Glycopyrronium 320 μg/mL in children and adolescents with severe sialorrhoea and neurodisabilities: A randomized, double-blind, placebo-controlled trial

Aim To investigate the efficacy, safety, and impact on quality of life (QoL) of an oral formulation of 320 mu g/mL glycopyrronium designed for children.Method A double-blind, placebo-controlled SALIVA (Sialanar plus orAl rehabiLitation against placebo plus oral rehabilitation for chIldren and adolescents with seVere sialorrhoeA and neurodisabilities) trial was conducted. Children (3-17 years) with neurodisabilities and severe sialorrhoea (modified Teachers Drooling Scale >= 6) were randomized to 320 mu g/mL glycopyrronium or placebo, in addition to non-pharmacological standard care.Results Of 87 participants, 44 were aged 10 years or under and 43 had cerebral palsy. The primary endpoint, change in total Drooling Impact Scale (DIS) score from baseline to day 84, was significantly greater (improved) with 320 mu g/mL glycopyrronium versus placebo (median [quartile 1, quartile 3] -29.5 [-44.5, 0] vs -1 [-16, 5]; p < 0.001), an effect also observed at day 28 (median - 25 vs -2; p < 0.01). Significant reduction in bibs/clothes used per day was seen with glycopyrronium versus placebo at day 84 (median - 2 vs 0; p < 0.01). Glycopyrronium significantly improved DIS items 9 and 10 related to the extent that drooling affects the child's and family's life (p <= 0.03). Adverse events were reported by 77.3% and 69.8% of children with glycopyrronium and placebo respectively; the most common treatment-related adverse event was constipation (20.5% and 16.3%).Interpretation The formulation of 320 mu g/mL glycopyrronium significantly improved drooling and reduced its impact on QoL, with good tolerability in children with neurodisabilities.