SAFETY AND EFFICACY OF THN102 ON SLEEPINESS IN NARCOLEPTIC PATIENTS

Phase 1

Conditions: This Proof-of-Concept, Phase IIa trial with THN102 should collect a sufficient body of information to assess efficacy and safety profile of THN102 versus modafinil alone in patient with a diagnosis of narcolepsy type 1 (i.e. with cataplexy) or type 2 (without cataplexy).
MedDRA version: 20.0Level: PTClassification code 10028713Term: NarcolepsySystem Organ Class: 10029205 - Nervous system disorders
MedDRA version: 20.0Level: LLTClassification code 10028715Term: Narcolepsy with cataplexySystem Organ Class: 10029205 - Nervous system disorders
MedDRA version: 20.0Level: LLTClassification code 10007738Term: Cataplexy and narcolepsySystem Organ Class: 10029205 - Nervous system disorders
Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Registration Number: EUCTR2015-005035-41-BE

Lead Sponsor: Theranexus SA

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 4

Inclusion Criteria

1.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 (see Appendix A for criteria).
2.The patient is willing and able to fulfill study restrictions and to attend regularly scheduled clinic visits as specified in this protocol, and has signed the informed consent prior to study start.
3.Males or females, aged between 18 and 65 year-old.
4.Body mass index >18 kg/m2 and <35 kg/m2.
5.Patients treated with modafinil at stable dosage for at least 2 months and still complaining of excessive daily somnolence (EDS) despite the treatment
6.Epworth Sleepiness Scale (ESS) score should be = 14/24 during the baseline period.
7.Patients with cataplexy are permitted to remain on their anticataplectic medications at stable doses (mainly sodium oxybate or venlafaxine). The authorized anticataplectic treatment should have been administered for at least 2 months prior to entry in the trial and the doses should not be changed throughout the trial.
8.Patients should have a transthoracic Doppler echocardiography considered as normal (left ventricular ejection fraction >55%, no significant morphological and/or no physiological anomaly, even if not symptomatic).
9.Women of childbearing potential (not surgically sterile or 2 years postmenopausal), must use a medically accepted method of contraception, and must continue one method for the duration of the study (and for 30 days after participation in the study). Acceptable methods of contraception include: abstinence, barrier method with spermicide, steroidal contraceptive (oral, transdermal, implanted, and injected) in conjunction with a barrier method, or intrauterine device (IUD).
10.Informed consent must be obtained for all subjects before enrollment in the study (including specific request for HIV serology and hepatitis as well as for urine screen for drug).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 48
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 48

Exclusion Criteria

1.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.
2.Patients working in an occupation requiring variable shift work or routine night shifts.
3.Patients with suicidal ideations or that has tried to commit suicide in the past 6 months.
4.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, BDI = 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.
5.Patients currently under one of the following medications (CNS indication):
a. Neuroleptic, anxiolytic, anticonvulsant, antiemetic (excepted domperidone), opioid, benzodiazepine (zolpidem/ zopiclone however authorized), psychostimulants (except modafinil).
b. Antidepressants (selective serotonin reuptake inhibitor or modulators, tri- and tetracyclic antidepressants, monoamine oxydase inhibitors) may be given to patients with mild or moderate unipolar depression providing the treatment is maintained at stable dose for at least 6 weeks, is anticipated to remain stable during the study, is well tolerated and devoid of orthostatic hypotension and QTc prolongation as documented at Visit 2 (baseline).
6.Current or recent (within one year) history of a substance abuse or dependence disorder including alcohol abuse as defined in Diagnostic and Statistical Manual of Mental Disorders (DSM-IV).
7.Other active clinically significant illness, including unstable cardiovascular, or neoplasic pathology which could interfere with the study conduct or counter-indicate the study treatments or place the patient at risk during the trial or compromise the study participation.
8.Contraindication to flecainide (2nd or 3rd grade atrioventricular block, bifascicular block, complete left bundle branch block, sick sinus syndrome and associated pathologies (such as alternating bradycardia-tachycardia), ventricular arrhythmias if considered as risk, cardiac insufficiency, documented Brugada syndrome, cardiogenic shock, recent or previous myocardial infarction).
9. Patients currently treated or planned to be treated with anti-arrhythmic drugs class I or with compounds eliciting bradycardia
10.Concomitant therapy which could elicit drug-drug interactions with flecainide as per SmPC, thus increasing or decreasing plasma concentrations
11.Patients with a known history of long QTc syndrome (e.g. syncope or arrhythmia) or presenting any significant serious abnormality of the ECG (e.g. recent myocardial infarction), or QTcf interval higher than 450 ms (electrocardiogram Fredericia’s corrected QT interval).
12.Patients with Severe Hepatic or Renal Impairment, or with any other significant abnormality in the physical examination or clinical laboratory results.
13.Known hypersensitivity to the tested treatment including active substances and excipients for modafinil SmPC and excipients for flecainide capsules (Section 5.1.1)
14.Women of childbearing potential who intend to be pregnant during the next few months.
15.Patients without any medical care insurance, or protected by the law (curatelle/tutelle).
16.Patients participating

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine the superiority of THN102 (combination modafinil and flecainide acetate) vs modafinil for improving the residual daytime sleepiness assessed by Epworth Sleepiness Scale (ESS) in patients with narcolepsy treated by modafinil;Secondary Objective: • To quantify the added value of THN102 (modafinil/flecainide acetate combination) for both daily doses (300/27 mg and 300/9 mg) vs modafinil (300/0 mg) for improving cataplexy, sleep paralysis, fatigue, hallucinations, and quality of life <br>• To determine the dose response profile of THN102 vs. modafinil on efficacy parameters<br>• To assess the safety profile of THN102 doses vs. modafinil<br>• To determine the plasma levels of modafinil and flecainide at steady state<br>;Primary end point(s): The primary endpoint is the mean Epworth Sleepiness Scale (ESS) total score at the end of each treatment period;Timepoint(s) of evaluation of this end point: ESS done at each visit: pre-study, V 1 to V6

Secondary Outcome Measures

Name	Time	Method

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