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Key inclusion & exclusion criteria
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Key Inclusion Criteria:
- Participant is male or female aged 3-10 years.
- Participants' parent(s)/legal representative is willing and able to give informed
consent for participation in the trial; where the participant possesses adequate
understanding, informed assent should also be taken.
- Participant and their caregiver are willing and able (in the investigator's opinion)
to comply with all trial requirements.
- Participant must have a clinical diagnosis of Lennox-Gastaut Syndrome (LGS), with
onset within the last 5 years. This includes certification from the investigator of
prior electroencephalogram (EEG) documenting slow spike wave (< 3 Hertz [Hz]) during
the participant's history and evidence of more than 1 type of generalized seizure,
including drop seizures (atonic, tonic, or tonic-clonic), for at least 6 months.
- Investigator can confirm that the addition of GWP42003-P to the participant's existing
antiepileptic drug (AED) regimen is warranted.
- Participant must have at least 1 drop seizure each week during the first 28 days of
the baseline period.
- A minimum level of general intellectual functioning as assessed at screening with the
Peabody Picture Vocabulary Test
- Participant's parent(s)/legal representative is willing to allow the responsible
authorities to be notified of participation in the trial, if mandated by local law.
- Participant's parent(s)/legal representative is willing to allow his or her primary
care practitioner (if they have one) and consultant (if they have one) to be notified
of participation in the trial, if the primary care practitioner/consultant is
different to the investigator.
Key Exclusion Criteria:
- Participant has clinically significant unstable medical conditions other than
epilepsy.
- Participant experiences > 300 total seizures within the first 28 days of the baseline
period.
- Participant has any prior exposure to GWP42003-P.
- Participant has initiated felbamate within the last 12 months.
- Participant has initiated mammalian target of rapamycin (mTOR) inhibitors for epilepsy
within the last 4 weeks.
- 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 had clinically relevant symptoms or a clinically significant illness,
other than epilepsy, in the 4 weeks prior to screening or Visit 2.
- Participant has laboratory values at screening or Visit 2 that are clinically
significantly abnormal in the investigator's opinion.
- Participant tests positive for ?9-tetrahydrocannabinol (THC) or cannabidiol (CBD) at
screening.
- Participant has any known or suspected hypersensitivity to cannabinoids or any of the
excipients of GWP42003-P.
- Participant has significantly impaired hepatic function at the screening visit,
defined as any of the following:
- Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 ×
upper limit of normal (ULN);
- Serum ALT or AST > 3 × ULN and (total bilirubin [TBL] > 2 × ULN or international
normalized ratio [INR] > 1.5);
- 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%).
- Participant has received an investigational medical product within the 3 months prior
to the screening visit.
- Participant has any other significant disease or disorder, which, in the opinion of
the investigator, may either put the participant at risk because of participation in
the trial, may influence the result of the trial, or may affect the participant's
ability to take part in the trial.
- Any abnormalities identified following a physical examination of the participant that,
in the opinion of the investigator, would jeopardize the safety of the participant if
he/she took part in the trial
- Participant has been previously enrolled into this trial.
Age minimum:
3 Years
Age maximum:
10 Years
Gender:
All
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Secondary Outcome(s)
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Change from Baseline to Day 91 (Visit 4) and Day 181 (end of treatment; Visit 5) in executive function and attention on the NIHTCB
[Time Frame: Baseline; Days 91 and 181]
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Change from Baseline to Day 91 (Visit 4) and Day 181 (end of treatment; Visit 5) in generic health status using the EQ-5D-Y Proxy Version 1
[Time Frame: Baseline; Days 91 and 181]
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Number of participants with clinically significant changes in laboratory parameter values
[Time Frame: Baseline; up to Day 191]
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Change from Baseline to Day 91 (Visit 4) and Day 181 (end of treatment; Visit 5) in the NIHTCB Childhood Composite Score
[Time Frame: Baseline; Days 91 and 181]
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Number of participants with clinically significant changes in physical examination findings
[Time Frame: Baseline; up to Day 191]
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Change from Baseline to Day 181 (end of treatment; Visit 5) in quality of life using the Pediatric Quality of Life Inventory (PEDS-QL4)
[Time Frame: Baseline; Day 181]
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Change from Baseline to Day 181 (end of treatment; Visit 5) in the participant's ability to perform day-to-day tasks
[Time Frame: Baseline; Day181]
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Change from Baseline to Day 91 (Visit 4) and Day 181 (end of treatment; Visit 5) in behavior using the Aberrant Behavior Checklist, Second Edition Community Forms (ABC-2-3)
[Time Frame: Baseline; Days 91 and 181]
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Number of participants with clinically significant changes in vital sign values
[Time Frame: Baseline; up to Day 191]
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Number of participants with the indicated type of adverse event
[Time Frame: up to Day 219]
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Change from Baseline to Day 91 (Visit 4) and Day 181 (end of treatment; Visit 5) in episodic memory on the NIHTCB
[Time Frame: Baseline; Days 91 and 181]
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Change from Baseline to Day 91 (Visit 4) and Day 181 (end of treatment; Visit 5) in language on the NIHTCB
[Time Frame: Baseline; Days 91 and 181]
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Change from Baseline to Day 91 (Visit 4) and Day 181 (end of treatment; Visit 5) in Patient-Reported Outcomes Measurement Information System (PROMIS®) - Parent Proxy Short Form Anxiety and Depression Subscales
[Time Frame: Baseline; Days 91 and 181]
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Change from Baseline to Day 91 (Visit 4) and Day 181 (end of treatment; Visit 5) in sleep characteristics using the Children's Sleep Habits Questionnaire (CSHQ)
[Time Frame: Baseline; Days 91 and 181]
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Change from Baseline to Day 91 (Visit 4) and Day 181 (end of treatment; Visit 5) in the Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2) or BRIEF, Preschool (BRIEF-P) for participants aged 5 years or younger
[Time Frame: Baseline; Days 91 and 181]
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Change from Baseline to Day 91 (Visit 4) and Day 181 (end of treatment; Visit 5) in the Caregiver Global Impression of Change (CGIC) score
[Time Frame: Baseline; Days 91 and 181]
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Change from Baseline to Day 91 (Visit 4) in processing speed on the NIHTCB
[Time Frame: Baseline; Day 91]
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Change from Baseline to Day 91 (Visit 4) and Day 181 (end of treatment; Visit 5) in the Physician Global Impression of Change (PGIC) score
[Time Frame: Baseline; Days 91 and 181]
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Change from Baseline to Day 91 (Visit 4) and Day 181 (end of treatment; Visit 5) in weekly seizure frequency
[Time Frame: Baseline; Days 91 and 181]
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Change from Baseline to Day 91 (Visit 4) and Day 181 (end of treatment; Visit 5) in Parenting Stress Index, Fourth Edition (PSI-4)
[Time Frame: Baseline; Days 91 and 181]
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