GLYCOPAR: A randomized, placebo-controlled, two-arm parallel-group superiority phase II study of glycopyrrolate for moderate-to-severe sialorrhea in Parkinson’s disease (2697)

Objective: To assess the long-term efficacy and safety of glycopyrrolate for moderate-to-severe sialorrhea in Parkinson’s disease (PD). Background: A systematic review reported that sialorrhea affects approximately 50% of patients with PD and concluded that drooling is a significant problem in about a quarter of PD patients. Chronic moderate-to-severe sialorrhea leads to substantial social issues with a detrimental effect on quality of life. An evidence-based review of commercially available therapies by the MDS in 2019 rated glycopyrrolate and botulinum toxin as the only efficacious therapies for the short-term treatment of sialorrhea in PD. There is no evidence for more prolonged treatments for sialorrhea in PD. Design/Methods: We conducted an exploratory, two-centred, double-blinded placebo-controlled two-arm parallel-group superiority phase II study, with block randomization and 1:1 allocation. Oral glycopyrrolate 1.5 mg TID (maximum dose) was compared to an equivalent dose of placebo for the reduction of sialorrhea related-disability (ROMP-saliva, primary outcome measure) at three months, in patients older than 30, with PD and moderate-to-severe sialorrhea (MDS-UPDRS, item 2.2>2). We used an intention-to-treat analysis. A P Results: We recruited 28 patients with PD (age: 71.1±6.9 years ;disease duration: 11.4±7.2;ROMP-saliva: 22.7±5.4). At 90 days, there was a treatment difference for ROMP saliva of −5.8 (95% CI: 10.16, −1.52) in favour of glycopyrrolate, present at day 45 (−4.4, 95% CI:−8.0, −0.8). There were six early terminations due to adverse events (glycopyrrolate, n=5). Dry mouth was the most common side effect (glycopyrrolate, n=6 vs. placebo, n=2) followed by constipation (glycopyrrolate, n=4 vs. placebo, n=2) Conclusions: The GLYCOPAR study suggests the efficacy of glycopyrrolate to treat sialorrhea related-disability up to 3 months of treatment. These results contribute to addressing a significant unmet nonmotor care need in PD. A phase III trial is warranted to determine the best compromise between efficacy and safety of using glycopyrrolate. Disclosure: Dr. Mestre has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Abbvie, CHDI, Medtronic, Valeo Pharma. Dr. Freitas has nothing to disclose. Dr. Basndwah has nothing to disclose. Dr. Lopez has nothing to disclose. Dr. Shinawi has nothing to disclose. Dr. Oliveira has nothing to disclose. Dr. Al-Shorafat has nothing to disclose. Dr. Mancini has nothing to disclose. Dr. Lui has nothing to disclose. Dr. Reddie has nothing to disclose. Dr. Grimes has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Ipsen, Allergan, and Department of Justice Canada / Government of Canada. Dr. Grimes has received research support from Canadian Institutes of Health Research, Parkinson Canada, Ontario Brain Institute, PSI Foundation, Parkinson Research Consortium, and uOBMRI.Dr. Fox has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Acadia; Atuka; CHDI; Merz; Kyowa; Palidan, Sunovion Pharmaceuticals Inc.; Teva; Zambon; Honoraria from The International Parkinson and Movement Disorder Society and American Academy of Neurology, Royalties from Oxford University Press. Dr. Fox has received research support from Michael J Fox Foundation for Parkinson Research, NIH (Dystonia Coalition); CIHR; Parkinson Canada.