Safety and Efficacy of THN102 in Patients With Parkinson's Disease and Excessive Daytime Sleepiness

Study Overview
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Brief Summary
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This is a randomized, placebo-controlled, 3-way cross-over phase IIa trial comparing two dose levels of THN102 to placebo in patients suffering from Parkinson's disease associated with excessive daytime sleepiness.

Detailed Description
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The treatment duration is 2 weeks per period. Each treatment period is followed by a one-week washout period.

Official Title
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Safety and Efficacy of THN102 in Patients With Parkinson's Disease and Excessive Daytime Sleepiness

Conditions
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Parkinson Disease

Intervention / Treatment
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* Drug: THN102 Dosage A
* Drug: THN102 Dosage B
* Drug: THN102 Dosage C


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with a diagnosis of idiopathic Parkinson's disease as defined by the Movement Disorders Society (MDS). Subjects with Hoehn and Yahr scale score ≤ 4. Body mass index > 18 kg/m2 and < 35 kg/m2. 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 television, while eating or talking with other people). Epworth Sleepiness Scale (ESS) score ≥ 14. Exclusion Criteria: Subjects with known or with a suspected sleep apnea syndrome or who have any other cause of excessive daytime sleepiness, such as shift work sleep disorder. Psychiatric and neurological disorders (other than Parkinson's disease), Cardiovascular disorders such as - but not limited to Uncontrolled moderate to severe hypertension History or current diagnosis of electrocardiogram (ECG) abnormalities indicating significant risk of safety for patients participating in the study Recent myocardial infarction Stable or unstable angina pectoris Cardiac insufficiency or history of heart failure Previous history of cardiac valvular surgery Subjects with current impulse control disorder. Subjects showing dementia or with MoCA < 23. Subjects with current suicidal risk Current or recent (within one year) history of substance abuse or dependence disorder Other active clinically significant illness Subjects with hepatic or renal impairment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Interventional Model Description: Complete 3 way-Crossover
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: THN102 Dosage A<br>THN102 Dosage A is a Placebo | Drug: THN102 Dosage A<br>* THN102 Dosages A: placebo<br>* Other names: Placebo;|
| Experimental: THN102 Dosage B<br>THN102 Dosage B : 200 mg/2 mg THN102 is a combination of modafinil 100mg and flecainide 1 mg daily dosage is 200 mg of modafinil and 2 mg of flecainide | Drug: THN102 Dosage B<br>* THN102 Dosage B : 200mg/2mg<br>* Other names: Dosage B;|
| Experimental: THN102 Dosage C<br>THN102 Dosage C : 200 mg/18 mg THN102 is a combination of modafinil 100mg and flecainide 9 mg daily dosage is 200 mg of modafinil and 18 mg of flecainide | Drug: THN102 Dosage C<br>* THN102 Dosage C: 200mg/18mg<br>* Other names: Dosage C;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Adverse Events | Number of participants with spontaneously reported treatment-related adverse events | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Epworth Sleeping Scale (ESS) | Range of the scale : 0 to 24. A low score indicates a good outcome. Results shown are corresponding to a change from baseline of the ESS score. | 2 weeks | 
| Psychomotor Vigilance Test (PVT) : Reaction Time (Miliseconds) Change From Baseline | PVT measures reaction time in milliseconds. The results below are corresponding to the reaction time change from baseline. | 2 weeks | 
| Montreal Cognitive Assessment Battery (MoCA) | MoCA score reflects the cognitive capacities of a person. Range of the total score of 10 test items: 0 to 30 points. A high score indicates good cognitive functioning. A score of 26 and above is considered normal. The results below are shown as change from baseline of the MoCA score. | 2 weeks | 
| Efficacy in Improving Sleepiness (ESS). Responders Rate, Change From Baseline | 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 | 2 weeks | 
| Efficacy in Improving Sleepiness (ESS). Patients in Remission, Change From Baseline | Number of patients in remission (=without residual sleepiness), i.e. ESS < 11 at the end of each treatment period | 2 weeks |