EP1 cannabidiol enriched cannabis oil in refractory epilepsy
A Double-blind, Placebo-controlled Study Investigating the Safety, Tolerability, Efficacy and Pharmacokinetics of EP1, an Enriched Cannabidiol Oil, in Children and Adolescents with Medication Resistant, Refractory Epilepsy
Cann Pharmaceutical Australia Limited
40 participants
Apr 6, 2020
Interventional
Conditions
Summary
This study is a multi-centre, randomised, double-blind, placebo-controlled study evaluating safety, tolerability, efficacy and PK of individually established efficacious/tolerated doses of EP1 compared to placebo. EP1 contains Cannabidiol (CBD) and Tetrahydrocannabinol (THC) in a ratio of approximately 20:1. The study will aim to determine if EP1 is an effective treatment for refractory epilepsy in children, adolescents and young adults by comparing different doses of EP1 against a placebo by measuring seizure frequency and character. Safety will also be measured over a long term open-label extension of the study for a year after the double blind phase.
Eligibility
Inclusion Criteria14
- Resident in NSW aged 2 to 15 years inclusive at the time Informed Consent is obtained, or resident elsewhere aged 2 to 18 years inclusive at the time Informed Consent is obtained.
- Weight at screening is less than/or equal to 100 kg.
- Diagnosed with drug resistant epilepsy, which has not
- responded to at least 3 AEDs at therapeutic doses, including one trial of a combination of 2 concomitant drugs. Vagal nerve stimulation, responsive neurostimulation, deep brain stimulation, or the ketogenic diet can each be considered equivalent to an AED.
- Baseline seizure frequency of at least 2 countable seizures per week (non-countable seizures includes absence and myoclonic seizures). Note: seizures to be classified according to the International League Against Epilepsy (ILAE) 2017 classification.
- Treatment with between 1-3 baseline anti-seizure medications at stable doses for a minimum of 4 weeks prior to enrolment.
- If being treated with vagal nerve stimulation, there has been no change of device setting in the 3 months prior to enrolment.
- If being treated with a ketogenic diet or Aitkin's diet, there has been no change of the diet's parameters in the 3 months prior to enrolment.
- Prepared to continue treatment with current AED therapy, with no change of dose, throughout the double blind study period. Note: AED use with dose (including changes to dose) will be recorded for the 3 months prior to screening.
- Clinical laboratory (haematology and biochemistry) values within the normal limits as defined by the local clinical laboratory, unless the investigator decides that out-of-range values are not clinically significant.
- An Independent Ethics Committee (IEC) approved written informed consent form is signed and dated by either the participant, where appropriate, or the parent or legal representative (guardian or person responsible).
- Able to fully conform with all study procedures, including visit schedules, seizure reports, PK study and continuation of other AEDs taken during the baseline period.
- Investigator can confirm consistent seizure count over the past 3 months. The subject will need to provide an updated diary at the time of enrolment.
- Investigator is able to confirm consistent seizure count over the past 3 months. The subject will need to provide an updated diary at the time of enrolment.
Exclusion Criteria35
- Epilepsies associated with neurodegenerative diseases, such as Rasmussen encephalitis and malignant brain tumours.
- Epilepsies associated with treatable inborn errors of metabolism.
- Presence of any medical disorder (including cardiovascular, renal, hepatic or endocrine disorders) considered clinically significant in the opinion of the Investigator.
- Non-epileptic seizures.
- Presence of significant medical illness such as heart disease,
- compromised renal function, abnormal liver function or an
- endocrine disorder requiring medication.
- Current treatment with clobazam at a dose > 20 mg/day.
- A significant oral or gastrointestinal condition that, in the
- opinion of the investigator, may affect the absorption of
- EP1.
- Allergy or sensitivity to CBD (or any cannabinoids), olive
- oil or flavouring agents.
- Clinically significant current infection.
- Females of child bearing potential who are currently
- pregnant or breastfeeding or planning on becoming pregnant
- during the study or within 3 months of study completion.
- Sexually active males who intend to father children or not
- using acceptable forms of contraception during the study and for 3 months thereafter. The acceptable methods of birth control are abstinence or double barrier birth control (i.e., condom plus spermicide or a condom plus diaphragm).
- Sexually active females of child-bearing potential who are not prepared to take effective contraception. The acceptable methods of birth control are abstinence (from 4 weeks prior to dosing) or double barrier birth control (i.e., condom plus spermicide or a condom plus diaphragm).
- Currently participating in an investigational drug or device
- study.
- Use of any cannabis related product, (including hemp oil)
- based product in the past 12 months as assessed by parental/caregiver questioning; negative screen for CBD and THC levels at Screening.
- Past treatment with CBD.
- History of uncontrolled diabetes or hypertension.
- History of severe personality disorder, suicidal history or
- other significant psychiatric disorder/psychosis.
- History of substance abuse/addiction including within the
- last year, or daily consumption of significant alcohol
- quantities.
- In Investigator’s judgement, active medical
- condition/treatment that impacts study activities
- In the opinion of the Investigator, the parent(s)/caregiver(s)
- are unable to comply with study requirements, including follow-up visits and tests.
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Interventions
The single intervention in this study is the administration of EP1 to treat epilepsy. EP1 is a drug which contains Cannabidiol (CBD) and Tetrahydrocannabinol (THC) in a ratio of approximately 20:1. It is theorised to reduce and prevent seizures. EP1 will be dosed using oral syringe (sublingually) twice daily, to provide between 5 and 25 mg/kg/day of CBD, and between 0.25 to 1.25 mg/kg/day of THC. The matching placebo is dosed using oral syringes (sublingually) twice daily. Participants will be randomised 3:1 to receive EP1 or placebo. They will undergo 1 to 5 weeks (barring any dose suspensions) of dose finding where the dose of EP1 or placebo is increased weekly to determine their own efficacious/tolerated dose. The individually set efficacious/tolerated dose will be administered for a maximum 12 week double-blind treatment period. Dosing will commence with either EP1 at 5 mg/kg/day or matching placebo solution given in divided doses twice daily. Weekly up-titration with increments of 5 mg/kg/day CBD and 0.25 mg/kg/day THC will be performed based on efficacy and tolerability. Clinical judgment will be used by the Investigator to support dose selection, considering any benefit to the subject and any adverse effects observed. Up-titration may be stopped if an unacceptable AE develops, or if the subject becomes seizure-free. Participants will complete a daily study specific diary where participants/caregivers will record daily dosing details for study medication. Participant will complete an 8 week screening/baseline period. This consists of a 1 to 4 week screening period, and a 4 week (baseline) open-label placebo run-in period to review subject eligibility. During the (baseline) run-in period, subjects will receive a placebo volume equivalent to a 10 mg/kg/day dose of CBD, given SL BD.
Locations(2)
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ACTRN12618001706268