A Study of Possible Drug-drug Interactions Between Stiripentol or Valproate and Cannabidiol in Patients With Epilepsy

NCT02607891 | Completed Phase 2

• 2 other identifiers: GWEP1447 Blinded Phase2015-002939-18
• Study Type: interventional
• Target: 35
• Locations: 3 countries
• Sites: 5

Brief Summary

This trial consists of 2 parts: a double-blinded phase and an open-label extension phase. The blinded phase only will be described in this record. Participants will be randomized in a 4:1 ratio to receive GWP42003-P or matching placebo. The hypothesis is that levels of stiripentol (STP) or valproate (VPA) may be altered (increased or decreased) as a result of using GWP42003-P.

Conditions

Epilepsy

Keywords

Cannabidiol; GWP42003-P; Epidiolex; Stiripentol; Valproate

Outcome Measures

Primary Outcomes (4)

• Maximum plasma concentration (Cmax) of STP, VPA, cannabidiol (CBD).

  The Cmax of STP, VPA and CBD is presented.

  0, 0.25, 0.5, 1, 1.5, 2, 4, 6, and 12 hours post-dose.

• Time to the maximum plasma concentration (Tmax) of STP, VPA and CBD.

  The Tmax of STP, VPA and CBD is presented.

  0, 0.25, 0.5, 1, 1.5, 2, 4, 6, and 12 hours post-dose.

• Area under the curve (AUC) from zero to final time of positive detection (0-t) of STP, VPA and CBD.

  The AUC(0-t) of STP, VPA and CBD is presented.

  0, 0.25, 0.5, 1, 1.5, 2, 4, 6, and 12 hours post-dose.

• Area under the plasma concentration time curve over a dosing interval, where tau is the dosing interval [AUCtau].

  The AUC(tau) of STP, VPA, and CBD is presented.

  0, 0.25, 0.5, 1, 1.5, 2, 4, 6, and 12 hours post-dose.

Secondary Outcomes (14)

• Number of participants who experienced an adverse event.

  Up to 11 weeks.

• Number of participants with a clinically significant change in 12-lead electrocardiogram (ECG).

  Up to 7 weeks.

• Number of participants with a clinically significant change in serum biochemistry.

  Up to 7 weeks.

• Number of participants with a clinically significant change in hematology.

  Up to 7 weeks.

• Number of participants with a clinically significant change in urinalysis.

  Up to 7 weeks.

Study Arms (4)

STP + GWP42003-P

EXPERIMENTAL

Administered orally, twice daily (morning and evening; immediately after the participant's STP dose), commencing with up-titration of 100 mg/mL GWP42003-P to a maintenance dose of 20 mg/kg/day over 11 days. Participants remain on the maintenance dose for a further 14 days. Dosing is tapered (10% each day) for participants who do not enter the open-label-extension (OLE) phase or who withdraw early. STP Arm: Last patient completion October 2018

Drug: GWP42003-P

STP + Placebo

PLACEBO COMPARATOR

Administered orally, twice daily (morning and evening; immediately after the participant's STP dose), commencing with up-titration of placebo to an equivalent maintenance dose of 20 mg/kg/day over 11 days. Participants remain on the maintenance dose for a further 14 days. Dosing is tapered (10% each day) for participants who do not enter the OLE phase or who withdraw early. STP Arm: Last patient completion February 2018

Drug: Placebo

VPA + GWP42003-P

EXPERIMENTAL

Administered orally, twice daily (morning and evening; immediately after the participant's VPA dose), commencing with up-titration of 100 mg/mL GWP42003-P to a maintenance dose of 20 mg/kg/day over 11 days. Participants remain on the maintenance dose for a further 14 days. Dosing is tapered (10% each day) for participants who do not enter the OLE phase or who withdraw early. VPA Arm: Last patient completion February 2018

Drug: GWP42003-P

VPA + Placebo

PLACEBO COMPARATOR

Administered orally, twice daily (morning and evening; immediately after the participant's VPA dose), commencing with up-titration of placebo to an equivalent maintenance dose of 20 mg/kg/day over 11 days. Participants remain on the maintenance dose for a further 14 days. Dosing is tapered (10% each day) for participants who do not enter the OLE phase or who withdraw early. VPA Arm: Last patient completion January 2018

Drug: Placebo

Interventions

GWP42003-P DRUG

Clear, colorless to yellow solution containing cannabidiol dissolved in the excipients sesame oil and anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring.

Also known as: Cannabidiol, CBD, Epidiolex

STP + GWP42003-P; VPA + GWP42003-P

Placebo DRUG

Clear, colorless to yellow solution containing the excipients sesame oil and anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring.

STP + Placebo; VPA + Placebo

Eligibility Criteria

• Age: 16 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Participant must be taking STP (for the STP arm) or VPA (for the VPA arm) and no more than 2 other antiepileptic drugs (AEDs) during the blinded period of the trial.
• In the VPA arm only, the participant must not be receiving STP (VPA allowed in STP arm).
• AED doses, including STP or VPA, must be stable for 4 weeks prior to screening and regimen must remain stable throughout the duration of the blinded period of the trial.
• Participant must have a documented magnetic resonance imaging/computerized tomography of the brain that ruled out a progressive neurologic condition.
• Participant must have experienced at least 1 countable uncontrolled seizure of any type (i.e., tonic-clonic, tonic, clonic, atonic, partial onset or focal: focal seizures with retained consciousness and a motor component, focal seizures with impaired consciousness, focal seizures evolving to bilateral secondary generalization) within 2 months prior to randomization.
• Intervention with vagus nerve stimulation and/or ketogenic diet must be stable for 4 weeks prior to baseline and the participant must be willing to maintain a stable regimen during the blinded period of the trial.
• Participant must abstain from alcohol during the blinded period of the trial.

You may not qualify if:

• Participant has clinically significant unstable medical conditions other than epilepsy.
• Participant has a history of symptoms related to a drop in blood pressure due to postural changes (e.g., dizziness, light-headedness, blurred vision, palpitations, weakness, syncope).
• Participant has a QT interval, corrected for heart rate with Bazett's formula (QTcB), greater than:
• msec for males.
• msec for females.
• msec if right bundle branch block is present.
• Participant has any history of suicidal behavior or any suicidal ideation of type 4 or 5 on the C-SSRS in the last month or at screening.
• Participant has had clinically relevant symptoms or a clinically significant illness in the 4 weeks prior to screening or enrollment, other than epilepsy.
• Participant is currently using felbamate and has been taking it for less than 12 months prior to screening.
• Participant has consumed alcohol during the 7 days prior to enrollment and is unwilling to abstain during the blinded phase of the trail.
• Participant is currently using or has in the past used recreational or medicinal cannabis, or synthetic cannabinoid-based medications (including Sativex®) within the 3 months prior to trial entry.
• Participant has any known or suspected history of any drug abuse or addiction.
• Participant is unwilling to abstain from recreational or medicinal cannabis, or synthetic cannabinoid based medications (including Sativex) for the duration for the study.
• Participant has consumed grapefruit or grapefruit juice 7 days prior to enrollment and is unwilling to abstain from drinking grapefruit juice within 7 days of pharmacokinetic visits.
• Participant has any known or suspected hypersensitivity to cannabinoids or any of the excipients of the Investigational Medicinal Product (IMP), e.g., sesame oil.

Sponsors & Collaborators

• Jazz Pharmaceuticals: lead

Study Sites (5)

SEIN - Epilepsy Institute in the Netherlands Foundation

Zwolle, Netherlands

Location

Hospital Universitari Vall d'Hebron

Barcelona, Spain

Location

Hospital Ruber Internacional

Madrid, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, Spain

Location

Sahlgrenska University Hospital

Gothenburg, Sweden

Location

Related Publications (1)

• Ben-Menachem E, Gunning B, Arenas Cabrera CM, VanLandingham K, Crockett J, Critchley D, Wray L, Tayo B, Morrison G, Toledo M. A Phase II Randomized Trial to Explore the Potential for Pharmacokinetic Drug-Drug Interactions with Stiripentol or Valproate when Combined with Cannabidiol in Patients with Epilepsy. CNS Drugs. 2020 Jun;34(6):661-672. doi: 10.1007/s40263-020-00726-4.

  PMID: 32350749 DERIVED

MeSH Terms

Conditions

Epilepsy

Interventions

Cannabidiol

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals

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: November 16, 2015
• First Posted: November 18, 2015
• Study Start: November 9, 2016
• Primary Completion: September 11, 2018
• Study Completion: October 2, 2018
• Last Updated: December 20, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

ES (3); SE (1); NL (1)