Jean-Christophe Corvol1, Jean-Philippe Azulay2, Björn Bosse3, Yves Dauvilliers4, Luc Defebvre5, Fabian Klostermann6, Norbert Kovacs7, David Maltête8, William G Ondo9, Rajesh Pahwa10, Werner Rein11, Stéphane Thobois12, Martin Valis13, Aleksandar Videnovic14, Olivier Rascol15. 1. Department of Neurology, Centre d'Investigation Clinique Neurosciences, NS-PARK/FCRIN Network, Sorbonne Université, Assistance Publique Hôpitaux de Paris, Paris Brain Institute-ICM, INSERM, CNRS, Hôpital Pitié-Salpêtrière, Paris, France. 2. Department of Neurology and Movement Disorders, La Timone Hospital, Assistance Publique-Hôpitaux de Marseille, NS-PARK/FCRIN Network, Marseille, France. 3. Scope International, Mannheim, Germany. 4. Sleep-Wake Disorders Center, Department of Neurology, Gui-de-Chauliac Hospital, CHU Montpellier, University of Montpellier, Montpellier, France. 5. Department of Neurology and Movement Disorders, Lille University Medical Center, NS-PARK/FCRIN Network, Lille, France. 6. Department of Neurology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany. 7. Department of Neurology, Medical School University of Pecs, Pecs, Hungary. 8. Department of Neurology, Rouen University Hospital and University of Rouen, NS-PARK/FCRIN Network, Rouen, France. 9. Movement Disorders-Methodist Neurological Institute, Weill Cornel Medical School, Houston, Texas, USA. 10. Movement Disorders Division, University of Kansas Medical Center, Kansas City, Kansas, USA. 11. Theranexus SA, Lyon, France. 12. Department of Neurology C, Pierre-Wertheimer Neurological Hospital, Hospices Civils de Lyon, NS-PARK/FCRIN Network, Univ Lyon, CNRS, Institut des Sciences Cognitives Marc Jeannerod, Bron, France. 13. Department of Neurology, Charles University, Faculty of Medicine and University Hospital, Hradec Kralove, Czechia. 14. Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA. 15. Departments of Neurology and Clinical Pharmacology, Centre of Clinique Investigations, NS-Park/FCRIN Network, Centre of Excellence for Neurodegenerative Disorders (COEN) of Toulouse, CHU de Toulouse, Toulouse 3 University, NS-PARK/FCRIN Network, Toulouse, France.
Abstract
BACKGROUND: Excessive daytime sleepiness (EDS) is a frequent and disabling symptom of Parkinson's disease (PD) without approved treatment. THN102 is a novel combination drug of modafinil and low-dose flecainide. OBJECTIVE: The aim of this study is to evaluate the safety and efficacy of THN102 in PD patients with EDS. METHODS: The method involved a randomized, double-blind, placebo-controlled, crossover trial testing two doses of THN102 (200 mg/d modafinil with 2 mg/d [200/2] or 18 mg/d flecainide [200/18]) versus placebo; 75 patients were exposed to treatment. The primary endpoint was safety. The primary efficacy outcome was the change in Epworth Sleepiness Scale (ESS) score. RESULTS: Both doses of THN102 were well tolerated. ESS significantly improved with THN102 200/2 (least square means vs. placebo [95% confidence interval, CI]: -1.4 [-2.49; -0.31], P = 0.012) but did not change significantly with the 200/18 dosage. CONCLUSIONS: THN102 was well tolerated and showed a signal of efficacy at the 200/2 dose, supporting further development for the treatment of EDS in PD.
BACKGROUND: Excessive daytime sleepiness (EDS) is a frequent and disabling symptom of Parkinson's disease (PD) without approved treatment. THN102 is a novel combination drug of modafinil and low-dose flecainide. OBJECTIVE: The aim of this study is to evaluate the safety and efficacy of THN102 in PD patients with EDS. METHODS: The method involved a randomized, double-blind, placebo-controlled, crossover trial testing two doses of THN102 (200 mg/d modafinil with 2 mg/d [200/2] or 18 mg/d flecainide [200/18]) versus placebo; 75 patients were exposed to treatment. The primary endpoint was safety. The primary efficacy outcome was the change in Epworth Sleepiness Scale (ESS) score. RESULTS: Both doses of THN102 were well tolerated. ESS significantly improved with THN102 200/2 (least square means vs. placebo [95% confidence interval, CI]: -1.4 [-2.49; -0.31], P = 0.012) but did not change significantly with the 200/18 dosage. CONCLUSIONS: THN102 was well tolerated and showed a signal of efficacy at the 200/2 dose, supporting further development for the treatment of EDS in PD.