Longer term tolerability and efficacy of zyn002 cannabidiol transdermal gel in children and adolescents with autism spectrum disorder: An open-label phase 2 study (bright [zyn2-cl-030])

Abstract

Background: ZYN002 is a pharmaceutically manufactured transdermal cannabidiol gel. BRIGHT is a single-centre, open-label Phase 2 study evaluating the tolerability and efficacy of ZYN002 in children/adolescents aged 3-17 years with ASD. Methods: Patients with Clinical Global Impression (CGI)-Severity scores ≥ 4 (moderate or greater) and Aberrant Behavior Checklist-Community (ABC-C) Irritability scores ≥ 18 were enrolled. Patients received ZYN002 250 or 500 mg/day on top of stable standard of care. Patients demonstrating ≥35% improvement in Irritability at Week 14 were allowed to continue treatment. Safety assessments included adverse events (AEs), laboratory tests, and electrocardiograms (ECGs). Results: Thirty-seven patients (mean age: 9.2 years) enrolled; 94% had moderate-to-severe symptoms; the mean baseline ABC-C Irritability score was 30.3. At Week 14, significant improvements (P ≤ 0.0053) were observed for each ABC-C subscale, the Parent-Rated Anxiety Scale-ASD (PRAS-ASD) score, the Autism Parenting Stress Index (APSI) score and each Autism Impact Measure (AIM) domain in 28 who completed Week 14. 57% of patients were improved ('much/very much improved') based on CGI-Improvement (CGI-I). Eighteen patients demonstrated ≥35% improvement in Irritability and elected to continue. At Week 38, improvements in the ABC-C subscale scores (50%-61% across domains; P < 0.0001), the PRAS-ASD (42%; P < 0.0001), APSI (40%; P < 0.0001) and the AIM (19%-36% across domains; P ≤ 0.0008) were maintained. 77% were improved on the CGI-I. 54% of patients reported AEs. AEs were mild (80%) or moderate (20%). Treatment-related AEs were reported in 19% of patients; most were mild and transient. One patient discontinued due to application site reaction. No serious or severe AEs or clinically significant changes in laboratory tests or ECGs were reported. Conclusion: BRIGHT provides initial evidence suggesting a positive risk-benefit profile for ZYN002 when added on top of stable standard of care in children/adolescents with ASD, which was maintained over 38 weeks. Further studies are warranted.L6358489822021-09-03 <br />