Dravet Syndrome MedDRA version: 18.0 Level: PT Classification code 10073677 Term: Severe myoclonic epilepsy of infancy System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Sponsors
GW Research Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria: Part A For inclusion in Part A of the study, patients must fulfil ALL of the following 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 4 and 10 years (inclusive). • Patient must have a documented history of DS which is not completely controlled by current AEDs. • Patient must be taking one or more AEDs at a dose which has been stable for at least four weeks. • All medications or interventions for epilepsy (including ketogenic diet and VNS) must have been stable for four weeks prior to screening and patient and caregiver are willing to maintain a stable regimen throughout the study. • 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. Inclusion Criteria: Part B For inclusion in Part B of the study, patients must fulfil ALL of the following 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 2 and 18 years (inclusive). • Patient must have a documented history of DS which is not completely controlled by current AEDs. • Patient must be taking one or more AEDs at a dose which has been stable for at least four weeks. • All medications or interventions for epilepsy (including ketogenic diet and VNS) must have been stable for four weeks prior to screening and patient and caregiver are willing to maintain a stable regimen throughout the study. • 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. Are the trial subjects under 18? yes Number of subjects for this age range: 120 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 5 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Exclusion Criteria: Parts A and B The patient may not enter the study (Part A or Part B) if ANY of the following apply: • 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 significantly abnormal, in the investigator’s opinion, laboratory values at screening or randomization. • Patient has clinically relevant abnormalities in the 12-lead ECG measured at screening or randomization. • Patient has any concurrent cardiovascular conditions, which will, in the investigators opinion, interfere with the ability to read 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 ingested alcohol in the 24 hour period prior to the first study visit and/or is unwilling to abstain from drinking alcohol throughout the treatment period. • Patient has consumed grapefruit or grapefruit juice three days prior to screening and/or is unwilling to abstain from consuming these during the study. • Patient has any known or suspected hypersensitivity to cannabinoids or any of the excipients of the IMP(s), e.g., sesame oil. • Female patients is of child bearing potential or male patient’s partner is of child bearing potential; unless willing to ensure that they or their partner use highly effective contraception for the duration of the study and for three months thereafter. Highly effective methods of contraception are defined as those, alone or in combination, that result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly. Such methods include hormonal contraceptives, intrauterine devices/hormone-releasing systems, bilateral tubal occlusion, vasectomized partner or sexual abstinence. • Female patient who is pregnant (positive pregnancy test), lactating or planning pregnancy during the course of the study and for three months thereafter. • Patients who have been part of a clinical trial involving an investigational product 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 A1 or B1) or randomization(Visit A2 or B2)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part A: To evaluate the safety of multiple doses of GWP42003-P compared with placebo with respect to: • Incidence, type and severity of adverse events (AEs). • Effect on vital signs, physical examination parameters including weight. • Effect on 12-lead electrocardiogram (ECG) findings. • Effect on laboratory parameters. • Changes in seizure frequency. Part B: • To assess the efficacy of GWP42003-P as an adjunctive antiepileptic treatment compared with placebo, with respect to the percentage change from baseline during the treatment period of the study in convulsive seizure frequency. ; Secondary Objective: Part A: • To determine the pharmacokinetics of CBD and its major metabolites following single and multiple doses of GWP42003-P. • To investigate the effect of GWP42003-P on the plasma concentration of clobazam and its primary metabolite, N-CLB, if taken as a concomitant medication. • Where possible, to investigate the effects of CBD on plasma concentrations of other concomitant AEDs, if applicable. Part B: • To assess changes from baseline in non-convulsive seizure frequency, duration of seizures, usage of rescue medication, number of inpatient hospitalizations due to epilepsy, sleep disruption, daytime sleepiness, quality of life, growth and development, menstruation cycles (in females) and conduct behavioral assessments in patients taking GWP42003-P as an adjunctive treatment, when compared with placebo. • To determine effects of GWP42003-P on plasma concentrations of concomitant AEDs, where available. • To assess the safety of GWP42003-P when compared with placebo. ; Primary end point(s): Part A: The primary endpoint is the safety profile of single and mu | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: • PK of GWP42003-P and 7-OH-CBD - Visits A2, A4: pre-dose, 2 to 3h post-dose, 4 to 6h post-dose • PK of clobazam and N-CLB - A2, A4: 2h post clobazam dose Part B. • Percentage change non-convulsive seizure freq : B1-B8 • Percentage change convulsive seizure freq: B1- B8 • Treatment responders, Number of status epilepticus episodes • Sleep disruption, daytime sleepiness, adaptive behavior - B2 to B6, B8 • CGIC, CGICSD: B3, B4, B6, B8 • Change in C-SSRS:B1-B4, B6, B8, B9 and Effect on menstruation:B2, B8 • Developmental changes in patients < 18 yrs: Height, weight, IGF-1 and Tanner Staging (signs of puberty) • Plasma concentrations of AEDs before/after treatment, • Incidence, type and severity of AEs: B1 to B9 • Vital signs, ECG, lab and physical exam parameters - B1to B4, B6, B8 ; Secondary end point(s): Part A – Pharmacokinetic: 1. GWP42003-P: The plasma concentration/time curve of CBD and its major metabolites will be described following single and multiple doses of GWP42003-P, with the aim being to define: • Cmax • tmax • AUC 0-8, AUC 0-t • t½ 2. If taken as a concomitant medication, the plasma concentrations of clobazam and N-CLB will be described pre-treatment and then after 21 days of treatment with GWP42003-P. As far as possible, the plasma concentration/time relationship pre-treatment will be compared with the results following treatment with GWP42003-P. The same analysis will be carried out for other concomitant AEDs, if possible and applicable. Part B – Efficacy and Safety: 1. The following will be analyzed: • Number of patients experiencing a 50% or | — |
Countries
France, Poland, United Kingdom, United States
Contacts
Public ContactGW Research Ltd Switchboard
GW Research Ltd
Outcome results
None listed