Clinical trial NCT02720744: Once-Nightly Sodium Oxybate for Treatment of Excessive Daytime Sleepiness and Cataplexy in Narcolepsy
Official title: A Double-blind, Randomized, Placebo Controlled, Two Arm Multi-center Study to Assess the Efficacy and Safety of a Once Nightly Formulation of Sodium Oxybate for Extended-Release Oral Suspension (FT218) for the Treatment of Excessive Daytime Sleepiness and Cataplexy in Subjects With Narcolepsy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Excessive Daytime Sleepiness
Cataplexy
Narcolepsy
Lead sponsor: Avadel
Sponsor class: INDUSTRY
First posted: 2016-03-28
Enrollment: 212
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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 exclusion criteria per protocol

Primary outcomes:
measure: Maintenance of Wakefulness Test (MWT)
timeFrame: Study Visit 8 at 14 weeks
measure: Proportion of Patients That Were Very Much Improved or Much Improved on Clinical Global Impression of Improvement as Compared to Screening
timeFrame: Study Visit 8 at 14 weeks
measure: Number of Cataplexy Attacks at Visit 8 (Week 14) as Compared to Baseline
timeFrame: Visit 8 - Change from Baseline at 14 Weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Pinnacle Research Group LLC
state: Alabama
city: Auburn
country: United States
facility: University Sleep Disorder Center
state: Alabama
city: Birmingham
country: United States
facility: Sleep Disorders Center of Alabama
state: Alabama
city: Little Rock
country: United States
facility: Baptist Health Center for Clinical Research
state: Arkansas
city: Alameda
country: United States
facility: California Center for Sleep Disorders
state: California
city: Redwood City
country: United States
facility: Stanford Sleep Medicine
state: California
city: Santa Ana
country: United States
facility: SDS Clinical Trials Inc
state: California
city: Boulder
country: United States
facility: Alpine Research Center
state: Colorado
city: North Haven
country: United States
facility: Yale-New Haven Hospital's Sleep Medicine Center
state: Connecticut
city: Kissimmee
country: United States
facility: Pulmonary Disease Specialist, PA
state: Florida
city: Miami
country: United States
facility: Sleep Medicine Specialists of South Florida
state: Florida
city: Miami
country: United States
facility: Sleep Medicine Specialist of South Florida
state: Florida
city: Panama City
country: United States
facility: NeuroMedical Research Institute/Global Research Holdings, LLC
state: Florida
city: Winter Park
country: United States
facility: FL Pediatric REsearch Institute
state: Florida
city: Winter Park
country: United States
facility: Florida Pulmonary Research Institute LLC
state: Florida
city: Atlanta
country: United States
facility: NeuroTrials Research Inc
state: Georgia
city: Atlanta
country: United States
facility: Sleep Disorders Center of Georgia
state: Georgia
city: Stockbridge
country: United States
facility: Clinical Research Institute
state: Georgia
city: Peoria
country: United States
facility: OSF Healthcare Saint Francis Medical Center
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Neurological Center
state: Indiana
city: Louisville
country: United States
facility: Norton Clinical Research Group
state: Kentucky
city: Chevy Chase
country: United States
facility: Center for Sleep and Wake Disorders
state: Maryland
city: North Dartmouth
country: United States
facility: Infinity Medical Research
state: Massachusetts
city: Chesterfield
country: United States
state: Missouri
city: Saint Louis
country: United States
state: Missouri
city: Bronx
country: United States
facility: Montefiore Sleep-Wake Disorders Center
state: New York
city: New Hyde Park
country: United States
facility: Northwell Health
state: New York
city: New York
country: United States
facility: Clinilabs Drug Development Corporation
state: New York
city: Huntersville
country: United States
facility: Research Carolina of Huntersville
state: North Carolina
city: Raleigh
country: United States
facility: Wake Research Associates, LLC
state: North Carolina
city: Cincinnati
country: United States
facility: Sleep Management Institute Intrepid Research
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: Dublin
country: United States
facility: Ohio Sleep Medicine Institute
state: Ohio
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina - Institute of Psychiatry
state: South Carolina
city: Columbia
country: United States
facility: SleepMed Of South Carolina
state: South Carolina
city: Houston
country: United States
facility: Sleep and Neurology Consultants
state: Texas
city: San Antonio
country: United States
facility: Sleep Therapy Research Center
state: Texas
city: Sydney
country: Australia
facility: NHMRC CEntre for Translational Sleep and Circadian Neurobiology
state: New South Wales
city: Sydney
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Queen Elizabeth Hospital
state: South Australia
city: Adelaide
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Melbourne
country: Australia
facility: Melbourne Sleep Disorders Centre
state: Victoria
city: Calgary
country: Canada
facility: Somni Research Inc. Calgary
state: Alberta
city: Kelowna
country: Canada
facility: Okanagan Clinical Trials Ltd
state: British Columbia
city: Parry Sound
country: Canada
facility: West Parry Sound Health Center
state: Ontario
city: Toronto
country: Canada
facility: Somni Research Inc
state: Ontario
city: Toronto
country: Canada
facility: Paediatric Sleep Research Inc
state: Ontario
city: Montreal
country: Canada
facility: CIUSS de Nord-de-I'ile-de- Montreal- Hopital de Sacre-Coeur de Montreal
state: Quebec
city: Praha
country: Czechia
facility: Vseobecna Facultni Nemocnice
city: Grenoble
country: France
facility: CHU Michallon
city: Montpellier
country: France
facility: Hospital Gui-de-de-Chauliac
city: Paris
country: France
facility: INSERM - Centre d'Investigation Clinque Hopital Robert Debre
city: Berlin
country: Germany
facility: Charit Universittsmedizin Berlin
city: Schwalmstadt
country: Germany
facility: Hephata Klinik
city: Schwerin
country: Germany
facility: Somni bene GmbH
Study officials:
References:
citation: Roth T, Dauvilliers Y, Thorpy MJ, Kushida C, Corser BC, Bogan R, Rosenberg R, Dubow J, Seiden D. Effect of FT218, a Once-Nightly Sodium Oxybate Formulation, on Disrupted Nighttime Sleep in Patients with Narcolepsy: Results from the Randomized Phase III REST-ON Trial. CNS Drugs. 2022 Apr;36(4):377-387. doi: 10.1007/s40263-022-00904-6. Epub 2022 Apr 5.
citation: Kushida CA, Shapiro CM, Roth T, Thorpy MJ, Corser BC, Ajayi AO, Rosenberg R, Roy A, Seiden D, Dubow J, Dauvilliers Y. Once-nightly sodium oxybate (FT218) demonstrated improvement of symptoms in a phase 3 randomized clinical trial in patients with narcolepsy. Sleep. 2022 Jun 13;45(6):zsab200. doi: 10.1093/sleep/zsab200.