period (14 weeks plus up to 6-week Down-titration and Follow-up) and the Second Period (Week 22 to the end of study).
AEs refer to the Full Analysis Set (FAS). FAS includes all subjects which received at least one dose of study medication.
|
|
General disorders
Irritability
|
5.5%
4/73 • Number of events 4 • Adverse Events (AEs) were collected over the whole study from Baseline (Visit 2) over the complete First Period (14 weeks plus up to 6-week Down-titration and Follow-up) and the Second Period (Week 22 to the end of study).
AEs refer to the Full Analysis Set (FAS). FAS includes all subjects which received at least one dose of study medication.
|
|
Infections and infestations
Nasopharyngitis
|
74.0%
54/73 • Number of events 205 • Adverse Events (AEs) were collected over the whole study from Baseline (Visit 2) over the complete First Period (14 weeks plus up to 6-week Down-titration and Follow-up) and the Second Period (Week 22 to the end of study).
AEs refer to the Full Analysis Set (FAS). FAS includes all subjects which received at least one dose of study medication.
|
|
Infections and infestations
Influenza
|
27.4%
20/73 • Number of events 24 • Adverse Events (AEs) were collected over the whole study from Baseline (Visit 2) over the complete First Period (14 weeks plus up to 6-week Down-titration and Follow-up) and the Second Period (Week 22 to the end of study).
AEs refer to the Full Analysis Set (FAS). FAS includes all subjects which received at least one dose of study medication.
|
|
Infections and infestations
Upper respiratory tract infection
|
16.4%
12/73 • Number of events 37 • Adverse Events (AEs) were collected over the whole study from Baseline (Visit 2) over the complete First Period (14 weeks plus up to 6-week Down-titration and Follow-up) and the Second Period (Week 22 to the end of study).
AEs refer to the Full Analysis Set (FAS). FAS includes all subjects which received at least one dose of study medication.
|
|
Infections and infestations
Gastroenteritis
|
9.6%
7/73 • Number of events 13 • Adverse Events (AEs) were collected over the whole study from Baseline (Visit 2) over the complete First Period (14 weeks plus up to 6-week Down-titration and Follow-up) and the Second Period (Week 22 to the end of study).
AEs refer to the Full Analysis Set (FAS). FAS includes all subjects which received at least one dose of study medication.
|
|
Infections and infestations
Impetigo
|
5.5%
4/73 • Number of events 4 • Adverse Events (AEs) were collected over the whole study from Baseline (Visit 2) over the complete First Period (14 weeks plus up to 6-week Down-titration and Follow-up) and the Second Period (Week 22 to the end of study).
AEs refer to the Full Analysis Set (FAS). FAS includes all subjects which received at least one dose of study medication.
|
|
Infections and infestations
Pharyngitis
|
5.5%
4/73 • Number of events 4 • Adverse Events (AEs) were collected over the whole study from Baseline (Visit 2) over the complete First Period (14 weeks plus up to 6-week Down-titration and Follow-up) and the Second Period (Week 22 to the end of study).
AEs refer to the Full Analysis Set (FAS). FAS includes all subjects which received at least one dose of study medication.
|
|
Injury, poisoning and procedural complications
Contusion
|
11.0%
8/73 • Number of events 11 • Adverse Events (AEs) were collected over the whole study from Baseline (Visit 2) over the complete First Period (14 weeks plus up to 6-week Down-titration and Follow-up) and the Second Period (Week 22 to the end of study).
AEs refer to the Full Analysis Set (FAS). FAS includes all subjects which received at least one dose of study medication.
|
|
Injury, poisoning and procedural complications
Excoriation
|
8.2%
6/73 • Number of events 8 • Adverse Events (AEs) were collected over the whole study from Baseline (Visit 2) over the complete First Period (14 weeks plus up to 6-week Down-titration and Follow-up) and the Second Period (Week 22 to the end of study).
AEs refer to the Full Analysis Set (FAS). FAS includes all subjects which received at least one dose of study medication.
|
|
Injury, poisoning and procedural complications
Wound
|
6.8%
5/73 • Number of events 10 • Adverse Events (AEs) were collected over the whole study from Baseline (Visit 2) over the complete First Period (14 weeks plus up to 6-week Down-titration and Follow-up) and the Second Period (Week 22 to the end of study).
AEs refer to the Full Analysis Set (FAS). FAS includes all subjects which received at least one dose of study medication.
|
|
Injury, poisoning and procedural complications
Arthropod bite
|
5.5%
4/73 • Number of events 21 • Adverse Events (AEs) were collected over the whole study from Baseline (Visit 2) over the complete First Period (14 weeks plus up to 6-week Down-titration and Follow-up) and the Second Period (Week 22 to the end of study).
AEs refer to the Full Analysis Set (FAS). FAS includes all subjects which received at least one dose of study medication.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
6.8%
5/73 • Number of events 5 • Adverse Events (AEs) were collected over the whole study from Baseline (Visit 2) over the complete First Period (14 weeks plus up to 6-week Down-titration and Follow-up) and the Second Period (Week 22 to the end of study).
AEs refer to the Full Analysis Set (FAS). FAS includes all subjects which received at least one dose of study medication.
|
|
Nervous system disorders
Somnolence
|
46.6%
34/73 • Number of events 48 • Adverse Events (AEs) were collected over the whole study from Baseline (Visit 2) over the complete First Period (14 weeks plus up to 6-week Down-titration and Follow-up) and the Second Period (Week 22 to the end of study).
AEs refer to the Full Analysis Set (FAS). FAS includes all subjects which received at least one dose of study medication.
|
|
Nervous system disorders
Headache
|
13.7%
10/73 • Number of events 20 • Adverse Events (AEs) were collected over the whole study from Baseline (Visit 2) over the complete First Period (14 weeks plus up to 6-week Down-titration and Follow-up) and the Second Period (Week 22 to the end of study).
AEs refer to the Full Analysis Set (FAS). FAS includes all subjects which received at least one dose of study medication.
|
|
Nervous system disorders
Convulsion
|
9.6%
7/73 • Number of events 8 • Adverse Events (AEs) were collected over the whole study from Baseline (Visit 2) over the complete First Period (14 weeks plus up to 6-week Down-titration and Follow-up) and the Second Period (Week 22 to the end of study).
AEs refer to the Full Analysis Set (FAS). FAS includes all subjects which received at least one dose of study medication.
|
|
Psychiatric disorders
Agitation
|
5.5%
4/73 • Number of events 4 • Adverse Events (AEs) were collected over the whole study from Baseline (Visit 2) over the complete First Period (14 weeks plus up to 6-week Down-titration and Follow-up) and the Second Period (Week 22 to the end of study).
AEs refer to the Full Analysis Set (FAS). FAS includes all subjects which received at least one dose of study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
8.2%
6/73 • Number of events 8 • Adverse Events (AEs) were collected over the whole study from Baseline (Visit 2) over the complete First Period (14 weeks plus up to 6-week Down-titration and Follow-up) and the Second Period (Week 22 to the end of study).
AEs refer to the Full Analysis Set (FAS). FAS includes all subjects which received at least one dose of study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
6.8%
5/73 • Number of events 10 • Adverse Events (AEs) were collected over the whole study from Baseline (Visit 2) over the complete First Period (14 weeks plus up to 6-week Down-titration and Follow-up) and the Second Period (Week 22 to the end of study).
AEs refer to the Full Analysis Set (FAS). FAS includes all subjects which received at least one dose of study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.5%
4/73 • Number of events 5 • Adverse Events (AEs) were collected over the whole study from Baseline (Visit 2) over the complete First Period (14 weeks plus up to 6-week Down-titration and Follow-up) and the Second Period (Week 22 to the end of study).
AEs refer to the Full Analysis Set (FAS). FAS includes all subjects which received at least one dose of study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
|
5.5%
4/73 • Number of events 4 • Adverse Events (AEs) were collected over the whole study from Baseline (Visit 2) over the complete First Period (14 weeks plus up to 6-week Down-titration and Follow-up) and the Second Period (Week 22 to the end of study).
AEs refer to the Full Analysis Set (FAS). FAS includes all subjects which received at least one dose of study medication.
|
|
Skin and subcutaneous tissue disorders
Acne
|
8.2%
6/73 • Number of events 6 • Adverse Events (AEs) were collected over the whole study from Baseline (Visit 2) over the complete First Period (14 weeks plus up to 6-week Down-titration and Follow-up) and the Second Period (Week 22 to the end of study).
AEs refer to the Full Analysis Set (FAS). FAS includes all subjects which received at least one dose of study medication.
|
|
Skin and subcutaneous tissue disorders
Heat rash
|
6.8%
5/73 • Number of events 5 • Adverse Events (AEs) were collected over the whole study from Baseline (Visit 2) over the complete First Period (14 weeks plus up to 6-week Down-titration and Follow-up) and the Second Period (Week 22 to the end of study).
AEs refer to the Full Analysis Set (FAS). FAS includes all subjects which received at least one dose of study medication.
|
|
Skin and subcutaneous tissue disorders
Eczema
|
5.5%
4/73 • Number of events 5 • Adverse Events (AEs) were collected over the whole study from Baseline (Visit 2) over the complete First Period (14 weeks plus up to 6-week Down-titration and Follow-up) and the Second Period (Week 22 to the end of study).
AEs refer to the Full Analysis Set (FAS). FAS includes all subjects which received at least one dose of study medication.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
5.5%
4/73 • Number of events 6 • Adverse Events (AEs) were collected over the whole study from Baseline (Visit 2) over the complete First Period (14 weeks plus up to 6-week Down-titration and Follow-up) and the Second Period (Week 22 to the end of study).
AEs refer to the Full Analysis Set (FAS). FAS includes all subjects which received at least one dose of study medication.
|
|
Skin and subcutaneous tissue disorders
Rash
|
5.5%
4/73 • Number of events 6 • Adverse Events (AEs) were collected over the whole study from Baseline (Visit 2) over the complete First Period (14 weeks plus up to 6-week Down-titration and Follow-up) and the Second Period (Week 22 to the end of study).
AEs refer to the Full Analysis Set (FAS). FAS includes all subjects which received at least one dose of study medication.
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
5.5%
4/73 • Number of events 4 • Adverse Events (AEs) were collected over the whole study from Baseline (Visit 2) over the complete First Period (14 weeks plus up to 6-week Down-titration and Follow-up) and the Second Period (Week 22 to the end of study).
AEs refer to the Full Analysis Set (FAS). FAS includes all subjects which received at least one dose of study medication.
|
Additional Information
UCB Clinical Trial Call Center
UCB
Phone: +1 877 822 9493 (UCB)
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60