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

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)

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

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease; Excessive Daytime Sleepiness
• Intervention / Treatment: 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

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 108
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Paris, France, 75013
    • Pitié-Salpêtrière Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Bioprojet
• Investigators: Principal Investigator: ARNULF Isabelle, Pitié-Salpêtrière Hospital, Paris, France; Principal Investigator: Carsten Moeller, Universitätsklinikum Giessen und Marburg, Marburg, Germany

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): March 1, 2009
• Study Completion (Actual): June 1, 2009

Study Registration Dates

• First Submitted: March 21, 2008
• First Submitted That Met QC Criteria: March 21, 2008
• First Posted (Estimate): March 25, 2008

Study Record Updates

• Last Update Posted (Estimate): June 11, 2012
• Last Update Submitted That Met QC Criteria: June 8, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: Parkinson's disease; Excessive Daytime Sleepiness
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Disorders of Excessive Somnolence; Sleepiness
• Other Study ID Numbers: P07-02 / BF 2.649; 2007-003512-57 (EudraCT Number)