A Dose-ranging Pharmacokinetics and Safety Study of GWP42003-P in Children With Dravet Syndrome (GWPCARE1)

NCT02091206 | Completed Phase 2 Results DMC

• 2 other identifiers: GWEP1332 Part A2014-002941-23
• Study Type: interventional
• Target: 34
• Locations: 2 countries
• Sites: 11

Brief Summary

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

Conditions

Epilepsy; Dravet Syndrome

Keywords

Cannabidiol; CBD; Epidiolex; GWP42003-P

Outcome Measures

Primary Outcomes (1)

• Number Of Participants Who Experienced Severe Treatment-Emergent Adverse Events (TEAEs)

  A TEAE was defined as an adverse event (AE) with an onset date on or after the first dose of IMP. If an AE had a partial onset date and it was unclear from the partial date (or the stop date) whether the AE started prior to or following the first dose of IMP then the AE was considered a TEAE. The number of participants who experienced one or more severe TEAEs after dosing on Day 1 through the Safety Follow-up Visit (Day 60) is presented. A summary of serious and all other non-serious AEs regardless of causality is located in the Adverse Events module.

  Baseline (Day 1) through Safety follow-up visit (Day 60)

Secondary Outcomes (2)

• 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

  Predose and 2-6 hours postdose on Days 1 and 22

• Mean Percentage Change From Baseline To End Of Treatment In Plasma Clobazam (CLB) And N-Desmethylclobazam (N-CLB) Concentrations

  Predose on Days 1 and 22

Study Arms (4)

GWP42003-P 5 mg/kg/day Dose

EXPERIMENTAL

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.

Drug: GWP42003-P 5 mg/kg/day Dose

GWP42003-P 10 mg/kg/day Dose

EXPERIMENTAL

Participants received GWP42003-P 10 mg/kg/day administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 10 mg/kg/day over 7 days and remained at this dose for the rest of the 21-day treatment period (15 days). The 21-day treatment period was followed by a 10-day taper (10% per day) period.

Drug: GWP42003-P 10 mg/kg/day Dose

GWP42003-P 20 mg/kg/day Dose

EXPERIMENTAL

Participants received GWP42003-P 20 mg/kg/day administered orally, half in the morning and half in the evening. Participants titrated GWP42003-P to 20 mg/kg/day over 11 days and remained at this dose for the rest of the 21-day treatment period (11 days). The 21-day treatment period was followed by a 10-day taper (10% per day) period.

Drug: GWP42003-P 20 mg/kg/day Dose

Placebo

PLACEBO COMPARATOR

Participants received placebo (0 mg/mL CBD), volume matched to one of the 3 dose levels (5, 10, or 20 mg/kg/day), administered orally, half in the morning and half in the evening for 21 days. To maintain the blinded aspect of the study, participants titrated the placebo dose over 3 to 11 days according to the matched investigational medicinal product (IMP) group (3, 7, and 11 days for the 5, 10, or 20 mg/kg/day GWP42003-P groups, respectively) and remained at this dose for the rest of the 21-day treatment period. The 21-day treatment period was followed by a 10-day taper (10% per day of the matched dose) period.

Drug: Placebo control

Interventions

GWP42003-P 5 mg/kg/day Dose DRUG

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.

Also known as: Cannabidiol, Epidiolex

GWP42003-P 5 mg/kg/day Dose

Placebo control DRUG

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).

Also known as: Placebo

Placebo

GWP42003-P 10 mg/kg/day Dose DRUG

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.

Also known as: Cannabidiol, Epidiolex

GWP42003-P 10 mg/kg/day Dose

GWP42003-P 20 mg/kg/day Dose DRUG

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.

Also known as: Cannabidiol, Epidiolex

GWP42003-P 20 mg/kg/day Dose

Eligibility Criteria

• Age: 4 Years - 10 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Jazz Pharmaceuticals: lead

Study Sites (11)

Unknown Facility

Miami, Florida, 33155, United States

Location

Unknown Facility

Atlanta, Georgia, 30328, United States

Location

Unknown Facility

Chicago, Illinois, 60611, United States

Location

Unknown Facility

Iowa City, Iowa, 52242, United States

Location

Unknown Facility

Boston, Massachusetts, 02114, United States

Location

Unknown Facility

Winston-Salem, North Carolina, 27408, United States

Location

Unknown Facility

Columbus, Ohio, 43205, United States

Location

Unknown Facility

Houston, Texas, 77030, United States

Location

Unknown Facility

Edinburgh, EH9 1LF, United Kingdom

Location

Unknown Facility

Liverpool, L12 2AP, United Kingdom

Location

Unknown Facility

London, WC1N 3JH, United Kingdom

Location

Related Publications (1)

• Devinsky O, Patel AD, Thiele EA, Wong MH, Appleton R, Harden CL, Greenwood S, Morrison G, Sommerville K; GWPCARE1 Part A Study Group. Randomized, dose-ranging safety trial of cannabidiol in Dravet syndrome. Neurology. 2018 Apr 3;90(14):e1204-e1211. doi: 10.1212/WNL.0000000000005254. Epub 2018 Mar 14.

  PMID: 29540584 BACKGROUND

MeSH Terms

Conditions

Epilepsy; Epilepsies, Myoclonic

Interventions

Cannabidiol

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy, Generalized; Epileptic Syndromes

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals

Limitations and Caveats

Analytical issues for 7-OH-CBD related to reference material batch used during analysis. Data are qualitative.

Results Point of Contact

• Title: Medical Enquires
• Organization: GW Research Ltd.

medinfo@gwpharm.com, medinfo@greenwichbiosciences.com

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2014
• First Posted: March 19, 2014
• Study Start: October 22, 2014
• Primary Completion: March 9, 2015
• Study Completion: March 9, 2015
• Last Updated: September 28, 2022
• Results First Posted: July 19, 2018

Record last verified: 2022-09

Locations

US (8); GB (3)