THN 102 for Excessive Daytime Sleepiness Associated with Parkinson's Disease: A Phase 2a Trial

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; THN102-202 Study Investigators

Collaborators, Affiliations

Affiliations

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.

PMID: 34709684
DOI: 10.1002/mds.28840

Clinical Trial

THN 102 for Excessive Daytime Sleepiness Associated with Parkinson's Disease: A Phase 2a Trial

Jean-Christophe Corvol et al. Mov Disord. 2022 Feb.

. 2022 Feb;37(2):410-415.

doi: 10.1002/mds.28840. Epub 2021 Oct 28.

Authors

Affiliations

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.

PMID: 34709684
DOI: 10.1002/mds.28840

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. © 2021 International Parkinson and Movement Disorder Society.

Keywords: Parkinson's disease; sleepiness; clinical trial; modafinil; flecainide.

PubMed Disclaimer

References

1. Chahine LM, Amara AW, Videnovic A. A systematic review of the literature on disorders of sleep and wakefulness in Parkinson's disease from 2005-2015. Sleep Med Rev 2017;35:33-50.
1. Chaudhuri KR, Prieto-Jurcynska C, Naidu Y, et al. The nondeclaration of nonmotor symptoms of Parkinson's disease to health care professionals: an international study using the non-motor symptoms questionnaire. Mov Disord 2010;25:697-701.
1. Gallagher DA, Lees AJ, Schrag A. What are the most important nonmotor symptoms in patients with Parkinson's disease and are we missing them? Mov Disord 2010;25:2493-2500.
1. Spindler M, Gooneratne NS, Siderowf A, Duda JE, Cantoe C, Dahodwala N. Daytime sleepiness is associated with falls in Parkinson's disease. J Parkinsons Dis 2013;3:387-391.
1. Ghorayeb I, Loundou A, Auquier P, Dauvilliers Y, Bioulac B, Tison F. A nationwide survey of excessive daytime sleepiness in Parkinson's disease in France. Mov Disord 2007;22:1567-1572.

Publication types

Actions
Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions

LinkOut - more resources

Full Text Sources
- Ovid Technologies, Inc.
- Wiley
Medical
- MedlinePlus Health Information

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

THN 102 for Excessive Daytime Sleepiness Associated with Parkinson's Disease: A Phase 2a Trial

Collaborators

Affiliations

THN 102 for Excessive Daytime Sleepiness Associated with Parkinson's Disease: A Phase 2a Trial

Authors

Collaborators

Affiliations

Abstract

References

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Medical