Abstracts

Rationale: Cannabidiol (CBD), the primary non-psychoactive cannabinoid in Cannabis, has demonstrated significant therapeutic effects in a number of chronic medical conditions, including epilepsy and pain, and shown a wide margin of safety and high tolerability across several routes of administration. ZYN002 is a synthetic form of CBD formulated as a transdermal gel at 1% and 2.5%. No human clinical studies of ZYN002 have been previously published. Methods: Two Phase 1, randomized, double-blind, placebo-controlled studies in healthy adults and epilepsy patients were conducted to evaluate the safety and tolerability of ZYN002 administered once or twice daily. One study was a single ascending-dose study in which 32 subjects and 12 epilepsy patients were treated with ZYN002 50 mg (n = 6), 100 mg (n = 6), 125 mg (n = 6), 250 mg (n = 15), or placebo (n=11). The other study was a seven-day multiple-dose study in which 24 subjects and 12 epilepsy patients were treated with ZYN002 200 mg (n=6), 250 mg (n=6), 500 mg (n = 15), or placebo (n = 9). In both studies, safety and tolerability were assessed using standard measures, including physical exams, examination of skin at application site, vital signs, electrocardiograms, safety laboratories, urinalysis, and adverse events. Results: No clinically significant changes in vital signs, laboratory test results, or electrocardiograms were seen in either study. In the single-dose study, both placebo and ZYN002 treated patients reported a similar number of adverse events including headache and erythema. Blinded data for the multiple dose study show that generally mild and transient application site events are most common. Conclusions: These results indicate that ZYN002 has excellent safety and tolerability in healthy subjects and epilepsy patients, with the most common adverse events related to the application site and similar in frequency and severity to those seen with other transdermal gels. The significance of this study is that it is the first published human clinical study of CBD via transdermal delivery, and it showed that ZYN002 is safe and well tolerated. Funding: This study was funded by Zynerba Pharmaceuticals Inc.