Narcolepsy MedDRA version: 15.1 Level: LLT Classification code 10048322 Term: Narcolepsy aggravated System Organ Class: 10029205 - Nervous system disorders MedDRA version: 15.1 Level: PT Classification code 10028713 Term: Narcolepsy System Organ Class: 10029205 - Nervous system disorders MedDRA version: 15.1 Level: PT Classification code 10007737 Term: Cataplexy System Organ Class: 10029205 - Nervous system disorders MedDRA version: 15.1 Level: LLT Classification code 10048323 Term: Cataplex
Conditions
Interventions
Product Name: Pitolisant
Product Code: BF2.649
Pharmaceutical Form: Capsule
INN or Proposed INN: Pitolisant
CAS Number: 903576-44-3
Current Sponsor code: BF2.649
Concentration unit: mg milligram(s)
Co
Sponsors
Bioprojet
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Males or females, aged 18 years old and over. • Patients with a diagnosis of narcolepsy according to the International Classification of Sleep Disorders (ICSD-2) criteria • Patients treated with sodium oxybate (Xyrem®) with a stable dosage for at least 2 months prior to the trial. • Patients complaining of residual EDS with an ESS score >= 12 • Patients should be free of non authorized drugs or discontinue any psychostimulant medication at least 3 weeks before randomisation (V2). • Females of child-bearing potential must use a medically accepted effective method of birth control, agree to continue this method for the duration of the study and be negative to serum pregnancy test performed at the screening visit. Females should not be breast-feeding patient. • In the opinion of the investigator, the patient must have adequate support to comply with the entire study requirements as described in the protocol (e.g. transportation to and from trial site, self rating scales, drug compliance, scheduled visits, etc). • Patient must have voluntarily expressed a willingness to participate in this study, signed and dated an informed consent prior to beginning this protocol required procedures. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 50 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: • Psychiatric and neurological disorders, other than narcolepsy/cataplexy, such as moderate or severe psychosis or dementia, bipolar illness, severe anxiety, clinical severe depression (BDI = 16) with suicidal risk (item G BDI > 0), or depression treated for less than 8 weeks, history of seizure disorder or other problem that in the investigator’s opinion would preclude the patient’s participation and completion of this trial or comprise reliable representation of subjective symptoms. • Patients working in an occupation requiring variable shift work or routine night shifts. • Patients with an untreated sleep apnea disorder (defined as an apnea index > 10/h or an apnea/hypopnea index>15/h) or who have any other cause of daytime sleepiness. • Use of hypnotics, tranquilizers, sedating antihistamines, psychostimulants for the treatment of EDS (amphetamine and amphetamine-like CNS stimulants, modafinil, methylphenidate or others), benzodiazepines, anticonvulsants or clonidine will not be accepted at least 3 weeks before randomization (V2) and during study. • Current or recent (within one year) history of a substance abuse or dependence disorder including alcohol abuse as defined in Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). • Other active clinically significant illness, including unstable cardiovascular, or neoplasic pathology which could interfere with the study conduct or counter-indicate the study treatments or place the patient at risk during the trial or compromise the study participation. • Patient with a known history of long QTc syndrome (e.g. syncope or arythmia) or presenting any significant serious abnormality of the ECG (e.g. recent myocardial infarction), or QTc interval strictly higher than 450 ms (electrocardiogram Bazett’s corrected QT interval (QT x/? [HR/60]). • Patients with Severe Hepatic Impairment or with Severe Renal Impairment, or with any other significant abnormality in the physical examination or clinical laboratory results. • Known hypersensitivity to the tested treatment including active substance and excipients. • Patients participating in an other study and the use of any investigational therapy within the 30 days prior to the entry in this study. • Patient without any medical care insurance
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To show relevant beneficial effect of BF2.649 on EDS compared to placebo in add on to sodium oxybate in narcoleptic patients with residual EDS. This trial will characterize the efficacy of BF2.649 compared to placebo in showing an incremental improvement to the situation achieved by the use of sodium oxybate particularly in terms of a reduction of EDS as measured by the ESS scale. In addition the change in the average number of cataplexy attacks per week will be assessed. ;Secondary Objective: NA ;Primary end point(s): The primary measure of efficacy will be the changes in Excessive Daytime Sleepiness (EDS) as measured by the Epworth Sleepiness Scale (ESS), and based on the change from baseline (average V1 and V2) of the score of ESS (average V5 and V6).;Timepoint(s) of evaluation of this end point: Throughout the study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Changes in EDS as measured by the Maintenance of Wakefulness Test (MWT), four sessions of 40-minute tests. •Number of sleep attacks and sleepiness episodes (as recorded in patient diaries), •Changes in the average number of cataplexy attacks per week (as recorded in patient diaries), between 2-week baseline (V1-V2) and the 4-week stable treatment period (V4-V6). •Severity of EDS measured by the Clinical Global Impression of Change and of Severity (CGI-C and CGI-S on EDS) •Severity of cataplexy measured by the Clinical Global Impression of Change and of Severity (CGI-C and CGI-S on cataplexy) •European Quality of life questionnaire (EQ-5D) •Patient’s Global Opinion on effect of treatment •Tolerability as measured by Treatment Emergent Adverse Events (TEAE), Changes in Physical examination and Vital signs •Withdrawal symptoms assessed by DSM IV questionnaire;Timepoint(s) of evaluation of this end point: The primary end point will be evaluated after 14 days, 28 days 49 days and 56 days double blind treatment and one week placebo follow-up. | — |
Countries
Finland, Germany, Spain
Contacts
Public ContactBioprojet clinical department
Bioprojet
Outcome results
None listed