Brief Title
A Dose-ranging Pharmacokinetics and Safety Study of GWP42003-P in Children With Dravet Syndrome (GWPCARE1)
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
Brief 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.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Number Of Participants Who Experienced Severe Treatment-Emergent Adverse Events (TEAEs)
Secondary Outcome
Area Under The Concentration-Time Curve Calculated To The Last Observable Concentration At Time T (AUC0-t) For CBD And Its Metabolites At Days 1 And 22
Condition
Epilepsy
Intervention
GWP42003-P 5 mg/kg/day Dose
Study Arms / Comparison Groups
GWP42003-P 5 mg/kg/day Dose
Description: Participants received GWP42003-P 5 mg/kg/day administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 5 mg/kg/day over 3 days and remained at this dose for the rest of the 21-day treatment period (19 days). The 21-day treatment period was followed by a 10-day taper (10% per day) period.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
34
Start Date
October 22, 2014
Completion Date
March 9, 2015
Primary Completion Date
March 9, 2015
Eligibility Criteria
Key Inclusion Criteria:
- Participants were male or female aged between 4 and 10 years (inclusive).
- Participants had a documented history of Dravet Syndrome that was not completely
controlled by AEDs.
- Participants took one or more AEDs at a dose which had been stable for at least 4
weeks.
- Participants had experienced fewer than 4 convulsive seizures (tonic-clonic, tonic,
clonic, atonic seizures) during the 28-day baseline period.
- All medications or interventions for epilepsy (including ketogenic diet and vagus
nerve stimulation [VNS]) were stable for four weeks prior to screening and
participants were willing to maintain a stable regimen throughout the study. The
ketogenic diet and VNS treatments were not counted as an AED.
Key Exclusion Criteria:
- Participants had clinically significant unstable medical conditions other than
epilepsy.
- Participants had clinically relevant abnormalities in the 12-lead electrocardiogram
measured at screening or randomization.
- Participants were currently using or had in the past used recreational or medicinal
cannabis, or synthetic CBD based medications (including Sativex®) within the 3 months
prior to study entry and were unwilling to abstain for the duration for the study.
- Participants had any known or suspected hypersensitivity to cannabinoids or any of the
excipients of the IMP.
- Participants who had been part of a clinical trial involving another investigational
product in the previous 6 months.
- There were plans for the participants to travel outside their country of residence
during the study.
- Participants were previously randomized into this study. In particular, participants
participating in Part A of the study cannot enter Part B.
Gender
All
Ages
4 Years - 10 Years
Accepts Healthy Volunteers
No
Contacts
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Location Countries
United Kingdom
Location Countries
United Kingdom
Administrative Informations
NCT ID
NCT02091206
Organization ID
GWEP1332 Part A
Secondary IDs
2014-002941-23
Responsible Party
Sponsor
Study Sponsor
Jazz Pharmaceuticals
Study Sponsor
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Verification Date
July 2018