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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 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: October 13, 2014
Last verified: October 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 its major metabolite 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: October 2014
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (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.

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 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.
  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: Kathleen Osborn 1-978-443-7411 kosborn@gwpharm.com

Locations
United States, Georgia
Center 2 Recruiting
Atlanta, Georgia, United States
United States, Illinois
Center 3 Recruiting
Chicago, Illinois, United States
United States, Texas
Center 1 Recruiting
Houston, Texas, United States
Sponsors and Collaborators
GW Research Ltd
Investigators
Study Director: Richard Potts 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: October 13, 2014
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by GW Research Ltd:
Cannabidiol

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

ClinicalTrials.gov processed this record on October 21, 2014