Safety and Tolerability of Cannabidivarin (CBDV) in Children and Young Adults With Autism Spectrum Disorder

• ClinicalTrials.gov Identifier: NCT03849456
• Recruitment Status: Not yet recruiting
• First Posted: February 21, 2019
• Last Update Posted: February 21, 2019
• Sponsor: GW Research Ltd
• Information provided by (Responsible Party): GW Research Ltd

Study Description

Brief Summary:

To determine the safety and tolerability of GWP42006 (cannabidivarin, CBDV) in children and young adults with autism spectrum disorder (ASD) and to examine the effect of GWP42006 on communication, social interactions, sleep, behaviour, and cognition profiles.

Condition or disease	Intervention/treatment	Phase
Autism Spectrum Disorder	Drug: GWP42006	Phase 2

Detailed Description:

This is a 52-week, open-label, single-site trial to evaluate the safety and tolerability of GWP42006. Patients who satisfy all eligibility criteria will titrate to a target GWP42006 dose of 10 mg/kg/day or 800 mg/day, whichever is smaller, during the first 4 weeks of treatment. If there is intolerance during titration, the patient may be maintained on a dose below 10 mg/kg/day. The maximum dose patients aged 6 years or older can receive will be 20 mg/kg/day or 1600 mg/day, whichever is smaller. Following the final treatment dose, patients will taper GWP42006 10% per day. The investigator will withdraw patients who fail to demonstrate any perceived benefit and may withdraw patients for whom tolerability is poor.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Safety and Tolerability of GWP42006 in Children and Young Adults With Autism Spectrum Disorder
• Estimated Study Start Date: May 2019
• Estimated Primary Completion Date: July 2021
• Estimated Study Completion Date: August 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: GWP42006; Oral solution taken twice daily with food for 52 weeks.	Drug: GWP42006; Oral solution containing cannabidivarin 50 mg/mL in sesame oil with anhydrous ethanol, sucralose, strawberry flavouring, and β-carotene.; Other Names: Cannabidivarin; CBDV

Outcome Measures

Primary Outcome Measures :

1. Number Of Patients Who Experienced Severe Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Day 1 to Day 403 ]
   A TEAE was defined as an adverse event (AE) with an onset date on or after the first dose of GWP42006. If an AE had a partial onset date and it was unclear from the partial date (or the stop date) whether the AE started prior to or following the first dose of GWP42006 then the AE was considered a TEAE. The number of patients who experienced one or more severe TEAEs after dosing on Day 1 through to the Safety Follow-up is presented.

Secondary Outcome Measures :

1. Change from Baseline in Mean Length of Utterance (MLU) [ Time Frame: Baseline to End of Treatment (Day 365) or Early Termination (ET) ]
   The MLU is a measure of linguistic productivity
2. Change from Baseline in Receptive and Expressive One-Word Picture Vocabulary Tests (ROWPVT and EOWPVT) [ Time Frame: Baseline to End of Treatment (Day 365) or ET ]
   The ROWPVT (for nonverbal patients) and EOWPVT (for verbal patients) target the ability to understand the meaning of words spoken and name what is depicted on a test plate without context
3. Change from Baseline in Pervasive Developmental Disorder Behavior Inventory (PDDBI) [ Time Frame: Baseline to End of Treatment (Day 365) or ET ]
   The PDDBI is an informant-based rating scale designed to assess responsiveness to intervention in children diagnosed with one of the pervasive developmental disorders (including ASD)
4. Change from Baseline in Autism Diagnostic Observation Schedule-Calibrated Severity Score (ADOS-CSS) [ Time Frame: Baseline to End of Treatment (Day 365) or ET ]
   The ADOS-CSS provides a measure of ASD severity and is less influenced by verbal IQ than ADOS raw scores
5. Change from Baseline in Social Responsiveness Scale (SRS) [ Time Frame: Baseline to End of Treatment (Day 365) or ET ]
   The SRS assesses social impairment associated with ASD
6. Change from Baseline in NIH Toolbox Cognition Battery [ Time Frame: Baseline to End of Treatment (Day 365) or ET ]
   The NIH Toolbox Cognition Battery has computerized instruments that measure several ability subdomains important for cognitive health
7. Change from baseline in Differential Ability Scales (DAS) [ Time Frame: Baseline to End of Treatment (Day 365) or ET ]
   The DAS is a comprehensive, individually administered, clinical instrument for assessing the cognitive abilities that are important to learning
8. Change from Baseline in Vineland Adaptive Behavior Scales [ Time Frame: Baseline to End of Treatment (Day 365) or ET ]
   The Vineland measures the personal and social skills of individuals from birth through adulthood
9. Change from Baseline in Repetitive Behavioral Scale - Revised (RBS-R) [ Time Frame: Baseline to End of Treatment (Day 365) or ET ]
   The RBS-R is used to measure the breadth of repetitive behaviour in children, adolescents, and adults with ASD
10. Change from Baseline in Children's Sleep Habits Questionnaire (CSHQ) [ Time Frame: Baseline to End of Treatment (Day 365) or ET ]
    The CSHQ is used to examine sleep behaviour in young children
11. Change from Baseline in Aberrant Behavior Checklist (ABC) [ Time Frame: Baseline to End of Treatment (Day 365) or ET ]
    The ABC assesses the presence and severity of various problem behaviours commonly observed in individuals diagnosed with intellectual and developmental disabilities
12. Clinical Global Impressions-Improvement (CGI-Improvement) [ Time Frame: Baseline to End of Treatment (Day 365) or ET ]
    The CGI-Improvement evaluates the change from the initiation of treatment in the severity of psychopathology using a 7-point scale

Eligibility Criteria

• Ages Eligible for Study: 4 Years to 18 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Key Inclusion Criteria:

• Diagnosis of ASD as defined by the Autism Diagnostic Observation Schedule, 2nd Ed. and The Diagnostic and Statistical Manual of Mental Disorders, 5th Ed.
• Intelligence quotient (IQ) of 40-120 (inclusive).
• Patient and their caregiver are English-speaking.
• In the opinion of the investigator, the patient presents with ASD symptoms that warrant a therapeutic trial with GWP42006.

Key Exclusion Criteria:

• Known single gene neurogenetic disorder with high rates of epilepsy/autism (e.g., fragile X, tuberous sclerosis complex), structural brain lesion (prior stroke or hemispheric brain malformations), or history of any other epileptic encephalopathy, including infantile spasms, before the diagnosis of ASD.
• More than 2 epileptic seizures per month within the 6 months prior to screening.
• Initiation of a behavioural therapy program, new psychotropic medication, or therapeutic diet within the 2 months prior to screening, or plan to change or start any of the above during the trial.
• Presence of a significant untreated medical problem (obstructive sleep apnoea, restless legs syndrome, gastroesophageal reflux disease, etc.) which may have significant impact on sleep study measures.
• Behavioural management issues (e.g., self-injury, aggression) severe enough to be of safety concerns (to patient and/or staff).
• ECG abnormality or clinically significant postural drop in systolic blood pressure at screening.
• Any known or suspected hypersensitivity to cannabinoids or any of the excipients of GWP42006, such as sesame oil.
• Known history of psychiatric disorder (defined as schizophrenia, bipolar disorder, or other psychiatric disease with a known history of hallucinations or delusions).
• History of any inborn errors of metabolism.
• Significantly impaired hepatic function at screening.
• Received an investigational product within the 3 months prior to screening.
• Patient has been taking felbamate for less than 1 year prior to screening.
• Currently using or has used recreational or medicinal cannabis or cannabinoid-based medications within the 3 months prior to screening and is unwilling to abstain for the duration of the trial.
• Any history of suicidal behaviour or any suicidal ideation within the month prior to or at screening.

Contacts and Locations

Contacts

Contact: Medical Enquiries; (833)424-6724; medinfo@gwpharm.com, medinfo@greenwichbiosciences.com

Sponsors and Collaborators

GW Research Ltd

Investigators

• Principal Investigator: Gregory N Barnes, MD PhD; University of Louisville

More Information

• Responsible Party: GW Research Ltd
• ClinicalTrials.gov Identifier: NCT03849456 History of Changes
• Other Study ID Numbers: GWND18089
• First Posted: February 21, 2019
• Last Update Posted: February 21, 2019
• Last Verified: February 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by GW Research Ltd:

Cannabidivarin; CBDV; GWP42006

Additional relevant MeSH terms:

Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders