The primary objective of this study is to evaluate the safety and tolerability of single ascending (increasing) and multiple doses of GWP42006 compared with placebo.
This is a single-centre, randomised, double-blind, placebo-controlled, parallel group dose escalation, safety, tolerability and pharmacokinetic (PK) study of single escalating and multiple doses of GWP42006 in healthy volunteers. The study consists of 5 single dosing occasions, and a five day repeated dose period. Part 1 Single Dosing: Four parallel groups of 11 subjects will participate in the oral single dosing, dose escalation study phase. In each group, subjects will be randomly assigned so that eight subjects receive active and three subjects receive placebo. It is planned for Groups 1 and 2, that a staggered 'sentinel' dose design will be used, with two sub-groups: * The first will comprise of one placebo and one active subject. * In the second, seven subjects will receive active and two will receive placebo after a review of the 24 h post-dose safety data of the first group. Sentinel subject dosing will be performed in higher-dose groups if there is no measurable plasma GWP42006 in Group 1 or 2. One group within the single dosing part (Group 3/dose level 3) will then receive an intravenous administration of 5 mg GWP42006 to allow assessment of bioavailability. There will be a minimum of seven days between doses. Up to three further groups may be added for further evaluations, e.g. to assess additional dose levels or food effect. The need for additional groups will be based on a review of the safety, tolerability and PK data by the safety advisory committee. Dose Escalation: The planned dose levels are 25 mg (Group 1/dose level 1), 75 mg (Group 2/dose level 2), 200 mg (Group 3/dose level 3) and 400 mg (Group 4/dose level 4), with a maximum dose of 800 mg. Administration of each successive dose will be dependent on safety, tolerability and PK data of previous doses. Part 2 Multiple Dosing: The doses and dose regimens assessed in Part 2 will be selected based upon the safety, and PK data from Part 1 of the study. It is planned that one group of 11 subjects will participate in the multiple dose phase, and subjects will be randomly assigned so that eight subjects receive active and three receive matching placebo. Each subject will receive the selected dose of GWP42006 or placebo once, twice or three times daily for a total of five days, with the final dose administered on the morning of Day 5. Up to two further groups may be added for further evaluations, e.g. to assess a different dose level or a different dosing frequency. As for single dosing, the decision to include further groups will be taken based on safety, tolerability and PK data. All further groups would be added on blinded information.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
66
Placebo control matched to the oral or intravenous experimental comparator drug
Oral administration of 25 (Group/dose level 1a and 1b), 75 (Group/dose level 2a and 2b), 200 (Group/dose level 3a and 3b) and 400 mg GWP42006 (Group/dose level 4a and 4b), provided as 50 mg/mL GWP42006 solution in sesame oil containing flavourings and sweetener, for dilution on the day of dosing, as required. Additional intravenous administration of 5 mg GWP42006 and 10 mL Solutol HS 15 solution to Group/dose level 3a and 3b subjects.
Quotient Clinical
Nottingham, United Kingdom
The incidence of adverse events as measure of subject safety
The number of subjects who experienced an adverse event during each arm of the study is presented.
Time frame: Day 0 - Day 10
To determine the plasma concentration time curves for GWP42006, 7-hydroxy-GWP42006 and 6-hydroxy-GWP42006 compounds, following escalating single doses and multiple doses of pure GWP42006.
* For oral dosing, the pre-dose blood sample was taken ≤1 h before dosing. * For intravenous dosing, the pre-dose sample was taken immediately before the intravenous bolus infusion. * 0 to 1 h post-dose samples were taken within ± 2 min of the nominal post-dose sampling time (the 0.04 and 0.08 h pharmacokinetic samples taken post-intravenous dosing only were taken at the middle and the end of the intravenous bolus infusion). * \>1 to 12 h post-dose samples were taken within ± 10 min of the nominal post-dose sampling time. * \>12 h post-dose samples were taken within ± 30 min of the nominal post-dose sampling time if subjects were resident in the clinic. The following pharmacokinetic parameters were investigated: Tmax, Area Under the plasma concentration Curve (AUC)(0-inf), AUC(0-t), T1/2el, F, AUC(0-tau) and Kel.
Time frame: Pre-dose then 0, 0.04, 0.08, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 36, 48 h post-dose
To investigate cognitive function following single ascending and multiples doses of GWP42006
A cognitive assessment was carried using the Fepsy battery. The following tests were carried out: auditory reaction times (left and right), recognition simultaneously (6 words, 4 figures), visual reaction task (white square, left and right), computerised visual searching task (24 small figures), finger tapping task, recognition serially (6 words, 4 figures) and binary choice task (random).
Time frame: Admission (Day -1) and 2 h post-dose
To investigate gene expression following multiple doses of GWP42006
Analysis of gene expression was carried out for subjects participating in the multiple dose phase of the study.
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Time frame: Pre-dose on multiple dose Days 1-4 then 2 h post-dose on multiple dose Day 5