Patients with Obstructive Sleep Apnoea Syndrome, Treated or Not by Nasal Continuous Positive Airway Pressure, but Still Complaining of Excessive Daytime Sleepiness (EDS) MedDRA version: 20.1 Level: LLT Classification code 10015595 Term: Excessive daytime sleepiness System Organ Class: 100000004852
Conditions
Interventions
Trade Name: Wakix
Product Name: pitolisant
Product Code: BF2.649
Pharmaceutical Form: Tablet
INN or Proposed INN: Pitolisant
CAS Number: 903576-44-3
Other descriptive name: BF2.649
Concentration unit:
Sponsors
Bioprojet Pharma
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Male and/or female outpatients aged from at least 18 years • Patients complaining of EDS refusing to be treated by nCPAP therapy or having been submitted to nCPAP therapy for a minimum period of 3 months, and still complaining of EDS despite the efforts made beforehand to obtain an efficient nCPAP therapy • Polysomnography performed (for patients submitted to nCPAP therapy – under nCPAP) between V1 and V2 or during the last 12 months with: - Apnea-Hypopnea Index (AHI): for patients without nCPAP therapy = 15; for patients under nCPAP therapy = 10; - Periodic limbs movement (PLM) disorders as defined by a PLM Arousal Index (PLMAI) =10 per hour. • For patients submitted to nCPAP therapy: nCPAP = 4 hours / day (compliance checked on the clock-time counter of the CPAP machine) • Mini Mental State Examination (MMSE) = 28 • Beck Depression Inventory – 13 items (BDI-13) score =65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: • Patients having previously been exposed to pitolisant either in previous clinical trials, or in compassionate program or being prescribed the commercial form (Wakix®), for those enrolled patients from January 2018 • Patients suffering from chronic severe insomnia in accordance with the International Classification of Sleep Disorders (ICSD 2005) without OSA. • Patients with co-existing narcolepsy (ICSD 2005), judged on clinical criteria • Patients with sleep debt not due to OSA (according to the physician‘ s judgment) • Patients with non-respiratory sleep fragmentation (restless leg syndrome…) • Shift work, professional drivers • Refusal from the patient to stop any current therapy for EDS or predictable risk for the patient to stop the therapy • Patients suffering from a psychiatric disease • Acute or chronic disease preventing the improvement assessment, e.g. severe chronic obstructive pulmonary disease (COPD) • Current or recent (within one year) history of drug, alcohol, narcotic or other substance abuse or dependence • Any significant serious abnormality of the cardiovascular system, e.g. recent myocardial infarction, angina, hypertension or dysrhythmias (within the previous 6 months), Electrocardiogram Fredericci corrected QT interval higher than 450 ms, history of left ventricular hypertrophy or mitral valve prolapse. • Severe co-morbid medical or biological conditions that may jeopardize study participation at the discretion of the investigator (particularly in the cardiovascular system and the instable diabetes) • Positive serology tests (optional HIV, HCV and HbsAg) • Pregnant or breast-feeding women • Women with child-bearing potential and no efficient birth-control method • Patients unable to understand the study protocol • Patients with suspected or known hypersensitivity to study medication • Patients with a dominant arm deficiency impeding the achievement of the tests • Patients using a prohibited medication • Congenital galactose poisoning, glucose and galactose malabsorption, deficit in lactase (lactose in placebo) • Patients participating in another study or being in a follow-up period for another study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main objective of this study is to demonstrate the efficacy and safety of pitolisant given at 10, 20, or 40 mg per day versus placebo during 12 weeks for the Double Blind period, to treat the Excessive Daytime Sleepiness (EDS) in patients with moderate to severe Obstructive Sleep Apnea (OSA) refusing the nasal Continuous Positive Airway Pressure (nCPAP) therapy or treated by nCPAP but still complaining of EDS. The efficacy of pitolisant will be assessed separately in patients treated with nCPAP and in patients without nCPAP use.;Secondary Objective: The secondary objectives of the Open Label Extension period are to assess the long-term tolerance as well as the maintenance of efficacy of pitolisant.and further investigating the co-variates or co-medications that affect the pharmacokinetics of pitolisant in the target population. ;Primary end point(s): The primary endpoint efficacy criterion is based on the score of Epworth Sleepiness Scale (ESS) by comparing the score differences between baseline (score at V2) and at the end of the Double Blind period (mean between V5 and V6) in pitolisant and placebo groups and the sustained improvement of ESS from baseline at week 52 in the Open Label Extension period. ;Timepoint(s) of evaluation of this end point: see protocol | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Percentage of ESS responders - Reduction of sleepiness and sleep episodes on the sleep diary - Improvement in vigilance according to Oxford Sleep Resistance (OSleR) test - Increase in quality of life - Improvement in cognitive function :Trail Making Test (TMT) Parts A & B - Clinical Global Impression (CGI)assesment of illness severity and Improvement - The Pichot fatigue scale - PK assessment - Z-score: composite score including ESS and OSLER results;Timepoint(s) of evaluation of this end point: see protocol | — |
Countries
Bulgaria, Macedonia, the former Yugoslav Republic of
Contacts
Public ContactBioprojet clinical department
Bioprojet Pharma
Outcome results
None listed