Biotie has announced that full data from a Phase 2b study evaluating tozadenant (SYN115) in Parkinson’s disease (PD) patients experiencing levodopa related end of dose wearing off were presented at the 65th Annual Meeting of the American Academy of Neurology (AAN) in San Diego, March 20, 2013.
These data were selected by the AAN for the Emerging Science Program (formerly Late-breaking Science Program) and were presented by Dr C. Warren Olanow, Professor of Neurology and Neuroscience at the Mount Sinai School of Medicine.
The study was an international, 12-week, double-blind, phase 2 trial in which patients on stable dosages of levodopa with at least 2.5 hours (hr) of OFF time per day were randomised to tozadenant 60, 120, 180 or 240 mg BID, or matching placebo. The primary outcome measure was the change from baseline to Week 12 in hours per day spent in the OFF state. A mixed-model repeated-measures ANCOVA was used for analyses with a pre-specified hierarchical step-down approach to test multiple dose groups.
Of 420 patients, 337 completed treatment. Their mean age was 63.3 years, mean duration of PD 8.7 years, and their mean OFF time at baseline was about 6 hr/day. Significant reductions in mean placebo-corrected change from baseline in OFF time were observed with tozadenant (modified Intention to Treat population) 120 mg BID (-1.1 hr, p=0.0039) and 180mg BID (-1.2 hr, p=0.0039). The amount of time patients spent in the ON time with troublesome dyskinesia was not significantly increased in any tozadenant group. Mean placebo-corrected scores on the Unified Parkinson’s Disease Rating Scale (UPDRS) part III significantly improved with tozadenant 120mg BID (-2.2, p=0.0325) and 180mg BID (-2.5, p=0.0325), and mean placebo-corrected UPDRS I-III scores improved significantly in all tozadenant groups (all groups, p< 0.03).
The changes were also perceptible to both physicians and patients, as reflected in statistically significant improvements on global ratings. Mean placebo-corrected scores on the clinician-administered global impressions of severity (CGI-S) and improvement (CGI-I) improved significantly in all tozadenant groups, and placebo-corrected scores on patient ratings (Patient Global Impression; PGI) significantly improved in the 120mg BID group. The most common adverse events in the combined tozadenant groups were dyskinesia, nausea, dizziness, constipation, PD worsening, insomnia and falls.
Steve Bandak, Chief Medical Officer of Biotie stated, “We are very pleased that these data were selected for inclusion in AAN’s Emerging Science Program and believe it reflects the scientific importance of these findings and the potential opportunity for tozadenant as a new treatment for Parkinson’s disease”. He continued, “We are now working closely with our partner UCB Pharma for further development of tozadenant and plan to start the phase 3 program by H1 2015”.