Study of ZYN002 (transdermal gel) in Healthy Volunteers and Patients with Epilepsy

INTERVENTION: During the first part of the study with 32 healthy volunteers, participants will be randomised to one of five treatment groups as indicated below. ‐ Treatment A: 5 g of 1% ZYN002 ‐ Treatment B: 10 g of 1% ZYN002 ‐ Treatment C: 5 g of 2.5% ZYN002 ‐ Treatment D: 10 g of 2.5% ZYN002 ‐ Treatment E: 5 g or 10g of placebo During the second part of the study with 12 patients diagnosed with epilepsy, will receive the highest tolerated dose (Treatment A, B, C or D) from the first part of study or placebo. ZYN002 or placebo gel will be applied to the skin on the right or left shoulder and/or upper arm as a single application. The gel will be thoroughly massaged into the shoulders and/or upper arms by a member of the research facility. Participants will not be permitted to wash their shoulder and/or upper arm (application site) for at least 12 hours after application. CONDITION: Epilepsy PRIMARY OUTCOME: To evaluate the safety and tolerability of two concentrations and two doses of ZYN002 in healthy volunteers to determine the appropriate dose for administration to patients with epilepsy. ; Assessed by: monitoring physical examinations, examination of skin application site, vital signs, 12‐lead ECG, laboratory tests, neuropsychological tests and adverse events throughout the study. Possible adverse events could include‐ appetite change, diarrhoea, sleepiness. ; SECONDARY OUTCOME: Secondary Outcome 1: evaluate the pharmacokinetics (PK) of ZYN002 assessed in plasma and urine ; Assessed by: collecting blood and urine samples for analysis. ; PK parameters include‐Cmax, Tmax, AUC ; Secondary Outcome 2: evaluate the pharmacokinetics (PK) of tetrahydrocannabinol assessed in plasma and urine ; Assessed by: collecting blood and urine samples for analysis. ; PK parameters include‐Cmax, Tmax, AUC ; Secondary Outcome 3: To administer neuropsychological tests to determine the effect of ZYN002 on visual attention, task switching, capacity and rate of information processing ; Assessed by: neuropsychological tests known as the Trail Making Test. The Trail Making Test is a neuropsychological test of visual attention and task switching. It consists of Part A and Part B in which the subject is instructed to connect a set of dots as fast as possible while maintaining accuracy. ; INCLUSION CRITERIA: 1. Healthy male or female adults, 18‐55 years of age, 2. Judged by the investigator to be in generally good health at screening based upon the results of a medical history, physical examination, 12‐lead ECG, and clinical laboratory test results. 3. Patients enrolled in Part 2 must have a diagnosis of epilepsy with partial onset seizures that is stable. Currently seizure‐free or controlled on one or two antiepileptic drugs [AEDs] with a monthly seizure frequency of less than 5 seizures per month. The patient should have had the diagnosis for at least one year which has been documented by review of the most informative electroencephalogram (EEG), scan (either computed tomography [CT] or magnetic resonance imaging [MRI]), and narrative, including detailed descriptions of each seizure type from the physician who manages the patient’s epilepsy. The historical baseline of seizures over the previous 8 weeks should show a reasonably stable pattern of seizure occur