The Phase 2a pilot trial was a 10-week randomized, double-blind, placebo controlled study of GWP42003 extract, which features Cannabidiol (CBD) as the primary cannabinoid and which also contains Tetrahyrdocannabinol (THC) and other cannabinoid and non-cannabinoid components. The trial included 60 adult patients with ulcerative colitis who had not been able to gain remission from the condition despite first line treatment with salicylates, and in some cases immunosuppressive therapy.
GWP42003 was given as a twice daily oral capsule in a dose titration regimen with an upper target dose of 250mg twice daily. Due to the pilot nature of the study, and the small patient population, the significance value was set at p=0.1.
The primary endpoint of this study was the percentage of participants achieving remission quantified by the MAYO score and included a range of secondary measures to determine whether GWP42003 has a positive benefit for subjects on symptom control.
The study included 60 patients, of which 29 patients were randomised to the active treatment group, and 31 to the placebo group. During the early weeks of the study, more patients withdrew from the active treatment group than from the placebo treatment group so that the per protocol population (those that took the investigational medicine as intended) comprised only 17 patients on GWP42003 and 27 on placebo. Most of these withdrawals were due to minor THC-related adverse events such as dizziness. For this reason, GW believes that the results for the protocol compliant population are most relevant to the assessment of efficacy. The intent to treat population (ITT) includes those patients who were only exposed to GWP42003 for a short period, and therefore had little if any opportunity to benefit.
The primary endpoint of disease remission, as assessed by a Mayo score of 2 or less at the end of the study was achieved by 41% of the protocol-compliant patients on GWP42003 and 30% of patients on placebo (Odds Ratio 1.3, 95% CI 0.4 to 4.0 [NS]). This difference was not statistically significant in either protocol-compliant patients or the ITT population.
Among the secondary efficacy endpoints, for the protocol-compliant population, the Inflammatory Bowel Disease Questionnaire was significantly in favour of GWP42003, as was the Physician Assessment of Disease severity. At the end of the treatment period, in this per protocol group, the physician assessed 82% of the patients in the GWP42003 group as having normal or mild disease, compared with 52% in the placebo group. The Patient Global Impression of Change showed that 93% of the patients in the per protocol population regarded their condition as "improved," compared with 60% of the placebo group. Both these differences were statistically significant.
For the ITT population, the Patient Global Impression of Change and the total partial MAYO score change from baseline (this includes stool frequency, bleeding and physician global impression) were statistically significantly in favour of GWP42003.
All patients on GWP42003 reported at least 1 adverse event, compared with 77% of patients on placebo. Of the adverse events on drug, 90% were mild or moderate. There were no serious adverse events (SAEs) on GWP42003, while there were 4 SAEs on placebo (two of which were exacerbations of the ulcerative colitis). However, as stated above, 13 patients withdrew from the study due to adverse events on drug, compared with 7 on placebo. There were no deaths in the study.
"There is a substantial unmet need for an effective treatment in patients with mild to moderate ulcerative colitis who have failed to enter remission following first line therapy or relapse whilst taking maintenance therapy. In particular, both physicians and patients recognise the importance of avoiding steroids due to their side effect profile," stated Dr. Peter Irving Guy's Hospital, London, and Chief Investigator of the study. "These results provide promising evidence that GWP42003 may produce clinically relevant improvement in the severity of ulcerative colitis compared with placebo, in patients who complete a course of treatment."
Dr. Stephen Wright, R&D Director at GW Pharmaceuticals, stated, "In patients who were able to take GWP42003 for a prolonged treatment period, these results provide good evidence for a therapeutic effect in the treatment of ulcerative colitis in patients who had previously failed to respond to first line therapy. The results support the further investigation of GWP42003 and have provided useful pointers as to how this further investigation should best be done. In addition, the relatively poor tolerability of the dosage form used in this study suggests that further reductions to the THC content may be helpful."