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To evaluate the efficacy of GWP42003-P as adjunctive treatment in reducing the number of drop seizures when compared with placebo, in participants with Lennox-Gastaut Syndrome (LGS).
Locally preserved from ClinicalTrials.govOpen ClinicalTrials.govlast source update 2022-09-28
What this record can show
Results are reported by the registry submitter and preserved exactly. They are not independent verification or a treatment recommendation.
Registry facts
This study was a 1:1 randomized, double-blind, 14-week comparison of 20 milligram \[mg\] per kilogram \[kg\] per day \[mg/kg/day\] of GWP42003-P versus placebo. The treatment period consisted of a 2-week titration period followed by a 12-week maintenance period. The study determined the efficacy, safety and tolerability of GWP42003-P compared with placebo. The dose was recommended by the Data Safety Monitoring Committee (DSMC) after assessment of safety and pharmacokinetic data from Part A of study GWEP1332. The first participants enrolled into this study after the DSMC reviewed the safety data from Part A of study GWEP1332. Following study completion, all participants were invited to continue to receive GWP42003-P in an open label extension (OLE) study (under a separate protocol).
Linked local records
Local links use governed condition terms or exact source-reported intervention names. They are navigation candidates, not efficacy claims.
Interventions
GWP42003-P was presented as an oral solution containing 100 mg/milliliter (mL) cannabidiol (CBD) in the excipients sesame oil and anhydrous ethanol (79 mg/mL) with added sweetener (0.5 mg/mL sucralose) and strawberry flavoring (0.2 mg/mL).
Cannabidiol · EpidiolexPlacebo was presented as an oral solution containing 0 mg/mL CBD in the excipients sesame oil and anhydrous ethanol (79 mg/mL) with added sweetener (0.5 mg/mL sucralose) and strawberry flavoring (0.2 mg/mL).
Source-reported results
Results are reported by the registry submitter and preserved exactly. They are not independent verification or a treatment recommendation.
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.
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.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| GWP42003-P 20 mg/kg/Day Dose | 86 | -43.90 | -69.62 to 1.93 |
| Placebo | 85 | -21.80 | -45.72 to 1.74 |
Eligibility
primary outcomes
Time frame: Baseline to End of Treatment (EOT) (Day 99) or Early Termination (ET)
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.
secondary outcomes
Time frame: 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.
Time frame: 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.
Time frame: 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.
Publications
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.
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.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| GWP42003-P 20 mg/kg/Day Dose | 86 | 38 | - |
| Placebo | 85 | 20 | - |
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.
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.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| GWP42003-P 20 mg/kg/Day Dose | 86 | -41.24 | -62.85 to -13.00 |
| Placebo | 85 | -13.70 | -45.00 to 7.27 |
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.
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.
| Group | N | Value | Spread / interval |
|---|---|---|---|
| GWP42003-P 20 mg/kg/Day Dose | 84 | 15 | - |
| Placebo | 85 | 5 | - |
| GWP42003-P 20 mg/kg/Day Dose | 84 | 14 | - |
| Placebo | 85 | 9 | - |
| GWP42003-P 20 mg/kg/Day Dose | 84 | 20 | - |
| Placebo | 85 | 15 | - |
| GWP42003-P 20 mg/kg/Day Dose | 84 | 27 | - |
| Placebo | 85 | 43 | - |
| GWP42003-P 20 mg/kg/Day Dose | 84 | 7 | - |
| Placebo | 85 | 9 | - |
| GWP42003-P 20 mg/kg/Day Dose | 84 | 1 | - |
| Placebo | 85 | 2 | - |
| GWP42003-P 20 mg/kg/Day Dose | 84 | 0 | - |
| Placebo | 85 | 2 | - |
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).
| Milestone | GWP42003-P 20 mg/kg/Day Dose | Placebo |
|---|---|---|
| STARTED | 86 | 85 |
| Safety Analysis Set | 86 | 85 |
| Intent to Treat (ITT) Analysis Set | 86 | 85 |
| COMPLETED | 72 | 84 |
| NOT COMPLETED | 14 | 1 |
| Event | System | Groups: affected / at risk |
|---|---|---|
| Constipation | Gastrointestinal disorders | GWP42003-P 20 mg/kg/Day Dose: 1 / 86 · Placebo: 0 / 85 |
| Vomiting | Gastrointestinal disorders | GWP42003-P 20 mg/kg/Day Dose: 1 / 86 · Placebo: 0 / 85 |
| Deep vein thrombosis | Vascular disorders | GWP42003-P 20 mg/kg/Day Dose: 1 / 86 · Placebo: 0 / 85 |
| Pyrexia | General disorders | GWP42003-P 20 mg/kg/Day Dose: 0 / 86 · Placebo: 1 / 85 |
| Acute hepatic failure | Hepatobiliary disorders | GWP42003-P 20 mg/kg/Day Dose: 1 / 86 · Placebo: 0 / 85 |
| Perirectal abscess | Infections and infestations | GWP42003-P 20 mg/kg/Day Dose: 1 / 86 · Placebo: 0 / 85 |
| Pilonidal cyst | Infections and infestations | GWP42003-P 20 mg/kg/Day Dose: 0 / 86 · Placebo: 1 / 85 |
| Pneumonia | Infections and infestations | GWP42003-P 20 mg/kg/Day Dose: 3 / 86 · Placebo: 0 / 85 |
| Pneumonia adenoviral | Infections and infestations | GWP42003-P 20 mg/kg/Day Dose: 1 / 86 · Placebo: 0 / 85 |
| Sepsis | Infections and infestations | GWP42003-P 20 mg/kg/Day Dose: 1 / 86 · Placebo: 0 / 85 |
| Urinary tract infection | Infections and infestations | GWP42003-P 20 mg/kg/Day Dose: 0 / 86 · Placebo: 1 / 85 |
| Viral infection | Infections and infestations | GWP42003-P 20 mg/kg/Day Dose: 2 / 86 · Placebo: 0 / 85 |
| Alanine aminotransferase increased | Investigations | GWP42003-P 20 mg/kg/Day Dose: 4 / 86 · Placebo: 0 / 85 |
| Aspartate aminotransferase increased | Investigations | GWP42003-P 20 mg/kg/Day Dose: 4 / 86 · Placebo: 0 / 85 |
| Drug level increased | Investigations | GWP42003-P 20 mg/kg/Day Dose: 1 / 86 · Placebo: 0 / 85 |
| Gamma-glutamyltransferase increased | Investigations | GWP42003-P 20 mg/kg/Day Dose: 3 / 86 · Placebo: 0 / 85 |
| Liver function test abnormal | Investigations | GWP42003-P 20 mg/kg/Day Dose: 1 / 86 · Placebo: 0 / 85 |
| Oxygen saturation decreased | Investigations | GWP42003-P 20 mg/kg/Day Dose: 0 / 86 · Placebo: 1 / 85 |
| Transaminases increased | Investigations | GWP42003-P 20 mg/kg/Day Dose: 1 / 86 · Placebo: 0 / 85 |
| Convulsion | Nervous system disorders | GWP42003-P 20 mg/kg/Day Dose: 2 / 86 · Placebo: 0 / 85 |
| Generalised tonic-clonic seizure | Nervous system disorders | GWP42003-P 20 mg/kg/Day Dose: 0 / 86 · Placebo: 1 / 85 |
| Lethargy | Nervous system disorders | GWP42003-P 20 mg/kg/Day Dose: 1 / 86 · Placebo: 0 / 85 |
| Seizure cluster | Nervous system disorders | GWP42003-P 20 mg/kg/Day Dose: 1 / 86 · Placebo: 1 / 85 |
| Somnolence | Nervous system disorders | GWP42003-P 20 mg/kg/Day Dose: 1 / 86 · Placebo: 0 / 85 |
| Status epilepticus | Nervous system disorders | GWP42003-P 20 mg/kg/Day Dose: 1 / 86 · Placebo: 1 / 85 |
| Acute respiratory distress | Respiratory, thoracic and mediastinal disorders | GWP42003-P 20 mg/kg/Day Dose: 1 / 86 · Placebo: 0 / 85 |
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | GWP42003-P 20 mg/kg/Day Dose: 3 / 86 · Placebo: 0 / 85 |
| Bronchial secretion retention | Respiratory, thoracic and mediastinal disorders | GWP42003-P 20 mg/kg/Day Dose: 1 / 86 · Placebo: 0 / 85 |
| Hypercapnia | Respiratory, thoracic and mediastinal disorders | GWP42003-P 20 mg/kg/Day Dose: 1 / 86 · Placebo: 0 / 85 |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | GWP42003-P 20 mg/kg/Day Dose: 2 / 86 · Placebo: 0 / 85 |
| Pneumonia aspiration | Respiratory, thoracic and mediastinal disorders | GWP42003-P 20 mg/kg/Day Dose: 1 / 86 · Placebo: 1 / 85 |
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | GWP42003-P 20 mg/kg/Day Dose: 1 / 86 · Placebo: 0 / 85 |
| Respiratory distress | Respiratory, thoracic and mediastinal disorders | GWP42003-P 20 mg/kg/Day Dose: 1 / 86 · Placebo: 0 / 85 |
| Sleep apnoea syndrome | Respiratory, thoracic and mediastinal disorders | GWP42003-P 20 mg/kg/Day Dose: 1 / 86 · Placebo: 0 / 85 |
| Dehydration | Metabolism and nutrition disorders | GWP42003-P 20 mg/kg/Day Dose: 0 / 86 · Placebo: 2 / 85 |
| Nephrolithiasis | Renal and urinary disorders | GWP42003-P 20 mg/kg/Day Dose: 1 / 86 · Placebo: 0 / 85 |
| Event | System | Groups: affected / at risk |
|---|---|---|
| Diarrhoea | Gastrointestinal disorders | GWP42003-P 20 mg/kg/Day Dose: 16 / 86 · Placebo: 7 / 85 |
| Vomiting | Gastrointestinal disorders | GWP42003-P 20 mg/kg/Day Dose: 8 / 86 · Placebo: 14 / 85 |
| Constipation | Gastrointestinal disorders | GWP42003-P 20 mg/kg/Day Dose: 5 / 86 · Placebo: 4 / 85 |
| Pyrexia | General disorders | GWP42003-P 20 mg/kg/Day Dose: 11 / 86 · Placebo: 7 / 85 |
| Fatigue | General disorders | GWP42003-P 20 mg/kg/Day Dose: 5 / 86 · Placebo: 2 / 85 |
| Sinusitis | Infections and infestations | GWP42003-P 20 mg/kg/Day Dose: 5 / 86 · Placebo: 2 / 85 |
| Upper respiratory tract infection | Infections and infestations | GWP42003-P 20 mg/kg/Day Dose: 2 / 86 · Placebo: 6 / 85 |
| Decreased appetite | Metabolism and nutrition disorders | GWP42003-P 20 mg/kg/Day Dose: 11 / 86 · Placebo: 2 / 85 |
| Somnolence | Nervous system disorders | GWP42003-P 20 mg/kg/Day Dose: 12 / 86 · Placebo: 8 / 85 |
| Sedation | Nervous system disorders | GWP42003-P 20 mg/kg/Day Dose: 7 / 86 · Placebo: 1 / 85 |
| Convulsion | Nervous system disorders | GWP42003-P 20 mg/kg/Day Dose: 3 / 86 · Placebo: 5 / 85 |
| Headache | Nervous system disorders | GWP42003-P 20 mg/kg/Day Dose: 2 / 86 · Placebo: 5 / 85 |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | GWP42003-P 20 mg/kg/Day Dose: 7 / 86 · Placebo: 2 / 85 |
| Cough | Respiratory, thoracic and mediastinal disorders | GWP42003-P 20 mg/kg/Day Dose: 5 / 86 · Placebo: 2 / 85 |
| Rash | Skin and subcutaneous tissue disorders | GWP42003-P 20 mg/kg/Day Dose: 6 / 86 · Placebo: 1 / 85 |