Double blind, multicentre, randomized, placebo-controlled trial to evaluate safety and efficacy of pitolisant in children from 6 to less than 18 years with narcolepsy with/without cataplexy, followed by a prolonged open-label period

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Bioprojet Pharma

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

completed 5 Jun 2025

Decision date (initial)

2024-12-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

External identifiers

EU CT number

2024-515568-30-00

EudraCT number

2013-001506-29

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

This trial will characterize the efficacy of pitolisant (5-, 10-, 20-, 40 mg/d in Double Blind Period and 5-, 10-, 15-, 20-, 30-, 40 mg/d in Open Label Period) compared to placebo in showing an incremental improvement to the situation particularly in terms of a reduction of EDS as measured by the UNS, and also on the number of cataplexy episodes, if any.The clinical and biological tolerance of pitolisant will also be checked.

Conditions and MedDRA coding

Narcolepsy

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-001176-PIP01-11

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Male and female children from 6 to less than 18 years of age (at 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 and Multiple Sleep Latency Test for patients without cataplexy (if these examinations were not performed within the last 12 months) (Italy) Male and female children from 6 to less than 18 years of age (at 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 (France)
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).

Exclusion criteria 19

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 450 ms.
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 β-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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Changes in UNS (Ullanlinna Narcolepsy Scale) measuring the intensity and frequency of symptoms of narcolepsy (Excessive Daytime Sleepiness and cataplexies), based on the change from baseline (mean of two pre-treatment measures at [(V1 + V2)/2]) of the UNS score and at the end of double-blind phase (mean of the last two measures [(V6 + V7)/2]).

Secondary endpoints 17

1. Changes in EDS as measured by the maintenance of wakefulness test (MWT) between baseline and V7
2. Changes in EDS measured by the Paediatric Daytime Sleepiness Scale (PDSS) between baseline: [V1 score (D-14) + V2 score (D0)]/2 and the end of treatment: [V6 score (D49) + V7 score (D56)]/2
3. Changes in EDS as measured by the Child and Adolescent Sleepiness Scale (CASS) between baseline and the end of treatment
4. 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)
5. 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 (V5 to V7)
6. Severity of EDS measured by the clinical Global Impression of severity and change. Changes between baseline and V6, V7
7. Severity of cataplexy measured by the clinical Global Impression of severity and change. Changes between baseline and V6, V7
8. Changes between baseline and V6 will be compared for the TEA-Ch test
9. Comparison between placebo and pitolisant groups on withdrawal symptoms questionnaire (DSM IV) on D59 during a phone call (T1) and at the end-of-study visit on D63 (V8) after a one-week period on placebo
10. Comparison between placebo and pitolisant groups on Patients’ Global Opinion on treatment effect at the end of treatment if able to express himself. If not will be reported either by parents or teachers
11. Comparison between placebo and pitolisant groups on Tolerability as measured by Treatment Emergent Adverse Events
12. Comparison between placebo and pitolisant groups on Changes in Physical examination and Vital signs
13. Comparison between placebo and pitolisant groups on ECG and calculation of Fridericia’s corrected QTc interval
14. Comparison between placebo and pitolisant groups on Blood laboratory tests (haematology, blood chemistry)
15. Comparison between placebo and pitolisant groups on Mood appraisal adapted to children (CDI and C-SSRS)
16. Changes between baseline and at each visit of the open-label period in EDS
17. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Bioprojet Pharma

Sponsor organisation

Bioprojet Pharma

Address

9 Rue Rameau

City

Paris

Postcode

75002

Country

France

Scientific contact point

Organisation

Bioprojet Pharma

Contact name

Regulatory Affairs Director

Public contact point

Organisation

Bioprojet Pharma

Contact name

Regulatory Affairs Director

Locations

2 EU/EEA countries · 2 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 20 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications