Epilepsy, Dravet Syndrome, Lennox-Gastaut Syndrome
Conditions
Keywords
Cannabidiol, CBD, GWP42003-P, GWPCARE5
Brief summary
To investigate the potential antiepileptic effects of cannabidiol (GWP42003-P) in children and adults with Dravet or Lennox-Gastaut syndromes.
Detailed description
This is a multi-center, open-label extension study for participants with Dravet syndrome or Lennox-Gastaut syndrome who have previously participated in double-blind, placebo-controlled clinical studies of GWP42003-P (Core Studies: GWEP1332A \[NCT02091206\], GWEP1332B \[NCT02091375\], GWEP1424 \[NCT02224703\], GWEP1414 \[NCT02224560\], GWEP1424 \[NCT02224703\], and GWEP1423 \[NCT02224690\]). The first participant was enrolled into the open-label extension study after the Data Safety Monitoring Committee reviewed the safety data from Part A of study GWEP1332.
Interventions
DRUGGWP42003-P
Sponsors
GW Research Ltd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: • Participant has completed the treatment phase of their Core Studies: GWEP1332A \[NCT02091206\], GWEP1332B \[NCT02091375\], GWEP1424 \[NCT02224703\], GWEP1414 \[NCT02224560\], GWEP1424 \[NCT02224703\], and GWEP1423 \[NCT02224690\]. Key
Exclusion criteria
* Participant is currently using or has in the past used recreational or medicinal cannabis, or synthetic cannabinoid-based medications (including Sativex®) within the 3 months prior to study entry other than the investigational medicinal product (IMP) received during the Core Study and are unwilling to abstain for the duration for the study. * Any history of suicidal behavior or any suicidal ideation of type 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) at Visit 1. * Participant has been part of a clinical trial involving an IMP during the inter-study period. * Female participant is of child bearing potential or male participant's partner is of child bearing potential, unless willing to ensure that they or their partner use highly effective contraception, for example, hormonal contraceptives, intrauterine devices/hormone-releasing systems, bilateral tubal occlusion, vasectomized partner or sexual abstinence, during the study and for 3 months thereafter (however, a male condom should not be used in conjunction with a female condom). * Participant has significantly impaired hepatic function at the 'End of Treatment' visit of their Core Study or at Visit 1 if re-assessed: i) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>5 × upper limit of normal (ULN); ii) ALT or AST \>3 × ULN and (total bilirubin \[TBL\] \>2 × ULN or international normalized ratio \[INR\] \>1.5); iii) ALT or AST \>3 × ULN with the presence of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, and/or eosinophilia (\>5%). This criterion must be confirmed prior to entering the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | up to Week 260 | 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. |
| Number of Participants With Clinically Significant Changes in the Indicated Vital Sign Values From the Pre-randomization Baseline of the Core Study at Any Time Post-dose | up to Week 260 | 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. |
| Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Body Mass Index (BMI) | up to Week 260 | 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. |
| Number of Participants With Clinically Significant Electrocardiogram (ECG) Values at the Pre-randomization Baseline of the Core Study and at Any Time Post-dose | up to Week 260 | 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. |
| Number of Participants With the Indicated Responses to Questions Regarding Suicidal Ideation and Behavior Using the Children's Columbia-Suicide Severity Rating Scale (C-SSRS) at Day 1 and at Any Time Post-dose | up to Week 260 | 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. |
| Mean Cannabis Withdrawal Scale Score at End of Taper (EOT), the Post-Taper Safety Call, and at Safety Follow-up | up to Week 260 | 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. |
| Mean Pediatric Cannabinoid Withdrawal Scale (PCWS) Score at the End of Treatment, the End of Taper, the Post-Taper Safety Call, and at Safety Follow-up | up to Week 260 | 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. |
| Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Red Blood Cells (RBCs) Values | up to Week 260 | 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. |
| Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Hemoglobin Levels | up to Week 260 | 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. |
| Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Hematocrit Values | up to Week 260 | 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. |
| Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Erythrocyte Mean Corpuscular Volume | up to Week 260 | 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. |
| Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Erythrocyte Mean Corpuscular Hemoglobin | up to Week 260 | 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. |
| Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Platelets, White Blood Cells, Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils | up to Week 260 | 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. |
| Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils in White Blood Cells (WBCs) | up to Week 260 | 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. |
| Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Sodium, Potassium, Blood Urea Nitrogen, Glucose, Calcium, and High-Density Lipoprotein (HDL) Cholesterol | up to week 260 | 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. |
| Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Creatinine (Jaffe), Creatinine (Enzymatic), and Bilirubin | up to Week 260 | 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. |
| Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Creatinine Clearance (Schwartz) and Creatinine Clearance (Cockcroft-Gault) | up to Week 260 | 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. |
| Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Alkaline Phosphatase, Aspartate Aminotransferase, Alanine Aminotransferase, and Gamma Glutamyl Transferase | up to Week 260 | 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. |
| Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Albumin and Protein | up to Week 260 | 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. |
| Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Prolactin | up to Week 260 | 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. |
| Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Prothrombin Time | up to Week 260 | 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. |
| Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Prothrombin International Normalized Ratio | up to Week 260 | 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. |
| Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Insulin-like Growth Factor-1 (IGF-1) Levels | up to Week 260 | 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. |
| Mean Subject/Caregiver Global Impression of Change (S/CGIC) Score | Baseline; up to Week 260 | 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. |
| Percent Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Total Seizure Frequency | Baseline; Week 49 to 60, Week 97 to 108, Week 145 to 156, Week 205 to 216, Week 253 to 264, and Last 12 Weeks | 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. |
| Percent Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Drop Seizure Frequency in Participants With Lennox-Gastaut Syndrome | Baseline; Week 49 to 60, Week 97 to 108, Week 145 to 156, Week 205 to 216, and Last 12 Weeks | 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. |
| Percent Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Convulsive Seizure Frequency in Participants With Dravet Syndrome | Baseline; Week 49 to 60, Week 97 to 108, Week 145 to 156, Week 205 to 216, Week 253 to 264, and Last 12 Weeks | 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. |
| Number of Participants With Convulsive and Non-convulsive Seizures Greater Than 30 Minutes in Duration (Status Epilepticus) | Baseline; At last 12 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WPPSI-IV Matrix Reasoning T Score | Baseline; up to Week 260 | 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. |
| Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Expressive One-Word Picture Vocabulary Test (EOWPVT) Scaled Score | Baseline; up to Week 260 | 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. |
| Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Quality of Life in Childhood Epilepsy (QOLCE) Scores | Baseline; up to Week 260 | 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. |
| Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Visual Perception Standard Scaled Score | Baseline; up to Week 260 | 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. |
| Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in a Developmental NEuroPSYchological Assessment (NEPSY)-2 Word Generation Scaled Score | Baseline; up to Week 260 | 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. |
| Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment QOL in Epilepsy Scores (QOLIE-31-P) in Participants With Lennox-Gastaut Syndrome | Baseline; up to Week 260 | 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. |
| Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Vineland Adaptive Behavior Scale, Second Edition (Vineland-II) Scores | Baseline; up to Week 260 | 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. |
| Number of Participants With Inpatient Hospitalizations Due to Epilepsy Since the Previous Visit | Week 48, 104, 156, 208, and End of Treatment (up to Week 260 based on when the participant discontinued treatment) | 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. |
| Number of Treatment Responders With Greater Than or Equal to 50% Reduction in Total Seizures | Baseline; Week 49 to 60, Week 97 to 108, Week 145 to 156, Week 205 to 216, Week 253 to 264, and Last 12 Weeks | 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. |
| Number of Participants With Changes in the Average Duration of Seizure Subtypes as Assessed by the Participant/Caregiver Global Impression of Change in Seizure Duration (S/CGICSD) | Up to Week 260 | 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). |
| Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Wechsler Adult Intelligence Scale (WAIS) Coding Scaled Score | Baseline; up to Week 260 | 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. |
| Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Delis-Kaplan Executive Function System (D-KEFS) Visual Scanning Completion Time Scaled Score | Baseline; up to Week 260 | 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. |
| Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in D-KEFS Number Sequencing Completion Time Scaled Score | Baseline; up to Week 260 | 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. |
| Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in D-KEFS Letter Sequencing Completion Time Scaled Score | Baseline; up to Week 260 | 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. |
| Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in D-KEFS Number-letter Switching Completion Time Scaled Score | Baseline; up to Week 260 | 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. |
| Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in D-KEFS Motor Speed Completion Time Scaled Score | Baseline; up to Week 260 | 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. |
| Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Purdue Pegboard Fine Motor Speed (Both Hands Z Score) | Baseline; up to Week 260 | 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. |
| Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Purdue Pegboard Fine Motor Speed (Dominant Hand Z Score) | Baseline; up to Week 260 | 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. |
| Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Purdue Pegboard Fine Motor Speed (Non Dominant Hand Z Score) | Baseline; up to Week 260 | 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. |
| Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WAIS Digit Span Backward Scaled Score | Baseline; up to Week 260 | 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. |
| Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WAIS Digit Span Forward Scaled Score | Baseline; up to Week 260 | 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. |
| Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WAIS Longest Digit Span Backward Scaled Score | Baseline; up to Week 260 | 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. |
| Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WAIS Longest Digit Span Forward Scaled Score | Baseline; up to Week 260 | 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. |
| Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Wechsler Abbreviated Scale of Intelligence (WASI)-II Vocabulary T Score | Baseline; up to Week 260 | 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. |
| Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WASI-II Matrix Reasoning T Score | Baseline; up to Week 260 | 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. |
| Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Wechsler Intelligence Scale for Children (WISC) Coding Scaled Score | Baseline; up to Week 260 | 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. |
| Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WISC Digit Span Backward Scaled Score | Baseline; up to Week 260 | 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. |
| Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WISC Digit Span Forward Scaled Score | Baseline; up to Week 260 | 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. |
| Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WISC Longest Digit Span Backward Scaled Score | Baseline; up to Week 260 | 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. |
| Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WISC Longest Digit Span Forward Scaled Score | Baseline; up to Week 260 | 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. |
| Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Wechsler Preschool & Primary Scale of Intelligence (WPPSI)-IV Bug Search T Score | Baseline; up to Week 260 | 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. |
| Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WPPSI-IV Receptive Vocabulary T Score | Baseline; up to Week 260 | 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. |
Participant flow
Pre-assignment details
Participants who completed the double-blind, placebo-controlled, clinical studies with GWP42003-P (Core Studies: GWEP1332A \[NCT02091206\], GWEP1332B \[NCT02091375\], GWEP1424 \[NCT02224703\], GWEP1414 \[NCT02224560\], and GWEP1423 \[NCT02224690\]) were eligible for enrollment.
Participants by arm
| Arm | Count |
|---|---|
| Dravet Syndrome Participants with Dravet Syndrome who completed double-blind, placebo-controlled, clinical studies of GWP42003-P (Core Studies: GWEP1332A \[NCT02091206\], GWEP1332B \[NCT02091375\], and GWEP1424 \[NCT02224703\]) were titrated up to 10 to 20 milligrams per kilogram per day (mg/kg/day) GWP42003-P using a recommended titration schedule during the Titration Period. Participants continued at this dose during the Maintenance Period. The maximum dose participants could receive was 30 mg/kg/day. | 315 |
| Lennox-Gastaut Syndrome Participants with Lennox-Gastaut Syndrome who completed double-blind, placebo-controlled, clinical studies of GWP42003-P (Core Studies: GWEP1414 \[NCT02224560\] and GWEP1423 \[NCT02224690\]) were titrated up to 10 to 20 milligrams per kilogram per day (mg/kg/day) GWP42003-P using a recommended titration schedule during the Titration Period. Participants continued at this dose during the Maintenance Period. The maximum dose participants could receive was 30 mg/kg/day. | 366 |
| Total | 681 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Taper Phase | Adverse Event | 1 | 1 |
| Taper Phase | Completed Incorrect Number of Taper Days | 1 | 0 |
| Taper Phase | Hospitalization/Dose Reduction | 1 | 0 |
| Taper Phase | Withdrawn by participants or parent/guardian | 0 | 3 |
| Treatment Phase | Adverse Event | 26 | 38 |
| Treatment Phase | Began Commercial Product | 1 | 0 |
| Treatment Phase | Caregiver Asked to Stop Investigational Medicinal Product (IMP) | 0 | 1 |
| Treatment Phase | Continued Compassionate Use | 1 | 0 |
| Treatment Phase | Lack of Efficacy | 15 | 8 |
| Treatment Phase | Lack of Efficacy per Participant/Caregiver | 3 | 3 |
| Treatment Phase | Lack of Efficiency | 2 | 1 |
| Treatment Phase | Lost to Follow-up | 2 | 1 |
| Treatment Phase | Met Withdrawal Criteria | 5 | 7 |
| Treatment Phase | Participant Did Not Return for Visits | 0 | 1 |
| Treatment Phase | Participant Discontinued IMP | 0 | 1 |
| Treatment Phase | Participant Moved | 2 | 0 |
| Treatment Phase | Participant with Protocol-Excluded Treatment | 0 | 1 |
| Treatment Phase | Placed in Group Home | 0 | 1 |
| Treatment Phase | Pursued Other Trials | 1 | 0 |
| Treatment Phase | Refused Medication | 1 | 1 |
| Treatment Phase | Started on Other IMP | 1 | 0 |
| Treatment Phase | Withdrawal by Participant or Parent/Guardian | 62 | 48 |
| Treatment Phase | Withdrawn by the Investigator | 23 | 11 |
Baseline characteristics
| Characteristic | Dravet Syndrome | Total | Lennox-Gastaut Syndrome |
|---|---|---|---|
| Age, Continuous | 9.737 years STANDARD_DEVIATION 4.4434 | 13.053 years STANDARD_DEVIATION 8.212 | 15.906 years STANDARD_DEVIATION 9.5392 |
| Age, Customized Adolescents (12-17 years) | 90 Participants | 179 Participants | 89 Participants |
| Age, Customized Adults (18-64 years) | 9 Participants | 129 Participants | 120 Participants |
| Age, Customized Children (2-11 years) | 216 Participants | 373 Participants | 157 Participants |
| Race American Indian/Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race Anglo-Indian | 1 Participants | 1 Participants | 0 Participants |
| Race Arab | 0 Participants | 1 Participants | 1 Participants |
| Race Asian | 6 Participants | 16 Participants | 10 Participants |
| Race Biracial | 2 Participants | 3 Participants | 1 Participants |
| Race Black/African American | 10 Participants | 25 Participants | 15 Participants |
| Race Caucasian and African American | 3 Participants | 4 Participants | 1 Participants |
| Race Caucasian/Asian | 1 Participants | 2 Participants | 1 Participants |
| Race Eurasian | 1 Participants | 1 Participants | 0 Participants |
| Race Hispanic/Caucasian | 1 Participants | 3 Participants | 2 Participants |
| Race Indian | 0 Participants | 2 Participants | 2 Participants |
| Race Latino | 1 Participants | 6 Participants | 5 Participants |
| Race Mulatto | 1 Participants | 1 Participants | 0 Participants |
| Race North African | 1 Participants | 1 Participants | 0 Participants |
| Race Not Applicable (As per country-specific data protection law. | 15 Participants | 16 Participants | 1 Participants |
| Race South American | 1 Participants | 1 Participants | 0 Participants |
| Race Unknown | 0 Participants | 2 Participants | 2 Participants |
| Race White and Black Caribbean | 1 Participants | 1 Participants | 0 Participants |
| Race White/Caucasian | 269 Participants | 594 Participants | 325 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 16 Participants | 10 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 25 Participants | 15 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 29 Participants | 45 Participants | 16 Participants |
| Race (NIH/OMB) White | 269 Participants | 594 Participants | 325 Participants |
| Sex: Female, Male Female | 159 Participants | 327 Participants | 168 Participants |
| Sex: Female, Male Male | 156 Participants | 354 Participants | 198 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 6 / 315 | 12 / 366 |
| other Total, other adverse events | 292 / 315 | 338 / 366 |
| serious Total, serious adverse events | 133 / 315 | 157 / 366 |
Outcome results
Primary
Mean Cannabis Withdrawal Scale Score at End of Taper (EOT), the Post-Taper Safety Call, and at Safety Follow-up
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.
Time frame: up to Week 260
Population: Safety Analysis Set. Only participants (18 years and above) with available Cannabis Withdrawal Scale score were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dravet Syndrome | Mean Cannabis Withdrawal Scale Score at End of Taper (EOT), the Post-Taper Safety Call, and at Safety Follow-up | L24S, End of Taper | 9.8 scores on a scale | Standard Deviation 10.64 |
| Dravet Syndrome | Mean Cannabis Withdrawal Scale Score at End of Taper (EOT), the Post-Taper Safety Call, and at Safety Follow-up | L24S, Post-Taper Safety Call | 3.4 scores on a scale | Standard Deviation 4.72 |
| Dravet Syndrome | Mean Cannabis Withdrawal Scale Score at End of Taper (EOT), the Post-Taper Safety Call, and at Safety Follow-up | L24S, Safety Follow-Up | 2.4 scores on a scale | Standard Deviation 3.36 |
| Dravet Syndrome | Mean Cannabis Withdrawal Scale Score at End of Taper (EOT), the Post-Taper Safety Call, and at Safety Follow-up | NIS, End of Taper | 9.5 scores on a scale | Standard Deviation 12.03 |
| Dravet Syndrome | Mean Cannabis Withdrawal Scale Score at End of Taper (EOT), the Post-Taper Safety Call, and at Safety Follow-up | NIS, Post-Taper Safety Call | 16.3 scores on a scale | Standard Deviation 3.79 |
| Dravet Syndrome | Mean Cannabis Withdrawal Scale Score at End of Taper (EOT), the Post-Taper Safety Call, and at Safety Follow-up | NIS, Safety Follow-Up | 5.3 scores on a scale | Standard Deviation 9.24 |
| Lennox-Gastaut Syndrome | Mean Cannabis Withdrawal Scale Score at End of Taper (EOT), the Post-Taper Safety Call, and at Safety Follow-up | NIS, Post-Taper Safety Call | 1.2 scores on a scale | Standard Deviation 3 |
| Lennox-Gastaut Syndrome | Mean Cannabis Withdrawal Scale Score at End of Taper (EOT), the Post-Taper Safety Call, and at Safety Follow-up | L24S, End of Taper | 4.9 scores on a scale | Standard Deviation 14 |
| Lennox-Gastaut Syndrome | Mean Cannabis Withdrawal Scale Score at End of Taper (EOT), the Post-Taper Safety Call, and at Safety Follow-up | NIS, End of Taper | 5.1 scores on a scale | Standard Deviation 10.96 |
| Lennox-Gastaut Syndrome | Mean Cannabis Withdrawal Scale Score at End of Taper (EOT), the Post-Taper Safety Call, and at Safety Follow-up | L24S, Post-Taper Safety Call | 0.0 scores on a scale | Standard Deviation 0 |
| Lennox-Gastaut Syndrome | Mean Cannabis Withdrawal Scale Score at End of Taper (EOT), the Post-Taper Safety Call, and at Safety Follow-up | NIS, Safety Follow-Up | 1.8 scores on a scale | Standard Deviation 3.82 |
| Lennox-Gastaut Syndrome | Mean Cannabis Withdrawal Scale Score at End of Taper (EOT), the Post-Taper Safety Call, and at Safety Follow-up | L24S, Safety Follow-Up | 4.9 scores on a scale | Standard Deviation 12.27 |
Primary
Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Albumin and Protein
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.
Time frame: up to Week 260
Population: Safety Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Albumin and Protein | Albumin | -0.2 grams (g)/L | Standard Deviation 3.43 |
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Albumin and Protein | Protein | -1.2 grams (g)/L | Standard Deviation 5.83 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Albumin and Protein | Albumin | -0.9 grams (g)/L | Standard Deviation 3.31 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Albumin and Protein | Protein | -2.0 grams (g)/L | Standard Deviation 5.75 |
Primary
Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Alkaline Phosphatase, Aspartate Aminotransferase, Alanine Aminotransferase, and Gamma Glutamyl Transferase
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.
Time frame: up to Week 260
Population: Safety Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Alkaline Phosphatase, Aspartate Aminotransferase, Alanine Aminotransferase, and Gamma Glutamyl Transferase | Alkaline phosphatase | -40.9 Units/L | Standard Deviation 88.18 |
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Alkaline Phosphatase, Aspartate Aminotransferase, Alanine Aminotransferase, and Gamma Glutamyl Transferase | Aspartate aminotransferase | 4.0 Units/L | Standard Deviation 26.14 |
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Alkaline Phosphatase, Aspartate Aminotransferase, Alanine Aminotransferase, and Gamma Glutamyl Transferase | Alanine aminotransferase | 7.0 Units/L | Standard Deviation 39.24 |
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Alkaline Phosphatase, Aspartate Aminotransferase, Alanine Aminotransferase, and Gamma Glutamyl Transferase | Gamma glutamyl transferase | 8.7 Units/L | Standard Deviation 42.35 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Alkaline Phosphatase, Aspartate Aminotransferase, Alanine Aminotransferase, and Gamma Glutamyl Transferase | Gamma glutamyl transferase | 4.9 Units/L | Standard Deviation 45.65 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Alkaline Phosphatase, Aspartate Aminotransferase, Alanine Aminotransferase, and Gamma Glutamyl Transferase | Alkaline phosphatase | -40.1 Units/L | Standard Deviation 73.62 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Alkaline Phosphatase, Aspartate Aminotransferase, Alanine Aminotransferase, and Gamma Glutamyl Transferase | Alanine aminotransferase | 9.5 Units/L | Standard Deviation 43.96 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Alkaline Phosphatase, Aspartate Aminotransferase, Alanine Aminotransferase, and Gamma Glutamyl Transferase | Aspartate aminotransferase | 2.8 Units/L | Standard Deviation 26.62 |
Primary
Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Body Mass Index (BMI)
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.
Time frame: up to Week 260
Population: Safety Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Body Mass Index (BMI) | 0.42 kilograms per meters squared (kg/m^2) | Standard Deviation 2.701 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Body Mass Index (BMI) | 0.05 kilograms per meters squared (kg/m^2) | Standard Deviation 5.863 |
Primary
Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Creatinine Clearance (Schwartz) and Creatinine Clearance (Cockcroft-Gault)
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.
Time frame: up to Week 260
Population: Safety Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Creatinine Clearance (Schwartz) and Creatinine Clearance (Cockcroft-Gault) | Creatinine Clearance, Schwartz, | 0.3 mL/min/1.73 m^2 | Standard Deviation 4.41 |
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Creatinine Clearance (Schwartz) and Creatinine Clearance (Cockcroft-Gault) | Creatinine Clearance, Cockcroft-Gault | 0.0 mL/min/1.73 m^2 | Standard Deviation 0 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Creatinine Clearance (Schwartz) and Creatinine Clearance (Cockcroft-Gault) | Creatinine Clearance, Schwartz, | 0.0 mL/min/1.73 m^2 | Standard Deviation 0 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Creatinine Clearance (Schwartz) and Creatinine Clearance (Cockcroft-Gault) | Creatinine Clearance, Cockcroft-Gault | -0.6 mL/min/1.73 m^2 | Standard Deviation 5.94 |
Primary
Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Creatinine (Jaffe), Creatinine (Enzymatic), and Bilirubin
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.
Time frame: up to Week 260
Population: Safety Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Creatinine (Jaffe), Creatinine (Enzymatic), and Bilirubin | Creatinine, Jaffe | 7.0 micromoles per Liter (µmol/L) | Standard Deviation 9.32 |
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Creatinine (Jaffe), Creatinine (Enzymatic), and Bilirubin | Creatinine, enzymatic | 3.8 micromoles per Liter (µmol/L) | Standard Deviation 8.83 |
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Creatinine (Jaffe), Creatinine (Enzymatic), and Bilirubin | Bilirubin | 0.48 micromoles per Liter (µmol/L) | Standard Deviation 2.339 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Creatinine (Jaffe), Creatinine (Enzymatic), and Bilirubin | Creatinine, Jaffe | 7.1 micromoles per Liter (µmol/L) | Standard Deviation 10.86 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Creatinine (Jaffe), Creatinine (Enzymatic), and Bilirubin | Creatinine, enzymatic | 4.0 micromoles per Liter (µmol/L) | Standard Deviation 9.44 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Creatinine (Jaffe), Creatinine (Enzymatic), and Bilirubin | Bilirubin | 0.45 micromoles per Liter (µmol/L) | Standard Deviation 2.626 |
Primary
Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Erythrocyte Mean Corpuscular Hemoglobin
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.
Time frame: up to Week 260
Population: Safety Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Erythrocyte Mean Corpuscular Hemoglobin | 0.10 picograms (pg) | Standard Deviation 1.482 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Erythrocyte Mean Corpuscular Hemoglobin | -0.15 picograms (pg) | Standard Deviation 1.926 |
Primary
Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Erythrocyte Mean Corpuscular Volume
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.
Time frame: up to Week 260
Population: Safety Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Erythrocyte Mean Corpuscular Volume | -1.0 femtoliters (fL) | Standard Deviation 5.1 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Erythrocyte Mean Corpuscular Volume | -1.3 femtoliters (fL) | Standard Deviation 5.01 |
Primary
Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Hematocrit Values
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.
Time frame: up to Week 260
Population: Safety Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Hematocrit Values | -0.0105 percentage of RBCs in whole blood (L/L) | Standard Deviation 0.02938 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Hematocrit Values | -0.0110 percentage of RBCs in whole blood (L/L) | Standard Deviation 0.02983 |
Primary
Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Hemoglobin Levels
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.
Time frame: up to Week 260
Population: Safety Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Hemoglobin Levels | -1.6 grams per Liter (g/L) | Standard Deviation 9.08 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Hemoglobin Levels | -2.4 grams per Liter (g/L) | Standard Deviation 11.14 |
Primary
Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Insulin-like Growth Factor-1 (IGF-1) Levels
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.
Time frame: up to Week 260
Population: Safety Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Insulin-like Growth Factor-1 (IGF-1) Levels | -0.28 nanomoles (nmol)/L | Standard Deviation 12.701 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Insulin-like Growth Factor-1 (IGF-1) Levels | 1.10 nanomoles (nmol)/L | Standard Deviation 15.97 |
Primary
Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Platelets, White Blood Cells, Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils
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.
Time frame: up to Week 260
Population: Safety Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Platelets, White Blood Cells, Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils | Basophils | 0.00 10^9 cells/L | Standard Deviation 0.041 |
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Platelets, White Blood Cells, Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils | Lymphocytes | -0.31 10^9 cells/L | Standard Deviation 0.988 |
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Platelets, White Blood Cells, Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils | White blood cells | -0.52 10^9 cells/L | Standard Deviation 2.531 |
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Platelets, White Blood Cells, Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils | Monocytes | -0.05 10^9 cells/L | Standard Deviation 0.276 |
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Platelets, White Blood Cells, Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils | Eosinophils | -0.02 10^9 cells/L | Standard Deviation 0.159 |
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Platelets, White Blood Cells, Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils | Neutrophils | -0.16 10^9 cells/L | Standard Deviation 2.041 |
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Platelets, White Blood Cells, Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils | Platelets | 5.4 10^9 cells/L | Standard Deviation 64.84 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Platelets, White Blood Cells, Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils | Neutrophils | 0.05 10^9 cells/L | Standard Deviation 1.878 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Platelets, White Blood Cells, Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils | Platelets | 5.0 10^9 cells/L | Standard Deviation 70.47 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Platelets, White Blood Cells, Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils | White blood cells | -0.09 10^9 cells/L | Standard Deviation 2.052 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Platelets, White Blood Cells, Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils | Basophils | 0.01 10^9 cells/L | Standard Deviation 0.04 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Platelets, White Blood Cells, Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils | Eosinophils | -0.02 10^9 cells/L | Standard Deviation 0.165 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Platelets, White Blood Cells, Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils | Lymphocytes | -0.14 10^9 cells/L | Standard Deviation 0.778 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Platelets, White Blood Cells, Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils | Monocytes | 0.01 10^9 cells/L | Standard Deviation 0.245 |
Primary
Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Prolactin
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.
Time frame: up to Week 260
Population: Safety Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Prolactin | 0.43 µInternational Units/millilitre (µIU/mL) | Standard Deviation 132.613 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Prolactin | 10.43 µInternational Units/millilitre (µIU/mL) | Standard Deviation 230.439 |
Primary
Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Prothrombin International Normalized Ratio
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.
Time frame: up to Week 260
Population: Safety Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Prothrombin International Normalized Ratio | -0.012 ratio | Standard Deviation 0.0784 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Prothrombin International Normalized Ratio | -0.010 ratio | Standard Deviation 0.0736 |
Primary
Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Prothrombin Time
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.
Time frame: up to Week 260
Population: Safety Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Prothrombin Time | -0.08 seconds | Standard Deviation 0.74 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Prothrombin Time | -0.09 seconds | Standard Deviation 0.706 |
Primary
Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Red Blood Cells (RBCs) Values
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.
Time frame: up to Week 260
Population: Safety Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Red Blood Cells (RBCs) Values | -0.068 10^12 cells per Liter (L) | Standard Deviation 0.3297 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Red Blood Cells (RBCs) Values | -0.059 10^12 cells per Liter (L) | Standard Deviation 0.3424 |
Primary
Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Sodium, Potassium, Blood Urea Nitrogen, Glucose, Calcium, and High-Density Lipoprotein (HDL) Cholesterol
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.
Time frame: up to week 260
Population: Safety Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Sodium, Potassium, Blood Urea Nitrogen, Glucose, Calcium, and High-Density Lipoprotein (HDL) Cholesterol | Sodium | -0.4 millimoles per Liter (mmol/L) | Standard Deviation 3.25 |
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Sodium, Potassium, Blood Urea Nitrogen, Glucose, Calcium, and High-Density Lipoprotein (HDL) Cholesterol | Potassium | -0.06 millimoles per Liter (mmol/L) | Standard Deviation 0.372 |
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Sodium, Potassium, Blood Urea Nitrogen, Glucose, Calcium, and High-Density Lipoprotein (HDL) Cholesterol | Blood urea nitrogen | -0.08 millimoles per Liter (mmol/L) | Standard Deviation 1.571 |
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Sodium, Potassium, Blood Urea Nitrogen, Glucose, Calcium, and High-Density Lipoprotein (HDL) Cholesterol | Glucose | -0.06 millimoles per Liter (mmol/L) | Standard Deviation 1.026 |
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Sodium, Potassium, Blood Urea Nitrogen, Glucose, Calcium, and High-Density Lipoprotein (HDL) Cholesterol | Calcium | -0.050 millimoles per Liter (mmol/L) | Standard Deviation 0.1148 |
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Sodium, Potassium, Blood Urea Nitrogen, Glucose, Calcium, and High-Density Lipoprotein (HDL) Cholesterol | HDL cholesterol | 0.06 millimoles per Liter (mmol/L) | Standard Deviation 0.372 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Sodium, Potassium, Blood Urea Nitrogen, Glucose, Calcium, and High-Density Lipoprotein (HDL) Cholesterol | Calcium | -0.054 millimoles per Liter (mmol/L) | Standard Deviation 0.1218 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Sodium, Potassium, Blood Urea Nitrogen, Glucose, Calcium, and High-Density Lipoprotein (HDL) Cholesterol | Sodium | -0.8 millimoles per Liter (mmol/L) | Standard Deviation 2.7 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Sodium, Potassium, Blood Urea Nitrogen, Glucose, Calcium, and High-Density Lipoprotein (HDL) Cholesterol | Glucose | 0.06 millimoles per Liter (mmol/L) | Standard Deviation 1.288 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Sodium, Potassium, Blood Urea Nitrogen, Glucose, Calcium, and High-Density Lipoprotein (HDL) Cholesterol | Potassium | -0.08 millimoles per Liter (mmol/L) | Standard Deviation 0.407 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Sodium, Potassium, Blood Urea Nitrogen, Glucose, Calcium, and High-Density Lipoprotein (HDL) Cholesterol | HDL cholesterol | 0.12 millimoles per Liter (mmol/L) | Standard Deviation 0.32 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Sodium, Potassium, Blood Urea Nitrogen, Glucose, Calcium, and High-Density Lipoprotein (HDL) Cholesterol | Blood urea nitrogen | 0.00 millimoles per Liter (mmol/L) | Standard Deviation 1.555 |
Primary
Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils in White Blood Cells (WBCs)
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.
Time frame: up to Week 260
Population: Safety Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils in White Blood Cells (WBCs) | Eosinophils/WBCs | -0.10 percentage in WBCs | Standard Deviation 2.064 |
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils in White Blood Cells (WBCs) | Monocytes/WBCs | -0.05 percentage in WBCs | Standard Deviation 3.125 |
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils in White Blood Cells (WBCs) | Lymphocytes/WBCs | -1.32 percentage in WBCs | Standard Deviation 12.396 |
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils in White Blood Cells (WBCs) | Neutrophils/WBCs | 1.47 percentage in WBCs | Standard Deviation 12.982 |
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils in White Blood Cells (WBCs) | Basophils/WBCs | 0.08 percentage in WBCs | Standard Deviation 0.284 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils in White Blood Cells (WBCs) | Neutrophils/WBCs | 1.27 percentage in WBCs | Standard Deviation 12.245 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils in White Blood Cells (WBCs) | Basophils/WBCs | 0.12 percentage in WBCs | Standard Deviation 0.287 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils in White Blood Cells (WBCs) | Eosinophils/WBCs | -0.24 percentage in WBCs | Standard Deviation 2.104 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils in White Blood Cells (WBCs) | Lymphocytes/WBCs | -1.32 percentage in WBCs | Standard Deviation 11.193 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils in White Blood Cells (WBCs) | Monocytes/WBCs | 0.18 percentage in WBCs | Standard Deviation 2.6 |
Primary
Mean Pediatric Cannabinoid Withdrawal Scale (PCWS) Score at the End of Treatment, the End of Taper, the Post-Taper Safety Call, and at Safety Follow-up
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.
Time frame: up to Week 260
Population: Safety Analysis Set. Only participants (4 to 17 years) with available Pediatric Cannabis Withdrawal Scale score were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dravet Syndrome | Mean Pediatric Cannabinoid Withdrawal Scale (PCWS) Score at the End of Treatment, the End of Taper, the Post-Taper Safety Call, and at Safety Follow-up | End of Treatment | 4.0 scores on a scale | — |
| Dravet Syndrome | Mean Pediatric Cannabinoid Withdrawal Scale (PCWS) Score at the End of Treatment, the End of Taper, the Post-Taper Safety Call, and at Safety Follow-up | End of Taper | 2.9 scores on a scale | Standard Deviation 3.77 |
| Dravet Syndrome | Mean Pediatric Cannabinoid Withdrawal Scale (PCWS) Score at the End of Treatment, the End of Taper, the Post-Taper Safety Call, and at Safety Follow-up | Post-Taper Safety Call | 2.4 scores on a scale | Standard Deviation 3.5 |
| Dravet Syndrome | Mean Pediatric Cannabinoid Withdrawal Scale (PCWS) Score at the End of Treatment, the End of Taper, the Post-Taper Safety Call, and at Safety Follow-up | Safety Follow-Up | 1.9 scores on a scale | Standard Deviation 2.72 |
| Lennox-Gastaut Syndrome | Mean Pediatric Cannabinoid Withdrawal Scale (PCWS) Score at the End of Treatment, the End of Taper, the Post-Taper Safety Call, and at Safety Follow-up | Safety Follow-Up | 1.8 scores on a scale | Standard Deviation 2.28 |
| Lennox-Gastaut Syndrome | Mean Pediatric Cannabinoid Withdrawal Scale (PCWS) Score at the End of Treatment, the End of Taper, the Post-Taper Safety Call, and at Safety Follow-up | End of Treatment | 6.0 scores on a scale | — |
| Lennox-Gastaut Syndrome | Mean Pediatric Cannabinoid Withdrawal Scale (PCWS) Score at the End of Treatment, the End of Taper, the Post-Taper Safety Call, and at Safety Follow-up | Post-Taper Safety Call | 2.0 scores on a scale | Standard Deviation 2.72 |
| Lennox-Gastaut Syndrome | Mean Pediatric Cannabinoid Withdrawal Scale (PCWS) Score at the End of Treatment, the End of Taper, the Post-Taper Safety Call, and at Safety Follow-up | End of Taper | 2.1 scores on a scale | Standard Deviation 2.78 |
Primary
Mean Subject/Caregiver Global Impression of Change (S/CGIC) Score
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.
Time frame: Baseline; up to Week 260
Population: Safety Analysis Set. Only those participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dravet Syndrome | Mean Subject/Caregiver Global Impression of Change (S/CGIC) Score | 3.0 Scores on a scale | Standard Deviation 1.47 |
| Lennox-Gastaut Syndrome | Mean Subject/Caregiver Global Impression of Change (S/CGIC) Score | 2.8 Scores on a scale | Standard Deviation 1.38 |
Primary
Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group
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.
Time frame: up to Week 260
Population: Safety Analysis Set: all participants who received at least 1 dose of investigational medicinal product (IMP).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dravet Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Contusion | 15 participants |
| Dravet Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Ear infection | 35 participants |
| Dravet Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Weight decreased | 21 participants |
| Dravet Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Diarrhoea | 135 participants |
| Dravet Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Alanine aminotransferase increased | 37 participants |
| Dravet Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Influenza | 37 participants |
| Dravet Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Aspartate aminotransferase increased | 38 participants |
| Dravet Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Fatigue | 39 participants |
| Dravet Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Gamma-glutamyltransferase increased | 32 participants |
| Dravet Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Urinary tract infection | 19 participants |
| Dravet Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Decreased appetite | 99 participants |
| Dravet Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Constipation | 20 participants |
| Dravet Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Convulsion | 79 participants |
| Dravet Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Pharyngitis streptococcal | 26 participants |
| Dravet Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Somnolence | 87 participants |
| Dravet Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Upper respiratory tract infection | 78 participants |
| Dravet Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Status epilepticus | 47 participants |
| Dravet Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Gastroenteritis viral | 15 participants |
| Dravet Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Lethargy | 21 participants |
| Dravet Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Total participants affected by any TEAE | 306 participants |
| Dravet Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Headache | 18 participants |
| Dravet Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Otitis media | 21 participants |
| Dravet Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Sedation | 16 participants |
| Dravet Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Nasopharyngitis | 78 participants |
| Dravet Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Drooling | 11 participants |
| Dravet Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Bronchitis | 15 participants |
| Dravet Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Abnormal behaviour | 34 participants |
| Dravet Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Nausea | 16 participants |
| Dravet Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Insomnia | 16 participants |
| Dravet Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Viral upper respiratory tract infection | 11 participants |
| Dravet Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Irritability | 26 participants |
| Dravet Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Sinusitis | 38 participants |
| Dravet Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Aggression | 20 participants |
| Dravet Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Gastroenteritis | 16 participants |
| Dravet Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Agitation | 9 participants |
| Dravet Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Vomiting | 63 participants |
| Dravet Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Cough | 42 participants |
| Dravet Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Fall | 22 participants |
| Dravet Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Nasal congestion | 13 participants |
| Dravet Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Pneumonia | 35 participants |
| Dravet Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Laceration | 8 participants |
| Dravet Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Pneumonia aspiration | 4 participants |
| Dravet Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Pyrexia | 124 participants |
| Dravet Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Hypoxia | 2 participants |
| Dravet Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Rhinorrhoea | 20 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Hypoxia | 21 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Total participants affected by any TEAE | 353 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Diarrhoea | 140 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Vomiting | 107 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Constipation | 43 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Nausea | 32 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Pyrexia | 126 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Fatigue | 38 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Upper respiratory tract infection | 104 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Nasopharyngitis | 58 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Sinusitis | 49 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Pneumonia | 51 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Ear infection | 50 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Influenza | 45 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Urinary tract infection | 51 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Pharyngitis streptococcal | 27 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Gastroenteritis viral | 30 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Otitis media | 22 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Bronchitis | 23 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Viral upper respiratory tract infection | 20 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Gastroenteritis | 7 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Fall | 23 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Laceration | 35 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Contusion | 25 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Weight decreased | 61 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Alanine aminotransferase increased | 30 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Aspartate aminotransferase increased | 19 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Gamma-glutamyltransferase increased | 20 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Decreased appetite | 93 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Convulsion | 141 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Somnolence | 107 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Status epilepticus | 42 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Lethargy | 34 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Headache | 26 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Sedation | 27 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Drooling | 21 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Abnormal behaviour | 23 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Insomnia | 40 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Irritability | 29 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Aggression | 30 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Agitation | 19 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Cough | 63 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Nasal congestion | 46 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Rhinorrhoea | 19 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) Occurring in ≥5% of Participants in Any Treatment Group | Pneumonia aspiration | 22 participants |
Primary
Number of Participants With Clinically Significant Changes in the Indicated Vital Sign Values From the Pre-randomization Baseline of the Core Study at Any Time Post-dose
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.
Time frame: up to Week 260
Population: Safety Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dravet Syndrome | Number of Participants With Clinically Significant Changes in the Indicated Vital Sign Values From the Pre-randomization Baseline of the Core Study at Any Time Post-dose | Sitting SBP < -20 mmHg | 59 participants |
| Dravet Syndrome | Number of Participants With Clinically Significant Changes in the Indicated Vital Sign Values From the Pre-randomization Baseline of the Core Study at Any Time Post-dose | Sitting SBP > 20 mmHg | 96 participants |
| Dravet Syndrome | Number of Participants With Clinically Significant Changes in the Indicated Vital Sign Values From the Pre-randomization Baseline of the Core Study at Any Time Post-dose | Sitting DBP < -10 mmHg | 139 participants |
| Dravet Syndrome | Number of Participants With Clinically Significant Changes in the Indicated Vital Sign Values From the Pre-randomization Baseline of the Core Study at Any Time Post-dose | Sitting DBP > 10 mmHg | 166 participants |
| Dravet Syndrome | Number of Participants With Clinically Significant Changes in the Indicated Vital Sign Values From the Pre-randomization Baseline of the Core Study at Any Time Post-dose | Pulse Rate < -15 bpm | 176 participants |
| Dravet Syndrome | Number of Participants With Clinically Significant Changes in the Indicated Vital Sign Values From the Pre-randomization Baseline of the Core Study at Any Time Post-dose | Pulse Rate > 15 bpm | 150 participants |
| Dravet Syndrome | Number of Participants With Clinically Significant Changes in the Indicated Vital Sign Values From the Pre-randomization Baseline of the Core Study at Any Time Post-dose | Weight ≤ -7 % | 47 participants |
| Dravet Syndrome | Number of Participants With Clinically Significant Changes in the Indicated Vital Sign Values From the Pre-randomization Baseline of the Core Study at Any Time Post-dose | Weight ≥ 7% | 213 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Clinically Significant Changes in the Indicated Vital Sign Values From the Pre-randomization Baseline of the Core Study at Any Time Post-dose | Weight ≥ 7% | 223 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Clinically Significant Changes in the Indicated Vital Sign Values From the Pre-randomization Baseline of the Core Study at Any Time Post-dose | Sitting SBP < -20 mmHg | 88 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Clinically Significant Changes in the Indicated Vital Sign Values From the Pre-randomization Baseline of the Core Study at Any Time Post-dose | Pulse Rate < -15 bpm | 192 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Clinically Significant Changes in the Indicated Vital Sign Values From the Pre-randomization Baseline of the Core Study at Any Time Post-dose | Sitting SBP > 20 mmHg | 120 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Clinically Significant Changes in the Indicated Vital Sign Values From the Pre-randomization Baseline of the Core Study at Any Time Post-dose | Weight ≤ -7 % | 106 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Clinically Significant Changes in the Indicated Vital Sign Values From the Pre-randomization Baseline of the Core Study at Any Time Post-dose | Sitting DBP < -10 mmHg | 176 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Clinically Significant Changes in the Indicated Vital Sign Values From the Pre-randomization Baseline of the Core Study at Any Time Post-dose | Pulse Rate > 15 bpm | 179 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Clinically Significant Changes in the Indicated Vital Sign Values From the Pre-randomization Baseline of the Core Study at Any Time Post-dose | Sitting DBP > 10 mmHg | 191 participants |
Primary
Number of Participants With Clinically Significant Electrocardiogram (ECG) Values at the Pre-randomization Baseline of the Core Study and at Any Time Post-dose
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.
Time frame: up to Week 260
Population: Safety Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dravet Syndrome | Number of Participants With Clinically Significant Electrocardiogram (ECG) Values at the Pre-randomization Baseline of the Core Study and at Any Time Post-dose | QTcB > 450 msec, Baseline | 13 participants |
| Dravet Syndrome | Number of Participants With Clinically Significant Electrocardiogram (ECG) Values at the Pre-randomization Baseline of the Core Study and at Any Time Post-dose | QTcB > 450 msec, any time post-dose | 62 participants |
| Dravet Syndrome | Number of Participants With Clinically Significant Electrocardiogram (ECG) Values at the Pre-randomization Baseline of the Core Study and at Any Time Post-dose | QTcB > 480 msec, Baseline | 2 participants |
| Dravet Syndrome | Number of Participants With Clinically Significant Electrocardiogram (ECG) Values at the Pre-randomization Baseline of the Core Study and at Any Time Post-dose | QTcB > 480 msec, any time post-dose | 10 participants |
| Dravet Syndrome | Number of Participants With Clinically Significant Electrocardiogram (ECG) Values at the Pre-randomization Baseline of the Core Study and at Any Time Post-dose | QTcB > 500 msec, Baseline | 2 participants |
| Dravet Syndrome | Number of Participants With Clinically Significant Electrocardiogram (ECG) Values at the Pre-randomization Baseline of the Core Study and at Any Time Post-dose | QTcB > 500 msec, any time post-dose | 7 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Clinically Significant Electrocardiogram (ECG) Values at the Pre-randomization Baseline of the Core Study and at Any Time Post-dose | QTcB > 500 msec, Baseline | 2 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Clinically Significant Electrocardiogram (ECG) Values at the Pre-randomization Baseline of the Core Study and at Any Time Post-dose | QTcB > 450 msec, Baseline | 21 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Clinically Significant Electrocardiogram (ECG) Values at the Pre-randomization Baseline of the Core Study and at Any Time Post-dose | QTcB > 480 msec, any time post-dose | 40 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Clinically Significant Electrocardiogram (ECG) Values at the Pre-randomization Baseline of the Core Study and at Any Time Post-dose | QTcB > 450 msec, any time post-dose | 120 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Clinically Significant Electrocardiogram (ECG) Values at the Pre-randomization Baseline of the Core Study and at Any Time Post-dose | QTcB > 500 msec, any time post-dose | 20 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Clinically Significant Electrocardiogram (ECG) Values at the Pre-randomization Baseline of the Core Study and at Any Time Post-dose | QTcB > 480 msec, Baseline | 4 participants |
Primary
Number of Participants With Convulsive and Non-convulsive Seizures Greater Than 30 Minutes in Duration (Status Epilepticus)
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.
Time frame: Baseline; At last 12 weeks
Population: Safety Analysis Set. Only participants with available data are analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dravet Syndrome | Number of Participants With Convulsive and Non-convulsive Seizures Greater Than 30 Minutes in Duration (Status Epilepticus) | Convulsive SE: Over the 4-week Baseline; Yes | 14 participants |
| Dravet Syndrome | Number of Participants With Convulsive and Non-convulsive Seizures Greater Than 30 Minutes in Duration (Status Epilepticus) | Non-Convulsive SE: Over the 4-week Baseline; Yes | 21 participants |
| Dravet Syndrome | Number of Participants With Convulsive and Non-convulsive Seizures Greater Than 30 Minutes in Duration (Status Epilepticus) | Convulsive SE: Over the 4-week Baseline; No | 277 participants |
| Dravet Syndrome | Number of Participants With Convulsive and Non-convulsive Seizures Greater Than 30 Minutes in Duration (Status Epilepticus) | Non-Convulsive SE: Last 12 Weeks; Yes | 14 participants |
| Dravet Syndrome | Number of Participants With Convulsive and Non-convulsive Seizures Greater Than 30 Minutes in Duration (Status Epilepticus) | Non-Convulsive SE: Over the 4-week Baseline; No | 270 participants |
| Dravet Syndrome | Number of Participants With Convulsive and Non-convulsive Seizures Greater Than 30 Minutes in Duration (Status Epilepticus) | Convulsive SE: Last 12 Weeks; Yes | 13 participants |
| Dravet Syndrome | Number of Participants With Convulsive and Non-convulsive Seizures Greater Than 30 Minutes in Duration (Status Epilepticus) | Non-Convulsive SE: Last 12 Weeks; No | 276 participants |
| Dravet Syndrome | Number of Participants With Convulsive and Non-convulsive Seizures Greater Than 30 Minutes in Duration (Status Epilepticus) | Convulsive SE: Last 12 Weeks; No | 277 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Convulsive and Non-convulsive Seizures Greater Than 30 Minutes in Duration (Status Epilepticus) | Non-Convulsive SE: Last 12 Weeks; No | 352 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Convulsive and Non-convulsive Seizures Greater Than 30 Minutes in Duration (Status Epilepticus) | Convulsive SE: Over the 4-week Baseline; Yes | 14 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Convulsive and Non-convulsive Seizures Greater Than 30 Minutes in Duration (Status Epilepticus) | Convulsive SE: Last 12 Weeks; Yes | 7 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Convulsive and Non-convulsive Seizures Greater Than 30 Minutes in Duration (Status Epilepticus) | Convulsive SE: Over the 4-week Baseline; No | 352 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Convulsive and Non-convulsive Seizures Greater Than 30 Minutes in Duration (Status Epilepticus) | Convulsive SE: Last 12 Weeks; No | 356 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Convulsive and Non-convulsive Seizures Greater Than 30 Minutes in Duration (Status Epilepticus) | Non-Convulsive SE: Over the 4-week Baseline; Yes | 17 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Convulsive and Non-convulsive Seizures Greater Than 30 Minutes in Duration (Status Epilepticus) | Non-Convulsive SE: Over the 4-week Baseline; No | 349 participants |
| Lennox-Gastaut Syndrome | Number of Participants With Convulsive and Non-convulsive Seizures Greater Than 30 Minutes in Duration (Status Epilepticus) | Non-Convulsive SE: Last 12 Weeks; Yes | 11 participants |
Primary
Number of Participants With the Indicated Responses to Questions Regarding Suicidal Ideation and Behavior Using the Children's Columbia-Suicide Severity Rating Scale (C-SSRS) at Day 1 and at Any Time Post-dose
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.
Time frame: up to Week 260
Population: Safety Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dravet Syndrome | Number of Participants With the Indicated Responses to Questions Regarding Suicidal Ideation and Behavior Using the Children's Columbia-Suicide Severity Rating Scale (C-SSRS) at Day 1 and at Any Time Post-dose | Suicidal ideation, Day 1 | 0 participants |
| Dravet Syndrome | Number of Participants With the Indicated Responses to Questions Regarding Suicidal Ideation and Behavior Using the Children's Columbia-Suicide Severity Rating Scale (C-SSRS) at Day 1 and at Any Time Post-dose | Suicidal behavior, Day 1 | 1 participants |
| Dravet Syndrome | Number of Participants With the Indicated Responses to Questions Regarding Suicidal Ideation and Behavior Using the Children's Columbia-Suicide Severity Rating Scale (C-SSRS) at Day 1 and at Any Time Post-dose | Any suicidality, any time post-dose | 1 participants |
| Dravet Syndrome | Number of Participants With the Indicated Responses to Questions Regarding Suicidal Ideation and Behavior Using the Children's Columbia-Suicide Severity Rating Scale (C-SSRS) at Day 1 and at Any Time Post-dose | Suicidal behavior, any time post-dose | 1 participants |
| Dravet Syndrome | Number of Participants With the Indicated Responses to Questions Regarding Suicidal Ideation and Behavior Using the Children's Columbia-Suicide Severity Rating Scale (C-SSRS) at Day 1 and at Any Time Post-dose | Suicidal ideation, any time post-dose | 1 participants |
| Dravet Syndrome | Number of Participants With the Indicated Responses to Questions Regarding Suicidal Ideation and Behavior Using the Children's Columbia-Suicide Severity Rating Scale (C-SSRS) at Day 1 and at Any Time Post-dose | Complete suicidality, any time post-dose | 0 participants |
| Dravet Syndrome | Number of Participants With the Indicated Responses to Questions Regarding Suicidal Ideation and Behavior Using the Children's Columbia-Suicide Severity Rating Scale (C-SSRS) at Day 1 and at Any Time Post-dose | Any suicidality, Day 1 | 1 participants |
| Lennox-Gastaut Syndrome | Number of Participants With the Indicated Responses to Questions Regarding Suicidal Ideation and Behavior Using the Children's Columbia-Suicide Severity Rating Scale (C-SSRS) at Day 1 and at Any Time Post-dose | Complete suicidality, any time post-dose | 0 participants |
| Lennox-Gastaut Syndrome | Number of Participants With the Indicated Responses to Questions Regarding Suicidal Ideation and Behavior Using the Children's Columbia-Suicide Severity Rating Scale (C-SSRS) at Day 1 and at Any Time Post-dose | Any suicidality, Day 1 | 1 participants |
| Lennox-Gastaut Syndrome | Number of Participants With the Indicated Responses to Questions Regarding Suicidal Ideation and Behavior Using the Children's Columbia-Suicide Severity Rating Scale (C-SSRS) at Day 1 and at Any Time Post-dose | Any suicidality, any time post-dose | 2 participants |
| Lennox-Gastaut Syndrome | Number of Participants With the Indicated Responses to Questions Regarding Suicidal Ideation and Behavior Using the Children's Columbia-Suicide Severity Rating Scale (C-SSRS) at Day 1 and at Any Time Post-dose | Suicidal ideation, Day 1 | 1 participants |
| Lennox-Gastaut Syndrome | Number of Participants With the Indicated Responses to Questions Regarding Suicidal Ideation and Behavior Using the Children's Columbia-Suicide Severity Rating Scale (C-SSRS) at Day 1 and at Any Time Post-dose | Suicidal ideation, any time post-dose | 2 participants |
| Lennox-Gastaut Syndrome | Number of Participants With the Indicated Responses to Questions Regarding Suicidal Ideation and Behavior Using the Children's Columbia-Suicide Severity Rating Scale (C-SSRS) at Day 1 and at Any Time Post-dose | Suicidal behavior, Day 1 | 0 participants |
| Lennox-Gastaut Syndrome | Number of Participants With the Indicated Responses to Questions Regarding Suicidal Ideation and Behavior Using the Children's Columbia-Suicide Severity Rating Scale (C-SSRS) at Day 1 and at Any Time Post-dose | Suicidal behavior, any time post-dose | 0 participants |
Primary
Percent Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Convulsive Seizure Frequency in Participants With Dravet Syndrome
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.
Time frame: Baseline; Week 49 to 60, Week 97 to 108, Week 145 to 156, Week 205 to 216, Week 253 to 264, and Last 12 Weeks
Population: Safety Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dravet Syndrome | Percent Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Convulsive Seizure Frequency in Participants With Dravet Syndrome | Week 49 to 60 | -52.9 percentage change |
| Dravet Syndrome | Percent Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Convulsive Seizure Frequency in Participants With Dravet Syndrome | Week 97 to 108 | -64.3 percentage change |
| Dravet Syndrome | Percent Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Convulsive Seizure Frequency in Participants With Dravet Syndrome | Week 145 to 156 | -69.4 percentage change |
| Dravet Syndrome | Percent Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Convulsive Seizure Frequency in Participants With Dravet Syndrome | Week 205 to 216 | -72.3 percentage change |
| Dravet Syndrome | Percent Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Convulsive Seizure Frequency in Participants With Dravet Syndrome | Week 253 to 264 | -55.6 percentage change |
| Dravet Syndrome | Percent Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Convulsive Seizure Frequency in Participants With Dravet Syndrome | Last 12 weeks | -40.0 percentage change |
Primary
Percent Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Drop Seizure Frequency in Participants With Lennox-Gastaut Syndrome
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.
Time frame: Baseline; Week 49 to 60, Week 97 to 108, Week 145 to 156, Week 205 to 216, and Last 12 Weeks
Population: Safety Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dravet Syndrome | Percent Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Drop Seizure Frequency in Participants With Lennox-Gastaut Syndrome | Week 49 to 60 | -59.4 percentage change |
| Dravet Syndrome | Percent Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Drop Seizure Frequency in Participants With Lennox-Gastaut Syndrome | Week 97 to 108 | -69.4 percentage change |
| Dravet Syndrome | Percent Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Drop Seizure Frequency in Participants With Lennox-Gastaut Syndrome | Week 145 to 156 | -70.8 percentage change |
| Dravet Syndrome | Percent Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Drop Seizure Frequency in Participants With Lennox-Gastaut Syndrome | Week 205 to 216 | -68.7 percentage change |
| Dravet Syndrome | Percent Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Drop Seizure Frequency in Participants With Lennox-Gastaut Syndrome | Last 12 weeks | -59.4 percentage change |
Primary
Percent Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Total Seizure Frequency
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.
Time frame: Baseline; Week 49 to 60, Week 97 to 108, Week 145 to 156, Week 205 to 216, Week 253 to 264, and Last 12 Weeks
Population: Safety Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dravet Syndrome | Percent Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Total Seizure Frequency | Week 205 to 216 | -81.5 percentage change |
| Dravet Syndrome | Percent Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Total Seizure Frequency | Week 145 to 156 | -79.8 percentage change |
| Dravet Syndrome | Percent Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Total Seizure Frequency | Week 253 to 264 | -70.0 percentage change |
| Dravet Syndrome | Percent Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Total Seizure Frequency | Last 12 weeks | -55.2 percentage change |
| Dravet Syndrome | Percent Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Total Seizure Frequency | Week 49 to 60 | -65.8 percentage change |
| Dravet Syndrome | Percent Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Total Seizure Frequency | Week 97 to 108 | -71.3 percentage change |
| Lennox-Gastaut Syndrome | Percent Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Total Seizure Frequency | Last 12 weeks | -51.9 percentage change |
| Lennox-Gastaut Syndrome | Percent Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Total Seizure Frequency | Week 49 to 60 | -58.9 percentage change |
| Lennox-Gastaut Syndrome | Percent Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Total Seizure Frequency | Week 97 to 108 | -66.4 percentage change |
| Lennox-Gastaut Syndrome | Percent Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Total Seizure Frequency | Week 145 to 156 | -65.3 percentage change |
| Lennox-Gastaut Syndrome | Percent Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Total Seizure Frequency | Week 205 to 216 | -78.4 percentage change |
Secondary
Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in a Developmental NEuroPSYchological Assessment (NEPSY)-2 Word Generation Scaled Score
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.
Time frame: Baseline; up to Week 260
Population: ITT Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in a Developmental NEuroPSYchological Assessment (NEPSY)-2 Word Generation Scaled Score | -1.00 Score on a scale | Standard Deviation 1.414 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in a Developmental NEuroPSYchological Assessment (NEPSY)-2 Word Generation Scaled Score | 3.39 Score on a scale | — |
Secondary
Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Delis-Kaplan Executive Function System (D-KEFS) Visual Scanning Completion Time Scaled Score
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.
Time frame: Baseline; up to Week 260
Population: ITT Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Delis-Kaplan Executive Function System (D-KEFS) Visual Scanning Completion Time Scaled Score | 0.00 Score on a scale | Standard Deviation 0 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Delis-Kaplan Executive Function System (D-KEFS) Visual Scanning Completion Time Scaled Score | -0.33 Score on a scale | Standard Deviation 0.577 |
Secondary
Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in D-KEFS Letter Sequencing Completion Time Scaled Score
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.
Time frame: Baseline; up to Week 260
Population: ITT Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in D-KEFS Letter Sequencing Completion Time Scaled Score | 0.00 Score on a scale | Standard Deviation 0 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in D-KEFS Letter Sequencing Completion Time Scaled Score | 0.00 Score on a scale | Standard Deviation 0 |
Secondary
Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in D-KEFS Motor Speed Completion Time Scaled Score
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.
Time frame: Baseline; up to Week 260
Population: ITT Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in D-KEFS Motor Speed Completion Time Scaled Score | 0.00 Score on a scale | Standard Deviation 0 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in D-KEFS Motor Speed Completion Time Scaled Score | -1.33 Score on a scale | Standard Deviation 2.309 |
Secondary
Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in D-KEFS Number-letter Switching Completion Time Scaled Score
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.
Time frame: Baseline; up to Week 260
Population: ITT Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in D-KEFS Number-letter Switching Completion Time Scaled Score | 0.00 Score on a scale | Standard Deviation 0 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in D-KEFS Number-letter Switching Completion Time Scaled Score | 0.00 Score on a scale | Standard Deviation 0 |
Secondary
Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in D-KEFS Number Sequencing Completion Time Scaled Score
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.
Time frame: Baseline; up to Week 260
Population: ITT Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in D-KEFS Number Sequencing Completion Time Scaled Score | 0.00 Score on a scale | Standard Deviation 0 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in D-KEFS Number Sequencing Completion Time Scaled Score | 0.00 Score on a scale | Standard Deviation 0 |
Secondary
Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Expressive One-Word Picture Vocabulary Test (EOWPVT) Scaled Score
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.
Time frame: Baseline; up to Week 260
Population: ITT Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Expressive One-Word Picture Vocabulary Test (EOWPVT) Scaled Score | -31.00 T score | Standard Deviation 56.569 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Expressive One-Word Picture Vocabulary Test (EOWPVT) Scaled Score | -31.00 T score | Standard Deviation 53.74 |
Secondary
Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Purdue Pegboard Fine Motor Speed (Both Hands Z Score)
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.
Time frame: Baseline; up to Week 260
Population: ITT Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Purdue Pegboard Fine Motor Speed (Both Hands Z Score) | 1.26 Z Score | Standard Deviation 3.272 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Purdue Pegboard Fine Motor Speed (Both Hands Z Score) | 9.55 Z Score | Standard Deviation 21.07 |
Secondary
Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Purdue Pegboard Fine Motor Speed (Dominant Hand Z Score)
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.
Time frame: Baseline; up to Week 260
Population: ITT Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Purdue Pegboard Fine Motor Speed (Dominant Hand Z Score) | 1.16 Z Score | Standard Deviation 3.192 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Purdue Pegboard Fine Motor Speed (Dominant Hand Z Score) | 9.23 Z Score | Standard Deviation 18.083 |
Secondary
Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Purdue Pegboard Fine Motor Speed (Non Dominant Hand Z Score)
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.
Time frame: Baseline; up to Week 260
Population: ITT Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Purdue Pegboard Fine Motor Speed (Non Dominant Hand Z Score) | 1.31 Z Score | Standard Deviation 3.329 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Purdue Pegboard Fine Motor Speed (Non Dominant Hand Z Score) | 10.21 Z Score | Standard Deviation 21.852 |
Secondary
Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Quality of Life in Childhood Epilepsy (QOLCE) Scores
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.
Time frame: Baseline; up to Week 260
Population: Safety Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Quality of Life in Childhood Epilepsy (QOLCE) Scores | 3.7 Scores on a scale | Standard Deviation 14.61 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Quality of Life in Childhood Epilepsy (QOLCE) Scores | 6.0 Scores on a scale | Standard Deviation 13.87 |
Secondary
Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Vineland Adaptive Behavior Scale, Second Edition (Vineland-II) Scores
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.
Time frame: Baseline; up to Week 260
Population: Safety Analysis Set. Only those participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Vineland Adaptive Behavior Scale, Second Edition (Vineland-II) Scores | Daily Living Skills: Domestic Subdomain v-Scale Score | -0.8 Scores on a scale | Standard Deviation 2.04 |
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Vineland Adaptive Behavior Scale, Second Edition (Vineland-II) Scores | Socialization: Coping Skills Subdomain v-Scale Score | -0.7 Scores on a scale | Standard Deviation 2.24 |
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Vineland Adaptive Behavior Scale, Second Edition (Vineland-II) Scores | Communication Domain Standard Score | -3.2 Scores on a scale | Standard Deviation 8.75 |
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Vineland Adaptive Behavior Scale, Second Edition (Vineland-II) Scores | Socialization Domain Standard Score | -3.3 Scores on a scale | Standard Deviation 9.38 |
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Vineland Adaptive Behavior Scale, Second Edition (Vineland-II) Scores | Daily Living Skills: Community Subdomain v-Scale Score | -0.9 Scores on a scale | Standard Deviation 2.75 |
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Vineland Adaptive Behavior Scale, Second Edition (Vineland-II) Scores | Motor Skills: Gross Subdomain v-Scale Score | -0.2 Scores on a scale | Standard Deviation 1.64 |
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Vineland Adaptive Behavior Scale, Second Edition (Vineland-II) Scores | Communication: Written Subdomain v-Scale Score | -1.1 Scores on a scale | Standard Deviation 1.8 |
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Vineland Adaptive Behavior Scale, Second Edition (Vineland-II) Scores | Motor Skills: Fine Subdomain v-Scale Score | -0.3 Scores on a scale | Standard Deviation 1.99 |
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Vineland Adaptive Behavior Scale, Second Edition (Vineland-II) Scores | Daily Living Skills Domain Standard Score | -5.0 Scores on a scale | Standard Deviation 9.68 |
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Vineland Adaptive Behavior Scale, Second Edition (Vineland-II) Scores | Motor Skills Domain Standard Score | -0.7 Scores on a scale | Standard Deviation 9.62 |
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Vineland Adaptive Behavior Scale, Second Edition (Vineland-II) Scores | Daily Living Skills: Personal Subdomain v-Scale Score | -1.0 Scores on a scale | Standard Deviation 1.92 |
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Vineland Adaptive Behavior Scale, Second Edition (Vineland-II) Scores | Adaptive Behavior Composite Standard Score | -3.4 Scores on a scale | Standard Deviation 8.09 |
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Vineland Adaptive Behavior Scale, Second Edition (Vineland-II) Scores | Socialization: Interpersonal Relationships Subdomain v-Scale Score | -0.7 Scores on a scale | Standard Deviation 1.66 |
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Vineland Adaptive Behavior Scale, Second Edition (Vineland-II) Scores | Maladaptive Behavior Index: Internalizing Subdomain v-Scale Score | -0.1 Scores on a scale | Standard Deviation 2.28 |
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Vineland Adaptive Behavior Scale, Second Edition (Vineland-II) Scores | Communication: Expressive Subdomain v-Scale Score | -0.8 Scores on a scale | Standard Deviation 1.65 |
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Vineland Adaptive Behavior Scale, Second Edition (Vineland-II) Scores | Maladaptive Behavior Index: Externalizing Subdomain v-Scale Score | -0.3 Scores on a scale | Standard Deviation 2.22 |
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Vineland Adaptive Behavior Scale, Second Edition (Vineland-II) Scores | Socialization: Play and Leisure Time Subdomain v-Scale Score | -0.9 Scores on a scale | Standard Deviation 2.29 |
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Vineland Adaptive Behavior Scale, Second Edition (Vineland-II) Scores | Maladaptive Behavior Index v-Scale Score | -0.3 Scores on a scale | Standard Deviation 1.92 |
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Vineland Adaptive Behavior Scale, Second Edition (Vineland-II) Scores | Communication: Receptive Subdomain v-Scale Score | -0.4 Scores on a scale | Standard Deviation 2.12 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Vineland Adaptive Behavior Scale, Second Edition (Vineland-II) Scores | Maladaptive Behavior Index v-Scale Score | -0.3 Scores on a scale | Standard Deviation 2.09 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Vineland Adaptive Behavior Scale, Second Edition (Vineland-II) Scores | Communication: Receptive Subdomain v-Scale Score | -0.5 Scores on a scale | Standard Deviation 2.76 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Vineland Adaptive Behavior Scale, Second Edition (Vineland-II) Scores | Communication: Expressive Subdomain v-Scale Score | -0.3 Scores on a scale | Standard Deviation 2.2 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Vineland Adaptive Behavior Scale, Second Edition (Vineland-II) Scores | Communication: Written Subdomain v-Scale Score | -0.7 Scores on a scale | Standard Deviation 1.8 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Vineland Adaptive Behavior Scale, Second Edition (Vineland-II) Scores | Communication Domain Standard Score | -1.6 Scores on a scale | Standard Deviation 13.5 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Vineland Adaptive Behavior Scale, Second Edition (Vineland-II) Scores | Daily Living Skills: Personal Subdomain v-Scale Score | -0.8 Scores on a scale | Standard Deviation 2.05 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Vineland Adaptive Behavior Scale, Second Edition (Vineland-II) Scores | Daily Living Skills: Domestic Subdomain v-Scale Score | -1.0 Scores on a scale | Standard Deviation 1.32 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Vineland Adaptive Behavior Scale, Second Edition (Vineland-II) Scores | Daily Living Skills: Community Subdomain v-Scale Score | -0.8 Scores on a scale | Standard Deviation 1.49 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Vineland Adaptive Behavior Scale, Second Edition (Vineland-II) Scores | Daily Living Skills Domain Standard Score | -3.9 Scores on a scale | Standard Deviation 8.4 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Vineland Adaptive Behavior Scale, Second Edition (Vineland-II) Scores | Socialization: Interpersonal Relationships Subdomain v-Scale Score | -0.6 Scores on a scale | Standard Deviation 2.17 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Vineland Adaptive Behavior Scale, Second Edition (Vineland-II) Scores | Socialization: Play and Leisure Time Subdomain v-Scale Score | -0.4 Scores on a scale | Standard Deviation 2.22 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Vineland Adaptive Behavior Scale, Second Edition (Vineland-II) Scores | Socialization: Coping Skills Subdomain v-Scale Score | -0.5 Scores on a scale | Standard Deviation 1.85 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Vineland Adaptive Behavior Scale, Second Edition (Vineland-II) Scores | Socialization Domain Standard Score | -3.4 Scores on a scale | Standard Deviation 11.29 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Vineland Adaptive Behavior Scale, Second Edition (Vineland-II) Scores | Motor Skills: Gross Subdomain v-Scale Score | -0.3 Scores on a scale | Standard Deviation 1.88 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Vineland Adaptive Behavior Scale, Second Edition (Vineland-II) Scores | Motor Skills: Fine Subdomain v-Scale Score | -0.4 Scores on a scale | Standard Deviation 2.19 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Vineland Adaptive Behavior Scale, Second Edition (Vineland-II) Scores | Motor Skills Domain Standard Score | -1.9 Scores on a scale | Standard Deviation 10.23 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Vineland Adaptive Behavior Scale, Second Edition (Vineland-II) Scores | Adaptive Behavior Composite Standard Score | -2.5 Scores on a scale | Standard Deviation 10.07 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Vineland Adaptive Behavior Scale, Second Edition (Vineland-II) Scores | Maladaptive Behavior Index: Internalizing Subdomain v-Scale Score | -0.1 Scores on a scale | Standard Deviation 2.64 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Vineland Adaptive Behavior Scale, Second Edition (Vineland-II) Scores | Maladaptive Behavior Index: Externalizing Subdomain v-Scale Score | -0.1 Scores on a scale | Standard Deviation 2.12 |
Secondary
Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Visual Perception Standard Scaled Score
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.
Time frame: Baseline; up to Week 260
Population: ITT Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Visual Perception Standard Scaled Score | 0.00 Score on a scale | — |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Visual Perception Standard Scaled Score | 2.67 Score on a scale | Standard Deviation 7.767 |
Secondary
Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WAIS Digit Span Backward Scaled Score
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.
Time frame: Baseline; up to Week 260
Population: ITT Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WAIS Digit Span Backward Scaled Score | Baseline | 0.0 Score on a scale | — |
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WAIS Digit Span Backward Scaled Score | Week 48 | 0.0 Score on a scale | — |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WAIS Digit Span Backward Scaled Score | Baseline | 0.0 Score on a scale | Standard Deviation 0 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WAIS Digit Span Backward Scaled Score | Week 48 | 0.25 Score on a scale | Standard Deviation 0.5 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WAIS Digit Span Backward Scaled Score | End of Treatment | -0.14 Score on a scale | Standard Deviation 0.378 |
Secondary
Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WAIS Digit Span Forward Scaled Score
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.
Time frame: Baseline; up to Week 260
Population: ITT Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WAIS Digit Span Forward Scaled Score | Baseline | 0.0 Score on a scale | — |
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WAIS Digit Span Forward Scaled Score | Week 48 | 0.0 Score on a scale | — |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WAIS Digit Span Forward Scaled Score | Baseline | 0.13 Score on a scale | Standard Deviation 1.808 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WAIS Digit Span Forward Scaled Score | Week 48 | -0.25 Score on a scale | Standard Deviation 1.258 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WAIS Digit Span Forward Scaled Score | End of Treatment | 0.14 Score on a scale | Standard Deviation 2.268 |
Secondary
Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WAIS Longest Digit Span Backward Scaled Score
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.
Time frame: Baseline; up to Week 260
Population: ITT Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WAIS Longest Digit Span Backward Scaled Score | Baseline | 0.00 Score on a scale | — |
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WAIS Longest Digit Span Backward Scaled Score | Week 48 | 0.00 Score on a scale | — |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WAIS Longest Digit Span Backward Scaled Score | Baseline | 0.00 Score on a scale | Standard Deviation 0 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WAIS Longest Digit Span Backward Scaled Score | Week 48 | 0.00 Score on a scale | Standard Deviation 0 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WAIS Longest Digit Span Backward Scaled Score | End of Treatment | 0.00 Score on a scale | Standard Deviation 0 |
Secondary
Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WAIS Longest Digit Span Forward Scaled Score
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.
Time frame: Baseline; up to Week 260
Population: ITT Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WAIS Longest Digit Span Forward Scaled Score | Baseline | 0.0 Score on a scale | — |
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WAIS Longest Digit Span Forward Scaled Score | Week 48 | 0.0 Score on a scale | — |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WAIS Longest Digit Span Forward Scaled Score | Baseline | 0.13 Score on a scale | Standard Deviation 1.642 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WAIS Longest Digit Span Forward Scaled Score | Week 48 | 0.25 Score on a scale | Standard Deviation 1.258 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WAIS Longest Digit Span Forward Scaled Score | End of Treatment | -0.14 Score on a scale | Standard Deviation 1.574 |
Secondary
Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WASI-II Matrix Reasoning T Score
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.
Time frame: Baseline; up to Week 260
Population: ITT Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WASI-II Matrix Reasoning T Score | -1.50 T Score | Standard Deviation 3 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WASI-II Matrix Reasoning T Score | -3.29 T Score | Standard Deviation 5.376 |
Secondary
Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Wechsler Abbreviated Scale of Intelligence (WASI)-II Vocabulary T Score
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.
Time frame: Baseline; up to Week 260
Population: ITT Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Wechsler Abbreviated Scale of Intelligence (WASI)-II Vocabulary T Score | 0.00 T Score | Standard Deviation 0 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Wechsler Abbreviated Scale of Intelligence (WASI)-II Vocabulary T Score | -4.00 T Score | Standard Deviation 12.247 |
Secondary
Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Wechsler Adult Intelligence Scale (WAIS) Coding Scaled Score
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.
Time frame: Baseline; up to Week 260
Population: ITT Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Wechsler Adult Intelligence Scale (WAIS) Coding Scaled Score | 0.00 Score on a scale | Standard Deviation 0 |
Secondary
Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Wechsler Intelligence Scale for Children (WISC) Coding Scaled Score
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.
Time frame: Baseline; up to Week 260
Population: ITT Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Wechsler Intelligence Scale for Children (WISC) Coding Scaled Score | -0.40 Score on a scale | Standard Deviation 1.817 |
Secondary
Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Wechsler Preschool & Primary Scale of Intelligence (WPPSI)-IV Bug Search T Score
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.
Time frame: Baseline; up to Week 260
Population: ITT Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Wechsler Preschool & Primary Scale of Intelligence (WPPSI)-IV Bug Search T Score | Baseline | 0.0 T Score | Standard Deviation 0 |
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in Wechsler Preschool & Primary Scale of Intelligence (WPPSI)-IV Bug Search T Score | Week 48 | 0.0 T Score | — |
Secondary
Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WISC Digit Span Backward Scaled Score
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.
Time frame: Baseline; up to Week 260
Population: ITT Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WISC Digit Span Backward Scaled Score | 0.00 Score on a scale | Standard Deviation 0.632 |
Secondary
Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WISC Digit Span Forward Scaled Score
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.
Time frame: Baseline; up to Week 260
Population: ITT Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WISC Digit Span Forward Scaled Score | 0.57 Score on a scale | Standard Deviation 0.787 |
Secondary
Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WISC Longest Digit Span Backward Scaled Score
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.
Time frame: Baseline; up to Week 260
Population: ITT Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WISC Longest Digit Span Backward Scaled Score | 0.00 Score on a scale | Standard Deviation 1.265 |
Secondary
Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WISC Longest Digit Span Forward Scaled Score
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.
Time frame: Baseline; up to Week 260
Population: ITT Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WISC Longest Digit Span Forward Scaled Score | 0.17 Score on a scale | Standard Deviation 0.408 |
Secondary
Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WPPSI-IV Matrix Reasoning T Score
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.
Time frame: Baseline; up to Week 260
Population: ITT Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WPPSI-IV Matrix Reasoning T Score | Week 48 | -0.75 T Score | Standard Deviation 6.994 |
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WPPSI-IV Matrix Reasoning T Score | Baseline | 0.75 T Score | Standard Deviation 6.994 |
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WPPSI-IV Matrix Reasoning T Score | Baseline | -19.0 T Score | — |
Secondary
Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WPPSI-IV Receptive Vocabulary T Score
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.
Time frame: Baseline; up to Week 260
Population: ITT Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Lennox-Gastaut Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment in WPPSI-IV Receptive Vocabulary T Score | -1.00 T Score |
Secondary
Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment QOL in Epilepsy Scores (QOLIE-31-P) in Participants With Lennox-Gastaut Syndrome
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.
Time frame: Baseline; up to Week 260
Population: Safety Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dravet Syndrome | Mean Change From the Pre-randomization Baseline of the Core Study to the End of Treatment QOL in Epilepsy Scores (QOLIE-31-P) in Participants With Lennox-Gastaut Syndrome | 1.3 Scores on a scale | Standard Deviation 16.33 |
Secondary
Number of Participants With Changes in the Average Duration of Seizure Subtypes as Assessed by the Participant/Caregiver Global Impression of Change in Seizure Duration (S/CGICSD)
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).
Time frame: Up to Week 260
Population: Safety Analysis Set. Only participants with available data are analyzed.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Dravet Syndrome | Number of Participants With Changes in the Average Duration of Seizure Subtypes as Assessed by the Participant/Caregiver Global Impression of Change in Seizure Duration (S/CGICSD) | Tonic-Clonic Seizures; End of Treatment | Decrease in average duration | 89 Participants |
| Dravet Syndrome | Number of Participants With Changes in the Average Duration of Seizure Subtypes as Assessed by the Participant/Caregiver Global Impression of Change in Seizure Duration (S/CGICSD) | Tonic-Clonic Seizures; End of Treatment | Increase in average duration | 17 Participants |
| Dravet Syndrome | Number of Participants With Changes in the Average Duration of Seizure Subtypes as Assessed by the Participant/Caregiver Global Impression of Change in Seizure Duration (S/CGICSD) | Tonic Seizures; End of Treatment | Decrease in average duration | 39 Participants |
| Dravet Syndrome | Number of Participants With Changes in the Average Duration of Seizure Subtypes as Assessed by the Participant/Caregiver Global Impression of Change in Seizure Duration (S/CGICSD) | Tonic Seizures; End of Treatment | Increase in average duration | 8 Participants |
| Dravet Syndrome | Number of Participants With Changes in the Average Duration of Seizure Subtypes as Assessed by the Participant/Caregiver Global Impression of Change in Seizure Duration (S/CGICSD) | Clonic Seizures; End of Treatment | Decrease in average duration | 41 Participants |
| Dravet Syndrome | Number of Participants With Changes in the Average Duration of Seizure Subtypes as Assessed by the Participant/Caregiver Global Impression of Change in Seizure Duration (S/CGICSD) | Clonic Seizures; End of Treatment | Increase in average duration | 4 Participants |
| Dravet Syndrome | Number of Participants With Changes in the Average Duration of Seizure Subtypes as Assessed by the Participant/Caregiver Global Impression of Change in Seizure Duration (S/CGICSD) | Atonic Seizures; End of Treatment | Decrease in average duration | 26 Participants |
| Dravet Syndrome | Number of Participants With Changes in the Average Duration of Seizure Subtypes as Assessed by the Participant/Caregiver Global Impression of Change in Seizure Duration (S/CGICSD) | Atonic Seizures; End of Treatment | Increase in average duration | 6 Participants |
| Dravet Syndrome | Number of Participants With Changes in the Average Duration of Seizure Subtypes as Assessed by the Participant/Caregiver Global Impression of Change in Seizure Duration (S/CGICSD) | Myoclonic Seizures; End of Treatment | Decrease in average duration | 48 Participants |
| Dravet Syndrome | Number of Participants With Changes in the Average Duration of Seizure Subtypes as Assessed by the Participant/Caregiver Global Impression of Change in Seizure Duration (S/CGICSD) | Myoclonic Seizures; End of Treatment | Increase in average duration | 14 Participants |
| Dravet Syndrome | Number of Participants With Changes in the Average Duration of Seizure Subtypes as Assessed by the Participant/Caregiver Global Impression of Change in Seizure Duration (S/CGICSD) | Countable Partial Seizures; End of Treatment | Decrease in average duration | 34 Participants |
| Dravet Syndrome | Number of Participants With Changes in the Average Duration of Seizure Subtypes as Assessed by the Participant/Caregiver Global Impression of Change in Seizure Duration (S/CGICSD) | Countable Partial Seizures; End of Treatment | Increase in average duration | 8 Participants |
| Dravet Syndrome | Number of Participants With Changes in the Average Duration of Seizure Subtypes as Assessed by the Participant/Caregiver Global Impression of Change in Seizure Duration (S/CGICSD) | Other Partial Seizures; End of Treatment | Decrease in average duration | 25 Participants |
| Dravet Syndrome | Number of Participants With Changes in the Average Duration of Seizure Subtypes as Assessed by the Participant/Caregiver Global Impression of Change in Seizure Duration (S/CGICSD) | Other Partial Seizures; End of Treatment | Increase in average duration | 6 Participants |
| Dravet Syndrome | Number of Participants With Changes in the Average Duration of Seizure Subtypes as Assessed by the Participant/Caregiver Global Impression of Change in Seizure Duration (S/CGICSD) | Absence Seizures; End of Treatment | Decrease in average duration | 42 Participants |
| Dravet Syndrome | Number of Participants With Changes in the Average Duration of Seizure Subtypes as Assessed by the Participant/Caregiver Global Impression of Change in Seizure Duration (S/CGICSD) | Absence Seizures; End of Treatment | Increase in average duration | 9 Participants |
| Lennox-Gastaut Syndrome | Number of Participants With Changes in the Average Duration of Seizure Subtypes as Assessed by the Participant/Caregiver Global Impression of Change in Seizure Duration (S/CGICSD) | Absence Seizures; End of Treatment | Increase in average duration | 3 Participants |
| Lennox-Gastaut Syndrome | Number of Participants With Changes in the Average Duration of Seizure Subtypes as Assessed by the Participant/Caregiver Global Impression of Change in Seizure Duration (S/CGICSD) | Tonic-Clonic Seizures; End of Treatment | Decrease in average duration | 101 Participants |
| Lennox-Gastaut Syndrome | Number of Participants With Changes in the Average Duration of Seizure Subtypes as Assessed by the Participant/Caregiver Global Impression of Change in Seizure Duration (S/CGICSD) | Myoclonic Seizures; End of Treatment | Decrease in average duration | 72 Participants |
| Lennox-Gastaut Syndrome | Number of Participants With Changes in the Average Duration of Seizure Subtypes as Assessed by the Participant/Caregiver Global Impression of Change in Seizure Duration (S/CGICSD) | Tonic-Clonic Seizures; End of Treatment | Increase in average duration | 24 Participants |
| Lennox-Gastaut Syndrome | Number of Participants With Changes in the Average Duration of Seizure Subtypes as Assessed by the Participant/Caregiver Global Impression of Change in Seizure Duration (S/CGICSD) | Other Partial Seizures; End of Treatment | Decrease in average duration | 29 Participants |
| Lennox-Gastaut Syndrome | Number of Participants With Changes in the Average Duration of Seizure Subtypes as Assessed by the Participant/Caregiver Global Impression of Change in Seizure Duration (S/CGICSD) | Tonic Seizures; End of Treatment | Decrease in average duration | 132 Participants |
| Lennox-Gastaut Syndrome | Number of Participants With Changes in the Average Duration of Seizure Subtypes as Assessed by the Participant/Caregiver Global Impression of Change in Seizure Duration (S/CGICSD) | Myoclonic Seizures; End of Treatment | Increase in average duration | 4 Participants |
| Lennox-Gastaut Syndrome | Number of Participants With Changes in the Average Duration of Seizure Subtypes as Assessed by the Participant/Caregiver Global Impression of Change in Seizure Duration (S/CGICSD) | Tonic Seizures; End of Treatment | Increase in average duration | 18 Participants |
| Lennox-Gastaut Syndrome | Number of Participants With Changes in the Average Duration of Seizure Subtypes as Assessed by the Participant/Caregiver Global Impression of Change in Seizure Duration (S/CGICSD) | Absence Seizures; End of Treatment | Decrease in average duration | 83 Participants |
| Lennox-Gastaut Syndrome | Number of Participants With Changes in the Average Duration of Seizure Subtypes as Assessed by the Participant/Caregiver Global Impression of Change in Seizure Duration (S/CGICSD) | Clonic Seizures; End of Treatment | Decrease in average duration | 38 Participants |
| Lennox-Gastaut Syndrome | Number of Participants With Changes in the Average Duration of Seizure Subtypes as Assessed by the Participant/Caregiver Global Impression of Change in Seizure Duration (S/CGICSD) | Countable Partial Seizures; End of Treatment | Decrease in average duration | 41 Participants |
| Lennox-Gastaut Syndrome | Number of Participants With Changes in the Average Duration of Seizure Subtypes as Assessed by the Participant/Caregiver Global Impression of Change in Seizure Duration (S/CGICSD) | Clonic Seizures; End of Treatment | Increase in average duration | 3 Participants |
| Lennox-Gastaut Syndrome | Number of Participants With Changes in the Average Duration of Seizure Subtypes as Assessed by the Participant/Caregiver Global Impression of Change in Seizure Duration (S/CGICSD) | Other Partial Seizures; End of Treatment | Increase in average duration | 0 Participants |
| Lennox-Gastaut Syndrome | Number of Participants With Changes in the Average Duration of Seizure Subtypes as Assessed by the Participant/Caregiver Global Impression of Change in Seizure Duration (S/CGICSD) | Atonic Seizures; End of Treatment | Decrease in average duration | 98 Participants |
| Lennox-Gastaut Syndrome | Number of Participants With Changes in the Average Duration of Seizure Subtypes as Assessed by the Participant/Caregiver Global Impression of Change in Seizure Duration (S/CGICSD) | Countable Partial Seizures; End of Treatment | Increase in average duration | 5 Participants |
| Lennox-Gastaut Syndrome | Number of Participants With Changes in the Average Duration of Seizure Subtypes as Assessed by the Participant/Caregiver Global Impression of Change in Seizure Duration (S/CGICSD) | Atonic Seizures; End of Treatment | Increase in average duration | 10 Participants |
Secondary
Number of Participants With Inpatient Hospitalizations Due to Epilepsy Since the Previous Visit
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.
Time frame: Week 48, 104, 156, 208, and End of Treatment (up to Week 260 based on when the participant discontinued treatment)
Population: Safety Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dravet Syndrome | Number of Participants With Inpatient Hospitalizations Due to Epilepsy Since the Previous Visit | Week 48 | 5 Participants |
| Dravet Syndrome | Number of Participants With Inpatient Hospitalizations Due to Epilepsy Since the Previous Visit | Week 156 | 3 Participants |
| Dravet Syndrome | Number of Participants With Inpatient Hospitalizations Due to Epilepsy Since the Previous Visit | End of Treatment | 16 Participants |
| Dravet Syndrome | Number of Participants With Inpatient Hospitalizations Due to Epilepsy Since the Previous Visit | Week 208 | 0 Participants |
| Dravet Syndrome | Number of Participants With Inpatient Hospitalizations Due to Epilepsy Since the Previous Visit | Week 104 | 4 Participants |
| Lennox-Gastaut Syndrome | Number of Participants With Inpatient Hospitalizations Due to Epilepsy Since the Previous Visit | End of Treatment | 17 Participants |
| Lennox-Gastaut Syndrome | Number of Participants With Inpatient Hospitalizations Due to Epilepsy Since the Previous Visit | Week 48 | 9 Participants |
| Lennox-Gastaut Syndrome | Number of Participants With Inpatient Hospitalizations Due to Epilepsy Since the Previous Visit | Week 104 | 9 Participants |
| Lennox-Gastaut Syndrome | Number of Participants With Inpatient Hospitalizations Due to Epilepsy Since the Previous Visit | Week 156 | 0 Participants |
| Lennox-Gastaut Syndrome | Number of Participants With Inpatient Hospitalizations Due to Epilepsy Since the Previous Visit | Week 208 | 0 Participants |
Secondary
Number of Treatment Responders With Greater Than or Equal to 50% Reduction in Total Seizures
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.
Time frame: Baseline; Week 49 to 60, Week 97 to 108, Week 145 to 156, Week 205 to 216, Week 253 to 264, and Last 12 Weeks
Population: Safety Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dravet Syndrome | Number of Treatment Responders With Greater Than or Equal to 50% Reduction in Total Seizures | Week 205 to 216 | 7 Participants |
| Dravet Syndrome | Number of Treatment Responders With Greater Than or Equal to 50% Reduction in Total Seizures | Week 145 to 156 | 48 Participants |
| Dravet Syndrome | Number of Treatment Responders With Greater Than or Equal to 50% Reduction in Total Seizures | Week 253 to 264 | 2 Participants |
| Dravet Syndrome | Number of Treatment Responders With Greater Than or Equal to 50% Reduction in Total Seizures | Last 12 Weeks | 153 Participants |
| Dravet Syndrome | Number of Treatment Responders With Greater Than or Equal to 50% Reduction in Total Seizures | Week 49 to 60 | 108 Participants |
| Dravet Syndrome | Number of Treatment Responders With Greater Than or Equal to 50% Reduction in Total Seizures | Week 97 to 108 | 73 Participants |
| Lennox-Gastaut Syndrome | Number of Treatment Responders With Greater Than or Equal to 50% Reduction in Total Seizures | Last 12 Weeks | 188 Participants |
| Lennox-Gastaut Syndrome | Number of Treatment Responders With Greater Than or Equal to 50% Reduction in Total Seizures | Week 49 to 60 | 169 Participants |
| Lennox-Gastaut Syndrome | Number of Treatment Responders With Greater Than or Equal to 50% Reduction in Total Seizures | Week 97 to 108 | 148 Participants |
| Lennox-Gastaut Syndrome | Number of Treatment Responders With Greater Than or Equal to 50% Reduction in Total Seizures | Week 145 to 156 | 128 Participants |
| Lennox-Gastaut Syndrome | Number of Treatment Responders With Greater Than or Equal to 50% Reduction in Total Seizures | Week 205 to 216 | 12 Participants |