Dose Range Finding Study of BF2.649 Versus Placebo to Treat Excessive Daytime Sleepiness in Parkinson's Disease Patients

Study Overview
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Brief Summary
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The objective of this trial is to define the minimum effective dose of BF 2.649 between 5 mg, 10 mg, 20 mg or 40 mg versus placebo in reducing the Excessive Daytime Sleepiness of Parkinson's disease patients

Detailed Description
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Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by resting tremor, rigidity, bradykinesia and loss of postural reflexes that affects 1% of the North American population. Besides these motor problems there are also so called non-motor problems. Excessive daytime sleepiness (EDS) is a bothersome non-motor problem, which affects 20% to 50% of all PD patients and currently, there isn't any registered treatment for that trouble. The study medication BF2.649 tested here is a novel, highly potent, selective, orally active inverse agonist at the histamine H3 receptor, therefore strengthens histaminergic transmission in the brain and increases wakefulness EDS is characterized by daytime somnolence and sudden sleep episodes. This problem has several consequences, e.g., an impairment of quality of life, an interference with activities of daily living and other handicaps in the management of social and family affairs. The primary endpoint of this study will be measured by the change in the well-validated Epworth sleepiness scale (ESS). The ESS is a simple self-administered 8-item questionnaire. The outcome is to get an impression about the level of the daytime sleepiness in several real-life situations. On the basis of this pharmacological and clinical rationale it is considered relevant to carry out a dose-finding study for this original, non-amphetamine molecule in PD patients affected by excessive daytime sleepiness. PD severity will be assessed by the routinely used UPDRS.

Official Title
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Randomized, Dose-finding Study of BF 2.649 5, 10 20 and 40 mg/d in Comparison to Placebo in Excessive Daytime Sleepiness in Parkinson's Disease Patients (PD)

Conditions
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Excessive Daytime Sleepiness, Parkinson's Disease

Intervention / Treatment
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* Drug: Placebo
* Drug: BF 2.649 5 mg
* Drug: BF 2.649 10 mg
* Drug: BF 2.649 20 mg
* Drug: BF 2.649 40 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Idiopathic Parkinson disease Hoehn and Yahr < 5 Stable treatment of Parkinson disease for at least 4 weeks Excessive Daytime Sleepiness : Epworth scale superior or equal to 13 None psychostimulant treatment intake for 2 weeks Exclusion Criteria: Other degenerative parkinsonian syndrome other condition than PD that is the primary cause of excessive daytime sleepiness Severe depression or suicidal risk Pregnant or breast-feeding women Patients having an occupation that requires night shift History of drugs, alcohol, narcotic or other substance abuse or dependence Refusal from the patient to stop any current therapy for excessive daytime sleepiness or predictable risks for the patient to stop the therapy Any significant abnormality in the physical examination or clinical laboratory results e.g. liver or kidney function deficiency Any significant serious abnormality of the ECG e.g. myocardial infarction, Electrocardiogram corrected QT interval higher than 450 ms Other active clinically significant illness which could interfere with the study conduct or contra-indicate the study treatments or put patients at risk Dementia with MMS inferior or equal to 24 Patients taking associated treatments which are not allowed during the study course and which cannot be stopped before the inclusion visit

Ages Eligible for Study
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Minimum Age: 18 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* 1 capsule per day during 4 weeks<br>|
| Experimental: BF 2.649-5 mg<br> | Drug: BF 2.649 5 mg<br>* one BF 2.649 capsule of 5 mg per day during 4 weeks<br>* Other names: pitolisant;|
| Experimental: BF 2.649 10 mg<br> | Drug: BF 2.649 10 mg<br>* One BF 2.649 capsule of 10 mg per day during 4 weeks<br>* Other names: pitolisant;|
| Experimental: BF 2.649 20 mg<br> | Drug: BF 2.649 20 mg<br>* One BF 2.649 capsule of 20 mg per day during 4 weeks<br>* Other names: pitolisant;|
| Experimental: BF 2.649 40 mg<br> | Drug: BF 2.649 40 mg<br>* One BF 2.649 capsule of 40 mg per day during 4 weeks<br>* Other names: pitolisant;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Epworth Sleepiness Scale scores (ESS) |  | At selection visit (Day-14 to Day-7)/Inclusion visit (Day0)/ Interim visit (Day14)/Final visit (Day28) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean number of daytime sleep or sleepiness episodes and their duration |  | During 5 days before each visit | 
| frequency of sleep attacks |  | recorded at each visit | 
| UPDRS III for motor function |  | at each visit | 
| Clinical global impression scale |  | at each visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Excessive Daytime Sleepiness, Parkinson's disease