Delving into the Latest Updates on Flecainide/Modafinil with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Modafinil/flecainide

Target

DAT x SCNA

Mechanism

DAT antagonists(Dopamine transporter antagonists), SCNA modulators(Sodium channel alpha subunit modulators)

Therapeutic Areas

Nervous System DiseasesEndocrinology and Metabolic DiseaseOther Diseases

Active Indication-

Inactive Indication

NarcolepsyParkinson DiseaseSleep Deprivation+ [1]

Originator Organization

Theranexus SA

Active Organization-

Inactive Organization

Theranexus SA

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC19H24F6N2O5

InChIKeyRKXNZRPQSOPPRN-UHFFFAOYSA-N

CAS Registry54143-56-5

View All Structures (2)

AbstractBackgroundExcessive 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.ObjectiveThe aim of this study is to evaluate the safety and efficacy of THN102 in PD patients with EDS.MethodsThe 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.ResultsBoth 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.ConclusionsTHN102 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

01 Nov 2019·British Journal of Clinical PharmacologyQ2 · MEDICINE

Efficacy of THN102 (a combination of modafinil and flecainide) on vigilance and cognition during 40‐hour total sleep deprivation in healthy subjects: Glial connexins as a therapeutic target

Q2 · MEDICINE

Article

Author: Dubourdieu, Dominique ; Mouthon, Franck ; Dauvilliers, Yves ; Gomez‐Merino, Danielle ; Arnal, Pierrick ; Chennaoui, Mounir ; Brunner‐Ferber, Francoise ; Sauvet, Fabien ; Rein, Werner ; Erblang, Mégane ; Van Beers, Pascal ; Bougard, Clément ; Lefloch, Hervé ; Rabat, Arnaud ; Leger, Damien ; Charvériat, Mathieu ; Drogou, Catherine ; Bourrrilhon, Cyprien ; Guillard, Mathias

AimsTHN102 is a novel combination of modafinil and low‐dose flecainide, targeting glial connexin activity to modulate modafinil effects. We investigated THN102 efficacy compared to modafinil and to placebo on vigilance and cognitive function during 40‐hour total sleep deprivation (TSD).MethodsTwenty healthy men participated in a double‐blind, randomized, incomplete‐block 3‐period cross‐over trial with 5 treatments (n = 12 per group): placebo (PBO), modafinil 100 mg (MOD100), THN102 100/1, 100/3, 100/9 (modafinil 100 mg and flecainide 1, 3 or 9 mg). Each period included a baseline day and a TSD day with treatments administered 3 times (01:00, 09:00 and 19:00). Reaction time in psychomotor vigilance test, subjective somnolence and vital signs were assessed before and during treatment. Working memory (2‐Back) and executive processes (Go/noGo for vigilance and inhibition, Wisconsin card sorting task for mental flexibility, and Tower of London test for planning) were evaluated at 16:30.ResultsAt 5 hours postdose−1 (after 23 hours TSD, primary endpoint), THN102 100/1 resulted in statistically higher psychomotor vigilance test speed vs MOD100 (3.97 ± 0.09 vs 3.74 ± 0.14, P < .05). No increase in effect was observed with higher flecainide doses in combinations. Most THN102 doses vs MOD100 also improved the number of correct responses in 2‐Back and Go errors in Go/noGo (P < .05 for all doses), and perseverative responses in Wisconsin card sorting task (for 100/1 and 100/9). No impact on cardiac conduction was noted with THN102, and safety was similar to MOD100.ConclusionsTHN102 seems more efficient than modafinil on vigilance, working memory and executive functions, opening new perspectives in management of hypersomnolence disorders.

01 Jul 2018·International Journal of NeuropsychopharmacologyQ2 · MEDICINE

Cortico-Amygdala-Striatal Activation by Modafinil/Flecainide Combination

Q2 · MEDICINE

ArticleOA

Author: Dauvilliers, Yves ; Lin, Jian-Sheng ; Vodovar, Dominique ; Mouthon, Franck ; Charvériat, Mathieu ; Duchêne, Adeline ; Leroy, Claire ; Wimberley, Catriona ; Tournier, Nicolas ; Pottier, Géraldine ; Giaume, Christian

BackgroundModafinil, a nonamphetaminic wake-promoting compound, is prescribed as first line therapy in narcolepsy, an invalidating disorder characterized by excessive daytime sleepiness and cataplexy. Although its mode of action remains incompletely known, recent studies indicated that modafinil modulates astroglial connexin-based gap junctional communication as administration of a low dose of flecainide, an astroglial connexin inhibitor, enhanced the wake-promoting and procognitive activity of modafinil in rodents and healthy volunteers. The aim of this study is to investigate changes in glucose cerebral metabolism in rodents, induced by the combination of modafinil+flecainide low dose (called THN102).MethodsThe impact of THN102 on brain glucose metabolism was noninvasively investigated using 18F-2-fluoro-2-deoxy-D-glucose Positron Emission Tomography imaging in Sprague-Dawley male rats. Animals were injected with vehicle, flecainide, modafinil, or THN102 and further injected with 18F-2-fluoro-2-deoxy-D-glucose followed by 60-minute Positron Emission Tomography acquisition. 18F-2-fluoro-2-deoxy-D-glucose Positron Emission Tomography images were coregistered to a rat brain template and normalized from the total brain Positron Emission Tomography signal. Voxel-to-voxel analysis was performed using SPM8 software. Comparison of brain glucose metabolism between groups was then performed.ResultsTHN102 significantly increased regional brain glucose metabolism as it resulted in large clusters of 18F-2-fluoro-2-deoxy-D-glucose uptake localized in the cortex, striatum, and amygdala compared with control or drugs administered alone. These regions, highly involved in the regulation of sleep-wake cycle, emotions, and cognitive functions were hence quantitatively modulated by THN102.ConclusionData presented here provide the first evidence of a regional brain activation induced by THN102, currently being tested in a phase II clinical trial in narcoleptic patients.

100 Deals associated with Flecainide/Modafinil

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Parkinson Disease	Phase 2	CZ	Theranexus SA	12 Jul 2018
Parkinson Disease	Phase 2	US	Theranexus SA	12 Jul 2018
Parkinson Disease	Phase 2	FR	Theranexus SA	12 Jul 2018
Parkinson Disease	Phase 2	DE	Theranexus SA	12 Jul 2018
Parkinson Disease	Phase 2	HU	Theranexus SA	12 Jul 2018
Narcolepsy	Phase 2	BE	Theranexus SA	01 Sep 2016
Narcolepsy	Phase 2	FR	Theranexus SA	01 Sep 2016
Sleepiness	Phase 2	BE	Theranexus SA	01 Sep 2016
Sleepiness	Phase 2	FR	Theranexus SA	01 Sep 2016
Sleep Deprivation	Phase 2	-	Theranexus SA	01 Sep 2015

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03624920 (CTgov)	Phase 2	Narcolepsy \| Parkinson Disease	77	Placebo+THN102 (Placebo)	ixqldzjrov(ergogmntmk) = pqvchobpck siyckeinue (hartyokhed, qxkxjskkjz - allykvshfn) View more	-	01 Dec 2020
				THN102 (THN102 200/2)	ixqldzjrov(ergogmntmk) = zhwsnpsnsp siyckeinue (hartyokhed, vwfzeuiqoi - nosumkfzzm) View more
NCT02821715 (CTgov)	Phase 2	Narcolepsy \| Sleepiness	51	Active comparator: Modafinil + placebo (Modafinil + Placebo)	ozanjtmwdx(irowbwrequ) = osozjssher njtgyjpvgf (kumwqbbhhd, yngqzyeirt - jivgmdvnbg) View more	-	04 Sep 2020
				THN102 300/3 (THN102 300/3)	ozanjtmwdx(irowbwrequ) = dqqovyhhdu njtgyjpvgf (kumwqbbhhd, axfzgnndii - lalfbnfnhh) View more