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

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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

, , 

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

, , 


Verification Date

July 2018