• De CockValérie CochenVCSleep and Neurology Department, Beau Soleil Clinic and EuroMov, Digital Health in Motion, University of Montpellier, Montpellier, France. Electronic address: valerie.cochen@gmail.com., Pauline Dodet, Smaranda Leu-Semenescu, Cécile Aerts, Giovanni Castelnovo, Beatriz Abril, Sophie Drapier, Hélène Olivet, Anne-Gaëlle Corbillé, Laurène Leclair-Visonneau, Magali Sallansonnet-Froment, Marie Lebouteux, Mathieu Anheim, Elisabeth Ruppert, Nicolas Vitello, Alexandre Eusebio, Isabelle Lambert, Ana Marques, Maria Livia Fantini, David Devos, Christelle Monaca, Nicolas Benard-Serre, Sandy Lacombe, Marie Vidailhet, Isabelle Arnulf, Mohamed Doulazmi, and Emmanuel Roze.
• Sleep and Neurology Department, Beau Soleil Clinic and EuroMov, Digital Health in Motion, University of Montpellier, Montpellier, France. Electronic address: valerie.cochen@gmail.com.
• Lancet Neurol. 2022 May 1; 21 (5): 428-437.

BackgroundInsomnia is a frequent complaint of patients with Parkinson's disease, and it negatively affects quality of life. Drugs that improve both sleep and parkinsonism would be of major benefit to patients with Parkinson's disease-related insomnia. We aimed to test the safety and efficacy of subcutaneous night-time only apomorphine infusion in patients with Parkinson's disease and insomnia.MethodsWe did a randomised, multicentre, double-blind, placebo-controlled, crossover trial in 11 expert centres in Parkinson's disease and sleep centres in France. Participants aged 35-90 years with fluctuating Parkinson's disease and moderate to severe insomnia (Insomnia Severity Index score ≥15) were randomly assigned to either first receive night-time subcutaneous apomorphine (up to 5 mg/h) or matching placebo. Randomisation was done using a computer-generated plan in blocks of four, stratified by centre. This first intervention was followed by a 14-night washout period, then crossover to the other intervention. The treatment periods consisted of a 10-night titration phase followed by a 7-night fixed-dose phase. The dose was adjusted during the titration phase on the basis of a daily telephone call assessing sleep quality and treatment tolerability. The primary efficacy endpoint was the difference in Parkinson's disease sleep scale (PDSS) scores from the beginning to the end of each treatment period. Analysis was done on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, NCT02940912.FindingsBetween Jan 31, 2017, and Jan 29, 2021, 46 participants were enrolled. 25 (54%) patients were randomly assigned to receive apomorphine first and 21 (46%) patients to receive placebo first. Mean change in PDSS score was significantly greater with night-time apomorphine infusion (15·18 [SD 24·34]) compared with placebo (5·23 [21·52]; treatment effect 9·95 [95% CI 0·88-19·03]; p=0·041). Adverse events were reported in 25 (54%) participants during the apomorphine period and in 17 (37%) participants during the placebo period (p=0·16). Apomorphine was associated with more frequent dizziness than was placebo (seven [15%] vs 0; p=0·041).InterpretationSubcutaneous night-time only apomorphine infusion improved sleep disturbances according to difference on PDSS score, with an overall safety profile consistent with previous studies in Parkinson's disease. This treatment might be useful to manage sleep disturbances in patients with advanced Parkinson's disease and moderate to severe insomnia.FundingOrkyn and Aguettant Pharma.TranslationFor the French translation of the abstract see Supplementary Materials section.Copyright © 2022 Elsevier Ltd. All rights reserved.

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