A Dose-ranging Pharmacokinetics and Safety Study of GWP42003-P in Children With Dravet Syndrome

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified September 2014 by GW Research Ltd
Sponsor:
Information provided by (Responsible Party):
GW Research Ltd
ClinicalTrials.gov Identifier:
NCT02091206
First received: March 17, 2014
Last updated: September 2, 2014
Last verified: September 2014
  Purpose

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


Condition Intervention Phase
Epilepsy
Dravet Syndrome
Drug: GWP42003-P
Drug: Placebo control
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double Blind, Placebo Controlled Two-part Study to Investigate the Dose-ranging Safety and Pharmacokinetics, Followed by the Efficacy and Safety of Cannabidiol (GWP42003-P) in Children and Young Adults With Dravet Syndrome

Resource links provided by NLM:


Further study details as provided by GW Research Ltd:

Primary Outcome Measures:
  • The incidence of adverse events as measure of subject safety [ Time Frame: Day -28 to Day 60 ] [ Designated as safety issue: Yes ]
    The number of subjects who experienced an adverse event during the study is presented. The time frame for adverse event reporting was from screening to the Part A follow-up visit.


Secondary Outcome Measures:
  • The plasma concentration time curves for cannabidiol and 7-hydroxy-cannabidiol following single and multiple doses of GWP42003-P [ Time Frame: Pre-dose then 2-3 and 4-6 h post-dose ] [ Designated as safety issue: Yes ]
  • Plasma concentrations of clobazam and N-desmethylclobazam, if taken concomitantly with GWP42003-P, prior to single and multiple doses of GWP42003-P [ Time Frame: Pre-dose ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 30
Study Start Date: September 2014
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group/dose level 1a
5 mg/kg/day GWP42003-P oral solution. All subjects will down-titrate (10% per day) over a 10-day period following 21 days of treatment or withdrawal.
Drug: GWP42003-P

GWP42003-P is an oral solution presented as an oily solution containing 25 mg/mL cannabidiol (CBD: FT0086) or 100 mg/mL CBD (FT0095) dissolved in the excipients sesame oil and anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring.

Subjects will be randomly assigned to receive either 5, 10 or 20 mg/kg/day.

Other Name: Cannabidiol
Experimental: Group/dose level 2a
10 mg/kg/day GWP42003-P oral solution. All subjects will down-titrate (10% per day) over a 10-day period following 21 days of treatment or withdrawal.
Drug: GWP42003-P

GWP42003-P is an oral solution presented as an oily solution containing 25 mg/mL cannabidiol (CBD: FT0086) or 100 mg/mL CBD (FT0095) dissolved in the excipients sesame oil and anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring.

Subjects will be randomly assigned to receive either 5, 10 or 20 mg/kg/day.

Other Name: Cannabidiol
Experimental: Group/dose level 3a
20 mg/kg/day GWP42003-P oral solution. All subjects will down-titrate (10% per day) over a 10-day period following 21 days of treatment or withdrawal.
Drug: GWP42003-P

GWP42003-P is an oral solution presented as an oily solution containing 25 mg/mL cannabidiol (CBD: FT0086) or 100 mg/mL CBD (FT0095) dissolved in the excipients sesame oil and anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring.

Subjects will be randomly assigned to receive either 5, 10 or 20 mg/kg/day.

Other Name: Cannabidiol
Placebo Comparator: Group/dose level 1b
Matching placebo for Group/dose level 1a.
Drug: Placebo control
Placebo oral solution contains the excipients sesame oil and anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring.
Other Name: Placebo
Placebo Comparator: Group/dose level 2b
Matching placebo for Group/dose level 2a.
Drug: Placebo control
Placebo oral solution contains the excipients sesame oil and anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring.
Other Name: Placebo
Placebo Comparator: Group/dose level 3b
Matching placebo for Group/dose level 3a.
Drug: Placebo control
Placebo oral solution contains the excipients sesame oil and anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring.
Other Name: Placebo

Detailed Description:

This multi-center study will consist of two parts: Part A and Part B. Part A only will be described in this record. Part A is a randomized, double blind 21-day treatment study period. Subjects will be randomized to one of three doses of active or placebo at a 4:1 ratio.

Subjects who satisfy all inclusion and none of the exclusion criteria will be assigned a unique participant number and then begin a 28-day baseline observation period.

The investigator will assess the subject's daily number of convulsive seizures from the subject's diary data. Subjects who have experienced fewer than four convulsive seizures (tonic-clonic seizures and/or drop attacks) during the baseline period and who meet all of the other inclusion and none of the exclusion criteria will be eligible to continue in the study.

Eligible subjects will then be randomly assigned to receive one of three dose levels of GWP42003-P: 5 mg/kg, 10 mg/kg or 20 mg/kg per day, or matching placebo.

There will be three groups of 10 subjects. In each group, subjects will be randomly assigned so that eight subjects receive active treatment and two subjects receive placebo. Subjects will receive GWP42003-P or placebo for a 21-day exposure period, which consists of a titration period, followed by a stable dose period.

A pharmacokinetic assessment will take place after the first single dose of GWP42003-P. There will be a second pharmacokinetic assessment after 21 days of consecutive dosing with GWP42003-P. Subjects who take clobazam as an adjunctive treatment will be asked to take their usual dose two hours prior to attending the clinic. The same recommendation will be made for other concomitant antiepileptic drugs, if applicable. This is so that the pre-treatment (with GWP42003-P) plasma concentrations of clobazam, its major metabolite N-desmethylclobazam, and any other concomitant antiepileptic drugs can 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 will take place at seven and 14 days of treatment.

After 21 days of treatment, all subjects will commence a 10-day down-titration taper period. An independent Data Safety Monitoring Committee will review unblinded safety and pharmacokinetic data and recommend 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 has taken place, subjects will have the option of entering the open label extension study.

A follow-up telephone call will be made 28 days after the end of dosing for subjects who do not enter the open label extension study within this time-frame.

Throughout the 21-day treatment period and the 10-day taper period, there will be regular safety telephone calls (i.e., approximately every two days) to check subject status. Weekly safety telephone calls will be made during the 28-day follow-up period.

  Eligibility

Ages Eligible for Study:   4 Years to 10 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Subject must be male or female aged between four and 10 years (inclusive).
  • Subject must have a documented history of Dravet syndrome which is not completely controlled by current antiepileptic drugs.
  • Subject must be experiencing fewer than four convulsive seizures (tonic-clonic, tonic, clonic, atonic seizures) during the 28-day baseline observation period.
  • Subject must be taking one or more antiepileptic drugs at a dose which has been stable for at least four weeks.
  • All medications or interventions for epilepsy (including ketogenic diet and vagus nerve stimulation) must have been stable for four weeks prior to screening and subject is willing to maintain a stable regimen throughout the study.

Key Exclusion Criteria:

  • Subject has clinically significant unstable medical conditions other than epilepsy.
  • Subject has had clinically relevant symptoms or a clinically significant illness in the four weeks prior to screening or randomization, other than epilepsy.
  • Subject is currently using or has in the past used recreational or medicinal cannabis, or synthetic cannabinoid based medications (including Sativex®) within the three months prior to study entry and is unwilling to abstain for the duration for the study.
  • Subject has any known or suspected hypersensitivity to cannabinoids or any of the excipients of the investigational medicinal products.
  • Subjects who have been part of a clinical trial involving another investigational product in the previous six months.
  • There are plans for the subject to travel outside their country of residence during the study.
  • Subjects previously randomized into this study. In particular, subjects participating in Part A of the study cannot enter Part B.
  • Any history of suicidal behavior or any suicidal ideation of type four or five on the Columbia-Suicide Severity Rating Scale (Children's) at screening.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02091206

Contacts
Contact: Richard Potts +44 (0) 1980 557000 rp@gwpharm.com

Sponsors and Collaborators
GW Research Ltd
  More Information

No publications provided

Responsible Party: GW Research Ltd
ClinicalTrials.gov Identifier: NCT02091206     History of Changes
Other Study ID Numbers: GWEP1332 Part A
Study First Received: March 17, 2014
Last Updated: September 2, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by GW Research Ltd:
Cannabidiol

Additional relevant MeSH terms:
Syndrome
Epilepsies, Myoclonic
Disease
Pathologic Processes
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases

ClinicalTrials.gov processed this record on September 22, 2014