E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028713 |
E.1.2 | Term | Narcolepsy |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the pharmacokinetic parameters of Pitolisant in children, including at least Cmax, Tmax, AUC 0-t and AUC 0-∞, t1/2 |
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E.2.2 | Secondary objectives of the trial |
Safety and tolerability assessments:
- Collection of observed or reported adverse events
- Physical examination including vital signs to be repeated at each sampling
- Biological work-up (haematology, biochemistry) at the pre-study screening visit (V0), on D1 before study drug administration for all patients, after treatment at H+10 for children and at H+24 for adolescents, then at V2 follow-up visit for all patients.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
* Male and female patients from 6 to less than 18 years of age
* Both, de novo or previously diagnosed narcoleptic patients with or without cataplexy could be included. All patients should meet the International Classification of Sleep Disorders (ICSD-2) criteria.
* Patients who are free of drugs for 3 days prior to study onset (with the exception of a contraceptive, if required for female patients).
* Patients with a complete physical examination including height (cm), weight (kg), a body mass index between 22 and 30 kg/m², an ECG within the normal range, and laboratory parameters strictly below the upper laboratory norm.
* Parents – and patients old enough to understand - have expressed a willingness to participate in and complete the study, signed and dated the informed consent form after getting acquainted with the patient’s information sheet, prior to beginning protocol required procedures.
* In the opinion of the investigator, the patient must have adequate support to comply with the entire study requirements as described in the protocol.
* Patients with no other morbid pathology than narcolepsy associated or not to cataplexy.
* Female patients likely to be pregnant shall have a hormonal contraception, and agree to continue this birth control method throughout the study and during the month following treatment discontinuation. They will be negative to the serum pregnancy test performed at the screening visit and on D1.
* Patients (adolescents) should be non-smokers or smoking less than 10 cigarettes per day.
* Patients should have normal eating habits
* Patients should be assured by appropriate health insurance system (only applicable where mandatory e.g. in France).
* Patients must not participate in another study or be in a follow–up period for another study.
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E.4 | Principal exclusion criteria |
* The use of BF2.649 within a 30-day period prior to initial screening visit (V0) for this trial.
* Narcoleptic patients should not have 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 ≥ 5 per hour, periodic limbs movement (PLM) disorders as defined by a PLM arousal index (PLMAI) ≥ 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.
* Patients who are unable or unwilling to temporarily discontinue other drugs or substances.
* Current or recent (within one year) history of a substance abuse or dependence disorder including alcohol abuse (more than 3 glasses of wine per day) as defined in Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) for adolescents from 12 to less than 18 years of age.
* Current of recent (within one year) history of drinking excessive amounts of tea, coffee, chocolate and/or beverages containing caffeine (more than 6 cups per day) or nicotine (more than 10 cigarettes/day) for adolescents from 12 to less than 18 years of age.
* History of severe allergy, asthma, allergic skin rash, or sensitivity to any drug.
* Severe headaches and/or migraine, recurrent nausea and/or vomiting (more than twice a month).
* Positive laboratory test for urine drug screening (opiates, barbiturates, amphetamine, cannabis, benzodiazepines, cocaine), and positive alcohol breath test for the group of patients from 12 to less than 18 years.
* Consumption of citrus fruits and their juices within 3 days before study drug administration
* Having a requirement of a restricted or special diet which would be non compliant with the study diet
* If patients of the female sex, pregnancy (defined as positive β-HCG blood test), breast-feeding, or unwilling to have a birth control method assessed to be efficient by the investigator
* Surgery or blood donation within the one month prior to the start of study
* Any medication within 3 days before hospitalization, or within 5 times the elimination half-life of that drug, whichever the longest, (with the exception of hormonal contraception).
* Any clinical condition or prior therapy which, in the investigator’s opinion, makes the patient unsuitable for the study.
* Any significant serious abnormality of the cardiovascular system, Electrocardiogram Fridericia’s corrected QTc interval (QTcF = QT / 3 60/HR) higher than 450 ms.
* Patients with any significant abnormality in the physical, psychological, or neurological examinations, or clinical laboratory results.
* 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.
* 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.
* Prior severe adverse reaction to CNS stimulants.
* Any patient presenting congenital galactosemia, glucose-galactose malabsorption or lactase deficiency due to the presence of lactose in investigational treatments.
* Any patient having previously participated in a study, the non-inclusion period of which is not over.
* Cannot be contacted in case of emergency.
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E.5 End points |
E.5.1 | Primary end point(s) |
To determine the pharmacokinetic parameters of Pitolisant in children, including at least Cmax, Tmax, AUC0-t and AUC0-∞, t1/2 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
endpoint is evaluated between the H-1 and H+10 for patients from 6 to less than 12 years of -endpoint is evaluated between the H-1 and H+24 for patients from 12 to less than 18 years of age
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E.5.2 | Secondary end point(s) |
Safety and tolerability assessments:
- Collection of observed or reported adverse events
- Physical examination including vital signs to be repeated at each sampling
- Biological work-up (haematology, biochemistry) at the pre-study screening visit (V0), on D1 before study drug administration for all patients, after treatment at H+10 for children and at H+24 for adolescents, then at V2 follow-up visit for all patients.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary endpoint is evaluated between Day-14 to Day +6. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
First trial in children and adolescent |
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E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |