An Open Label Extension Study of Cannabidiol (GWP42003-P) in Children and Adults With Dravet or Lennox-Gastaut Syndromes

TEAEs, defined as AEs that started, or worsened in severity or seriousness, following the first dose of investigational medicinal product in this study, are reported. Any AEs that continued from the Core Study (GWEP1332A [NCT02091206], GWEP1332B [NCT02091375], GWEP1424 [NCT02224703], GWEP1414 [NCT02224560], and GWEP1423 [NCT02224690]) were only classified as treatment emergent if they worsened in this study.

Clinical significance was determined by the investigator. Pre-randomization Baseline of the Core Study (GWEP1332A [NCT02091206], GWEP1332B [NCT02091375], GWEP1424 [NCT02224703], GWEP1414 [NCT02224560], and GWEP1423 [NCT02224690]) is defined as Baseline of the double-blind, placebo-controlled, clinical studies with GWP42003-P. bpm = beats per minute; DBP = Diastolic Blood Pressure; mmHg = millimeters of mercury; SBP = Systolic Blood Pressure. Data for change from Baseline at pre-randomization of the Core Study are presented; however, the time frame represents the duration for which participants were enrolled in GWEP1415. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study.

BMI is an estimate of body fat based on body weight divided by height squared. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Pre-randomization Baseline of the Core Study (GWEP1332A [NCT02091206], GWEP1332B [NCT02091375], GWEP1424 [NCT02224703], GWEP1414 [NCT02224560], and GWEP1423 [NCT02224690]) is defined as Baseline of the double-blind, placebo-controlled, clinical studies with GWP42003-P. Data for change from Baseline at pre-randomization of the Core Study are presented; however, the time frame represents the duration for which participants were enrolled in GWEP1415. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study.

Clinical significance was determined by the investigator. Pre-randomization Baseline of the Core Study (GWEP1332A [NCT02091206], GWEP1332B [NCT02091375], GWEP1424 [NCT02224703], GWEP1414 [NCT02224560], and GWEP1423 [NCT02224690]) is defined as Baseline of the double-blind, placebo-controlled, clinical studies with GWP42003-P. msec = milliseconds; QTcB = corrected QT interval with Bazett's correction. The time frame represents the duration for which participants were enrolled in GWEP1415. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study.

The C-SSRS questionnaire is a brief, standardized measure that uniquely assesses the essential information (behavior, ideation, lethality, and severity) and distinguishes between suicidal occurrences and non-suicidal self-injury.

The Cannabis Withdrawal Scale is a 19-item scale administered to participants (18 years and above), with each item (withdrawal symptom) measured on a 0 to 10 numerical rating scale (0 = Not at all; 5 = Moderately; 10 = Extremely). Total score, calculated as the sum of the 19 item sub-scores ranging from 0-190 are reported. Higher scores indicate more withdrawal symptoms and an increased negative impact to quality of life. The participant or participant's caregiver was asked to record the extent to which each withdrawal symptom was experienced in the last 24 hours and also to rate the negative impact on normal daily activities. L24S = Last 24 Hours Score; NIS = Negative Impact on Normal Daily Activity Score. The End of Treatment visit occurred after a maximum of 260 weeks of treatment. The End of Taper occurred up to 10 days after the End of Treatment visit. The Safety Call and Safety Follow-up occurred 2 and 4 weeks, respectively, after the End of Taper.

The PCWS was administered to participants aged 4 to 17 (inclusive) that was developed from the 19-item validated CWS (adults) to assess mood, behavioral, and physical symptoms associated with cannabis. The total score, calculated as the sum of 10 items (rated on a 4-point scale: 0 = none; 1 = a little bit; 2 = quite a bit; 3 = a lot) ranging from 0-30 are reported. Higher scores indicate more withdrawal symptoms and an increased negative impact to quality of life. The End of Treatment visit occurred after a maximum of 260 weeks of treatment. The participant or participant's caregiver was asked to record the extent to which each withdrawal symptom was experienced in the last 24 hours and also to rate the negative impact on normal daily activities. The End of Taper occurred up to 10 days after the End of Treatment visit. The Safety Call and Safety Follow-up occurred 2 and 4 weeks, respectively, after the End of Taper.

Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Pre-randomization Baseline of the Core Study (GWEP1332A [NCT02091206], GWEP1332B [NCT02091375], GWEP1424 [NCT02224703], GWEP1414 [NCT02224560], and GWEP1423 [NCT02224690]) is defined as Baseline of the double-blind, placebo-controlled, clinical studies with GWP42003-P. Data for change from Baseline at pre-randomization of the Core Study are presented; however, the time frame represents the duration for which participants were enrolled in GWEP1415. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study.

Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Pre-randomization Baseline of the Core Study (GWEP1332A [NCT02091206], GWEP1332B [NCT02091375], GWEP1424 [NCT02224703], GWEP1414 [NCT02224560], and GWEP1423 [NCT02224690]) is defined as Baseline of the double-blind, placebo-controlled, clinical studies with GWP42003-P. Data for change from Baseline at pre-randomization of the Core Study are presented; however, the time frame represents the duration for which participants were enrolled in GWEP1415. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study.

Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Pre-randomization Baseline of the Core Study (GWEP1332A [NCT02091206], GWEP1332B [NCT02091375], GWEP1424 [NCT02224703], GWEP1414 [NCT02224560], and GWEP1423 [NCT02224690]) is defined as Baseline of the double-blind, placebo-controlled, clinical studies with GWP42003-P. Data for change from Baseline at pre-randomization of the Core Study are presented; however, the time frame represents the duration for which participants were enrolled in GWEP1415. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study.

Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Pre-randomization Baseline of the Core Study (GWEP1332A [NCT02091206], GWEP1332B [NCT02091375], GWEP1424 [NCT02224703], GWEP1414 [NCT02224560], and GWEP1423 [NCT02224690]) is defined as Baseline of the double-blind, placebo-controlled, clinical studies with GWP42003-P. Data for change from Baseline at pre-randomization of the Core Study are presented; however, the time frame represents the duration for which participants were enrolled in GWEP1415. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study.

Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Pre-randomization Baseline of the Core Study (GWEP1332A [NCT02091206], GWEP1332B [NCT02091375], GWEP1424 [NCT02224703], GWEP1414 [NCT02224560], and GWEP1423 [NCT02224690]) is defined as Baseline of the double-blind, placebo-controlled, clinical studies with GWP42003-P. Data for change from Baseline at pre-randomization of the Core Study are presented; however, the time frame represents the duration for which participants were enrolled in GWEP1415. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study.

Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Pre-randomization Baseline of the Core Study (GWEP1332A [NCT02091206], GWEP1332B [NCT02091375], GWEP1424 [NCT02224703], GWEP1414 [NCT02224560], and GWEP1423 [NCT02224690]) is defined as Baseline of the double-blind, placebo-controlled, clinical studies with GWP42003-P. Data for change from Baseline at pre-randomization of the Core Study are presented; however, the time frame represents the duration for which participants were enrolled in GWEP1415. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study.

Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Pre-randomization Baseline of the Core Study (GWEP1332A [NCT02091206], GWEP1332B [NCT02091375], GWEP1424 [NCT02224703], GWEP1414 [NCT02224560], and GWEP1423 [NCT02224690]) is defined as Baseline of the double-blind, placebo-controlled, clinical studies with GWP42003-P. Data for change from Baseline at pre-randomization of the Core Study are presented; however, the time frame represents the duration for which participants were enrolled in GWEP1415. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study.

Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Pre-randomization Baseline of the Core Study (GWEP1332A [NCT02091206], GWEP1332B [NCT02091375], GWEP1424 [NCT02224703], GWEP1414 [NCT02224560], and GWEP1423 [NCT02224690]) is defined as Baseline of the double-blind, placebo-controlled, clinical studies with GWP42003-P. Data for change from Baseline at pre-randomization of the Core Study are presented; however, the time frame represents the duration for which participants were enrolled in GWEP1415. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study.

Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Pre-randomization Baseline of the Core Study (GWEP1332A [NCT02091206], GWEP1332B [NCT02091375], GWEP1424 [NCT02224703], GWEP1414 [NCT02224560], and GWEP1423 [NCT02224690]) is defined as Baseline of the double-blind, placebo-controlled, clinical studies with GWP42003-P. Data for change from Baseline at pre-randomization of the Core Study are presented; however, the time frame represents the duration for which participants were enrolled in GWEP1415. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study.

Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Pre-randomization Baseline of the Core Study (GWEP1332A [NCT02091206], GWEP1332B [NCT02091375], GWEP1424 [NCT02224703], GWEP1414 [NCT02224560], and GWEP1423 [NCT02224690]) is defined as Baseline of the double-blind, placebo-controlled, clinical studies with GWP42003-P. mL/min/1.73 m^2 = millilitres per minute per 1.73 meters squared. Data for change from Baseline at pre-randomization of the Core Study are presented; however, the time frame represents the duration for which participants were enrolled in GWEP1415. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study.

Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Pre-randomization Baseline of the Core Study (GWEP1332A [NCT02091206], GWEP1332B [NCT02091375], GWEP1424 [NCT02224703], GWEP1414 [NCT02224560], and GWEP1423 [NCT02224690]) is defined as Baseline of the double-blind, placebo-controlled, clinical studies with GWP42003-P. Data for change from Baseline at pre-randomization of the Core Study are presented; however, the time frame represents the duration for which participants were enrolled in GWEP1415. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study.

Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Pre-randomization Baseline of the Core Study (GWEP1332A [NCT02091206], GWEP1332B [NCT02091375], GWEP1424 [NCT02224703], GWEP1414 [NCT02224560], and GWEP1423 [NCT02224690]) is defined as Baseline of the double-blind, placebo-controlled, clinical studies with GWP42003-P. Data for change from Baseline at pre-randomization of the Core Study are presented; however, the time frame represents the duration for which participants were enrolled in GWEP1415. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study.

Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Pre-randomization Baseline of the Core Study (GWEP1332A [NCT02091206], GWEP1332B [NCT02091375], GWEP1424 [NCT02224703], GWEP1414 [NCT02224560], and GWEP1423 [NCT02224690]) is defined as Baseline of the double-blind, placebo-controlled, clinical studies with GWP42003-P. Data for change from Baseline at pre-randomization of the Core Study are presented; however, the time frame represents the duration for which participants were enrolled in GWEP1415. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study.

Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Pre-randomization Baseline of the Core Study (GWEP1332A [NCT02091206], GWEP1332B [NCT02091375], GWEP1424 [NCT02224703], GWEP1414 [NCT02224560], and GWEP1423 [NCT02224690]) is defined as Baseline of the double-blind, placebo-controlled, clinical studies with GWP42003-P. Data for change from Baseline at pre-randomization of the Core Study are presented; however, the time frame represents the duration for which participants were enrolled in GWEP1415. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study.

Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Pre-randomization Baseline of the Core Study (GWEP1332A [NCT02091206], GWEP1332B [NCT02091375], GWEP1424 [NCT02224703], GWEP1414 [NCT02224560], and GWEP1423 [NCT02224690]) is defined as Baseline of the double-blind, placebo-controlled, clinical studies with GWP42003-P. Data for change from Baseline at pre-randomization of the Core Study are presented; however, the time frame represents the duration for which participants were enrolled in GWEP1415. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study.

IGF-1 levels in serum were analyzed as part of the clinical laboratory testing in participants. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Pre-randomization Baseline of the Core Study (GWEP1332A [NCT02091206], GWEP1332B [NCT02091375], GWEP1424 [NCT02224703], GWEP1414 [NCT02224560], and GWEP1423 [NCT02224690]) is defined as Baseline of the double-blind, placebo-controlled, clinical studies with GWP42003-P. Data for change from Baseline at pre-randomization of the Core Study are presented; however, the time frame represents the duration for which participants were enrolled in GWEP1415. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study.

The S/CGIC allows participants and caregivers to rate the participant's overall condition on a scale of 1 to 7 (1 = Very Much Improved, and 7 = Very Much Worse). The combined caregiver and participant summary used either the caregiver or participant version if only one version was completed, or the caregiver version when both the caregiver and participant versions were completed. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study.

Total seizures included the sum of all seizures (tonic-clonic, tonic, atonic, clonic, myoclonic, countable partial, other partial, and absence seizures) recorded by the participant or caregiver. Change from Baseline was calculated as the percentage change from Baseline for each 12-week period. Pre-randomization Baseline of the Core Study (GWEP1332A [NCT02091206], GWEP1332B [NCT02091375], GWEP1424 [NCT02224703], GWEP1414 [NCT02224560], and GWEP1423 [NCT02224690]) is defined as Baseline of the double-blind, placebo-controlled, clinical studies with GWP42003-P. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study. "Last 12 weeks" is equal to the last 12 weeks' data for each participant irrespective of time in study.

Drop seizures are defined as the subset of tonic-clonic, tonic, or atonic seizures. Change from Baseline was calculated as the percentage change from Baseline for each 12-week period. Pre-randomization Baseline of the Core Study (GWEP1332A [NCT02091206], GWEP1332B [NCT02091375], GWEP1424 [NCT02224703], GWEP1414 [NCT02224560], and GWEP1423 [NCT02224690]) is defined as Baseline of the double-blind, placebo-controlled, clinical studies with GWP42003-P. Data for change from Baseline at pre-randomization of the Core Study are presented; however, the time frame represents the duration for which participants were enrolled in GWEP1415. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study. The outcome was reported for Lennox-Gastaut Syndrome participants only. "Last 12 weeks" is equal to the last 12 weeks' data for each participant irrespective of time in study.

Convulsive seizures are defined as tonic-clonic, tonic, clonic, or atonic seizures. Change from Baseline was calculated as the percentage change from Baseline for each 12-week period. Pre-randomization Baseline of the Core Study (GWEP1332A [NCT02091206], GWEP1332B [NCT02091375], GWEP1424 [NCT02224703], GWEP1414 [NCT02224560], and GWEP1423 [NCT02224690]) is defined as Baseline of the double-blind, placebo-controlled, clinical studies with GWP42003-P. Data for change from Baseline at pre-randomization of the Core Study are presented; however, the time frame represents the duration for which participants were enrolled in GWEP1415. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study. The outcome was reported for Dravet Syndrome participants only. "Last 12 weeks" is equal to the last 12 weeks' data for each participant irrespective of time in study.

Status epilepticus is defined as any seizure lasting for 30 minutes or longer. The number of convulsive seizures greater than 30 minutes in duration and the number of non-convulsive seizures greater than 30 minutes in duration were collected weekly. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study. mins = minutes. "Last 12 weeks" is equal to the last 12 weeks' data for each participant irrespective of time in study.

The QOLCE is a parent-reported questionnaire that evaluates health-related QOL in children aged 2-18 years old. It contains 76 items with 16 subscales covering 7 domains (physical activities, social activities, cognition, emotional well-being, behavior, general health, and general QOL). All items in the questionnaire are rated on a 5-point or 6-point categorical scale. Based on the responses to the items in each domain, scores for 16 subscales are derived. Score range from 0 to 100. Higher score indicate highest level of functioning. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Pre-randomization Baseline of the Core Study is defined as the Baseline of the double-blind, placebo-controlled, clinical studies with GWP42003-P. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study.

The QOLIE-31-P is a survey of health-related QOL for adults with epilepsy. It is comprised of 38 questions about health daily activities and evaluates how much distress the participant feels about problems and worries related to epilepsy. The questionnaire consists of 7 subscales (energy, mood, daily activities, cognition, medication effects, seizure worry, and overall QOL). Scores range from 0 to 100. Higher scores indicate better QOL. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Pre-randomization Baseline of the Core Study is defined as Baseline of the double-blind, placebo-controlled, clinical studies with GWP42003-P. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study. The outcome was reported for Lennox-Gastaut Syndrome participants only.

The Vineland-II is an individually administered instrument for assessing adaptive behaviors. It consists of 4 adaptive behavior domains (1 = low; 5 = high) and a maladaptive behavior domain (1 = clinically significant; 3 = average), and an overall Adaptive Behavior Composite Score. Standard scores (population mean = 100, SD = 15, range = 20 to 160) are produced for the domain and composite scores, and scaled scores (called v-scale scores, with a population mean = 15, SD = 3, range = 1 to 24) are produced for the subscale scores. Higher scores indicate better functioning.

Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Pre-randomization Baseline of the Core Study is defined as Baseline of the double-blind, placebo-controlled, clinical studies with GWP42003-P. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study.

Inpatient hospitalizations due to epilepsy were recorded by the investigator. The timing of the "End of Treatment" varied per participant based on when the participant discontinued IMP.

Total seizures included the sum of all seizures (tonic-clonic, tonic, atonic, clonic, myoclonic, countable partial, other partial, and absence seizures) recorded by the participant or caregiver.

The SGICSD and CGICSD are comprised of the following questions rated on a 3-point scale for each seizure type. The CGICSD score is used to assess the average duration of the participant's seizures (comparing their condition now to their condition before treatment) and the SGICSD score is used to assess the average duration of seizures (comparing condition now to condition before treatment). Scores range from 1 to 3 (1 = Decrease in average duration; 3 = Increase in average duration).

D-KEFS Visual Scanning Completion Time Scale was used to measure visual attention and processing speed. The cognitive assessment battery items are age-specific, used to measure a variety of functions for both children and adults. The items were administered by an experienced psychometrician to a sub-group of sites that had the expertise to conduct the test. The raw score i.e., total time in seconds for completing the visual scanning trial was measured in the range of 0-150; higher scores indicated worse functioning. The raw score was normed with a referenced score to convert into a scaled score (i.e., score on a scale) ranging from 1-19; higher scores indicated better functioning. Change from the pre-randomization Baseline of the core study to the End of Treatment are reported as score on a scale. Negative values indicate worsening and positive values indicate improvement in cognitive function.

D-KEFS Number Sequencing Completion Time Scale was used to measure processing speed. The raw score i.e., total time in seconds for completing the number sequencing trial was measured in the range of 0-150; higher scores indicated worse functioning. The raw score was normed with a referenced score to convert into a scaled score (i.e., score on a scale) ranging from 1-19; higher scores indicated better processing speed. Change from the pre-randomization Baseline of the core study to the End of Treatment are reported as score on a scale. Negative values indicate worsening and positive values indicate improvement in processing speed. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study.

D-KEFS Letter Sequencing Completion Time Scaled was used to measure processing speed. The raw score i.e., total time in seconds for completing the letter sequencing trial was measured in the range of 0-150; higher scores indicated worse functioning. The raw score was normed with a referenced score to calculate a scaled score (i.e., score on a scale) ranging from 1-19; higher scores indicated better processing speed. Change from the pre-randomization Baseline of the core study to the End of Treatment are reported as score on a scale. Negative values indicate worsening and positive values indicate improvement in processing speed. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study.

D-KEFS Number-letter Switching Completion Time Scale was used to measure cognitive flexibility, task-set switching, and general executive functioning. The raw score i.e., total time in seconds for completing the number-letter switching trial was measured in the range of 0-240; higher scores indicated worse functioning. The raw score was normed with a referenced score to calculate a scaled score (i.e., score on a scale) ranging from 1-19; higher scores indicated better functioning. Change from the pre-randomization Baseline of the core study to the End of Treatment are reported as score on a scale. Negative values indicate worsening and positive values indicate improvement in cognitive function. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study.

D-KEFS Motor Speed Completion Time Scale was used to measure motor speed. The raw score i.e., total time in seconds for completing the motor speed trial was measured in the range of 0-150; higher scores indicated worse functioning. The raw score was normed with a referenced score to calculate a scaled score (i.e., score on a scale) ranging from 1-19; higher scores indicated better motor speed. Change from the pre-randomization Baseline of the core study to the End of Treatment are reported as score on a scale. Negative values indicate worsening and positive values indicate improvement in motor speed. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study.

Purdue Pegboard test was used to measure fine motor dexterity of both hands. The raw score was calculated as the total number of pegs in 30 seconds; higher scores indicated higher level of motor dexterity. The raw score was converted to a Z-score ranging from 0-19; higher scores indicate a higher level of motor dexterity. Change from the pre-randomization Baseline of the core study to the End of Treatment are reported as Z-score (i.e., score on a scale). Negative values indicate worsening and positive values indicate improvement in motor dexterity. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study.

Purdue Pegboard test was used to measure fine motor dexterity of the dominant hand. The raw score was calculated as the total number of pegs in 30 seconds; higher scores indicated higher level of motor dexterity. The raw score was converted to a Z-score ranging from 0-19; higher scores indicate a higher level of motor dexterity. Change from the pre-randomization Baseline of the core study to the End of Treatment are reported as Z-score (i.e., score on a scale). Negative values indicate worsening and positive values indicate improvement in motor dexterity. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study.

Purdue Pegboard test was used to measure fine motor dexterity of the non dominant hand. The raw score was calculated as the total number of pegs in 30 seconds; higher scores indicated higher level of motor dexterity. The raw score was converted to a Z-score ranging from 0-19; higher scores indicate a higher level of motor dexterity. Change from the pre-randomization Baseline of the core study to the End of Treatment are reported as Z-score (i.e., score on a scale). Negative values indicate worsening and positive values indicate improvement in motor dexterity. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study.

WAIS Coding Scale was used to measure processing speed. The raw score i.e., sum of correct substitutions was measured in the range of 0-16. The raw score was normed with a referenced score to calculate a scaled score (i.e., score on a scale) ranging from 1-19; higher scores indicated better processing speed. Change from the pre-randomization Baseline of the core study to the End of Treatment are reported as score on a scale. Negative values indicate worsening and positive values indicate improvement in processing speed. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study.

WAIS Digit Span Backward Scale was used to measure working memory. The raw score i.e., sum of correct trials was measured in the range of 0-16. The raw score was normed with a referenced score to calculate a scaled score (i.e., score on a scale) ranging from 1-19; higher scores indicated better working memory. Change from the pre-randomization Baseline of the core study to the End of Treatment are reported as score on a scale. Negative values indicate worsening and positive values indicate improvement in working memory. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study.

WAIS Digit Span Forward Scale was used to measure auditory memory. The raw score i.e., sum of correct trials was measured in the range of 0-16. The raw score was normed with a referenced score to calculate a scaled score (i.e., score on a scale) ranging from 1-19; higher scores indicated better auditory memory. Change from the pre-randomization Baseline of the core study to the End of Treatment are reported as score on a scale. Negative values indicate worsening and positive values indicate improvement in auditory memory. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study.

WAIS Longest Digit Span Backward Scale was used to measure working memory. The raw score i.e., sum of correct trials was measured in the range of 2-8. The raw score was normed with a referenced score to calculate a scaled score (i.e., score on a scale) ranging from 1-19; higher scores indicated better working memory. Change from the pre-randomization Baseline of the core study to the End of Treatment are reported as score on a scale. Negative values indicate worsening and positive values indicate improvement in working memory. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study.

WAIS Longest Digit Span Forward Scale was used to measure auditory memory. The raw score i.e., sum of correct trials was measured in the range of 2-8. The raw score was normed with a referenced score to calculate a scaled score (i.e., score on a scale) ranging from 1-19; higher scores indicated better auditory memory. Change from the pre-randomization Baseline of the core study to the End of Treatment are reported as score on a scale. Negative values indicate worsening and positive values indicate improvement in auditory memory. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study.

WAIS-II Vocabulary T Score was used to estimate general intellectual ability based on fund of information and verbal intelligence. The raw score i.e., the sum of correct responses was converted to a T-score ranging from 20-80 using the WASI assessment manual; T-scores are standard scores with a mean of 50 and a standard deviation of 10. Higher scores indicate a higher level of intelligence. Change from the pre-randomization Baseline of the core study to the End of Treatment are reported as T-score (i.e., score on a scale). Negative values indicate worsening and positive values indicate improvement in intelligence. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study.

WASI-II Matrix Reasoning T Score was used to estimate general intellectual ability based abstract reasoning. The raw score i.e., the sum of correct responses was converted to a T-score ranging from 20-80 using the WASI assessment manual; T-scores are standard scores with a mean of 50 and a standard deviation of 10. Higher scores indicate a higher level of abstract reasoning. Change from the pre-randomization Baseline of the core study to the End of Treatment are reported as T-score (i.e., score on a scale). Negative values indicate worsening and positive values indicate improvement in abstract reasoning. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study.

WISC Coding Scale was used to measure processing speed in children aged 6-16 years 11 months, with scores ranging from 0 to 119. Higher scores indicate better processing speed. Change from the pre-randomization Baseline of the core study to the End of Treatment are reported as score on a scale. Negative values indicate worsening and positive values indicate improvement in processing speed. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study.

WISC Digit Span Backward Scale was used to measure working memory. The raw score i.e., sum of correct trials was measured on a scale of 0-18; higher scores indicated better working memory. Change from the pre-randomization Baseline of the core study to the End of Treatment are reported as score on a scale. Negative values indicate worsening and positive values indicate improvement in working memory. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study.

WISC Digit Span Forward Scale was used to measure auditory memory. The raw score i.e., sum of correct trials was measured on a scale of 0-18; higher scores indicated better auditory memory. Change from the pre-randomization Baseline of the core study to the End of Treatment are reported as score on a scale. Negative values indicate worsening and positive values indicate improvement in auditory memory. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study.

WISC Longest Digit Span Backward Scale was used to measure working memory. The raw score i.e., sum of correct trials was measured on a scale of 2-8; higher scores indicated better working memory. Change from the pre-randomization Baseline of the core study to the End of Treatment are reported as score on a scale. Negative values indicate worsening and positive values indicate improvement in working memory. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study.

WISC Longest Digit Span Forward Scale was used to measure auditory memory. The raw score i.e., sum of correct trials was measured on a scale of 2-10; higher scores indicated better auditory memory. Change from the pre-randomization Baseline of the core study to the End of Treatment are reported as score on a scale. Negative values indicate worsening and positive values indicate improvement in auditory memory. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study.

WPPSI-IV Bug Search T Score was used to measure processing speed and complex attention. The raw score i.e., the sum of correct responses was measured on a scale of 1-19 and converted to a T-score ranging from 20-80; T-scores are standard scores with a mean of 50 and a standard deviation of 10. Higher scores indicate a higher level of attention. Change from the pre-randomization Baseline of the core study to the End of Treatment are reported as T-score (i.e., score on a scale). Negative values indicate worsening and positive values indicate improvement in attention. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study.

WPPSI-IV Receptive Vocabulary T Score was used to measure fund of information. The raw score i.e., the sum of correct responses was measured on a scale of 1-19 and converted to a T-score ranging from 20-80; T-scores are standard scores with a mean of 50 and a standard deviation of 10. Higher scores indicate a higher level of intelligence. Change from the pre-randomization Baseline of the core study to the End of Treatment are reported as as T-score (i.e., score on a scale). Negative values indicate worsening and positive values indicate improvement in intelligence. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study.

WPPSI-IV Matrix Reasoning T Score was used to measure abstract reasoning. The raw score i.e., the sum of correct responses was measured on a scale of 1-19 and converted to a T-score ranging from 20-80; T-scores are standard scores with a mean of 50 and a standard deviation of 10. Higher scores indicate a higher level of abstract reasoning. Change from the pre-randomization Baseline of the core study to the End of Treatment are reported as T-score (i.e., score on a scale). Negative values indicate worsening and positive values indicate improvement in abstract reasoning. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study.

Expressive One-Word Picture Vocabulary Test-4th edition was used to test vocabulary. The raw score i.e., the sum of correct responses was measured on a scale of 1-19 and converted to a T-score ranging from 0-83; T-scores are standard scores with a mean of 100 and a standard deviation of 15. Higher scores indicate a higher level of language performance. Change from the pre-randomization Baseline of the core study to the End of Treatment are reported as as T-score (i.e., score on a scale). Negative values indicate worsening and positive values indicate improvement in language performance. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study.

Developmental NEuroPSYchological Assessment (NEPSY)-2 Word Generation Scale was used to measure verbal fluency. The raw score i.e., the sum of correct responses was converted to a scaled score (i.e., score on a scale) ranging from 1-19; higher scores indicate a higher level of verbal fluency. Change from the pre-randomization Baseline of the core study to the End of Treatment are reported as score on a scale. Negative values indicate worsening and positive values indicate improvement in verbal fluency. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study.

Visual Perception Standard scale was used to measure visual motor functioning. The raw score i.e., the sum of the correct responses was measured on a 6-standard score range. Score range of 70-79 indicated "low," 80-89 indicated "below average," 90-109 indicated "average," 110-119 indicated "above average," 120-129 indicated "high," and >129 indicated "very high" visual motor functioning. Change from the pre-randomization Baseline of the core study to the End of Treatment are reported as score on a scale. Negative values indicate worsening and positive values indicate improvement in visual motor functioning. The only data presented from the Core Studies in this report are the comparison of the Extension Study data with the Baseline data at pre-randomization of the Core Study.