Safety and Efficacy of THN102 on Sleepiness in Narcoleptic Patients

This Phase 2 study is a 8-site, double-blind, randomised, placebo-controlled, 3-way cross-over trial, involving 3 treatments with Modafinil 300 mg or the combination drug THN102 (Modafinil/Flecainide 300 /3 mg, Modafinil/Flecainide 300 /27 mg).

Study Overview

• Status: Completed
• Conditions: Narcolepsy
• Intervention / Treatment: Drug: Active comparator: Modafinil + placebo; Drug: THN102 300/3; Drug: THN102 300/27

Detailed Description

The 3 double blind periods (2-week) follow a stabilisation period for modafinil at 300 mg/day (open, 2-week) and are followed by a one-week washout period with the same modafinil dose.

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Erpent, Belgium
    • Respisom
• France
  • Bordeaux, France, 33076
    • CHU Pellegrin
  • Dijon, France
    • Chu Dijon Bourgogne
  • Garches, France, 92380
    • Hopital Raymond Poincare
  • Grenoble, France
    • Chu Grenoble Alpes
  • Lille, France, 59037
    • CHRU Lilles
  • Montpellier, France, 34090
    • University Hospital
  • Paris, France, 75013
    • Groupe Hospitalier Pitié Salpêtrière

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Main inclusion Criteria:

• Patients with a diagnosis of narcolepsy type 1 (i.e. with cataplexy) or type 2 (without cataplexy) according to the International Classification of Sleep Disorders (ICSD-3) criteria.
• Body mass index >18 kg/m2 and <35 kg/m2.
• Patients treated with modafinil at stable dosage for at least 2 months and still complaining of excessive daily somnolence (EDS) despite the treatment
• Epworth Sleepiness Scale (ESS) score should be ≥ 14/24 during the baseline period.

Main exclusion Criteria:

• Patients with an untreated sleep apnea syndrome (respiratory disorder index > 30/h) or who have any other cause of daytime sleepiness as assessed on patient history.
• Psychiatric and neurological disorders, other than narcolepsy/cataplexy, such as Parkinson's disease, Alzheimer's disease, Huntington's Chorea, multiple sclerosis, moderate or severe psychosis or dementia, bipolar illness, epilepsy, severe clinical anxiety or depression, Beck Depression Inventory ≥ 21 or with suicidal risk (if item > 0), or other problem that in the investigator's opinion would preclude the patient's participation and completion of this trial or comprise reliable representation of subjective symptoms.
• Contraindication to flecainide

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Modafinil + placebo; 3 tablets modafinil 100 mg per day and 3 capsules flecainide placebo per day for 2 weeks	Drug: Active comparator: Modafinil + placebo; Other Names: Modafinil 300 mg; Flecainide Placebo
Experimental: THN102 300/3; 3 tablets modafinil 100 mg per day and 3 capsules flecainide 1 mg per day (THN102 as 300 + 3 mg) for 2 weeks	Drug: THN102 300/3; Other Names: Modafinil 300 mg; Flecainide 3 mg
Experimental: THN102 300/27; 3 tablets modafinil 100 mg per day and 3 capsules flecainide 9 mg per day(THN102 as 300 + 27 mg) for 2 weeks	Drug: THN102 300/27; Other Names: Modafinil 300 mg; Flecainide 27 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Epworth Sleepiness Scale (ESS)	Range 0 to 24, low score indicates good outcome	14 days after the beginning of treatment period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
14-item Fatigue Scale	Fatigue scale is a rating scale completed by the participants at each visit starting from baseline to last visit; 14 questions to be ticked off by "yes" or "No" by the patient. 0 : No fatigue 14 : worst fatigue condition	14 days after the beginning of treatment period
Questionnaire EQ-5D (European Quality of Life EQ-5D) (Questionnaire Part)	EQ-5D is a quality of life questionnaire filled in by the participants from screening to the last visit (all visits). The EQ-5D assesses the status on the day of visit and not over the past week. It has two parts: The first part is a descriptive system that assesses five distinct health states/dimensions: Mobility (MO), Self-care (SC), Usual activities (UA), Pain/discomfort, Anxiety/depression (AD). A higher score signifies a higher number of symptoms present. The second part is a 100 mm VAS (EQ-VAS). An increase in VAS indicates an improvement in health state.	14 days after the beginning of the screening
Patient Global Impression of Change (PGI-C)	PGI-C is a scale completed by the participants starting from screening to last Last visit (all the visits). Participants have to chose 1 condition among 7 : Very much improved/ Much improved/ Minimally improved/ No change/ Minimally worse/ Much worse/ Very much worse. 1 is the best score (very much improved) 7 is the worse score (very much worse)	14 days after the beginning of treatment period
Clinical Global Impression of Change (CGI-C) Global Impression	CGI-C (change from baseline) is a scale completed by the investigator at V3, V4 , V5 and V6 for global impression the investigator or his/her designee has to score 3 items : global impression/ sleepiness and Cataplexy. For each item the investigator or his/her designee has to chose 1 condition among 7 : Very much improved/ Much improved/ Minimally improved/ No change/ Minimally worse/ Much worse/ Very much worse. 1 is the best score (very much improved) 7 is the worse score (very much worse)	14 days after the end of treatment period I
Beck Depression Inventory (BDI)	Beck Depression Inventory (BDI) evaluation for depressive symptoms (including suicidal thoughts). The scale is completed by the participants from baseline, to last visit (all except screening visit). The questionnaire contains 21 items. Each must be scored from 0 to 3, minimum score = 0, maximum score = 63. A high score indicates increased severity of depression.	14 days
Patient Global Impression for Severity (PGI-S) Global Score	PGI-S us a scale filled by the participant from screening to last visit (all the visits) Participants have to chose 1 condition among 7 : 1 Normal-Not ill at all/ 2 borderline ill/ 3 mildly ill/ 4 moderately ill/ 5 markedly ill/ 6 severely ill/ 7 among the most extremely ill patient 1 is the best score (very much improved) 7 is the worse score (very much worse)	14 days
Clinical Global Impression of Change (CGI-C) Sleepiness	CGI-C (change from baseline) is a scale completed by the investigator at V3, V4 , V5 and V6 for sleepiness the investigator or his/her designee has to score 3 items : global impression/ sleepiness and Cataplexy. For each item the investigator or his/her designee has to chose 1 condition among 7 : Very much improved/ Much improved/ Minimally improved/ No change/ Minimally worse/ Much worse/ Very much worse. 1 is the best score (very much improved) 7 is the worse score (very much worse)	14 days after the end of treatment period I
Clinical Global Impression of Change (CGI-C) Cataplexy	CGI-C (change from baseline) is a scale completed by the investigator at V3, V4 , V5 and V6 for Cataplexy the investigator or his/her designee has to score 3 items : global impression/ sleepiness and Cataplexy. For each item the investigator or his/her designee has to chose 1 condition among 7 : Very much improved/ Much improved/ Minimally improved/ No change/ Minimally worse/ Much worse/ Very much worse. 1 is the best score (very much improved) 7 is the worse score (very much worse)	14 days after the end of treatment period I
Clinical Global Impression for Severity (CGI-S) Global Score	CGI-S is a scale completed by the investigator at each visit : Item global impression CGI-S us a scale filled by the Investigator or his/her designee from screening to last visit (all the visits) Investigators have to chose 1 condition among 7 : 1 normal-not ill at all/ 2 borderline ill/ 3 mildly ill/ 4 moderately ill/ 5 markedly ill/ 6 severely ill/ 7 among hte most extremely ill patient 1 is the best score (very much improved) 7 is the worse score (very much worse) CGI-S scale explores 3 items : Global impression/ Sleepiness/ Cataplexy	14 days after the end of treatment period I
Clinical Global Impression for Severity (CGI-S) Sleepiness	CGI-S is a scale completed by the investigator at each visit for Sleepiness CGI-S us a scale filled by the Investigator or his/her designee from screening to last visit (all the visits) Investigators have to chose 1 condition among 7 : 1 Normal-Not ill at all/ 2 Borderline ill/ 3 Mildly ill/ 4 Moderately ill/ 5 Markedly ill/ 6 severely ill/ 7 Among the most extremely ill patient 1 is the best score (very much improved) 7 is the worse score (very much worse) CGI-S scale explores 3 items : Global impression/ Sleepiness/ Cataplexy	14 days after the end of treatment period I
Clinical Global Impression for Severity (CGI-S) Cataplexy	CGI-S is a scale completed by the investigator at each visit for Cataplexy CGI-S us a scale filled by the Investigator or his/her designee from screening to last visit (all the visits) Investigators have to chose 1 condition among 7 : 1 Normal-Not ill at all/ 2 Borderline ill/ 3 Mildly ill/ 4 Moderately ill/ 5 Markedly ill/ 6 severely ill/ 7 Among the most extremely ill patient 1 is the best score (very much improved) 7 is the worse score (very much worse) CGI-S scale explores 3 items : Global impression/ Sleepiness/ Cataplexy	14 days after the end of treatment period I
EQ-5D European Quality of Life EQ-5D (Visual Analogic Scale Part)	EQ-5D is a quality of life questionnaire filled in by the participants from screening to the last visit (all visits). The EQ-5D is a questionnaire assessing the quality of life of the patient. It has two parts: The first part is a descriptive system that assesses five distinct health states/dimensions: Mobility (MO), Self-care (SC), Usual activities (UA), Pain/discomfort, Anxiety/depression (AD). A higher score signifies a higher number of symptoms present. The second part is a 100 mm Visual analogic scale (EQ-VAS). An higher score in VAS indicates a better health state. The questionnaire is assessed at baseline and all subsequent visits	14 days

Collaborators and Investigators

• Sponsor: Theranexus
• Investigators: Principal Investigator: Yves Dauvilliers, MD, PhD, CHRU Montpellier, France

Study record dates

Study Major Dates

• Study Start: September 1, 2016
• Primary Completion (Actual): December 1, 2018
• Study Completion (Actual): February 1, 2019

Study Registration Dates

• First Submitted: June 23, 2016
• First Submitted That Met QC Criteria: June 29, 2016
• First Posted (Estimate): July 1, 2016

Study Record Updates

• Last Update Posted (Actual): September 4, 2020
• Last Update Submitted That Met QC Criteria: August 18, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Disorders of Excessive Somnolence; Sleepiness; Narcolepsy; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Membrane Transport Modulators; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Central Nervous System Stimulants; Wakefulness-Promoting Agents; Flecainide; Modafinil
• Other Study ID Numbers: THN102-201; 2015-005035-41 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided