Safety and Efficacy of THN102 on Sleepiness in Narcoleptic Patients

Narcolepsy Clinical Trial

Official title:

Safety and Efficacy of THN102 on Sleepiness in Narcoleptic Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02821715
• Other study ID #: THN102-201
• Secondary ID: 2015-005035-41
• Status: Completed
• Phase: Phase 2
• Start date: September 2016
• Est. completion date: February 2019

Study information

• Verified date: August 2020
• Source: Theranexus
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 51
• Est. completion date: February 2019
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Narcolepsy
• Sleepiness

Intervention

Drug:
• Active comparator: Modafinil + placebo

• THN102 300/3

• THN102 300/27

Locations

Country	Name	City	State
Belgium	RespiSom	Erpent
France	CHU Pellegrin	Bordeaux
France	CHU Dijon Bourgogne	Dijon
France	Hôpital Raymond Poincaré	Garches
France	CHU Grenoble Alpes	Grenoble
France	CHRU Lilles	Lille
France	University Hospital	Montpellier
France	Groupe Hospitalier Pitié Salpêtrière	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Theranexus

Countries where clinical trial is conducted

Belgium,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Epworth Sleepiness Scale (ESS)	Range 0 to 24, low score indicates good outcome	14 days after the beginning of treatment period
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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