Cataplexy, Excessive Daytime Sleepiness, Narcolepsy
Conditions
Brief summary
The purpose of this study is to determine whether once-nightly FT218 is safe and effective for the treatment of excessive daytime sleepiness and cataplexy in subjects with narcolepsy.
Interventions
DRUGFT218
DRUGPlacebo
Sponsors
Avadel
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female subjects 16 years of age or older 2. Willing and able to give written informed consent for study participation. For young adults (16 and 17 years old) who have not reached the age of majority they must be capable of giving assent and consent from a legally authorized guardian must be obtained, as required by local laws and regulations 3. Documented evidence of a diagnosis of NT1 (type 1 narcolepsy) or NT2 (type 2 narcolepsy) as, in part, determined by an overnight PSG (polysomnography) and next-day MSLT (maintenance of sleep latency test) with 2 or more SOREMPs (sleep onset REM) with mean sleep latency in the pathological range i.e. \< 8 minutes and meeting the NT1 and NT2 as defined by the International Classification of Sleep Disorders -3 criteria. 4. Current continuing presence of EDS (excessive daytime sleepiness) as defined by subject report for the last 3 months and an ESS (Epworth sleepiness scale) \> 10 5. For NT1 only, current continuing presence of cataplexy as defined by subject report for the last 3 months 6. Subjects may use concomitant stimulants, but must comply with the following: 1. They must be on a stable dose of stimulants for at least 3 weeks prior to starting the screening process for this study; AND 2. They must use the same stimulant regimen throughout the entire study period, including during screening and posttreatment periods 3. They must discontinue all anti cataplexy drugs 7. Addition inclusion criteria per protocol
Exclusion criteria
1. Any prior use of sodium oxybate is allowed in the study but within the following exclusions: 1. Previous dosing must have been limited to no more than 4.5g per night 2. Patient should not have taken sodium oxybate for more than 2 weeks. 3. All previous dosing must not have occurred within the last year prior to entry to the study. 2. Current use of sodium valproate 3. Any use of the following prohibited medications for the duration of the clinical study: 1. Anticonvulsants 2. Clonidine 3. SSRIs (selective serotonin re-uptake inhibitors) and serotonin and norepinephrine re-uptake inhibitors (SNRIs) 4. MAOIs (monoamine oxidase inhibitors) 5. TCAs (tricyclic antidepressants) 6. Hypnotics 7. Anxiolytics 8. Sedating antihistamines 9. Antipsychotics 10. Other experimental medications designed to treat narcolepsy, cataplexy or any other condition 4. Treatment with any investigational products within 3 months before study enrollment 5. Any drug known to affect sleep-wake function. Concomitant stimulant use is permitted 6. Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maintenance of Wakefulness Test (MWT) | Study Visit 8 at 14 weeks | Change from Baseline for MWT, which is the mean latency across 5 naps, averaged over the test day |
| Proportion of Patients That Were Very Much Improved or Much Improved on Clinical Global Impression of Improvement as Compared to Screening | Study Visit 8 at 14 weeks | The CGI is the clinician's global impression of improvement in daytime sleepiness. For the CGI, a GLIMMIX (generalized linear mixed models) model for binomial data with logit link was used to analyze the categorized CGI response, i.e., the proportions of subjects who were Very Much Improved or Much Improved as compared to Screening |
| Number of Cataplexy Attacks at Visit 8 (Week 14) as Compared to Baseline | Visit 8 - Change from Baseline at 14 Weeks | Mean number of cataplexy events recorded on the Sleep and Symptom Daily Diary during the period |
Countries
Australia, Canada, Czechia, France, Germany, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| FT218 Patients treated with FT218, once nightly sodium oxybate granules for oral suspension. | 107 |
| Placebo Matching Placebo | 105 |
| Total | 212 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 21 | 3 |
| Overall Study | Excluded Concomitant Medication | 0 | 1 |
| Overall Study | Lack of Efficacy | 2 | 8 |
| Overall Study | Lost to follow up | 2 | 0 |
| Overall Study | Non Compliance with Investigational Product | 0 | 1 |
| Overall Study | Pregnancy | 2 | 0 |
| Overall Study | Protocol Violation | 0 | 2 |
| Overall Study | Withdrawal by Subject | 11 | 11 |
Baseline characteristics
| Characteristic | FT218 | Total | Placebo |
|---|---|---|---|
| Age, Categorical <=18 years | 9 Participants | 21 Participants | 12 Participants |
| Age, Categorical >=65 years | 1 Participants | 3 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 97 Participants | 188 Participants | 91 Participants |
| Age, Continuous | 30.9 years STANDARD_DEVIATION 10.7 | 31.2 years STANDARD_DEVIATION 10.95 | 31.6 years STANDARD_DEVIATION 11.24 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 11 Participants | 8 Participants |
| Race (NIH/OMB) Black or African American | 21 Participants | 36 Participants | 15 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 | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) White | 80 Participants | 160 Participants | 80 Participants |
| Region of Enrollment Australia | 4 Participants | 11 Participants | 7 Participants |
| Region of Enrollment Canada | 28 Participants | 59 Participants | 31 Participants |
| Region of Enrollment Czechia | 1 Participants | 2 Participants | 1 Participants |
| Region of Enrollment Denmark | 6 Participants | 13 Participants | 7 Participants |
| Region of Enrollment France | 3 Participants | 8 Participants | 5 Participants |
| Region of Enrollment Netherlands | 1 Participants | 1 Participants | 0 Participants |
| Region of Enrollment United Kingdom | 1 Participants | 2 Participants | 1 Participants |
| Region of Enrollment United States | 63 Participants | 116 Participants | 53 Participants |
| Sex: Female, Male Female | 69 Participants | 144 Participants | 75 Participants |
| Sex: Female, Male Male | 38 Participants | 68 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 77 | 0 / 80 |
| other Total, other adverse events | 23 / 77 | 6 / 80 |
| serious Total, serious adverse events | 1 / 77 | 0 / 80 |
Outcome results
Primary
Maintenance of Wakefulness Test (MWT)
Change from Baseline for MWT, which is the mean latency across 5 naps, averaged over the test day
Time frame: Study Visit 8 at 14 weeks
Population: Maintenance of Wakefulness Test (MWT) Mean Sleep Latency (Minutes) Change from Baseline to the End of the 9.0g Treatment Period - MMRM (mixed model repeat measure) Analysis (mITT Population)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FT218 | Maintenance of Wakefulness Test (MWT) | 10.8 minutes | Standard Deviation 0.96 |
| Placebo | Maintenance of Wakefulness Test (MWT) | 4.7 minutes | Standard Deviation 0.92 |
p-value: <0.00195% CI: [3.52, 8.75]Mixed Models Analysis
Primary
Number of Cataplexy Attacks at Visit 8 (Week 14) as Compared to Baseline
Mean number of cataplexy events recorded on the Sleep and Symptom Daily Diary during the period
Time frame: Visit 8 - Change from Baseline at 14 Weeks
Population: Mean Weekly Number of Cataplexy Attacks (NCA) of Each Dosing Period, Change from Baseline to the End of 9.0g Treatment Period - MMRM Analysis (NT1 Subjects in mITT Population)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FT218 | Number of Cataplexy Attacks at Visit 8 (Week 14) as Compared to Baseline | -11.5 Cataplexy Attacks | Standard Deviation 0.96 |
| Placebo | Number of Cataplexy Attacks at Visit 8 (Week 14) as Compared to Baseline | -4.9 Cataplexy Attacks | Standard Deviation 0.95 |
p-value: <0.00195% CI: [-9.32, -3.98]Mixed Models Analysis
Primary
Proportion of Patients That Were Very Much Improved or Much Improved on Clinical Global Impression of Improvement as Compared to Screening
The CGI is the clinician's global impression of improvement in daytime sleepiness. For the CGI, a GLIMMIX (generalized linear mixed models) model for binomial data with logit link was used to analyze the categorized CGI response, i.e., the proportions of subjects who were Very Much Improved or Much Improved as compared to Screening
Time frame: Study Visit 8 at 14 weeks
Population: Clinical Global Impression - Improvement (CGI-I) by the End of 9.0g Treatment Period
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FT218 | Proportion of Patients That Were Very Much Improved or Much Improved on Clinical Global Impression of Improvement as Compared to Screening | 72.0 percentage of subjects |
| Placebo | Proportion of Patients That Were Very Much Improved or Much Improved on Clinical Global Impression of Improvement as Compared to Screening | 31.6 percentage of subjects |
p-value: <0.00195% CI: [2.76, 11.23]GLIMMIX model