Experimental drug for PD well-tolerated, offers cognitive benefits

In the treatment of patients with Parkinson’s disease (PD), the muscarinic acetylcholine M1 positive allosteric modulator TAK-071 falls short of improving gait, according to the results of a phase II study. However, the drug appears to be well-tolerated and have positive effect on cognition.

The study included 54 PD patients (mean age 69.7 years, 83 percent male) who had experienced at least one episode fall in the prior 12 months, had a Montreal Cognitive Assessment score of 11–26 (median 24), and had received stable antiparkinsonian medications and no acetylcholinesterase inhibitors. These patients were randomly assigned to receive once-daily oral TAK-071 or placebo for 6 weeks, followed by washout and 6 weeks of crossover treatment.

Change in gait variability, the primary efficacy endpoint, was assessed using stride time variability during a 2-minute walk test with or without cognitive load. Change in cognitive composite score consisting of performance on attention, executive function, and memory tests was also assessed as the secondary efficacy endpoint.

After 6 weeks of treatment, no significant difference in the change from baseline in stride time variability was seen between the TAK-071 and the placebo groups. This held true in conditions with cognitive load (geometric mean ratio, 1.15, 95 percent confidence interval [CI], 0.94–1.41; p=0.16) and without cognitive load (geometric mean ratio, 1.02, 95 percent CI, 0.88–1.18; p=0.78).

Meanwhile, the change in the cognitive composite score from baseline was significantly greater with TAK-071 than with placebo (least squares mean difference, 0.22, 95 percent CI, 0.05–0.38; p=0.01).

In terms of safety, treatment-emergent adverse events occurred in 36 percent of patients on TAK-071 and in 37 percent of those on placebo. Of note, 8 percent of TAK-071-treated patients had adverse events (gastrointestinal tract events) resulting in withdrawal of the study drug.