Epilepsy MedDRA version: 19.0 Level: LLT Classification code 10016843 Term: Focal seizures System Organ Class: 100000004852
Conditions
Interventions
Product Name: GWP42006 Oral Solution
Product Code: GWP42006
Pharmaceutical Form: Oral solution
INN or Proposed INN: n/a
Current Sponsor
Sponsors
GW Research Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Patient must be willing and able to give informed consent for participation in the study. • Male or female aged between 18 and 65 years, inclusive. • Documented CT/MRI that shows no progressive neurologic abnormality. • Patient is willing to keep any factors expected to affect seizures stable (such as the level of alcohol consumption and smoking). • Patient is able (in the investigators opinion) and willing to comply with all study requirements (including accurate diary completion). • Patient is willing to allow his or her primary care practitioner and consultant to be notified of participation in the study. Part A only • Well-documented history of focal epilepsy, with focal seizures as the primary seizure type, compatible electroencephalogram and clinical history. • Has focal seizures despite prior treatment with at least two AEDs (whether as monotherapies or in combination). • Currently treated with one to three AEDs as follows: Group 1 - including Carbamazepine, Phenobarbital, Primidone or Phenytoin and excluding Valproic Acid (VPA). Group 2 - including VPA and excluding Carbamazepine, Phenobarbital, Primidone and Phenytoin. Group 3 - excluding VPA, Carbamazepine, Phenobarbital, Primidone and Phenytoin. • All medications or interventions for epilepsy (including ketogenic diet and any neurostimulation devices for epilepsy) must have been stable for two weeks prior to screening and the patient is willing to maintain a stable regimen throughout the study. Part B only •Well-documented history of focal epilepsy, compatible electroencephalogram and clinical history. • Currently treated with one to three AEDs. •Has focal seizures, as defined in the protocol (focal motor seizures without impairment of consciousness or awareness, focal seizures with impairment of consciousness or awareness, and focal seizures evolving to bilateral convulsive seizures), despite prior treatment with at least two AEDs (whether as monotherapies or in combination). • All medications or interventions for epilepsy (including ketogenic diet) must have been stable for four weeks prior to screening and the patient is willing to maintain a stable regimen throughout the study. • At the end of the baseline period patients must also meet the following exclusion criteria: - Complied with diary completion, having no more than three missed diary entries during baseline. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 166 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
Exclusion criteria: • Episode(s) of status epilepticus during one year prior to screening. • History of pseudo-seizures. • Patient has clinically significant unstable medical conditions other than epilepsy. • Patient has an illness in the four weeks prior to screening or randomization, other than epilepsy, which in the opinion of the investigator would affect seizure frequency. • Patient has, in the investigator’s opinion, clinically significantly abnormal laboratory values. • In the opinion of the investigator the patient has clinically significant abnormalities in the 12-lead electrocardiogram (ECG) measured at screening or randomization or any concurrent cardiovascular conditions, which will interfere with the ability to read their ECGs. • Active suicidal plan/intent in the past six months, or a history of suicide attempt in the last two years, or more than one lifetime suicide attempt. • Patient has a history or presence of alcohol or substance abuse within the two years prior to screening 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 cannabinoid based medications within the three months prior to screening and is unwilling to abstain for the duration for the study. • Patient has taken St John’s Wort in the two weeks prior to screening and/or is unwilling to abstain throughout the study. • Any known or suspected hypersensitivity to cannabinoids, sesame oil or any of the excipients of the IMP(s). • Female patients of child bearing potential and male patients whose partner is of child bearing potential, unless willing to ensure that they and/or their partner use a highly effective method of contraception. • Female patient who is pregnant, lactating or planning pregnancy during the course of the study and for three months thereafter. • Patients who have received an IMP within the 12 weeks prior to the screening visit. • 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 the patient’s ability to participate in the study. • Following a physical examination, the patient has any abnormalities that, in the opinion of the investigator would prevent the patient from safe participation in the study. • Unwilling to abstain from donation of blood during the study. • Travel outside the country of residence planned during the study. • Patients previously randomized into this study. • Patient has consumed grapefruit or grapefruit juice three days prior to randomization and/or unwilling to abstain in the three days prior to PK sampling visits. Part A only •Time of onset of epilepsy treatment is less than two years prior to enrolment. •Patient has significantly impaired hepatic function at Visit 1 (Alanine aminotransferase [ALT] >5 x upper limit of normal [ULN] or 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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part A: To determine the pharmacokinetics (PK) of GWP42006 and human metabolites, 7-hydroxy- cannabidivarin (7-OH-CBDV) and 6-hydroxy- cannabidivarin (6-OHCBDV), in the presence of other antiepileptic drugs (AEDs). Part B: To evaluate the efficacy of GWP42006, compared with placebo, as add-on therapy to treat inadequately controlled focal seizures. ; Secondary Objective: Part A: • To evaluate the safety and tolerability of GWP42006 compared with placebo, in the presence of other AEDs. • To evaluate effects of GWP42006 on plasma concentrations of concomitant AEDs. Part B: • To evaluate the effect of GWP42006 compared with placebo on other efficacy measures. • To evaluate the safety and tolerability of GWP42006 compared with placebo. • To evaluate the effect of GWP42006 on health utilization compared with placebo. • To evaluate the effects of GWP42006 on cognitive function. • To determine plasma concentrations of GWP42006 and main metabolites following multiple doses of GWP42006. • To evaluate effects of GWP42006 on plasma concentrations of concomitant AEDs. ; Primary end point(s): Part A - Primary endpoint is the plasma concentrations of GWP42006, 7-OHCBDV and 6-OH-CBDV with the aim of defining Cmax, Cmin, tmax, AUC0-t, AUC0-inf, and t1/2. Part B - Primary endpoint is the mean percentage change from baseline to the end of treatment in focal seizure frequency in patients taking GWP42006 compared to placebo. ; Timepoint(s) of evaluation of this end point: Part A: •Visit A2 - pre-IMP-dose and 30min, 1h, 2h, 4h and 8h after IMP dose. •Visit A4 - pre-IMP-dose and 30min, 1h, 2h, 4h and 8h after IMP dose. •Visit A5 - 24 +/ | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints for Part A are: • Safety and tolerability (adverse events [AEs], clinical laboratory testing, vital signs) • Plasma concentrations of concomitant AEDs. For Part B, efficacy safety and other endpoints are as follows: Efficacy endpoints: • Number of patients considered treatment responders defined as those with a =25%, =50%, =75% and 100% reduction in focal seizure frequency. • Proportion of patients with a 0-24%, =25-50%, =50%-74% and =75%-100% reduction in focal seizure frequency. • Change in seizure subtypes frequency. • Change in composite seizure score. • Change in number of focal seizure free days. • Change in use of rescue medication. • Subject Global Impression of Change (SGIC). • Physician Global Impression of Change (PGIC). Safety and tolerability endpoints: • AEs. • Clinical laboratory testing. • Vital signs. • Columbia Suicide Severity Rating Scale (C-SSRS). • Cannabis Withdrawal Scale (CWS) score. • Abuse liability. Other endpoints: • Change in number of inpatient hospitalizations or out of visit contact with medical staff due to epilepsy. • Cognitive assessment scores. • Plasma concentrations of GWP42006 and main metabolites. • Plasma concentrations of concomitant AEDs. ; Timepoint(s) of evaluation of this end point: Part A: •Safety and tolerability - Visit A1 to visit A7 •AEDs - Visits A2 (baseline) and A4 Part B: •Safety and tolerability - Visit B1 to visit B9 •Efficacy - | — |
Countries
Czech Republic, Hungary, Italy, Poland, Spain, United Kingdom
Contacts
Public ContactGW Research Ltd. Switchboard
GW Research Ltd
Outcome results
None listed