Clinical Trial: Effects of BF2.649 in the Treatment of Excessive Daytime Sleepiness in Narcolepsy.

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Randomized, Double-blind, Placebo and Comparator-controlled, Parallel-group, Multi-center Trial Assessing the Effects of BF2.649 in the Treatment of Excessive Daytime Sleepiness in 3. RATIONALE FOR BF2.649 IN NARCOLEPSY Narcolepsy is a disabling syndrome affecting the generation and organizations of sleep and wakefulness, first described by Westphal and Gelineau in 19th century. Excessive Daytime Sleepiness (EDS) and cataplexy are two main symptoms of narcolepsy. Other symptoms referred to as auxiliary symptoms are hypnagogic and hypnopompic hallucinations, sleep paralysis, dyssomnia and automatic behaviour. The prevalence of narcolepsy is estimated around 25 per 100 000 in Causasian population. It is often extremely incapacitating, interfering with every aspect of life, in work and social settings.

Several breakthroughs in the understanding of physiopathology of narcolepsy have recently shown that most narcoleptic patients display a strongly decreased CSF level of orexins, a group of hypothalamic peptides with wake-promoting activity. It was also found that sporadic narcolepsy in dogs, mice and humans may also be related to a deficiency in the production of orexin ligands. Narcolepsy may be a neurodegenerative or autoimmune disorder resulting in a loss of hypothalamic neurons containing the orexin [Baumann CR & Bassetti CL Lancet Neurol. 2005 ; Dauvilliers Y et al, Clin Neurophysiol. 2003 ].

In accordance with guidelines published by the European task force [Billiard M et al, Eur J Neurol. 2006] , management of narcolepsy with or without cataplexy relies on several classes of drugs, namely stimulants for EDS, antidepressants for cataplexy and hypnosedative drugs for disturbed nocturnal sleep. The first line pharmacological treatment of EDS and irresistible episodes of sleep rely on Modafinil, 100-400 mg/day, given in two doses, one in the morning and one early in the afternoon, the need for amphetamines and amphetamine-like stimulants (e.g. methylphenidate) has been decreased. Sodium oxybate and

Detailed Summary:
Sponsor: Bioprojet

Current Primary Outcome: Epworth Sleepiness Scale scores (ESS) [ Time Frame: 10 weeks ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

• patient sleep diary [ Time Frame: 10 weeks ]

  Following secondary outcome measures will be reported in the patient sleep diary:

  1. Number and duration of diurnal involuntary sleep attacks and episodes of severe sleepiness
  2. Number of cataplexy total and partial.
  3. Number of hallucinations.
  4. Number of sleep paralysis.
  5. Number and duration of nocturnal awakening and total duration of nocturnal sleep time.
• Maintenance of Wakefulness Test (MWT) [ Time Frame: 10 weeks ]
  The Maintenance of Wakefulness Test (MWT) is used in this study to assess an individual's ability to maintain awake while resisting the pressure to fall asleep. Patients will be administrated four 40-minute MWT sessions at 2 hours interval at inclusion visit (V3) and at endpoint visit (V7 or the last on-study visit), according to validated standard [Doghramji K et al, Electroencephalogr Clin Neurophysiol. 1997] . The changes in MWT will be compared between the treatment groups. The MWT will be renewed at V7 only for patients who had a MWT <11 at V3.
• Test of Sustained Attention to Response Task (SART) [ Time Frame: 10 weeks ]
  The Test of Sustained Attention to Response Task (SART) has been used for the quantification of vigilance and attention in narcolepsy patients [Fronczek R et al, Sleep 2006] . The SART will be performed at inclusion visit (V3) and at endpoint (V7 or the last on-study visit for prematurely withdrawn patients). The changes in SART will be compared between the treatment groups.
• Clinical Global Impressions of Change [ Time Frame: 10 weeks ]
  The severities of EDS and of cataplexy will be measured at baseline by the investigator using the Clinical Global Impression of Severity (CGI-S) in order to describe the population. At each follow-up visit, the patients' change in EDS and in cataplexy compared to baseline will be rated by the same investigator using Clinical Global Impression of Change (CGI-C) to document the perceived change in patients' illness.
• European Quality of life questionnaire (EQ-5D) [ Time Frame: 10 weeks ]
  EQ-5D is a reliable and validated measure of quality of life. Narcolepsy has a clear negative effect on this outcome measure [Dodel R. et al, Sleep Med. 2007] . EQ-5D will be completed at baseline visit (V2), inclusion visit (V3), stable-dose visit (V5), endpoint visit (V7) and withdrawal visit (V8). The changes between treatment groups will be analysed as an evaluation of the illness evolution.
• Patient's Global Opinion on the effect of treatment [ Time Frame: 10 weeks ]
  At each visit under treatment (V4, V5, V6, V7 and V8 or last on-study visit), patients evaluate the Global effect of their treatment by comparing the period prior to that visit with the patient's prestudy condition.

Original Secondary Outcome: Same as current

Information By: Bioprojet

Dates:
Date Received: July 9, 2012
Date Started: November 2010
Date Completion:
Last Updated: January 30, 2017
Last Verified: January 2017