Safety and Efficacy of THN102 on Sleepiness in Narcoleptic Patients

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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Safety and Efficacy of THN102 on Sleepiness in Narcoleptic Patients

Conditions
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Narcolepsy

Intervention / Treatment
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* Drug: Active comparator: Modafinil + placebo
* Drug: THN102 300/3
* Drug: THN102 300/27


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Modafinil + placebo<br>3 tablets modafinil 100 mg per day and 3 capsules flecainide placebo per day for 2 weeks | Drug: Active comparator: Modafinil + placebo<br> <br> * Other names: Flecainide Placebo;|
| Experimental: THN102 300/3<br>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<br> <br> * Other names: Flecainide 3 mg;|
| Experimental: THN102 300/27<br>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<br> <br> * Other names: Flecainide 27 mg;|

What is the study measuring?
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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 |