Narcolepsy MedDRA version: 20.0 Level: PT Classification code 10007737 Term: Cataplexy System Organ Class: 10029205 - Nervous system disorders MedDRA version: 20.0 Level: PT Classification code 10028713 Term: Narcolepsy System Organ Class: 10029205 - Nervous system disorders MedDRA version: 20.0 Level: LLT Classification code 10048322 Term: Narcolepsy aggravated System Organ Class: 10029205 - Nervous system disorders MedDRA version: 20.0 Level: LLT Classification code 10048323 Term: Cataplex
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
Current Sponsor code: BF2.649
Concentration unit: m
Sponsors
Bioprojet
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Male and female children from 6 to less than 18 years of age (until V8) suffering from narcolepsy with or without cataplexy - meeting the International Classification of Sleep Disorders (ICSD-3) criteria (narcolepsy type 1 and 2). Diagnosis confirmed with polysomnography (to be performed if this examination was not performed within the last 12 months) and Multiple Sleep Latency Test for patients without cataplexy. 2) PDSS score = 15 during baseline period (V1+V2) / 2. 3) Patients should be free of non-authorized medication, in particular psychostimulant treatments as from the screening visit (V0) onwards. 4) Parents – and patients old enough to understand who have expressed a willingness to participate in the study, who have signed and dated the informed consent form prior to beginning protocol required procedures. 5) 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 and diaries completion, drug compliance, scheduled visits, tests). 6) Female pubescent patients shall use a birth control method, judged efficient by the investigator, throughout the study and during the month following treatment discontinuation. 7) Patients should benefit from appropriate healthy insurance system (only applicable where mandatory e.g. in France). Are the trial subjects under 18? yes Number of subjects for this age range: 60 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1) Any other conditions that can be considered the primary causes of EDS: such as sleep related breathing disorders as defined by a sleep Apnea Index = 5 per hour or/and an Apnea/Hypopnea Index = 10 per hour, chronic sleep deprivation, circadian sleep wake rhythm disorder or any other medical or neurological causes that could account for narcolepsy symptoms associated with EDS. 2) Cataplectic patients treated by anticataplectics (SNRI, SSRI, sodium oxybate) which are not under a stable treatment since at least 4 weeks at the time of inclusion (V2). 3) Patients treated for cataplexy or any other pathology, by tricyclic antidepressants (clomipramine, imipramine, mirtazapine, desmethylimipramine and protriptyline) are not authorized because they display histamine H1 receptor antagonist activity. 4) The use of pitolisant within a 30-day period prior to initial screening visit (V0) for this trial. 5) 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). 6) Any significant abnormality of the electrocardiogram and particularly Fridericia’s QTc interval (QTcF = QT/3? 60/HR) higher than 450ms. 7) Patients with severe depression (CDI = 16) 8) Patient with suicidal risk (C-SSRS) 9) Positive urinary drug testing (test applicable to patients from 12 years) 10) Pregnancy (defined as positive ß-HCG blood test), breast-feeding, or patients and unable to use an efficient method of birth control shall not be included in the study (for pubescent female only). 11) Patients with severe hepatic Impairment (Child Pugh C) or with any other significant abnormality in the physical examination or clinical laboratory results. 12) Psychiatric and neurological disorders, such as moderate or severe psychosis or dementia, depression, 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. 13) Active clinically significant illness, including unstable cardiovascular, endocrine, neoplastic, gastrointestinal, haematological, hepatic, immunologic, metabolic, neurological (other than narcolepsy/cataplexy), pulmonary, and/or renal disease 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 objectives. 14) Prior severe adverse reactions to CNS stimulants. 15) Known hypersensitivity to the tested treatment including active substance and excipients. 16) The inability to continue daily activities safely, without the use of treatment against EDS. 17) Any patient presenting congenital galactosemia, glucose-galactose malabsorption or lactase deficiency due to the presence of lactose in investigational treatments. 18) Patients participating in another study or being in a follow–up period for another study. 19) Cannot be contacted in case of emergency.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of pitolisant in reducing residual Excessive Daytime Sleepiness (EDS) and the number of cataplectic episodes (for patients with cataplexy). To determine safety in children and adolescents.;Secondary Objective: To assess the long-term safety of BF2.649 in the treatment of EDS in narcoleptic patients with or without cataplexy. To assess the drug-drug interactions with possible concomitant therapies. To assess the efficacy of long-term therapy with BF2.649 on EDS after a prolonged treatment period.;Primary end point(s): Change in EDS measured by the Paediatric Daytime Sleepiness Scale (PDSS). We will compare the results between pitolisant and placebo groups.;Timepoint(s) of evaluation of this end point: The primary end point will be evaluated between baseline: [V1 score (D-14) + V2 score (D0)]/2 and the end of treatment: [V6 score (D49) + V7 score (D56)]/2. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Changes in EDS as measured by the maintenance of wakefulness test (MWT) between baseline and V7, in pitolisant and placebo groups. - Changes in EDS as measured by the Child and Adolescent Sleepiness Scale (CASS) between baseline and the end of treatment, in pitolisant and placebo groups. - Changes in the average number of cataplexy episodes per weeks (recorded in sleep diary by patient and/or parent/teacher) between the 2 weeks of baseline and the 2 weeks of end study treatment period (V6, V7), in pitolisant and placebo groups. - Differences in weekly frequency of cataplexy episodes (recorded in sleep diary by patient and/or parent/teacher) between baseline and the 4 weeks of stable treatment period (V4 to V7), in pitolisant and placebo groups. - Severity of EDS measured by the Clinical Global Impression of severity and change. Changes between baseline and V6, V7, in pitolisant and placebo groups. - Severity of cataplexy measured by the Clinical Global Impression of severity and change. Changes between baseline and V6, V7, in pitolisant and placebo groups. - Changes between baseline and V6, V7 will be compared for the Ullanlina narcolepsy test, in pitolisant and placebo groups. - Changes between baseline and V6 will be compared for the TEA-Ch test, in pitolisant and placebo groups. - Comparison between placebo and pitolisant groups on: - Withdrawal symptoms questionnaire (DSM IV) - Patients’ Global Opinion on treatment effect at the end of treatment. - Parents’ and/or Teachers’ Global Opinion on treatment effect at the end of treatment. - Changes between baseline and at each visit of the open-label period in EDS. - Safety assessment will be done on monitoring of adverse events, physical examination, vital signs, ECG and Blood Laboratory tests modifications and the mood appraisal throughout the study.;Timepoint(s) of evaluation of this end point: Throughout the study. | — |
Countries
Finland, France, Germany, Netherlands, Russian Federation
Contacts
Public ContactBioprojet clinical department
Bioprojet
Outcome results
None listed