Approval Probability
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Label indication EPIDIOLEX is indicated for the treatment of seizures associated with Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), or tuberous sclerosis complex (TSC) in patients 1 year of age and older. EPIDIOLEX is indicated for the treatment of seizures associated with Lennox-Gastaut syndrome, Dravet syndrome, or tuberous sclerosis complex in patients 1 year of age and older ( 1 ) FDA label
Also known as GWP42003-P, Cannabidiol, Cannabidiol oral solution (CBD-OS), CBD, CBD-OS, Cannabidiol Oral Solution [Epidiolex], Cannabidiol (CBD), Epidyolex
Epidiolex · 11 trials · 19 indications
Change from baseline to Week 104 in the positive symptom subscale score (P1-P4) of the Comprehensive Assessment of At-Risk Mental States (CAARMS). Higher scores indicate greater symptom severity.
All patients will undergo video recording of their eyelid kinematics at days 0, 45, 90, 135, and 180. A high-resolution commercially available video camera will capture the eyelid positions at a sampling rate of thirty frames per second. Patients will be assessed in three different lighting conditions - in regular exam room lighting, under examination with the glare source of an indirect ophthalmoscope (at 2000 lux on both eyes from 5 feet), and in dim lighting. The upper and lower eyelid positions captured from each frame of the videos will be input into custom software developed by Visage Technologies, which fits a feature template to the facial features in each frame, including the upper and lower lids of each eye. The difference between the upper and lower lid positions defined the lid aperture, also known as the palpebral fissure. The eyeblink parameters will then calculated from the eyelid aperture time series with custom software written in MATLAB.
Measured in millimeters (mm)
Effects of CBD on in-vivo glutamatergic levels within mesocorticolimbic brain regions using Proton-Magnetic resonance spectroscopy.
Change in fMRI blood-oxygen-level dependent (BOLD) signal acquired during the cue reactivity task at the 2nd MRI conducted 1 week after intervention as compared to the 1st MRI.
Change in fMRI blood-oxygen-level dependent (BOLD) signal acquired during resting-state at the 2nd MRI conducted 1 week after intervention as compared to the 1st MRI.
Severity of each specific adverse event was scored as 0=no adverse event, 1=mild adverse event, 2=moderate adverse event, and 3=sever adverse event. The range of severity is 0-3. Higher scores mean a worse outcome. The severity was expressed as mean (standard deviation).
Orthostatic blood pressure will be monitored at each study visit.
A physical exam will be performed at each study visit.
EKG will be performed at each study visit.
Laboratory tests (hematology, serum chemistry, and urinalysis) will be evaluated at each study visit.
Assessing the proportion of subjects that drop out of the study due to study drug intolerance.
There are four parts: Part I (Non-motor experiences of daily living, scores range 0-52), Part II (motor experiences of daily living, scores range 0-52), Part III (motor examination, scores range 0-132) and Part IV (motor complications scores range 0-24). Subscales are summed to a total score, ranging 0-260. Higher scores mean a worse outcome.
MoCA - is designed as a rapid screening instrument for mild cognitive dysfunction. It assesses different cognitive domains: attention and concentration, executive functions, memory, language, visual -constructional skills, conceptual thinking, calculation. Scores range 0-30. Higher values represent a better outcome.
This includes 8 items that assess severity of anxiety. Scores range 8-40. Higher values represent a worse outcome.
Assessing neuropsychiatric symptoms and psychopathology of patients with Alzheimer's disease and other neurodegenerative disorders. It has proven to be sensitive to change and has been employed to capture treatment related behavioral.Total NPI scores range 0-120. Higher values represent a worse outcome.
This includes 8 items that assess severity of depression. Score range 8-40. Higher values represent a worse outcome.
A valid, reliable, short scale that is used to evaluate night time sleep problems in PD. Scores range 0-18. Higher values represent a worse outcome.
10-item, patient self-rating instrument assessing the subject's sleep behavior with short questions that have to be answered by either "yes" or "no". Scores range 0-13. Higher values represent a worse outcome.
8 items that assess severity of emotional and behavioral dyscontrol. Scores range 8-40. Higher values represent a worse outcome.
This will assess severity of pain. Scores range 3-15. Higher scores represent a worse outcome.
To measure severity of symptoms and support a diagnosis of impulse control disorders and related disorders in PD. Total QUIP-RS scores were summed by 6 subscores (gambling 0-16, Sex 0-16, Buying 0-16, Eating 0-16, Hobbyism-punding 0-32, and PD Medication use 0-16), range 0-112. Higher scores represent a worse outcome.
A self-report 9-item questionnaire with questions related to how fatigue interferes with certain activities and rates its severity. Scores range 9-63. Higher values represent a worse outcome.
This encompasses a ten-question instrument for measuring severity of restless legs syndrome (RLS). Score range 0-40. Higher values represent a worse outcome.
To evaluate involuntary movements often associated with treated Parkinson's disease. Total UDysRS scores is the sum of historical sub-scores (0-60) and objective sub-score (0-44). Total scores range 0-104. Higher values represent a worse outcome.
Data on cognitive function was collected using the List Sorting Working Memory Test from the NIH Toolbox. Data was collected on working memory performance, which was transformed into a t-score from 0 to 100 where a higher t-score indicates better performance. T-score of 50 indicates the population mean with a standard deviation of 10. Data was collected at baseline and after 6 months on study drug.
Assess the reduction in spike wave index by evaluating the differences in activity from the four 24-hour ambulatory EEGs each participant obtains while enrolled in this study
Measurement of brain activity using the Blood Oxygenation Level Dependent (BOLD) signal Neural (BOLD) functional response to acute stress and network hierarchy in resting state functional connectivity. BOLD response will measure neural activity during stress conditions as compared to rest and control conditions
Concentration of brain chemicals (N-acetylaspartate, Glutamate/Glutamine Levels) as an indicator of brain health measured using non-invasive imaging of magnetic resonance spectroscopy.
The cortisol blood test measures the level of cortisol in the blood. Cortisol is a steroid (glucocorticoid or corticosteroid) hormone produced by the adrenal gland.
The cortisol saliva test measures the level of cortisol in the saliva. Cortisol is a steroid (glucocorticoid or corticosteroid) hormone produced by the adrenal gland.
A baseline seizure frequency was recorded for each subject in a diary for eight weeks prior to investigational drug initiation and parents/caregivers documented seizures on a daily basis throughout the trial using a seizure log. For assessing the efficacy of CBD, the investigator counted the change in frequency of seizures per month. The number of seizures within 56 days of the baseline and the number of seizures within 56 days of week 14 were calculated. Higher seizure frequency indicates worse outcome. This outcome is measured as the change in number of seizures per month between the baseline and week 14 time points.
| Arm | Type | Description |
|---|---|---|
| Cannabidiol 100g/ml oral solution | ACTIVE_COMPARATOR | Participants will take the intervention for 106 weeks (104 weeks plus a 2-week taper). Doses depend on age and weight: Adults (16 years and older) over 50kg: daily dose 600mg (6ml); 300mg (3ml) twice a day (b.i.d); Adults (16 years and older) less than 50kg: daily dose 10mg/kg; 5mg/kg twice a day (b.i.d); Children (\<16 years old): daily dose 5mg/kg twice a day (b.i.d), following on from a two-week rapid titration schedule. n=188 |
| Placebo | PLACEBO_COMPARATOR | Participants will take the intervention for 106 weeks (104 weeks plus a 2-week taper). Doses depend on age and weight: Adults (16 years and older) over 50kg: daily dose 600mg (6ml); 300mg (3ml) twice a day (b.i.d). Adults (16 years and older) less than 50kg: daily dose 10mg/kg; 5mg/kg twice a day (b.i.d). Children (\<16 years old): daily dose 5mg/kg twice a day (b.i.d), following on from a two-week rapid titration schedule. n=188 |
| Healthy controls | NO_INTERVENTION | A healthy control in the context of this trial is someone who does not meet CHR-P criteria or have a diagnosis of a mental health condition. They will not take the trial intervention and attend one trial visit for clinical assessments and biomarker sampling only. n=150 |
| CBD-OS | EXPERIMENTAL | Participants with DEE will be randomized to CBD-OS up to 10 mg/kg twice daily for a 6-week treatment period. |
| Open-Label Extension: CBD-OS | EXPERIMENTAL | Participants with DEE who completed the double-blind phase of the study and enter the optional OLE will begin a 22-week open-label treatment period with CBD-OS up to 10 mg/kg twice daily following a 2-week Blinded Transition Period. |
| Group A - active medication followed by placebo | ACTIVE_COMPARATOR | - |
| Group B - placebo followed by active medication | ACTIVE_COMPARATOR | - |
| Control | PLACEBO_COMPARATOR | Participants will receive a harmless, inactive solution to compare and validate the results of the other arms of the study |
| CBD 800mg | EXPERIMENTAL | Participants in Arm CBD 800 mg will receive 800mg of Cannabidiol in each of the three test sessions |
| cannabidiol | EXPERIMENTAL | GWP42003-P oral solution, is purified cannabidiol (purity of ≥98%, 100 mg/ml cannabidiol in sesame oil with anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring). Started at 5 mg/kg/day and is increased by 2.5-5 mg/kg at 3-5 day intervals to a target dose of 20 mg/kg/day. |
| Cannabidiol/ Epidiolex | EXPERIMENTAL | All subjects will receive the experimental Epidiolex (cannabidiol) oral solution to be taken at home twice a day, and will be treated on an outpatient basis. The drug will be taken for 24 weeks unless the subject chooses to participate in the extension phase of the study, in which case the subject will continue to receive the drug for one additional year or until the drug is approved for clinical use for the treatment of cognitive impairments in patients with Sturge-Weber syndrome. |
| Presymptomatic Epidiolex Treatment | EXPERIMENTAL | Epidiolex will be started at 2.5 mg/kg/day divided twice daily. The dose will increase weekly as tolerated over the next 5 weeks to a target dose of 20 mg/kg/day. |
| IP | ACTIVE_COMPARATOR | Epidiolex (Cannabidiol) is a colorless to yellow solution in a 100mL vial that is to be administered with a 5mL syringe.The starting dosage is 2.5 mg/kg twice daily, or 5 mg/kg/day. After one week, the dosage can be increased to a maintenance dosage of 5mg/kg twice daily, or 10 mg/kg/day. Patients who are tolerating Epidiolex at 10mg/kg per day and require further reduction of seizures may benefit from a dosage increase up to a maximum recommended maintenance. Dosage of 10mg/kg twice daily (20mg/kg/day), in weekly increments of 2.5 mg/kg twice daily(5mg/kg/day), as tolerated. For patients in whom a more rapid titration from 10 mg/kg/day to 20 mg/kg/day is warranted, the dosage may be increased to no more frequently than every other day administration of the 20 mg/kg/day. Dosage resulted in somewhat greater reductions in seizure rates than the recommended maintenance dosage of 10 mg/kg/day, but with an increase in adverse reactions. |
| Cannabidiol (CBD) | EXPERIMENTAL | Cannabidiol - oral CBD solution 400 mg |
| Name | Type | Description |
|---|---|---|
| Cannabidiol (CBD) | DRUG | CBD 100 mg/mL Oral Solution |
| Placebo | DRUG | Placebo for Cannabidiol oral solution 100mg/mL oral solution |
| CBD-OS | DRUG | Oral solution, twice daily |
| Cannabidiol Oral Solution [Epidiolex] | DRUG | 100 mg BID for three months Placebo oral solution for three months |
| cannabidiol | DRUG | Purified CBD, is a strawberry flavored liquid, in sesame oil, provided as 100 mg/ml, extracted from high CBD plant material. A component of cannabis that has evidence suggesting it is relatively safe and perhaps neuroprotective, reduces tremor, anxiety and psychosis and is well tolerated in PD. Besides limiting the psychoactive effect of THC, studies support that CBD has anti-inflammatory, anticonvulsant, anti-oxidant, anxiolytic and antipsychotic properties. |
| Epidiolex 100 mg/mL Oral Solution | DRUG | Epidiolex is a prescription form of cannabidiol used to treat seizures. Epidiolex will be started at 2.5 mg/kg/day divided twice daily. The dose will increase weekly as tolerated over the next 5 weeks to a target dose of 20 mg/kg/day. |
CHR-P patients: Inclusion Criteria 1. 12 to 35 years of age inclusive, willing and able to provide written informed consent/assent. 2. Meet criteria for either the Attenuated Psychotic Symptoms (APS) or Brief Limited Intermittent Psychotic Symptoms (BLIPS) subgroups of the CHR-P state, defined usi...
Epidiolex is being studied for Electrical Status Epilepticus of Slow-Wave Sleep and Sturge-Weber Syndrome. It is an investigational small molecule developed by Jazz Pharmaceuticals plc (ticker JAZZ). These are the two indications currently under clinical evaluation for this asset.
Epidiolex is developed by Jazz Pharmaceuticals plc, which trades under the ticker JAZZ. The company is the sponsor of the clinical program evaluating the drug in Electrical Status Epilepticus of Slow-Wave Sleep and Sturge-Weber Syndrome.
Epidiolex is in Phase 1 development for Electrical Status Epilepticus of Slow-Wave Sleep, with a completed Phase 1 trial. A separate Phase 2 trial in Sturge-Weber Syndrome is planned but not yet recruiting. The drug remains investigational and is not approved for these indications.
Epidiolex has been studied in NCT04721691, a completed Phase 1 trial in Electrical Status Epilepticus of Sleep that enrolled 16 patients. A Phase 2 trial, NCT07778810, is planned for presymptomatic treatment of Sturge-Weber Syndrome with 10 patients and is not yet recruiting.