|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Tuberous Sclerosis Complex (TSC)
|Medical condition in easily understood language
|Genetic disease of benign tumour growth with multiple symptoms including seizures
|Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
|E.1.2 Medical condition or disease under investigation
|System Organ Class
|10010331 - Congenital, familial and genetic disorders
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
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.
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.
|Secondary objectives of the trial
• To evaluate the effect of GWP42003-P compared with placebo on antiepileptic measures.
• To evaluate the safety and tolerability of GWP42003-P compared with placebo.
• To evaluate the long term effects of GWP42003-P, as add-on therapy, on antiepileptic measures.
• To evaluate the long term safety and tolerability of GWP42003-P.
|Trial contains a sub-study
|Principal inclusion criteria
|• Patient is male or female aged between one and 65 years
• Patient and/or parent(s)/legal representative is willing and able
to give informed consent/assent for participation in the study.
• Well-documented clinical history of epilepsy which is not completely controlled by their current AEDs.
• Clinical diagnosis of TSC according to criteria agreed by the 2012 International Tuberous Sclerosis Complex Consensus Conference.
• Taking one or more AEDs at a dose which has been stable for at least four
weeks prior to screening.
• 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.
At the end of the baseline period patients must also meet the
• Completed at least 90% of calls to IVRS during the first
28 days of the baseline period (a minimum of 25 completed calls).
|Principal exclusion criteria
|• Patient has a history of pseudo-seizures.
• Patient has undergone general anesthetic in the four weeks prior to screening or randomization.
• Patient has undergone surgery for epilepsy in the six months prior to screening.
• Patient is being considered for epilepsy surgery or any procedure involving general anesthesia during the blinded phase of the study.
• Patient has been taking felbamate for less than one year prior to screening.
• Patient is taking an oral (mTOR) inhibitor.
• 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.
• Patient has tumor growth which, in the opinion of the Investigator, could affect the primary endpoint.
• 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.
• Female patient who is pregnant (positive pregnancy test), lactating or planning pregnancy during the course of the study and for three months thereafter.
• Patient has received an IMP less than 12 weeks prior to the screening visit.
|E.5 End points
|Primary end point(s)
The primary endpoint is the change in number of TSC-associated seizures* during the treatment period (maintenance and titration) in patients taking GWP42003-P compared with placebo.
The safety of GWP42003-P will be evaluated by assessing the incidence, type and severity of AEs.
|Timepoint(s) of evaluation of this end point
|Baseline (Visit 2 to Visit 3) and the last 28 days of the evaluable period.
|Secondary end point(s)
The following endpoints will be compared between treatment groups over the 16-week, double-blind
treatment period (all changes relative to baseline):
• Number of patients considered treatment responders defined as those with a
≥ 50% reduction in TSC-associated seizure* frequency.
• Change in Caregiver Global Impression of Change (CGIC) or Subject Global Impression of Change
• Change in total seizures.
• Antiepileptic Efficacy Measures
• Quality of life
• Safety and Tolerability
Will include secondary endpoints as in the core study, with the addition of percentage change in the TSC associated seizures and with removal of PK analysis.
|Timepoint(s) of evaluation of this end point
|Blinded phase (seizures) - Baseline (Visit 2 to Visit 3) and the last 28 days of the evaluable period.
Blinded phase (other efficacy) - Visits 3, 4, 5, 6, 7, 8 , 9 and 10.
Blinded phase (safety) - Visits 3, 4, 5, 6, 7, 8, 9 and 10.
OLE - ALL visit beginning at B1.
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
| Comparator of controlled trial
|Other medicinal product(s)
|Number of treatment arms in the trial
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|Number of sites anticipated in Member State concerned
|The trial involves multiple Member States
|Number of sites anticipated in the EEA
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
|If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
|Trial has a data monitoring committee
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|E.8.9 Initial estimate of the duration of the trial
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days
|In all countries concerned by the trial years
|In all countries concerned by the trial months
|In all countries concerned by the trial days