Trial Outcomes & Findings for A Study to Investigate the Efficacy and Safety of Cannabidiol (GWP42003-P; CBD) as Adjunctive Treatment for Seizures Associated With Lennox-Gastaut Syndrome in Children and Adults (NCT NCT02224690)

Last Updated: 2022-09-28

Results Overview

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) \* 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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

171 participants

Primary outcome timeframe

Baseline to End of Treatment (EOT) (Day 99) or Early Termination (ET)

Results posted on

2022-09-28

Participant Flow

The dose level of 20 milligram (mg) per kilogram (kg) per day (mg/kg/day) was recommended by the GWEP1332 Part A (NCT02091206) Data Safety Monitoring Committee after assessment of safety and pharmacokinetic data. The investigational medicinal product (IMP) was given daily in 2 divided doses (the preferred dosing regimen for antiepileptic drugs).

Participant milestones

Participant milestones
Measure	GWP42003-P 20 mg/kg/Day Dose Participants received GWP42003-P 20 mg/kg/day administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the open-label extension (OLE) study, the maintenance period was followed by a 10-day taper (10% per day) period.	Placebo Participants received placebo (0 mg/milliliter \[mL\] cannabidiol \[CBD\]), volume matched to the 20 mg/kg/day dose, administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.
Overall Study STARTED	86	85
Overall Study Safety Analysis Set	86	85
Overall Study Intent to Treat (ITT) Analysis Set	86	85
Overall Study COMPLETED	72	84
Overall Study NOT COMPLETED	14	1

Reasons for withdrawal

Reasons for withdrawal
Measure	GWP42003-P 20 mg/kg/Day Dose Participants received GWP42003-P 20 mg/kg/day administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the open-label extension (OLE) study, the maintenance period was followed by a 10-day taper (10% per day) period.	Placebo Participants received placebo (0 mg/milliliter \[mL\] cannabidiol \[CBD\]), volume matched to the 20 mg/kg/day dose, administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.
Overall Study Adverse Event	8	1
Overall Study Met Withdrawal Criteria	4	0
Overall Study Use of G-tube	1	0
Overall Study Did not meet eligibility criteria	1	0

Baseline Characteristics

A Study to Investigate the Efficacy and Safety of Cannabidiol (GWP42003-P; CBD) as Adjunctive Treatment for Seizures Associated With Lennox-Gastaut Syndrome in Children and Adults

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	GWP42003-P 20 mg/kg/Day Dose n=86 Participants Participants received GWP42003-P 20 mg/kg/day administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.	Placebo n=85 Participants Participants received placebo (0 mg/mL CBD), volume matched to the 20 mg/kg/day dose, administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.	Total n=171 Participants Total of all reporting groups
Age, Continuous	15.478 years STANDARD_DEVIATION 8.685 • n=5 Participants	15.284 years STANDARD_DEVIATION 9.7945 • n=7 Participants	15.381 years STANDARD_DEVIATION 9.2264 • n=5 Participants
Sex: Female, Male Female	41 Participants n=5 Participants	42 Participants n=7 Participants	83 Participants n=5 Participants
Sex: Female, Male Male	45 Participants n=5 Participants	43 Participants n=7 Participants	88 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to End of Treatment (EOT) (Day 99) or Early Termination (ET)

Population: ITT Analysis Set: All randomized participants who received at least 1 dose of IMP and had at least 1 post-baseline efficacy endpoint measurement. Participants were analyzed according to the treatment group to which they were randomized.

Outcome measures

Outcome measures
Measure	GWP42003-P 20 mg/kg/Day Dose n=86 Participants Participants received GWP42003-P 20 mg/kg/day administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.	Placebo n=85 Participants Participants received placebo (0 mg/mL CBD), volume matched to the 20 mg/kg/day dose, administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.
Percentage Change From Baseline In Drop Seizure Frequency During The Treatment Period	-43.90 percentage change Interval -69.62 to 1.93	-21.80 percentage change Interval -45.72 to 1.74

SECONDARY outcome

Timeframe: Baseline to EOT (Day 99) or ET

Drop seizures were recorded by the participant or caregiver using an IVRS diary. Drop seizures included the subset of tonic-clonic, tonic or atonic seizures that were reported as drop seizures in IVRS. Percentage change from baseline was calculated as per the primary outcome measure.

Outcome measures

Outcome measures
Measure	GWP42003-P 20 mg/kg/Day Dose n=86 Participants Participants received GWP42003-P 20 mg/kg/day administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.	Placebo n=85 Participants Participants received placebo (0 mg/mL CBD), volume matched to the 20 mg/kg/day dose, administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.
Number Of Participants With a ≥50% Reduction From Baseline in Drop Seizure Frequency During The Treatment Period	38 Participants	20 Participants

SECONDARY outcome

Timeframe: Baseline to EOT (Day 99) or ET

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 using an IVRS diary. Percentage change from baseline was calculated as per the primary outcome measure. Negative percentages show an improvement from baseline.

Outcome measures

Outcome measures
Measure	GWP42003-P 20 mg/kg/Day Dose n=86 Participants Participants received GWP42003-P 20 mg/kg/day administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.	Placebo n=85 Participants Participants received placebo (0 mg/mL CBD), volume matched to the 20 mg/kg/day dose, administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.
Percentage Change From Baseline In Total Seizure Frequency During The Treatment Period	-41.24 percentage change Interval -62.85 to -13.0	-13.70 percentage change Interval -45.0 to 7.27

SECONDARY outcome

Timeframe: Baseline to Last Visit (Day 99) or ET

The S/CGIC was used to assess the participant's overall condition on a 7-point scale, using the markers "very much improved, much improved, slightly improved, no change, slightly worse, much worse, or very much worse" (1 = very much improved; 7 = very much worse). On Day 1 (prior to starting IMP), the caregiver was asked to write a brief description of the participant's overall condition as a memory aid for the S/CGIC questionnaire at subsequent visits. If both a CGIC and SGIC were completed then the CGIC was used; if only a CGIC was completed then the CGIC was used; if only a SGIC was completed then the SGIC was used. Last visit for endpoints assessed at clinic visits was defined as the last scheduled visit (not including the end of taper or safety follow-up visits) at which participant's last evaluation was performed.

Outcome measures

Outcome measures
Measure	GWP42003-P 20 mg/kg/Day Dose n=84 Participants Participants received GWP42003-P 20 mg/kg/day administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.	Placebo n=85 Participants Participants received placebo (0 mg/mL CBD), volume matched to the 20 mg/kg/day dose, administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.
Subject/Caregiver Global Impression Of Change Assessment (S/CGIC) Very Much Improved	15 Participants	5 Participants
Subject/Caregiver Global Impression Of Change Assessment (S/CGIC) Much Improved	14 Participants	9 Participants
Subject/Caregiver Global Impression Of Change Assessment (S/CGIC) Slightly Improved	20 Participants	15 Participants
Subject/Caregiver Global Impression Of Change Assessment (S/CGIC) No Change	27 Participants	43 Participants
Subject/Caregiver Global Impression Of Change Assessment (S/CGIC) Slightly Worse	7 Participants	9 Participants
Subject/Caregiver Global Impression Of Change Assessment (S/CGIC) Much Worse	1 Participants	2 Participants
Subject/Caregiver Global Impression Of Change Assessment (S/CGIC) Very Much Worse	0 Participants	2 Participants

Adverse Events

GWP42003-P 20 mg/kg/Day Dose

Serious events: 20 serious events

Other events: 53 other events

Deaths: 0 deaths

Placebo

Serious events: 4 serious events

Other events: 43 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Enquires

GW Research Ltd.

Email: [email protected], [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	GWP42003-P 20 mg/kg/Day Dose n=86 participants at risk Participants received GWP42003-P 20 mg/kg/day administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.	Placebo n=85 participants at risk Participants received placebo (0 mg/mL CBD), volume matched to the 20 mg/kg/day dose, administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.
Gastrointestinal disorders Constipation	1.2% 1/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	0.00% 0/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
Gastrointestinal disorders Vomiting	1.2% 1/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	0.00% 0/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
Vascular disorders Deep vein thrombosis	1.2% 1/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	0.00% 0/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
General disorders Pyrexia	0.00% 0/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	1.2% 1/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
Hepatobiliary disorders Acute hepatic failure	1.2% 1/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	0.00% 0/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
Infections and infestations Perirectal abscess	1.2% 1/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	0.00% 0/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
Infections and infestations Pilonidal cyst	0.00% 0/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	1.2% 1/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
Infections and infestations Pneumonia	3.5% 3/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	0.00% 0/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
Infections and infestations Pneumonia adenoviral	1.2% 1/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	0.00% 0/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
Infections and infestations Sepsis	1.2% 1/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	0.00% 0/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
Infections and infestations Urinary tract infection	0.00% 0/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	1.2% 1/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
Infections and infestations Viral infection	2.3% 2/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	0.00% 0/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
Investigations Alanine aminotransferase increased	4.7% 4/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	0.00% 0/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
Investigations Aspartate aminotransferase increased	4.7% 4/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	0.00% 0/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
Investigations Drug level increased	1.2% 1/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	0.00% 0/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
Investigations Gamma-glutamyltransferase increased	3.5% 3/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	0.00% 0/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
Investigations Liver function test abnormal	1.2% 1/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	0.00% 0/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
Investigations Oxygen saturation decreased	0.00% 0/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	1.2% 1/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
Investigations Transaminases increased	1.2% 1/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	0.00% 0/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
Nervous system disorders Convulsion	2.3% 2/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	0.00% 0/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
Nervous system disorders Generalised tonic-clonic seizure	0.00% 0/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	1.2% 1/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
Nervous system disorders Lethargy	1.2% 1/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	0.00% 0/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
Nervous system disorders Seizure cluster	1.2% 1/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	1.2% 1/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
Nervous system disorders Somnolence	1.2% 1/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	0.00% 0/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
Nervous system disorders Status epilepticus	1.2% 1/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	1.2% 1/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress	1.2% 1/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	0.00% 0/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	3.5% 3/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	0.00% 0/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
Respiratory, thoracic and mediastinal disorders Bronchial secretion retention	1.2% 1/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	0.00% 0/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
Respiratory, thoracic and mediastinal disorders Hypercapnia	1.2% 1/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	0.00% 0/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
Respiratory, thoracic and mediastinal disorders Hypoxia	2.3% 2/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	0.00% 0/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	1.2% 1/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	1.2% 1/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
Respiratory, thoracic and mediastinal disorders Pneumothorax	1.2% 1/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	0.00% 0/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
Respiratory, thoracic and mediastinal disorders Respiratory distress	1.2% 1/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	0.00% 0/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	1.2% 1/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	0.00% 0/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
Metabolism and nutrition disorders Dehydration	0.00% 0/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	2.4% 2/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
Renal and urinary disorders Nephrolithiasis	1.2% 1/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	0.00% 0/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.

Measure	GWP42003-P 20 mg/kg/Day Dose n=86 participants at risk Participants received GWP42003-P 20 mg/kg/day administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.	Placebo n=85 participants at risk Participants received placebo (0 mg/mL CBD), volume matched to the 20 mg/kg/day dose, administered orally, half in the morning and half in the evening. To maintain the blinded aspect of the study, participants titrated the placebo dose over 11 days and remained at this dose for the 12-week maintenance period. If the participant did not immediately enter the OLE study, the maintenance period was followed by a 10-day taper (10% per day) period.
Gastrointestinal disorders Diarrhoea	18.6% 16/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	8.2% 7/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
Gastrointestinal disorders Vomiting	9.3% 8/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	16.5% 14/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
Gastrointestinal disorders Constipation	5.8% 5/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	4.7% 4/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
General disorders Pyrexia	12.8% 11/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	8.2% 7/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
General disorders Fatigue	5.8% 5/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	2.4% 2/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
Infections and infestations Sinusitis	5.8% 5/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	2.4% 2/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
Infections and infestations Upper respiratory tract infection	2.3% 2/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	7.1% 6/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
Metabolism and nutrition disorders Decreased appetite	12.8% 11/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	2.4% 2/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
Nervous system disorders Somnolence	14.0% 12/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	9.4% 8/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
Nervous system disorders Sedation	8.1% 7/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	1.2% 1/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
Nervous system disorders Convulsion	3.5% 3/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	5.9% 5/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
Nervous system disorders Headache	2.3% 2/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	5.9% 5/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
Respiratory, thoracic and mediastinal disorders Nasal congestion	8.1% 7/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	2.4% 2/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
Respiratory, thoracic and mediastinal disorders Cough	5.8% 5/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	2.4% 2/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.
Skin and subcutaneous tissue disorders Rash	7.0% 6/86 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.	1.2% 1/85 • Day 1 through Day 137 (Safety Follow-up) Safety Analysis Set: All participants randomized to treatment who received at least 1 dose of IMP. Participants were analyzed according to the treatment they received.