Safety and efficacy study of two THN102 doses in subjects with excessive daytime sleepiness associated with Parkinson’s disease.

• Register: EUCTR
• Last refreshed on: 26 March 2024
• Main ID: EUCTR2017-004475-31-HU
• Date of registration: 09/02/2018
• Prospective Registration: Yes
• Primary sponsor: Theranexus S.A.
• Public title: Safety and efficacy study of two THN102 doses in subjects with excessive daytime sleepiness associated with Parkinson’s disease.
• Scientific title: Randomised, double-blind, placebo-controlled, complete 3-way cross-over phase IIa trial to investigate safety and efficacy of two THN102 doses in subjects with excessive daytime sleepiness associated with Parkinson’s disease
• Date of first enrolment: 17/04/2018
• Target sample size: 60
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-004475-31
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: yes Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Czech Republic, France, Germany, Hungary, United States

Contacts

• Name: Damien Bouvier
• Affiliation: Theranexus S.A.

• Name: Damien Bouvier
• Affiliation: Theranexus S.A.

Key inclusion & exclusion criteria

Inclusion criteria:
Inclusion criteria:
1. Subjects with a diagnosis of idiopathic Parkinson’s disease as defined by the Movement Disorders Society (MDS).
2. Subjects with Hoehn and Yahr scale score = 4.
3. Males or females, aged between 18 and 75 years.
4. Body mass index > 18 kg/m2 and < 30 kg/m2.
5. Subjects should have a complaint of daytime sleepiness impacting their quality of life and/or daytime functioning (e.g. falling asleep while reading or watching TV, while eating or talking with other people).
6. Epworth Sleepiness Scale (ESS) score = 14.
7. Women of childbearing potential (not surgically sterile or < 2 years postmenopausal), must use a medically accepted method of contraception, and must continue for the duration of the trial (and for 2 months after participation in the trial). Acceptable methods of contraception include barrier method with spermicide, steroidal contraceptive (oral, transdermal, implanted, and injected) in conjunction with a barrier method, intrauterine device (IUD), or true abstinence, i.e. when this is in line with the preferred and usual lifestyle of the subject (periodic abstinence, such as calendar, ovulation, sympto-thermal, post-ovulation methods, and withdrawal are not acceptable methods of contraception).
8. Subjects willing and able to follow trial procedures (including to swallow IMP capsules) and to regularly attend scheduled clinic visits as specified in the protocol, and who have signed the informed consent prior to any screening procedure.
All above-mentioned inclusion criteria will be checked at VS1.
At VR the following inclusion criteria will be re-checked: 5, 6, 7, 8.
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 45
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15

Exclusion criteria:
Exclusion criteria
1. Subjects with known or with a suspected sleep apnea syndrome or who have any other cause of excessive daytime sleepiness.
2. Psychiatric and neurological disorders (other than Parkinson’s disease), such as idiopathic narcolepsy, Alzheimer’s disease, Huntington’s Chorea, multiple sclerosis, epilepsy, psychosis, bipolar disorder, severe clinical anxiety or depression or other problem that in the investigator’s opinion would preclude the subject’s participation and completion of this trial or comprise reliable representation of subjective symptoms.
3. Cardiovascular disorders such as 2nd or 3rd grade atrioventricular block or chronic bifascicular block, unless an adequate pacemaker is present. Sinus node dysfunction, atrial fibrillation and ventricular arrhythmias considered as medically significant (except chronic atrial fibrillation controlled by stable doses of amiodarone, calcium channel blocker or beta-blocker), cardiac insufficiency, documented Brugada syndrome, recent myocardial infarction (less than three months before VS1).
4. Subjects with current impulse control disorder.
5. Subjects showing dementia or with MoCA < 23.
6. Subjects with current suicidal risk, based on investigator’s clinical judgement or with a “yes” answer to item 4 or 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) at VS1.
7. Current or recent (within one year) history of substance abuse or dependence disorder as defined in Diagnostic and Statistical Manual of Mental Disorders (DSM-V), e. g. alcohol. Tobacco use is accepted.
8. Other active clinically significant illness, including unstable cardiovascular, or malignant pathology which could interfere with the trial conduct or counter-indicate the trial treatments or place the subject at risk during the trial or compromise the trial participation.
9. Subjects with severe hepatic or renal impairment, or with any other significant abnormality in the physical examination or clinical laboratory results at VS1.
10. Known hypersensitivity to IMP (active ingredients or excipients of modafinil or flecainide capsules).
11. Subjects currently (or within 6 weeks before VS1) under one of the following medications (isolated intake up to 1 week can be accepted):
a. Neuroleptics, anxiolytics, anticonvulsants. Benzodiazepines and benzodiazepine-like drugs are only authorised if used regularly at stable indicated doses with an evening intake as sleep promoting agents.
b. Flecainide or other class I antiarrhythmic drugs.
c. Psychostimulants (except caffeine if no abuse and stable consumption) such as, but not limited to, modafinil, methylphenidate, amphetamine.
d. Antidepressants except if maintained at stable dose for at least 6 weeks before visit VS1 and anticipated to remain stable during the trial in subjects with mild or moderate unipolar depression.
e. Antiemetic medications (except domperidone), myo-relaxing drugs and opioids.
f. Dopaminergic medications, unless they have been used at stable doses for at least 4 weeks before screening and it is anticipated that the doses will not be changed throughout the trial.
12. Pregnancy or lactation. Women of childbearing potential who intend to be pregnant during the next few months.
13. Subjects protected by the law (legal guardianship).
14. Subjects participating in any other clinical trial within 60 days prior to visit VS1 in this trial or still in the protected period imposed by a previous trial.
15. Subjects working in an occupation requiring var

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Excessive daytime sleepiness associated with Parkinson’s disease
MedDRA version: 20.0 Level: SOC Classification code 10029205 Term: Nervous system disorders System Organ Class: 10029205 - Nervous system disorders
MedDRA version: 20.0 Level: PT Classification code 10041349 Term: Somnolence System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Product Name: Flecainide acetate
Product Code: THN02
Pharmaceutical Form: Capsule
INN or Proposed INN: Flecainidum
CAS Number: 54143-56-5
Other descriptive name: FLECAINIDE ACETATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1 -
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Product Name: Flecainide acetate
Product Code: THN02
Pharmaceutical Form: Capsule
INN or Proposed INN: Flecainidum
CAS Number: 54143-56-5
Other descriptive name: FLECAINIDE ACETATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 9 -
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Trade Name: Modiodal
Product Name: over-encapsulated Modafinil
Pharmaceutical Form: Capsule
INN or Proposed INN: MODAFINIL
CAS Number: 68693-11-8
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: 1.To quantify the efficacy of THN102 versus placebo in improving sleepiness.
2.To quantify the efficacy of THN102 versus placebo in improving
a.attention, vigilance
b.cognition
3.To determine the dose response profile of THN102 versus placebo on efficacy parameters.
4.To determine the plasma levels of modafinil and flecainide at steady state.

Primary end point(s): Safety endpoints
1. Adverse events
2. Safety laboratory
3. Vital signs change
4. Electrocardiogram assessments
5. Columbia-Suicide Severity Rating Scale (C-SSRS)
6. UPDRS Part III

Efficacy endpoints
Key efficacy endpoint
7. Mean ESS score change from baseline at the end of each treatment period
Secondary efficacy endpoints
8. ESS score responder rate, defined as the proportion of subjects with at least 25% ESS improvement from baseline, at the end of each treatment period
9. Absence of residual somnolence, i.e. ESS < 11 at the end of each treatment period
10. Psychomotor Vigilance Test (PVT) variables change from baseline at the end of each treatment period
11. MoCA score change from baseline at the end of each treatment period
12. Actimetry change (inactivity) from baseline at the end of each treatment period
13. Number and duration of diurnal involuntary sleep attacks (subject diaries) change from baseline at the end of each treatment period
14. Episodes of somnolence (subject diaries) change from baseline at the end of each treatment period

Timepoint(s) of evaluation of this end point: After trial termination.

Main Objective: To assess the safety profile of THN102 (modafinil/flecainide combination) at two doses (200 mg/18 mg and 200 mg/2 mg) versus placebo in subjects with excessive daytime sleepiness associated with Parkinson’s disease (PD).

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Not applicable.

Secondary end point(s): Not applicable.

Secondary ID(s)

THN102-202

Source(s) of Monetary Support

Theranexus S.A.

Ethics review

Status: Approved
Approval date: 09/04/2018
Contact:

Results

• Results available: Yes
• Date Posted: 07/07/2021
• Date Completed: 20/12/2019
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-004475-31/results