Helen Shaw

Aims: To test the long‐term efficacy, safety, and impact on quality of life (QoL) of an oral paediatric formulation of 320 μg/mL glycopyrronium in the 36‐week SALIVA (Sialanar plus orAl rehabiLitation against placebo plus oral rehabilitation for chIldren and adolescents with seVere sialorrhoeA and neurodisabilities) trial.Method: In the initial 12‐week blinded period, 87 children with neurodisabilities and severe sialorrhoea were randomized to 320 μg/mL glycopyrronium versus placebo. In the subsequent 24‐week open‐label study extension, 74 children received 320 μg/mL glycopyrronium (37 continued glycopyrronium, 37 switched from placebo).Results: The open‐label study extension population included 39 males and 35 females. The median age was 10 years 2 months (quartile 1, quartile 3: 7 years 5 months, 14 years 7 months; range: 3 years 5 months–17 years 8 months). Over 36 weeks, continued 320 μg/mL glycopyrronium resulted in a median 39‐point reduction in Drooling Impact Scale (DIS) score from baseline (quartile 1, quartile 3: −51, −21; p < 0.001), with an 81.1% response rate (DIS improvement ≥ 13.6 points) and a 70.3% good response rate (≥ 28 points). Improvements in the impact of drooling on QoL seen in the blinded period were sustained with continued glycopyrronium. Treatment‐related adverse events occurred most frequently during titration (0–4 weeks: 40.9%; 5–20 weeks: 32.4% in those who switched). Constipation was the most common adverse event.Interpretation: Long‐term treatment with 320 μg/mL glycopyrronium resulted in significant sustained improvements in drooling and QoL, with fewer adverse events after initial titration and overall good tolerability.

Aim: To investigate the efficacy, safety, and impact on quality of life (QoL) of an oral formulation of 320 μg/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 μg/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 μg/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 μg/mL glycopyrronium significantly improved drooling and reduced its impact on QoL, with good tolerability in children with neurodisabilities.What this paper adds: The formulation of 320 μg/mL glycopyrronium significantly improved Drooling Impact Scale score versus placebo at day 84. The formulation reduced the impact of drooling on the child's and family's quality of life. There were no safety or tolerability concerns with this specific formulation.

Introduction Severe sialorrhoea is a common, distressing problem in children/adolescents with neurodisabilities, which has adverse health and social consequences. The SALIVA trial is designed to evaluate the efficacy and safety of a paediatric-specific oral solution of glycopyrronium along with its impact on quality-of-life (QoL), which has been lacking from previous trials of sialorrhoea treatments. Methods and analysis A double-blind, placebo-controlled, randomised phase IV trial is ongoing in several centres across France. Eighty children aged 3–17 years with severe sialorrhoea (≥6 on the modified Teachers Drooling Scale) related to chronic neurological disorders in whom non-pharmacological standard of care has already been implemented or has failed, will be recruited. Patients will be randomised 1:1 to receive a 2 mg/5 mL solution of glycopyrronium bromide (Sialanar 320 µg/mL glycopyrronium) or placebo three times daily during a 3-month blinded period. After Day 84, participants will be invited into a 6-month, open-label study extension period, where they will all receive glycopyrronium. The primary endpoint of the double-blind period will be the change from baseline to Day 84 in the Drooling Impact Scale (DIS), a validated measure to assess sialorrhoea. A series of secondary efficacy endpoints involving change in total DIS, specific DIS items and response (DIS improvement ≥13.6 points) will be analysed in a prespecified hierarchy. QoL data will be collected from parents, caregivers and patients where possible using specific DIS questions and DISABKIDS questionnaires. Safety endpoints, including adverse events, will be assessed throughout the trial periods. Ethics and dissemination In total, 87 children have been recruited and recruitment is now complete. Final results are expected by the end of 2023. Findings will be presented at conferences and published in peer-reviewed journals. Trial registration number EudraCT 2020-005534-15.