GWEP 1521

Principal Investigator: Francis  Filloux
Keywords: Seizure , Cannabidiol , tuberous sclerosis complex Department: Pediatric Neurology
IRB Number: 00092348 Co Investigator:  
Specialty: Neurology, Pediatrics, General
Sub Specialties: Epilepsy,
Recruitment Status: Recruiting

Contact Information

Fumiko Alger
fumiko.alger@hsc.utah.edu
801-213-4180

Brief Summary

Blinded Phase:

To evaluate the efficacy of GWP42003-P as add-on therapy in reducing the frequency of seizures when compared with placebo in patients with TSC.

Open-label Extension:

To evaluate via the adverse events (AE) profile the long term safety and tolerability of GWP42003-P as add-on therapy in children and adults with TSC who experience inadequately-controlled seizures.

Inclusion Criteria

  1. Patient is male or female aged between one and 65 years inclusive.
  2. Patient and/or parent(s)/legal representative is willing and able to give informed consent/assent for participation in the study.
  3. Patient and their caregiver are willing and able (in the Investigator’s opinion) to comply with all study requirements (including accurate diary and IVRS completion).
  4. Well-documented clinical history of epilepsy.
  5. Clinical diagnosis of TSC according to criteria agreed by the 2012 International Tuberous Sclerosis Complex Consensus Conference.
  6. All medications or interventions for epilepsy (including ketogenic diet and any neurostimulation devices for epilepsy) must have been stable for one month prior to screening and the patient is willing to maintain a stable regimen throughout the study.
  7. Patient is willing to keep any factors expected to affect seizures stable (such as the level of alcohol consumption and smoking).
  8. Patient and/or parent(s)/legal representative is willing to allow the responsible authorities to be notified of participation in the study, if mandated by local law.
  9. Patient and/or parent(s)/legal representative is willing to allow his or her primary care practitioner and consultant (if they have one) to be notified of participation in the study, if mandated by local law.

At the end of the baseline period patients must also meet the following criteria:

  1. Experienced at least eight seizures during the first 28 days of the baseline period with at least one seizure occurring in at least three of the four weeks (seizures include: focal motor seizures without impairment of consciousness or awareness; focal seizures with impairment of consciousness or awareness; focal seizures evolving to bilateral generalized convulsive seizures and generalized seizures [tonic-clonic, tonic, clonic or atonic]) that are countable.
  2. Completed at least 90% of calls to IVRS during the first 28 days of the baseline period (a minimum of 25 completed calls).

Exclusion Criteria

  1. Patient has a history of pseudo-seizures.
  2. Patient has clinically significant unstable medical conditions other than epilepsy.
  3. Patient has an illness in the four weeks prior to screening or randomization, other than epilepsy, which in the opinion of the Investigator could affect seizure frequency.
  4. Patient has undergone general anesthetic in the four weeks prior to screening or randomization.
  5. Patient has undergone surgery for epilepsy in the six months prior to screening.
  6. Patient is being considered for epilepsy surgery or any procedure involving general anesthesia during the blinded phase of the study.
  7. Patient has been taking felbamate for less than one year prior to screening.
  8. Patient is taking an oral mammalian target of rapamycin (mTOR) inhibitor.
  9. Patient has, in the investigator’s opinion, clinically significantly abnormal laboratory values.
  10. Patient has any known or suspected hypersensitivity to cannabinoids or any of the excipients of the Investigational Medicinal Product) (IMP), such as sesame oil.
  11. Any history of suicidal behavior or any suicidal ideation of type 4 or 5 on C-SSRS in the last month or at  screening.
  12. Patient is currently using or has in the past used recreational or medicinal cannabis, or cannabinoid-based medications, within the three months prior to screening and is unwilling to abstain for the duration for the study.
  13. Patient has tumor growth which, in the opinion of the Investigator, could affect the primary endpoint.
  14. In the opinion of the Investigator the patient has clinically significant abnormalities in the ECG measured at screening or randomization or any concurrent cardiovascular conditions, which will interfere with the ability to read their ECGs.
  15. Patient has significantly impaired hepatic function at the screening visit (Visit 1) or the randomization visit (Visit 3), defined as any of the following:
    1. Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 × upper limit of normal (ULN).
    2. TBL* [serum total bilirubin] ≥ 2 × ULN or international normalized ratio [INR] > 1.5). (*TBL ≥ 2 × ULN exclusion will not apply for patients diagnosed with Gilbert’s disease)
    3. Serum ALT or AST ≥ 3 × ULN with the presence of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, and/or eosinophilia (> 5%).

                   This criterion can only be confirmed once the laboratory results are available.

16. Patient is female and of child bearing potential, or is male whose partner is of child bearing potential, unless willing to ensure that they or their partner use a highly effective method of birth control (e.g., hormonal contraceptives, intrauterine devices/hormone-releasing systems, bilateral tubal occlusion, vasectomized partner, sexual abstinence) during the study and for three months thereafter.

17. Female patient who is pregnant (positive pregnancy test), lactating or planning pregnancy during the course of the study and for three months thereafter.

18. Patient has received an IMP as part of a clinical trial less than 12 weeks prior to the screening visit.

19. Patient has any other significant disease or disorder which, in the opinion of the Investigator, may either put the patient at risk because of participation in the study, may influence the result of the study, or may affect the patient’s ability to take part in the study.

20. Any abnormalities identified following a physical examination of the patient that, in the opinion of the Investigator, would jeopardize the safety of the patient if they take part in the study.

21. Patient has donated blood during the past 12 weeks and is unwilling to abstain from donation of blood during the study.

22. Patient has been previously randomized into this study.

23. Patient has any known or suspected history of alcohol or substance abuse.

24. Patient has travel outside the country and/or state of residence planned during the trial, unless the patient has confirmed that the IMP is permitted in the destination country/state.