Objective: To assess the 3-month efficacy and safety of glycopyrrolate for moderate-to-severe sialorrhea in Parkinson’s disease.

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. (1) Chronic moderate-to-severe sialorrhea leads to substantial social issues with a detrimental effect on quality of life. (2) In 2019, an MDS-sponsored evidence-based review on commercially available therapies rated Botulinum toxin type A and B as ‘clinically useful’ with an ‘Acceptable risk with specialized monitoring’. Glycopyrrolate was considered ‘efficacious’ for a 1-week treatment only (3). There is no evidence for more prolonged treatments for sialorrhea in PD.

Method: We conducted a phase II two-centre, double-blinded placebo-controlled, two-arm parallel-group superiority 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 (primary outcome measure – Radboud Oral Motor Inventory for Parkinson’s Disease/ROMP-saliva; range: 9 – 45 points) after 90 days of treatment, in patients with PD older than 30 and moderate-to-severe sialorrhea (MDS-UPDRS, item 2.2>2). We used an intention-to-treat analysis and an analysis of covariance (co-variate- baseline value of sialorrhea related-disability) for the primary outcome. A P<0.05 was deemed significant.

Results: We recruited 28 patients with PD (age: 71.1±6.9 years; disease duration: 11.4±7.2 years; ROMP-saliva: 22.7±5.4 points). At 90 days, there was a treatment difference for sialorrhea related-disability in favour of glycopyrrolate (ROMP saliva: -5.3 (95% CI: -9.55, -1.04). Dry mouth was the most common side effect (glycopyrrolate, n=6 vs. placebo, n=2) followed by constipation (glycopyrrolate, n=5 vs. placebo, n=2). There were six early terminations (glycopyrrolate, n=5).

Conclusion: The GLYCOPAR study supports the efficacy of glycopyrrolate to treat sialorrhea related-disability up to 3 months of treatment. These results inform the management of sialorrhea, a significant unmet nonmotor care need in PD. The identification of the dose associated with the best compromise between efficacy and safety is required. A phase III trial is warranted.

References: 1. Kalf JG, de Swart BJ, Borm GF, Bloem BR, Munneke M. Prevalence and definition of drooling in Parkinson’s disease: a systematic review. Journal of neurology. 2009;256(9):1391-6. 2. Hockstein NG, Samadi DS, Gendron K, Handler SD. Sialorrhea: a management challenge. Am Fam Physician. 2004;69(11):2628-34. 3. Seppi K, Ray Chaudhuri K, Coelho M, Fox SH, Katzenschlager R, Perez Lloret S, Weintraub D, Sampaio C; and the collaborators of the Parkinson’s Disease Update on Non-Motor Symptoms Study Group on behalf of the Movement Disorders Society Evidence-Based Medicine Committee.Update on treatments for nonmotor symptoms of Parkinson’s disease-an evidence-based medicine review. Mov Disord. 2019 Feb;34(2):180-198

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MDS Abstracts - https://www.mdsabstracts.org/abstract/glycopar-a-randomized-placebo-controlled-2-arm-parallel-group-superiority-phase-ii-study-of-glycopyrrolate-for-moderate-to-severe-sialorrhea-in-parkinsons-disease/