epilepsy Lennox Gastaut Syndrome
Conditions
Interventions
A total of 80 patients will be enrolled to receive GWP42003-P (the
active investigational medicinal product [IMP]) or placebo on a 1:1
basis (40 patients per treatment group).
cannabidiol
epilepsy
Lennox Gastaut syndrome
Sponsors
GW Research Ltd.
Eligibility
Age
2 Years to 64 Years
Inclusion criteria
Inclusion criteria: * Patient and/or parent(s)/legal representative must be willing and able to give informed assent/consent for participation in the study.;* Patient and their caregiver must be willing and able (in the investigator*s opinion) to comply with all study requirements.;* Patient must be male or female aged between two and 55 years (inclusive).;* Patient must have a clinical diagnosis of of LGS. This includes written documentation of having met electroencephalogram (EEG) diagnostic criteria during the patient*s history and evidence of more than one type of generalized seizure, including drop seizures (atonic, tonic or tonic-clonic), for at least six months. Care should be taken not to include benign myoclonic epilepsy of infancy, atypical benign partial epilepsy (pseudo-Lennox syndrome), or continuous spike-waves of slow sleep (CSWS);* Patients who have a history of slow (<3.0 Hz) spike-and-wave pattern in an EEG prior to the enrollment into the baseline period.;* Patients must have at least two drop seizures each week during the 28-day baseline period.;* Patients should be refractory; that is having documented failures on more than one antiepileptic drug (AED).;* Patient must be taking one or more AEDs at a dose which has been stable for at least four weeks prior to screening.;* All medications or interventions for epilepsy (including ketogenic diet and vagus nerve stimulation [VNS]) must have been stable for four weeks prior to screening and patient is willing to maintain a stable regimen throughout the study. The ketogenic diet and VNS treatments are not counted as an AED.;* Patient and/or parent(s)/legal representative is willing to allow his or her primary care practitioner and consultant to be notified of participation in the study.
Exclusion criteria
Exclusion criteria: * Etiology of patient's seizures is a progressive neurologic disease. Patients with tuberous sclerosis will not be excluded from study participation, unless there is a progressive tumor.;* Patient has had an anoxic episode requiring resuscitation within six months of screening.;* Patient has clinically significant unstable medical conditions other than epilepsy.;* Patient has had clinically relevant symptoms or a clinically significant illness in the four weeks prior to screening or randomization, other than epilepsy.;* Patient has clinically significant abnormal laboratory values, in the investigator*s opinion, at screening or randomization.;* Patient has clinically relevant abnormalities in the ECG measured at screening or randomization.;* Patient has any concurrent cardiovascular conditions, which will, in the investigators opinion, interfere with the ability to assess their ECGs.;* Patient has a history or presence of alcohol or substance abuse within the last two years prior to the study or daily consumption of five or more alcohol-containing beverages.;* Patient is currently using or has in the past used recreational or medicinal cannabis, or synthetic cannabinoid based medications (including Sativex®) within the three months prior to study entry. ;* Patient is unwilling to abstain from using recreational or medicinal cannabis, or synthetic cannabinoid based medications (including Sativex) during the study.;* Patient has a history of symptoms (e.g., dizziness, light-headedness, blurred vision, palpitations, weakness, syncope) related to a drop in blood pressure due to postural changes.;* Patient has any known or suspected hypersensitivity to cannabinoids or any of the excipients of the IMP, such as sesame oil.;* Female patient is of child bearing potential and must have a negative pregnancy test and be willing and able to use a reliable method of contraception throughout the trial and for three months after last dose. Male patient*s partner is of child bearing potential; unless willing to ensure that they or their partner use a highly effective method of contraception. In the context of this trial, a highly effective method is defined as those which result in low failure rate (i.e., less than 1% per year) when used consistently and correctly such as: combined or progesterone only oral contraceptives, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomized partner or sexual abstinence;* Female patient who is pregnant, lactating or planning pregnancy during the course of the study and for three months thereafter.;* Patient has been part of a clinical trial involving another IMP in the previous six months.;* Any other significant disease or disorder which, in the opinion of the investigator, may either put the patient at risk because of participation in the study, may influence the result of the study, or affect the patient*s ability to participate in the study. * Patient has significantly impaired hepatic function at screening (Visit 1) or randomization (Visit 2) (Alanine aminotransferase [ALT] >5 x upper limit of normal [ULN] and total bilirubin [TBL] >2 x ULN) OR the ALT or Aspartate aminotransferase (AST) >3 x ULN and (TBL >2 x ULN or international normalized ratio [INR] >1.5). This criterion can only be confirmed once the laboratory results are available; patients randomized into the study who are later found to meet this criterion must be withdrawn from the study.;* Follow
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint is the mean percentage change from baseline in number of drop seizures (average per week) during the maintenance period (Day 15 to the end of the evaluable period) in patients taking GWP42003-P compared with placebo. | — |
Secondary
| Measure | Time frame |
|---|---|
| The following endpoints will be compared between treatment groups over the 12-week, double-blind maintenance period: * Percentage change from baseline in number of drop seizures (average per week) during the Weeks 1*4, 5*8 and 9*12. * Number of patients considered treatment responders, defined as those with a *25%, *50%, *75%, or 100% reduction in drop seizures from baseline. Summaries will be presented overall and four-weekly. * Number of patients experiencing a >25% worsening, *25 to +25% no change, 25* 50% improvement, 50*75% improvement or >75% improvement in drop seizures from baseline. * Percentage change from baseline in number of non-drop seizures (average per week). * Percentage change from baseline in the frequencies of subtypes of seizures (average per week). * Changes from baseline in duration of seizure subtypes as assessed by the Subject/Caregiver Global Impression of Change in Seizure Duration (S/CGICSD). * Changes from baseline in number of episodes of status epilepticus. * Changes from baseline in number of inpatient hospitalizations due to epilepsy. * Changes from baseline in quality of life as assessed by the Quality of Life in Childhood Epilepsy (QOLCE), for patients aged between two and 18 years of age, or Quality of Life in Epilepsy, version 2, (QOLIE-31-P) for patients aged 19 years and older. * Changes from baseline in the Subject/Caregiver Global Impression of Change (S/CGIC) score. * Change from baseline in adaptive behavior as measured with the Vineland Adaptive Behavior Scales, Second Edition (Vineland-II). * Change from baseline in cognitive function as measured with the Cognitive Assessment Battery. * Changes from baseline in Sleep Disruption 0*10 Numerical Rating Scale (0*10 NRS) score. * Changes from baseline in Epworth Daytime Sleepiness Scale (EDSS) score. * Change from baseline in growth and development by measurement of height, weight, , insulin-like growth factor-1 (IGF-1) levels, menstruation and | — |
Countries
Poland, United States of America
Outcome results
None listed