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

Abstract

Trial registration: ClinicalTrials.gov NCT03182413.

Keywords: executive function; flecainide; modafinil; psychomotor vigilance task; safety; sleep deprivation; sustained attention; working memory.

Conflict of interest statement

This study has been funded by the Armaments Procurement Agency (Direction Générale de l'Armement, DGA, program RAPID MODEFI, French Ministry of Defense). F.M., W.R. and M.Cha. are full time employees of Theranexus, F.B. is a consultant to Theranexus. D.L. received funding or has been main investigator in studies sponsored by Merck, Vanda, Actelion, Vitalaire and Jazz. Y.D. is consultant for Theranexus, UCB Pharma, JAZZ, Bioprojet, Flamel, NLS‐pharma and Theranexus. Other authors have no competing interests to declare.

Figures

Figure 1

Trial design. Treatments were composed of placebo (PBO, placebo_modafinil and placebo_flecainide), modafinil 100 mg with placebo_flecainide (MOD100) or with flecainide 1, 3 or 9 mg (THN102 100/1, THN102 100/3, THN102 100/9)

Figure 2

Reaction time (RT, 1/RT * 1000) in the PVT test at each time‐point for the 3 doses THN102 (100/1, 100/3, and 100/9), modafinil alone (MOD100), and placebo (PBO) (A) and area under the curve between 0–9 hours and 0–20 hours post‐treatment (B). Values are mean ± standard error. 100/1, 100/3, 100/9: combination of 100 mg modafinil with 1, 3 and 9 mg flecainide, respectively. PVT, psychomotor vigilance test. * THN102 100/1 vs MOD100 (P < .05), $ THN102 100/1 vs PBO (P < .05) and # MOD100 vs PBO (P < .05). Graphs in (A) are displaced slightly so that they are not graphically overlapping

Figure 3

Number of correct responses in the 2‐Back working memory test for the 3 doses THN102 (100/1, 100/3 and 100/9), modafinil alone (MOD100), and placebo (PBO) * THN102 100/1, 100/3 and 100/9 vs MOD100 (P < .05), $ THN102 100/1, 100/3 and 100/9 vs PBO (P < .05), ns nonsignificant difference with placebo

Figure 4

Variation (% baseline) in perseverative errors (A) and responses (B; flexibility) in the WCST test, in Go (C; inhibition) and noGo (D) errors in the Go/noGo test, and score (E) and pickup time (F; planning) in the ToL test for the 3 doses THN102 (100/1, 100/3, and 100/9), modafinil alone (MOD100), and placebo (PBO). WCST, Wisconsin card sorting test; ToL, Tower of London. * THN102 100/1, 100/3 and 100/9 vs MOD100 (P < .05), $ THN102 100/1, 100/3 and 100/9 vs PBO (P < .05)