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

NCT ID: NCT02607891

Last Updated: 2022-12-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-09
• Study Completion Date: 2018-10-02

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

STP + GWP42003-P

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

Group Type: EXPERIMENTAL

GWP42003-P

Intervention Type: DRUG

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

STP + Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

VPA + GWP42003-P

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

Group Type: EXPERIMENTAL

GWP42003-P

Intervention Type: DRUG

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

VPA + Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

GWP42003-P

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

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Other Intervention Names

Cannabidiol; CBD; Epidiolex

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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:

• 450 msec for males.
• 470 msec for females.
• 480 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.
• Participant has received an IMP within the 12 weeks prior to the screening visit.
• Participant has significantly impaired hepatic function at the screening or randomization visit, defined as any of the following:

• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 × upper limit of normal (ULN).
• ALT or AST > 3 × ULN and total bilirubin (TBL) > 2 × ULN or international normalized ratio (INR) > 1.5.
• ALT or AST > 3 × ULN with the presence of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, and/or eosinophilia (> 5%).

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jazz Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

SEIN - Epilepsy Institute in the Netherlands Foundation

Zwolle, , Netherlands

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Hospital Ruber Internacional

Madrid, , Spain

Hospital Universitario Virgen del Rocio

Seville, , Spain

Sahlgrenska University Hospital

Gothenburg, , Sweden

Countries

France; Poland; Romania; Netherlands; Spain; Sweden

References

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.

Reference Type: DERIVED

PMID: 32350749 (View on PubMed)

Other Identifiers

2015-002939-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GWEP1447 Blinded Phase

Identifier Type: -

Identifier Source: org_study_id