A Study of the Safety and Tolerability of GWP42006 in Healthy Subjects
Condition: Epilepsy
MeSH terms: Epilepsy
Study type: Interventional
Phase: Phase 1

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Placebo; GWP42006
Intervention type(s): Drug; Drug
Intervention description(s): 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.
Other intervention name(s): Placebo control
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Safety; Tolerability; Assessment of potential adverse events; Assessment of potential laboratory abnormalities