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* = Presenting author

P414 Cannabidiol for symptomatic treatment of ulcerative colitis: Results from a randomised, double-blind, placebo-controlled, parallel group, multi-centred pilot study

P. Irving*1, T. Iqbal2, C. Nwokolo3, S. Subramanian4, S. Bloom5, N. Prasad6, A. Hart7, C. Murray8, J. Lindsay9, A. Taylor10, R. Barron10, S. Wright11

1Guy's and St Thomas' NHS Foundation Trust, Department of Gastroenterology, London, United Kingdom, 2University Hospitals Birmingham NHS Foundation Trust, Department of Gastroenterology, Birmingham, United Kingdom, 3University Hospitals Coventry and Warwickshire NHS Trust, Department of Gastroenterology, Coventry, United Kingdom, 4The Royal Liverpool and Broadgreen University Hospitals NHS Trust, Department of Gastroenterology, Liverpool, United Kingdom, 5University College London Hospitals NHS Foundation Trust, Department of Colorectal Surgery, London, United Kingdom, 6Wrightington, Wigan and Leigh NHS Foundation Trust, Department of Gastroenterology, Wigan, United Kingdom, 7The North West London Hospitals NHS Trust, Inflammatory Bowel Disease Unit, Middlesex, United Kingdom, 8Royal Free London NHS Foundation Trust, Department of Gastroenterology, London, United Kingdom, 9Barts Health NHS Trust, Department of Gastroenterology, London, United Kingdom, 10GW Pharmaceuticals plc, Medical Writing Department, Salisbury, United Kingdom, 11GW Pharmaceuticals plc, Research and Development, Salisbury, United Kingdom

Background

There is accumulating evidence that cannabidiol (CBD) has anti-inflammatory properties that could be exploited for the symptomatic relief of IBD. This proof-of-concept double blind, randomised, placebo controlled trial assessed the efficacy, safety and tolerability of CBD botanical drug substance (BDS) in patients with mild to moderate UC.

Methods

Patients with left-sided or extensive UC aged ≥18 years, with a Mayo score 4-10 (endoscopy score ≥1) and on a stable dose of 5-ASA (or previously used 5-ASA), were randomised 1:1 to receive either CBD BDS (GWP42003) (29 patients) or placebo (31 patients). The IMP was presented as hard gelatin capsules containing 50 mg GWP42003 (purified from a proprietary Cannabis sativa L. chemotype containing predominantly CBD and 4% Δ9-tetrahydrocannabinol [THC]); or excipients alone for the placebo. Patients titrated to their maximal tolerated dose over two-weeks, aiming to achieve 500 mg daily (250 mg b.d.) and maintained this dose for 10 weeks. The primary endpoint was the number of patients in remission (Mayo total score ≤2; no sub-score >1) at week 10. Statistical tests were two-sided at the 10% significance level.

Results

Patients in the active group found the IMP more difficult to tolerate than placebo patients, taking on average one-third fewer capsules during the maintenance period, and having a higher number of compliance-related major protocol deviations than placebo (12 vs. 4); principally insufficient exposure. With only 59% protocol-compliance in the GWP42003 group, the more relevant per-protocol (PP) analysis set was used to assess many efficacy measures. Remission was observed in both treatment groups at the end of treatment; whilst proportionally in favour of GWP42003 (28% vs. 26%), the difference was not significant (p=0.753; Intention to treat analysis set). PP analysis of the Mayo total and partial Mayo scores revealed significant treatment differences in favour of GWP42003 (p=0.068 and p=0.038, respectively). PP analysis of Physician's Global Assessment of Illness Severity, Subject Global Impression of Change and patient-reported quality of life outcomes also significantly favoured GWP42003 (p=0.069, p=0.003 and p=0.065, respectively). All 60 patients were included in the safety analysis; the majority of AEs were mild to moderate in severity and many in the GWP42003 group were likely attributed to the THC. A higher proportion of GI-related AEs, indicative of a worsening in underlying UC, were seen in placebo patients.

Conclusion

Whilst this exploratory trial did not reach its primary endpoint, several signals suggest that GWP42003 may be beneficial for the symptomatic treatment of UC; larger trials are warranted.

ClinicalTrials.gov ID: NCT01562314

Funding: GW Research Ltd