1. Incidence of Treatment Emergent Adverse Events

Supplemental Tables

Results of the post hoc analyses based onthe number and the combination of concomitant antiepileptic drugs taken at baseline are presented here. Concomitant AEDs at baseline are defined as those AEDs initiated before, or on Day 1 of the study and co-administered for at least 3 days with levetiracetam.

1. Incidence of treatment emergent adverse events

1.1. Incidence of TEAEs analysed according to the number of concomitant AEDs taken at baseline

1.2. Incidence of TEAEs analysed according to the combination of concomitant AEDs taken at baseline.

2. Incidence of serious treatment emergent adverse events

2.1. Incidence of serious TEAEs analysed according to the number of concomitant AEDs taken at baseline

2.2 Incidence of serious TEAEs analysed according to the combination of concomitant AEDs taken at baseline

3. Body weight – observed values and changes from baseline

3.1. Body weight analysed according to the number of concomitant AEDs taken at baseline

3.2. Body weight analysed according to the combination of concomitant AEDs taken at baseline

4. Body length (height) – observed values and changes from baseline

4.1. Body length analysed according to the number of concomitant AEDs taken at baseline

4.2. Body length analysed according to the combination of concomitant AEDs taken at baseline

5. Head circumference – observed values and changes from baseline

5.1. Head circumference analysed according to the number of concomitant AEDs taken at baseline

5.2. Head circumference analysed according to the combination of concomitant AEDs taken at baseline

6. Change in psychomotor development

6.1. Change in psychomotor development analysed according to the number of concomitant AEDs taken at baseline.

6.2. Change in psychomotor development analysed according to the combination of concomitant AEDs taken at baseline.

7. Change in epilepsy severity

7.1. Change in epilepsy severity analysed according to the number of concomitant AEDs taken at baseline.

7.2. Change in epilepsy severity analysed according to the combination of concomitant AEDs taken at baseline

1. Incidence of treatment emergent adverse events

1.1. Incidence of TEAEsanalysed according to the number of concomitant AEDs taken at baseline

TEAEs reported for at least two patients in any subgroup (safety set)

Preferred term according to MedDRA version 16.1 / None (n=40)
n (%) / 1 AED(n=33)
n (%) / ≥2 AEDs (n=28)
n (%)
Diarrhoea / 3 (7.5) / 1 (3.0) / 2 (7.1)
Vomiting / 2 (5.0) / 1 (3.0) / 0
Pyrexia / 4 (10.0) / 0 / 4 (14.3)
Irritability / 2 (5.0) / 1 (3.0) / 1 (3.6)
Bronchiolitis / 3 (7.5) / 0 / 0
Bronchitis / 2 (5.0) / 4 (12.1) / 4 (14.3)
Gastroenteritis / 3 (7.5) / 1 (3.0) / 0
Urinary tract infection / 0 / 2 (6.1) / 0
Nasopharyngitis / 2 (5.0) / 1 (3.0) / 1 (3.6)
Ear infection / 1 (2.5) / 0 / 2 (7.1)
Convulsion / 2 (5.0) / 4 (12.1) / 4 (14.3)
Epilepsy / 1 (2.5) / 0 / 2 (7.1)
Hypotonia / 0 / 2 (6.1) / 0
Infantile spasms / 0 / 2 (6.1) / 1 (3.6)

1.2. Incidence of TEAEsanalysed according tothe combination of concomitant AEDs taken at baseline.

No TEAEs were reported for ≥2 patients in any subgroup (vigabatrin, phenobarbital, valproate sodium, diazepam)

2. Incidence of serious treatment emergent adverse events

2.1. Incidence of serious TEAEsanalysed according tothe number of concomitant AEDs taken at baseline

Serious TEAEs reported for at least two patients in any subgroup (safety set).

Preferred term according to MedDRA version 16.1 / None (n=40)
n (%) / 1 AED (n=33)
n (%) / ≥2 AEDs (n=28)
n (%)
Diarrhoea / 2 (5.0) / 0 / 0
Vomiting / 2 (5.0) / 0 / 0
Bronchiolitis / 2 (5.0) / 0 / 0
Gastroenteritis / 2 (5.0) / 0 / 0
Convulsion / 2 (5.0) / 4 (12.1) / 4 (14.3)
Epilepsy / 1 (2.5) / 0 / 2 (7.1)

2.2 Incidence of serious TEAEsanalysed according tothe combination of concomitant AEDs taken at baseline

No serious TEAEs were reported for ≥2 patients in any subgroup (vigabatrin, phenobarbital, valproate sodium, diazepam)

3. Body weight – observed values and changes from baseline

3.1. Body weight analysed according to the number of concomitant AEDs taken at baseline

No concomitant AEDs
Visit / N* / Mean observed value
kg (SD) / Baseline mean
kg / Mean change
kg (SD)
Visit 1 / 40 / 6.39 (2.03) / Not applicable / Not applicable
Visit 2 / 29 / 7.18 (1.87) / 6.26 / 0.92 (0.48)
Visit 3 / 21 / 7.62 (1.47) / 5.45 / 2.17 (0.87)
Visit 4 / 15 / 8.51(1.01) / 4.91 / 3.60 (0.93)
Visit 5 / 5 / 8.38 (1.36) / 4.20 / 4.18 (1.15)
Visit 6 / 0
Visit 7 / 31 / 9.16 (1.74) / 6.42 / 2.74 (1.73)
One concomitant AED
Visit 1 / 32 / 7.69 (1.73) / Not applicable / Not applicable
Visit 2 / 25 / 8.51 (1.32) / 7.97 / 0.54(0.76)
Visit 3 / 11 / 9.30 (1.51) / 7.65 / 1.65 (1.12)
Visit 4 / 2 / 8.75 (1.06) / 6.65 / 2.10 (0.00)
Visit 5 / 1 / 10.50 / 6.60 / 3.90
Visit 6 / 0
Visit 7 / 29 / 9.39 (2.05) / 7.94 / 1.45 (1.60)
Two or more concomitant AEDs
Visit 1 / 28 / 7.10 (1.82) / Not applicable / Not applicable
Visit 2 / 19 / 7.77 (1.69) / 6.78 / 0.99 (0.59)
Visit 3 / 12 / 8.73 (2.13) / 6.38 / 2.34 (1.66)
Visit 4 / 6 / 8.92 (2.89) / 5.68 / 3.23 (2.16)
Visit 5 / 2 / 8.00 (1.13) / 3.95 / 4.05 (0.92)
Visit 6 / 0
Visit 7 / 21 / 10.00 (2.92) / 7.24 / 2.76 (2.56)

*Number of observed values at the given visit

3.2. Body weight analysed according to the combination of concomitant AEDs taken at baseline

Vigabatrin
Visit / N* / Mean observed value kg (SD) / Baseline mean
kg / Mean change
kg (SD)
Visit 1 / 9 / 8.11 (1.91) / Not applicable / Not applicable
Visit 2 / 9 / 8.73 (1.75) / 8.11 / 0.62 (1.01)
Visit 3 / 2 / 8.25 (3.04) / 6.30 / 1.95 (1.48)
Visit 4 / 0
Visit 5 / 0
Visit 6 / 0
Visit 7 / 9 / 9.14 (2.00) / 8.11 / 1.03 (1.19)
Phenobarbital
Visit 1 / 6 / 6.52 (1.65) / Not applicable / Not applicable
Visit 2 / 5 / 7.78 (0.66) / 7.10 / 0.68 (0.39)
Visit 3 / 2 / 8.50 (0.85) / 6.65 / 1.85 (0.21)
Visit 4 / 2 / 8.75 (1.06) / 6.65 / 2.10 (0.00)
Visit 5 / 0
Visit 6 / 0
Visit 7 / 4 / 8.30 (1.22) / 7.40 / 0.90 (1.01)
Benzodiazepines
Visit 1 / 7 / 6.86 (1.62) / Not applicable / Not applicable
Visit 2 / 4 / 8.40 (1.41) / 7.68 / 0.72 (0.43)
Visit 3 / 3 / 10.10 (0.85) / 7.73 / 2.37 (1.23)
Visit 4 / 0
Visit 5 / 1 / 10.50 / 6.60 / 3.90
Visit 6 / 0
Visit 7 / 6 / 9.95 (3.41) / 6.95 / 3.00 (2.43)
Valproate
Visit 1 / 8 / 8.68 (1.17) / Not applicable / Not applicable
Visit 2 / 5 / 8.84 (0.83) / 8.70 / 0.14 (0.86)
Visit 3 / 4 / 9.63 (1.35) / 8.78 / 0.85 (1.00)
Visit 4 / 0
Visit 5 / 0
Visit 6 / 0
Visit 7 / 8 / 9.74 (1.15) / 8.68 / 1.06 (1.05)

*Number of observed values at the given visit

4. Body length (height) – observed values and changes from baseline

4.1. Body length analysed according to the number of concomitant AEDs taken at baseline

No concomitant AEDs
Visit / N* / Mean observed value cm (SD) / Baseline mean
cm / Mean change
cm (SD)
Visit 1 / 37 / 61.59 (7.72) / Not applicable / Not applicable
Visit 2 / 22 / 65.02 (7.17) / 60.69 / 4.33 (2.49)
Visit 3 / 19 / 67.06 (5.35) / 58.45 / 8.62 (4.17)
Visit 4 / 14 / 68.87 (4.29) / 56.15 / 12.72 (4.41)
Visit 5 / 4 / 69.25 (2.50) / 54.25 / 15.00 (2.16)
Visit 6 / 0
Visit 7 / 29 / 73.47 (5.51) / 61.43 / 11.81 (7.08)
One concomitant AED
Visit 1 / 28 / 67.16 (6.98) / Not applicable / Not applicable
Visit 2 / 18 / 72.83 (4.30) / 69.74 / 3.38 (2.83)
Visit 3 / 10 / 73.33 (4.25) / 66.11 / 7.06 (2.31)
Visit 4 / 2 / 76.50 (2.12) / 67.25 / 9.25 (1.06)
Visit 5 / 1 / 78.50 / 62.00 / 16.50
Visit 6 / 0
Visit 7 / 22 / 74.77 (4.99) / 68.55 / 6.22 (4.02)
Two or more concomitant AEDs
Visit 1 / 27 / 64.56 (8.60) / Not applicable / Not applicable
Visit 2 / 15 / 65.75 (7.25) / 62.85 / 2.91 (3.12)
Visit 3 / 11 / 68.00 (4.32) / 58.11 / 9.89 (5.40)
Visit 4 / 5 / 68.50 (6.67) / 57.54 / 10.96 (5.76)
Visit 5 / 2 / 66.50 (0.71) / 48.35 / 18.15 (1.20)
Visit 6 / 0
Visit 7 / 16 / 75.72 (8.23) / 64.73 / 10.99 (13.75)

*Number of observed values at the given visit

4.2. Body length analysed according to the combination of concomitant AEDs taken at baseline

Vigabatrin
Visit / N* / Mean observed value cm (SD) / Baseline mean
cm / Mean change
cm (SD)
Visit 1 / 7 / 69.16 (8.54) / Not applicable / Not applicable
Visit 2 / 6 / 74.67 (4.19) / 71.85 / 2.82 (2.45)
Visit 3 / 2 / 68.90 (8.34) / 53.00 / 10.00
Visit 4 / 0
Visit 5 / 0
Visit 6 / 0
Visit 7 / 6 / 74.83 (4.84) / 69.97 / 4.87 (5.32)
Phenobarbital
Visit 1 / 5 / 64.40 (9.35) / Not applicable / Not applicable
Visit 2 / 4 / 70.00 (1.63) / 68.67 / 2.00 (3.50)
Visit 3 / 2 / 75.50 (2.12) / 67.25 / 8.25 (1.06)
Visit 4 / 2 / 76.50 (2.12) / 67.25 / 9.25 (1.06)
Visit 5 / 0
Visit 6 / 0
Visit 7 / 3 / 72.83 (2.02) / 68.67 / 4.17 (3.88)
Benzodiazepines
Visit 1 / 7 / 62.86 (5.18) / Not applicable / Not applicable
Visit 2 / 3 / 70.33 (5.69) / 65.67 / 4.67 (4.04)
Visit 3 / 2 / 72.75 (3.18) / 64.00 / 8.75 (0.35)
Visit 4 / 0
Visit 5 / 1 / 78.50 / 62.00 / 16.50
Visit 6 / 0
Visit 7 / 4 / 72.25 (8.95) / 62.00 / 10.25 (4.25)
Valproate
Visit 1 / 8 / 70.29 (3.18) / Not applicable / Not applicable
Visit 2 / 4 / 73.00 (3.24) / 69.88 / 3.13 (1.55)
Visit 3 / 4 / 74.75 (2.63) / 69.88 / 4.88 (1.31)
Visit 4 / 0
Visit 5 / 0
Visit 6 / 0
Visit 7 / 8 / 76.06 (3.39) / 70.29 / 5.78 (1.70)

*Number of observed values at the given visit

5. Head circumference – observed values and changes from baseline

5.1. Head circumference analysed according to the number of concomitant AEDs taken at baseline

No concomitant AEDs
Visit / N* / Mean observed value cm (SD) / Baseline mean
cm / Mean change
cm (SD)
Visit 1 / 39 / 41.01 (3.97) / Not applicable / Not applicable
Visit 2 / 27 / 42.41 (2.86) / 41.30 / 1.11 (1.88)
Visit 3 / 21 / 42.73 (2.70) / 39.72 / 3.01 (2.29)
Visit 4 / 13 / 42.67 (2.82) / 37.98 / 4.68 (1.34)
Visit 5 / 5 / 43.02 (3.39) / 37.70 / 5.32 (2.55)
Visit 6
Visit 7 / 29 / 44.94 (2.38) / 41.11 / 3.76 (3.22)
One concomitant AED
Visit 1 / 32 / 42.15 (3.09) / Not applicable / Not applicable
Visit 2 / 21 / 43.55 (2.90) / 42.53 / 1.01 (0.86)
Visit 3 / 11 / 44.06 (2.49) / 41.79 / 2.27 (1.23)
Visit 4 / 2 / 45.00 (2.12) / 41.85 / 3.15 (0.92)
Visit 5 / 0
Visit 6 / 0
Visit 7 / 26 / 44.24 (3.34) / 42.52 / 1.72 (1.31)
Two or more concomitant AEDs
Visit 1 / 28 / 40.98 (3.58) / Not applicable / Not applicable
Visit 2 / 18 / 42.05 (2.83) / 40.57 / 1.48 (1.58)
Visit 3 / 11 / 42.23 (2.66) / 38.48 / 3.75 (2.29)
Visit 4 / 6 / 42.53 (4.38) / 38.72 / 3.82 (1.93)
Visit 5 / 2 / 37.00 (9.90) / 35.25 / 1.75 (6.01)
Visit 6
Visit 7 / 17 / 44.28 (2.47) / 41.12 / 3.16 (3.34)

*Number of observed values at the given visit

5.2. Head circumference analysed according to the combination of concomitant AEDs taken at baseline

Vigabatrin
Visit / N* / Mean observed value
cm (SD) / Baseline mean
cm / Mean change
Cm (SD)
Visit 1 / 8 / 42.38 (3.11) / Not applicable / Not applicable
Visit 2 / 7 / 43.09 (3.33) / 42.36 / 0.73 (0.93)
Visit 3 / 2 / 43.70 (2.40) / 41.00 / 2.70 (0.28)
Visit 4 / 0
Visit 5 / 0
Visit 6 / 0
Visit 7 / 8 / 43.83 (2.97) / 42.38 / 1.45 (1.31)
Phenobarbital
Visit 1 / 7 / 41.60 (3.73) / Not applicable / Not applicable
Visit 2 / 5 / 42.92 (3.07) / 41.74 / 1.18 (0.68)
Visit 3 / 2 / 44.50 (2.83) / 41.85 / 2.65 (0.21)
Visit 4 / 2 / 45.00 (2.12) / 41.85 / 3.15 (0.92)
Visit 5 / 0
Visit 6 / 0
Visit 7 / 5 / 44.80 (3.82) / 43.10 / 1.70 (1.10)
Benzodiazepines
Visit 1 / 7 / 40.79 (2.41) / Not applicable / Not applicable
Visit 2 / 3 / 43.27 (2.86) / 41.83 / 1.43 (1.79)
Visit 3 / 3 / 43.77 (3.36) / 41.00 / 2.77 (2.14)
Visit 4 / 0
Visit 5 / 0
Visit 6 / 0
Visit 7 / 4 / 41.58 (3.68) / 39.75 / 1.83 (1.50)
Valproate
Visit 1 / 8 / 43.00 (2.76) / Not applicable / Not applicable
Visit 2 / 5 / 43.90 (1.82) / 42.90 / 1.00 (0.00)
Visit 3 / 4 / 44.25 (2.87) / 42.75 / 1.50 (0.82)
Visit 4 / 0
Visit 5 / 0
Visit 6 / 0
Visit 7 / 8 / 44.93 (2.64) / 43.00 / 1.93 (1.62)

*Number of observed values at the given visit

6. Change in psychomotor development

Change from baseline to visit 7 evaluated using the Physician's Global Evaluation Scale

6.1. Change in psychomotor development analysed according to the number of concomitant AEDs taken at baseline.

Change category / None (Nobs=34)
n (%) / 1 AED (Nobs=30)
n (%) / ≥2 AEDs (Nobs=21)
n (%)
Improved / 20 (58.8%) / 13 (43.3%) / 12 (57.1%)
Stable / 12 (35.3%) / 13 (43.3%) / 6 (28.6%)
Worsened / 2 (5.9%) / 4 (13.3%) / 3 (14.3%)

Nobsis the number of patients in the subgroup with a non-missing measurement at Visit 7

6.2. Change in psychomotor development analysed according to the combination of concomitant AEDs taken at baseline.

Change category / Vigabatrin
(Nobs=9)
n (%) / Phenobarbital
(Nobs=5)
n (%) / Benzodiazepines
(Nobs=6)
n (%) / Valproate
(Nobs=8)
n (%)
Improved / 7 (77.8%) / 3 (60.0%) / 0 / 3 (37.5%)
Stable / 2 (22.2%) / 1 (20.0%) / 4 (66.7%) / 4 (50.0%)
Worsened / 0 / 1 (20.0%) / 2 (33.3%) / 1 (12.5%)

Nobsis the number of patients in the subgroup with a non-missing measurement at Visit 7

7. Change in epilepsy severity

Change from baseline to visit 7 evaluated using the Physician's Global Evaluation Scale

7.1. Change in epilepsy severityanalysed according to the number of concomitant AEDs taken at baseline.

Change category / None
(Nobs=34)
n (%) / 1 AED
(Nobs=30)
n (%) / ≥2 AEDs
(Nobs=21)
n (%)
Improved / 26 (76.5%) / 21 (70.0%) / 14 (66.7%)
Stable / 6 (17.6%) / 5 (16.7%) / 5 (23.8%)
Worsened / 2 (5.9%) / 4 (13.3%) / 2 (9.5%)

Nobs is the number of patients in the subgroup with a non-missing measurement at Visit 7

7.2. Change in epilepsy severityanalysed according to the combination of concomitant AEDs taken at baseline

Change category / Vigabatrin
(Nobs=9)
n (%) / Phenobarbital
(Nobs=5)
n (%) / Benzodiazepines
(Nobs=6)
n (%) / Valproate
(Nobs=8)
n (%)
Improved / 6 (66.7%) / 3 (60.0%) / 4 (66.7%) / 7 (87.5%)
Stable / 3 (33.3%) / 1 (20.0%) / 0 / 0
Worsened / 0 / 1 (20.0%) / 2 (33.3%) / 1 (12.5%)

Nobs is the number of patients in the subgroup with a non-missing measurement at Visit 7

1