"For the 420 patients randomized, mean age was 63 and mean disease duration was 9 years. At 12 weeks, the mean daily off-time (the primary outcome) was significantly better than placebo in the tozadenant 120 mg twice-daily group (−1.1 hours), in the tozadenant 180 mg twice-daily group (−1.2 hours), and in these two dosing groups combined (−1.1 hours). The 60-mg group did not meet the primary outcome; nor did the 240-mg group, which had substantial dropouts resulting from adverse events. Dyskinesia, and to a lesser extent nausea and dizziness, were more common in those on active drug than in those on placebo.

Comment by Dr. M. Okin :

Adenosine A2A receptors are abundant in the brain; many are colocated next to dopamine receptors. Istradefylline and preladenant, two other adenosine A2A receptor antagonists, recently had disappointing phase III results. The authors of the current study believe that they have addressed several issues with the methodology of previous trials. However, several important questions remain. Should we employ the adenosine approach early or later in PD? What symptoms are best addressed by adenosine antagonists? What is the adverse-event profile, particularly in elders with multiple comorbidities? Will patients prefer a change in doses and intervals of dopaminergic drugs, rather than adding another compound? How cost-effective will this approach be? If phase III results with tozadenant are positive, we will need to begin to answer these questions.

- See more at: NEJM watch

[QUOTE=olsen;1089914]"For the 420 patients randomized, mean age was 63 and mean disease duration was 9 years. At 12 weeks, the mean daily off-time (the primary outcome) was significantly better than placebo in the tozadenant 120 mg twice-daily group (−1.1 hours), in the tozadenant 180 mg twice-daily group (−1.2 hours), and in these two dosing groups combined (−1.1 hours). The 60-mg group did not meet the primary outcome; nor did the 240-mg group, which had substantial dropouts resulting from adverse events. Dyskinesia, and to a lesser extent nausea and dizziness, were more common in those on active drug than in those on placebo.


Tozadenant (SYN115) has had a sort of strange history behind it the past few years. Biotie Therapies, the manufacturer, and their partner, UCB Pharma, completed a somewhat successful Phase 2b study almost two years ago (one dose level showed efficacy, the others didn't). They announced that they were preparing for a phase 3 study a few months later, and they also presented their results at several events. The past March, over a year later, UCB announced they were backing out and returned all drug rights to Biotie. As of their last report, Biotie has stated that they are still evaluating the best strategy for SYN115 to enhance shareholder value. They are also looking for another licensing partner. Makes me wonder if they will ever go forward with the next phase.

Hi, would you check your private messages? Thanks madelyn

Isn't caffeine an adenosine receptor antagonist? Caffeine only worsens my PD symptoms, therefore adenosine receptor antagonists are not for me!