Narcolepsy With Cataplexy, Narcolepsy Without Cataplexy
Conditions
Brief summary
The purpose of this multicenter double blind study is to assess efficacy and safety of Pitolisant versus placebo in paediatric Narcoleptic patients with or without cataplexy.
Interventions
DRUGpitolisant
Tablet
DRUGPlacebo
Tablet
Sponsors
Bioprojet
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
6 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
* Male and female children from 6 to less than 18 years of age suffering from narcolepsy with or without cataplexy - ICSD-3 criteria (narcolepsy type 1 and 2). * PDSS * Patients should be free of non-authorized medication, in particular psychostimulant treatments as from the screening visit onwards. * 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. * 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).
Exclusion criteria
* Any other conditions that can be considered the primary causes of EDS. * Cataplectic patients treated by anticataplectics which are not under a stable treatment at the time of inclusion. * Patients treated for cataplexy or any other pathology, by tricyclic antidepressants. * Any significant abnormality of the electrocardiogram and particularly Fridericia's QTc interval. * Patients with significant abnormality or clinical laboratory results. * Psychiatric and neurological disorders in the investigator's opinion, would preclude the patient's participation and completion of this trial or comprise reliable representation of subjective symptoms. * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To Evaluate the Efficacy of Pitolisant in Reducing Residual Excessive Daytime Sleepiness (EDS), Ullanlinna Narcolepsy Scale Score. | 8 weeks | Changes in EDS measured by the Ullanlinna Narcolepsy Scale Score (UNS) from baseline (mean of two pre-treatment measures) to the end of double-blind period (mean of the last two measures). The UNS is an 11-item scale used to measure the intensity and frequency of symptoms of narcolepsy (EDS and cataplexy). The total score varies from 0 to 44, with higher scores denoting greater narcoleptic tendencies. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To Evaluate the Efficacy of Pitolisant in Reducing Residual Excessive Daytime Sleepiness (EDS), Pediatric Daytime Sleepiness Scale. | 8 weeks | Changes in EDS measured by the Pediatric Daytime Sleepiness Scale (PDSS) from baseline (mean of two pre-treatment measures) to the end of double-blind period (mean of the last two measures). The PDSS total score can range from 0 and 32 and a score \>13 is considered abnormal sleepiness. |
| To Evaluate the Efficacy of Pitolisant in Reducing Residual Excessive Daytime Sleepiness (EDS), Ullanlinna Narcolepsy Scale-Cataplexy Subscore . | 8 weeks | Changes in EDS measured by Ullanlinna Narcolepsy Scale-Cataplexy Subscore (UNS-CTP) in patients with type 1 narcolepsy from baseline (mean of two pre-treatment measures) to the end of double-blind period (mean of the last two measures). This subscore is defined as the sum of the first 4 items of the UNS, UNS-CTP subscore ranges from 0 to 16, with higher scores indicating more severe symptoms. |
Countries
Finland, France, Italy, Netherlands, Russia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pitolisant tablet, oral, once a day.
pitolisant: Tablet | 72 |
| Placebo tablet, oral, once a day.
Placebo: Tablet | 38 |
| Total | 110 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-blind Period (0 to 8 Weeks) | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Pitolisant | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 72 Participants | 38 Participants | 110 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 13.0 years STANDARD_DEVIATION 3 | 12.5 years STANDARD_DEVIATION 3 | 12.9 years STANDARD_DEVIATION 3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 72 Participants | 38 Participants | 110 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Finland | 1 participants | 1 participants | 2 participants |
| Region of Enrollment France | 19 participants | 9 participants | 28 participants |
| Region of Enrollment Italy | 17 participants | 9 participants | 26 participants |
| Region of Enrollment Netherlands | 3 participants | 2 participants | 5 participants |
| Region of Enrollment Russia | 32 participants | 17 participants | 49 participants |
| Sex: Female, Male Female | 35 Participants | 14 Participants | 49 Participants |
| Sex: Female, Male Male | 37 Participants | 24 Participants | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 73 | 0 / 37 |
| other Total, other adverse events | 15 / 73 | 11 / 37 |
| serious Total, serious adverse events | 0 / 73 | 0 / 37 |
Outcome results
Primary
To Evaluate the Efficacy of Pitolisant in Reducing Residual Excessive Daytime Sleepiness (EDS), Ullanlinna Narcolepsy Scale Score.
Changes in EDS measured by the Ullanlinna Narcolepsy Scale Score (UNS) from baseline (mean of two pre-treatment measures) to the end of double-blind period (mean of the last two measures). The UNS is an 11-item scale used to measure the intensity and frequency of symptoms of narcolepsy (EDS and cataplexy). The total score varies from 0 to 44, with higher scores denoting greater narcoleptic tendencies.
Time frame: 8 weeks
Population: Full Analysis Set
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pitolisant | To Evaluate the Efficacy of Pitolisant in Reducing Residual Excessive Daytime Sleepiness (EDS), Ullanlinna Narcolepsy Scale Score. | -6.29 score on a scale | Standard Error 1.14 |
| Placebo | To Evaluate the Efficacy of Pitolisant in Reducing Residual Excessive Daytime Sleepiness (EDS), Ullanlinna Narcolepsy Scale Score. | -2.60 score on a scale | Standard Error 1.35 |
Secondary
To Evaluate the Efficacy of Pitolisant in Reducing Residual Excessive Daytime Sleepiness (EDS), Pediatric Daytime Sleepiness Scale.
Changes in EDS measured by the Pediatric Daytime Sleepiness Scale (PDSS) from baseline (mean of two pre-treatment measures) to the end of double-blind period (mean of the last two measures). The PDSS total score can range from 0 and 32 and a score \>13 is considered abnormal sleepiness.
Time frame: 8 weeks
Population: Full Analysis Set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pitolisant | To Evaluate the Efficacy of Pitolisant in Reducing Residual Excessive Daytime Sleepiness (EDS), Pediatric Daytime Sleepiness Scale. | -5.53 score on a scale | Standard Error 0.66 |
| Placebo | To Evaluate the Efficacy of Pitolisant in Reducing Residual Excessive Daytime Sleepiness (EDS), Pediatric Daytime Sleepiness Scale. | -2.11 score on a scale | Standard Error 0.89 |
Secondary
To Evaluate the Efficacy of Pitolisant in Reducing Residual Excessive Daytime Sleepiness (EDS), Ullanlinna Narcolepsy Scale-Cataplexy Subscore .
Changes in EDS measured by Ullanlinna Narcolepsy Scale-Cataplexy Subscore (UNS-CTP) in patients with type 1 narcolepsy from baseline (mean of two pre-treatment measures) to the end of double-blind period (mean of the last two measures). This subscore is defined as the sum of the first 4 items of the UNS, UNS-CTP subscore ranges from 0 to 16, with higher scores indicating more severe symptoms.
Time frame: 8 weeks
Population: Full Analysis Set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pitolisant | To Evaluate the Efficacy of Pitolisant in Reducing Residual Excessive Daytime Sleepiness (EDS), Ullanlinna Narcolepsy Scale-Cataplexy Subscore . | -2.88 score on a scale | Standard Error 0.44 |
| Placebo | To Evaluate the Efficacy of Pitolisant in Reducing Residual Excessive Daytime Sleepiness (EDS), Ullanlinna Narcolepsy Scale-Cataplexy Subscore . | -1.12 score on a scale | Standard Error 0.64 |