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Safety and Efficacy of THN102 on Sleepiness in Narcoleptic Patients

Primary Purpose

Narcolepsy

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Active comparator: Modafinil + placebo
THN102 300/3
THN102 300/27
Sponsored by
Theranexus
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Narcolepsy

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • RespiSom
  • CHU Pellegrin
  • CHU Dijon Bourgogne
  • Hôpital Raymond Poincaré
  • CHU Grenoble Alpes
  • CHRU Lilles
  • University Hospital
  • Groupe Hospitalier Pitié Salpêtrière

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Experimental

Experimental

Arm Label

Modafinil + placebo

THN102 300/3

THN102 300/27

Arm Description

3 tablets modafinil 100 mg per day and 3 capsules flecainide placebo per day for 2 weeks

3 tablets modafinil 100 mg per day and 3 capsules flecainide 1 mg per day (THN102 as 300 + 3 mg) for 2 weeks

3 tablets modafinil 100 mg per day and 3 capsules flecainide 9 mg per day(THN102 as 300 + 27 mg) for 2 weeks

Outcomes

Primary Outcome Measures

Epworth Sleepiness Scale (ESS)
Range 0 to 24, low score indicates good outcome

Secondary Outcome Measures

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
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.
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)
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)
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.
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)
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)
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)
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
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
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
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

Full Information

First Posted
June 23, 2016
Last Updated
August 18, 2020
Sponsor
Theranexus
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1. Study Identification

Unique Protocol Identification Number
NCT02821715
Brief Title
Safety and Efficacy of THN102 on Sleepiness in Narcoleptic Patients
Official Title
Safety and Efficacy of THN102 on Sleepiness in Narcoleptic Patients
Study Type
Interventional

2. Study Status

Record Verification Date
August 2020
Overall Recruitment Status
Completed
Study Start Date
September 2016 (undefined)
Primary Completion Date
December 2018 (Actual)
Study Completion Date
February 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Theranexus

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Narcolepsy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
51 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Modafinil + placebo
Arm Type
Active Comparator
Arm Description
3 tablets modafinil 100 mg per day and 3 capsules flecainide placebo per day for 2 weeks
Arm Title
THN102 300/3
Arm Type
Experimental
Arm Description
3 tablets modafinil 100 mg per day and 3 capsules flecainide 1 mg per day (THN102 as 300 + 3 mg) for 2 weeks
Arm Title
THN102 300/27
Arm Type
Experimental
Arm Description
3 tablets modafinil 100 mg per day and 3 capsules flecainide 9 mg per day(THN102 as 300 + 27 mg) for 2 weeks
Intervention Type
Drug
Intervention Name(s)
Active comparator: Modafinil + placebo
Other Intervention Name(s)
Modafinil 300 mg, Flecainide Placebo
Intervention Type
Drug
Intervention Name(s)
THN102 300/3
Other Intervention Name(s)
Modafinil 300 mg, Flecainide 3 mg
Intervention Type
Drug
Intervention Name(s)
THN102 300/27
Other Intervention Name(s)
Modafinil 300 mg, Flecainide 27 mg
Primary Outcome Measure Information:
Title
Epworth Sleepiness Scale (ESS)
Description
Range 0 to 24, low score indicates good outcome
Time Frame
14 days after the beginning of treatment period
Secondary Outcome Measure Information:
Title
14-item Fatigue Scale
Description
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
Time Frame
14 days after the beginning of treatment period
Title
Questionnaire EQ-5D (European Quality of Life EQ-5D) (Questionnaire Part)
Description
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.
Time Frame
14 days after the beginning of the screening
Title
Patient Global Impression of Change (PGI-C)
Description
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)
Time Frame
14 days after the beginning of treatment period
Title
Clinical Global Impression of Change (CGI-C) Global Impression
Description
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)
Time Frame
14 days after the end of treatment period I
Title
Beck Depression Inventory (BDI)
Description
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.
Time Frame
14 days
Title
Patient Global Impression for Severity (PGI-S) Global Score
Description
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)
Time Frame
14 days
Title
Clinical Global Impression of Change (CGI-C) Sleepiness
Description
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)
Time Frame
14 days after the end of treatment period I
Title
Clinical Global Impression of Change (CGI-C) Cataplexy
Description
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)
Time Frame
14 days after the end of treatment period I
Title
Clinical Global Impression for Severity (CGI-S) Global Score
Description
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
Time Frame
14 days after the end of treatment period I
Title
Clinical Global Impression for Severity (CGI-S) Sleepiness
Description
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
Time Frame
14 days after the end of treatment period I
Title
Clinical Global Impression for Severity (CGI-S) Cataplexy
Description
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
Time Frame
14 days after the end of treatment period I
Title
EQ-5D European Quality of Life EQ-5D (Visual Analogic Scale Part)
Description
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
Time Frame
14 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yves Dauvilliers, MD, PhD
Organizational Affiliation
CHRU Montpellier, France
Official's Role
Principal Investigator
Facility Information:
Facility Name
RespiSom
City
Erpent
Country
Belgium
Facility Name
CHU Pellegrin
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Facility Name
CHU Dijon Bourgogne
City
Dijon
Country
France
Facility Name
Hôpital Raymond Poincaré
City
Garches
ZIP/Postal Code
92380
Country
France
Facility Name
CHU Grenoble Alpes
City
Grenoble
Country
France
Facility Name
CHRU Lilles
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
University Hospital
City
Montpellier
ZIP/Postal Code
34090
Country
France
Facility Name
Groupe Hospitalier Pitié Salpêtrière
City
Paris
ZIP/Postal Code
75013
Country
France

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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Safety and Efficacy of THN102 on Sleepiness in Narcoleptic Patients

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