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.

• MeSH
• dvojitá slepá metoda MeSH
• fixní kombinace léků MeSH
• flekainid * škodlivé účinky   MeSH
• lidé MeSH
• modafinil * škodlivé účinky   MeSH
• Parkinsonova nemoc * farmakoterapie   MeSH
• poruchy nadměrné spavosti * etiologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

BACKGROUND: Modafinil is a psychostimulant drug prescribed mainly for treatment of narcolepsy but is used as a "smart drug" by wide populations to increase wakefulness, concentration and overall mental performance. The aim of this study was to assess potential developmental toxicity of modafinil. MATERIALS AND METHODS: Pregnant female mice were given either saline or modafinil (50 mg/kg orally) from gestational day (GD) 3 to GD 10 and then a challenge dose on the GD 17. The male offspring were treated analogously at the age of 10 weeks. Changes in the spontaneous locomotor/exploratory behaviour and anxiogenic profile in the open-field test were assessed in naive animals, after an acute and 8th modafinil dose and the challenge dose following a 7-day wash-out period. One month after completion of the behavioural study, the leukocyte phagocytosis was examined by zymosan induced and luminol-aided chemiluminiscence assay in vitro. RESULTS: The most important finding of this study was the immunosuppressing effect on leukocyte activity, hypolocomotion and increased behavioural response to modafinil-induced psychostimulation caused by prenatal exposure to the same drug. We did not detect significantly altered anxiety-related behaviour in any group disregarding the pre- and postnatal treatments. CONCLUSION: This is the first evidence of developmental toxicity of modafinil which needs to be taken into account as a potential risk factor when modafinil is administered to women who may become or are pregnant.

• MeSH
• fagocytóza účinky léků   MeSH
• gestační stáří MeSH
• leukocyty účinky léků   MeSH
• lokomoce účinky léků   MeSH
• luminiscenční měření MeSH
• luminol MeSH
• modafinil škodlivé účinky   MeSH
• modely nemocí na zvířatech * MeSH
• myši inbrední ICR MeSH
• myši MeSH
• těhotenství MeSH
• věkové faktory MeSH
• zpožděný efekt prenatální expozice * MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• dospělí MeSH
• hyperkinetická porucha * diagnóza   etiologie   terapie   MeSH
• inhibitory vychytávání adrenergních neurotransmiterů aplikace a dávkování   škodlivé účinky   MeSH
• inhibitory vychytávání dopaminu aplikace a dávkování   škodlivé účinky   MeSH
• komorbidita MeSH
• lidé MeSH
• modafinil aplikace a dávkování   škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• přehledy MeSH