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

Jazz Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: Epilepsy

Treatments: Drug: GWP42003-P; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02607891

2015-002939-18 (EudraCT Number)

GWEP1447 Blinded Phase

Details and patient eligibility

About

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.

Enrollment: 35 patients

Sex: All

Ages: 16 to 55 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Note: Participants who enroll in Sweden must be aged 18-55 years.

Key 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.

Key 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%).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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35 participants in 4 patient groups, including a placebo group

STP + GWP42003-P

Experimental group

Description:

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

Treatment:

Drug: GWP42003-P

STP + Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

VPA + GWP42003-P

Experimental group

Description:

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

Treatment:

Drug: GWP42003-P

VPA + Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo