GWP42003-P/kg/Day Dose

TEAEs were collected in members of the Safety Population, comprised of all participants who received at least 1 dose of GWP42003-P. TEAEs are defined as all adverse events not present prior to the first investigational medicinal product (IMP) or placebo administration or any event already present that worsened in severity or frequency following IMP.

Clinical relevance was determined by the investigator.

Clinical significance was determined by the investigator.

Clinical significance was determined by the investigator.

Clinical significance was determined by the investigator.

Clinical relevance was determined by the investigator.

An adverse event (AE) was defined as any new unfavorable/unintended signs/symptoms (including abnormal laboratory findings), or diagnosis or worsening of a pre-existing condition, which occurred following screening and at any point up to the post-treatment safety follow-up visit, which may or may not be related to the IMP. An AE that started, or worsened in severity or seriousness, following the first dose of IMP was considered a TEAE. A serious AE was defined as any AE that results in any of the following outcomes: death, life-threatening adverse experience, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or cancer, any other experience that suggests a significant hazard, contraindication, side effect or precaution that may require medical or surgical intervention to prevent one of the outcomes listed above, or an event that changes the risk/benefit ratio of the study.

An adverse event (AE) was defined as any new unfavorable/unintended signs/symptoms (including abnormal laboratory findings), or diagnosis or worsening of a pre-existing condition, which occurred following screening and at any point up to the post-treatment safety follow-up visit, which may or may not be related to the IMP. An AE that started, or worsened in severity or seriousness, following the first dose of IMP was considered a TEAE. Grade 1 (Mild) is defined as asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 (Moderate) is defined as minimal, local or noninvasive intervention indicated; limiting age appropriate instrumental activities of daily living (ADL). Grade 3 (Severe) is defined as medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL.

TSC-associated seizures included: focal motor seizures without impairment of consciousness or awareness (Type 1 focal motor); focal seizures with impairment of consciousness or awareness (Type 2 focal); focal seizures evolving to bilateral generalized convulsive seizures (Type 3 focal); and tonic-clonic, tonic, clonic, or atonic seizures that are countable. Percent change from Baseline was calculated as the (post-Baseline value minus the Baseline value) divided by the Baseline value x 100.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Drop seizures were recorded by the participant or caregiver using an interactive voice response system (IVRS) diary. Drop seizures were defined as the subset of tonic-clonic, tonic or atonic seizures that were reported as drop seizures in the IVRS. Percentage change from baseline was calculated as: (\[frequency during the treatment period - frequency during baseline\]/frequency during baseline) x 100. The frequency during each period was based on 28-day averages and calculated as: (number of seizures in the period/number of reported days in the IVRS period) x 28. Baseline included all available data prior to Day 1 (28-day average). Negative percentages show an improvement from baseline.

Convulsive seizures were defined as tonic-clonic, tonic, clonic, or atonic. Participants or their caregivers recorded the number and type of convulsive seizures each day from screening until completion of dosing using an interactive voice response system (IVRS) diary. The primary endpoint was analyzed using negative binomial regression on the sum of the convulsive seizure counts during the treatment period, based on the ITT analysis set. Baseline included all available data prior to Day 1. Data reported as the ratio of geometric least squares mean in convulsive seizures and expressed as a percentage reduction.

Convulsive seizures (atonic, clonic, tonic, or tonic-clonic) were recorded by the participant or caregiver using an interactive voice response system (IVRS) diary. Percentage change from baseline was calculated as: (\[frequency during the treatment period - frequency during baseline\]/frequency during baseline) \* 100. The frequency during each period was based on 28-day averages and calculated as: (number of seizures in the period/number of reported days in the IVRS period) \* 28. Baseline included all available data prior to Day 1 (28-day average). Negative percentages show an improvement from baseline.

The caregiver-assessed ABC was designed to assess the presence and severity of various problem behaviors commonly observed in individuals diagnosed with intellectual and developmental disability. The checklist contains 5 subscales: Irritability (15 items); Social Withdrawal (16 items); Stereotypic Behavior (7 items); Hyperactivity/Noncompliance (16 items); and Inappropriate Speech (4 items). Each item is scored as 0 (never a problem), 1 (slight problem), 2 (moderately serious problem), or 3 (severe problem). The total score of all items for each subscale range from 0-45 (irritability), 0-48 (social withdrawal and hyperactivity/noncompliance), 0-21 (stereotypic behavior), and 0-12 (inappropriate speech) where higher scores indicate worse clinical outcome. The change from baseline to Week 4, Week 8, and Week 12 is reported with lower scores indicating better clinical outcome.

The VABS-3 scales assess what a person does, rather than what he or she can do. The Vineland-3 assesses adaptive behavior in 3 domains: Communication, Daily Living Skills, and Socialization. Each domain is comprised of 3 subdomains: receptive expression and written (communication); personal, domestic and community (daily living skills); Interpersonal relationships, play and leisure and copying skills (socialization). The adaptive behavior composite score is calculated as arithmetic mean of all 3 domain scores. The total score range is 20 to 140, where low scores indicate low (worst) clinical outcome and high scores indicate high (best) clinical outcome. The change from baseline in VABS-3 is being reported with positive values indicating a positive improvement in adaptive behavior.

The CGI-I is a 7-point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. The clinician is asked: Compared to the patient's condition at admission to the project, how much has the patient changed? This is rated as: 1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse; or 7 = very much worse. Higher scores indicate worse clinical outcome. The number of patients in each CGI-I category is reported.

The CGI-S is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's experience with patients who have the same diagnosis. The clinician is asked: Considering your total clinical experience with this particular population, how ill is the patient at this time? This is rated as: 1 = normal, not at all ill; 2 = borderline ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; or 7 = extremely ill. Higher scores indicate worse outcome. The change from baseline in CGI-S scores is reported and lower mean scores indicate better outcome.

The number of participants who experienced an adverse event during the trial is presented.

The Cmax of STP, VPA and CBD is presented.

The Tmax of STP, VPA and CBD is presented.

The AUC(0-t) of STP, VPA and CBD is presented.

The AUC(tau) of STP, VPA, and CBD is presented.

An OLE-emergent AE was defined as an AE with an onset date after the first dose of IMP in the OLE phase of the study. The number of participants who experienced 1 or more severe OLE-emergent AEs after the first dose of IMP in the OLE phase of the study up to the Safety follow-up visit (28 \[± 3\] days following the last dose of IMP) is presented. A summary of serious and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.

The Cmax of CLB and its primary metabolite N-desmethylclobazam (N-CLB) was measured on Day 1 (before beginning GWP42003-P treatment; participants were taking CLB only) and Day 33 (following 21 days of GWP42003-P or placebo maintenance; participants were taking CLB and GWP42003-P or CLB and placebo). PK samples were taken at time points relative to the morning dose of CLB, as follows: Predose, 15 minutes (min), 30 min, 1 hour (h), 1.5 h, 2 h, 4 h, 6 h, 12 h, and 24 h. One participant in the placebo group was excluded from the PK set because placebo was administered on Day 1, after predose sampling. Six participants in the GWP42003-P group were excluded from the PK set because of GWP42003-P and/or CLB dose modification, discontinuation of IMP, discontinuation from trial, or administration of incorrect IMP dose.

The tmax of CLB and its primary metabolite N-CLB was measured on Day 1 (before beginning GWP42003-P treatment; participants were taking CLB only) and Day 33 (following 21 days of GWP42003-P or placebo maintenance; participants were taking CLB and GWP42003-P or CLB and placebo). PK samples were taken at time points relative to the morning dose of CLB, as follows: Predose, 15 min, 30 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 12 h, and 24 h. One participant in the placebo group was excluded from the PK set because placebo was administered on Day 1, after predose sampling. Six participants in the GWP42003-P group were excluded from the PK set because of GWP42003-P and/or CLB dose modification, discontinuation of IMP, discontinuation from trial, or administration of incorrect IMP dose.

The AUCtau of CLB and its primary metabolite N-CLB was measured on Day 1 (before first GWP42003-P dose; participants were taking CLB only) and Day 33 (following 21 days of GWP42003-P or placebo maintenance; participants were taking CLB and GWP42003-P or CLB and placebo). PK samples were taken at time points relative to the morning dose of CLB, as follows: Predose, 15 min, 30 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 12 h, and 24 h. One participant in the placebo group was excluded from the PK set because placebo was administered on Day 1, after predose sampling. Six participants in the GWP42003-P group were excluded from the PK set because of GWP42003-P and/or CLB dose modification, discontinuation of IMP, discontinuation from trial, or administration of incorrect IMP dose.

The Day 33 compared to Day 1 geometric mean ratios of CLB and N-CLB were calculated for Cmax to look for evidence of drug-drug interactions between GWP42003-P/Placebo and CLB and between GWP42003-P/Placebo and N-CLB. A standard 90% confidence interval (CI) approach for the between time point ratios of geometric means of Cmax was carried out on a logarithmic scale using a linear mixed effect model. The no-effect boundary was set between 0.5 and 2.0, and if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval \[0.5, 2.0\], a lack of meaningful effect was declared. Estimates were back transformed to provide summaries on the original scale. The model included a fixed effect term for PK assessment period. An unstructured covariance matrix was used. Kenward and Roger's method was used to calculate the denominator degrees of freedom for the fixed effects.

The Day 33 compared to Day 1 geometric mean ratios of CLB and N-CLB were calculated for AUCtau to look for evidence of drug-drug interactions between GWP42003-P/Placebo and CLB and between GWP42003-P/Placebo and N-CLB. A standard 90% CI approach for the between time point ratios of geometric means of AUCtau was carried out on a logarithmic scale using a linear mixed effect model. The no-effect boundary was set between 0.5 and 2.0, and if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval \[0.5, 2.0\], a lack of meaningful effect was declared. Estimates were back transformed to provide summaries on the original scale. The model included a fixed effect term for PK assessment period. An unstructured covariance matrix was used. Kenward and Roger's method was used to calculate the denominator degrees of freedom for the fixed effects.

A TEAE was defined as an adverse event (AE) with an onset date on or after the first dose of IMP. If an AE had a partial onset date and it was unclear from the partial date (or the stop date) whether the AE started prior to or following the first dose of IMP then the AE was considered a TEAE. The number of participants who experienced one or more severe TEAEs after dosing on Day 1 through the Safety Follow-up Visit (Day 60) is presented. A summary of serious and all other non-serious AEs regardless of causality is located in the Adverse Events module.