A Dose-ranging Pharmacokinetics and Safety Study of GWP42003-P in Children With Dravet Syndrome (GWPCARE1)
Condition: Epilepsy; Dravet Syndrome
MeSH terms: Epilepsies, Myoclonic; Syndrome
Study type: Interventional
Phase: Phase 2

Summary: 
      To evaluate the safety and pharmacokinetics (PK) of multiple doses of GWP42003-P compared
      with placebo in children with Dravet syndrome.
    

Detailed description: 
      This multi-center study consisted of 2 parts: Part A and Part B. Only Part A is described in
      this record. Part A was a randomized, double-blind 21-day treatment study period.
      Participants were randomized to one of 3 doses of active drug or placebo at a 4:1 ratio.

      Participants who satisfied all inclusion and none of the exclusion criteria were assigned a
      unique participant number and then began a 28-day baseline observation period.

      Eligible participants were then randomly assigned to receive one of 3 dose levels of
      GWP42003-P: 5 milligrams (mg) per kilogram (kg) per day, 10 mg/kg/day, 20 mg/kg/day, or
      matching placebo.

      There were three groups of ten participants. In each group, participants were randomly
      assigned so that eight participants received active treatment and two participants received
      placebo. Participants received GWP42003-P or placebo for a 21-day exposure period, which
      consisted of a titration period, followed by a stable dose period.

      A PK assessment took place after the first single dose of GWP42003-P. There was a second PK
      assessment after 21 days of consecutive dosing with GWP42003-P. Participants who took
      clobazam (CLB) as an adjunctive treatment were asked to take their usual dose 2 hours prior
      to attending the clinic. The same recommendation was made for other concomitant antiepileptic
      drugs (AEDs), if applicable. This was so that the pre-treatment (with GWP42003-P) plasma
      concentrations of CLB, its major metabolite N-desmethylclobazam, and any other concomitant
      AEDs could be measured, and the impact of GWP42003-P treatment on these levels evaluated.
      Interim clinic visits to (primarily) evaluate safety and adherence to the titration regimen
      took place at 7 and 14 days of treatment.

      After 21 days of treatment, all participants commenced a 10-day down-titration taper period.
      An independent Data Safety Monitoring Committee reviewed unblinded safety and PK data and
      recommended the target dose (up to 20 mg/kg/day) for Part B of the study and for an open
      label extension study. Once the safety review of Part A data had taken place, participants
      had the option of entering the open label extension study.

      A follow-up telephone call was made 28 days after the end of dosing for participants who did
      not enter the open label extension study within this time-frame.

      Throughout the 21-day treatment period and the 10-day taper period, there were regular safety
      telephone calls (approximately every 2 days) to check participant status. Weekly safety
      telephone calls were made during the 28-day follow-up period.
    

Intervention name(s): GWP42003-P 5 mg/kg/day Dose; Placebo control; GWP42003-P 10 mg/kg/day Dose; GWP42003-P 20 mg/kg/day Dose
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): GWP42003-P was an oral solution containing 25 mg/milliliter (mL) cannabidiol (CBD) or 100 mg/mL CBD dissolved in the excipients sesame oil and anhydrous ethanol (79 mg/mL) with added sweetener (0.5 mg/mL sucralose) and strawberry flavoring (0.2 mg/mL). Participants were randomly assigned to receive either 5, 10 or 20 mg/kg/day.; Placebo oral solution contained the excipients sesame oil and anhydrous ethanol (79 mg/mL) with added sweetener (0.5 mg/mL sucralose) and strawberry flavoring (0.2 mg/mL).; GWP42003-P was an oral solution containing 25 mg/mL CBD or 100 mg/mL CBD dissolved in the excipients sesame oil and anhydrous ethanol (79 mg/mL) with added sweetener (0.5 mg/mL sucralose) and strawberry flavoring (0.2 mg/mL). Participants were randomly assigned to receive either 5, 10 or 20 mg/kg/day.; GWP42003-P was an oral solution containing 25 mg/mL CBD or 100 mg/mL CBD dissolved in the excipients sesame oil and anhydrous ethanol (79 mg/mL) with added sweetener (0.5 mg/mL sucralose) and strawberry flavoring (0.2 mg/mL). Participants were randomly assigned to receive either 5, 10 or 20 mg/kg/day.
Other intervention name(s): Cannabidiol; Epidiolex; Placebo; Cannabidiol; Epidiolex; Cannabidiol; Epidiolex
Intervention MeSH terms: Cannabidiol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Cannabidiol; CBD; Epidiolex; GWP42003-P