Once-Nightly Sodium Oxybate for Treatment of Excessive Daytime Sleepiness and Cataplexy in Narcolepsy

Phase 3

Completed

• Conditions: Narcolepsy; Excessive Daytime Sleepiness; Cataplexy
• Interventions: Drug: FT218; Drug: Placebo

• Registration Number: NCT02720744
• Lead Sponsor: Avadel

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-03-22
• Study First Submitted QC: 2016-03-25
• Study First Posted: 2016-03-28
• Study Start: 2016-11-17
• Primary Completion: 2020-03-25
• Study Completion: 2020-03-25
• Results First Submitted: 2022-01-06
• Status Verified: 2022-03
• Results First Submitted QC: 2022-03-18
• Last Update Submitted: 2022-03-18
• Results First Posted: 2022-03-22
• Last Update Posted: 2022-03-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 212

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sodium Oxybate	FT218	Patients will undergo a screening period and will then be titrated to the following once-nightly doses: 4.5 g sodium oxybate, 6.0 g sodium oxybate, 7.5 g sodium oxybate, and 9.0 g sodium oxybate.
Placebo	Placebo	Patients will undergo a screening period and will then be titrated to the following once-nightly doses: 4.5 g placebo, 6.0 g placebo, 7.5 g placebo, and 9.0 g placebo.

Primary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (55)

Okanagan Clinical Trials Ltd; 🇨🇦 Kelowna, British Columbia, Canada

Stanford Sleep Medicine; 🇺🇸 Redwood City, California, United States

FL Pediatric REsearch Institute; 🇺🇸 Winter Park, Florida, United States

Wake Research Associates, LLC; 🇺🇸 Raleigh, North Carolina, United States

Sleep Medicine Specialists of South Florida; 🇺🇸 Miami, Florida, United States

NeuroTrials Research Inc; 🇺🇸 Atlanta, Georgia, United States

Sleep Disorders Center of Georgia; 🇺🇸 Atlanta, Georgia, United States

University Hospitals Case Medical Center; 🇺🇸 Cleveland, Ohio, United States

Sleep and Neurology Consultants; 🇺🇸 Houston, Texas, United States

Sleep Therapy Research Center; 🇺🇸 San Antonio, Texas, United States

University Sleep Disorder Center; 🇺🇸 Auburn, Alabama, United States

SDS Clinical Trials Inc; 🇺🇸 Santa Ana, California, United States

Sleep Medicine Specialist of South Florida; 🇺🇸 Miami, Florida, United States

Baptist Health Center for Clinical Research; 🇺🇸 Little Rock, Arkansas, United States

Sleep Disorders Center of Alabama; 🇺🇸 Birmingham, Alabama, United States

Pinnacle Research Group LLC; 🇺🇸 Anniston, Alabama, United States

California Center for Sleep Disorders; 🇺🇸 Alameda, California, United States

Pulmonary Disease Specialist, PA; 🇺🇸 Kissimmee, Florida, United States

Florida Pulmonary Research Institute LLC; 🇺🇸 Winter Park, Florida, United States

Geisinger Medical Center; 🇺🇸 Danville, Pennsylvania, United States

Northwell Health; 🇺🇸 New Hyde Park, New York, United States

Clinical Research Institute; 🇺🇸 Stockbridge, Georgia, United States

Infinity Medical Research; 🇺🇸 North Dartmouth, Massachusetts, United States

Ohio Sleep Medicine Institute; 🇺🇸 Dublin, Ohio, United States

NHMRC CEntre for Translational Sleep and Circadian Neurobiology; 🇦🇺 Sydney, New South Wales, Australia

CIUSS de Nord-de-I'ile-de- Montreal- Hopital de Sacre-Coeur de Montreal; 🇨🇦 Montreal, Quebec, Canada

Queen Elizabeth Hospital; 🇦🇺 Adelaide, South Australia, Australia

Princess Alexandra Hospital; 🇦🇺 Brisbane, Queensland, Australia

Vseobecna Facultni Nemocnice; 🇨🇿 Praha, Czechia

Somni Research Inc. Calgary; 🇨🇦 Calgary, Alberta, Canada

Melbourne Sleep Disorders Centre; 🇦🇺 Melbourne, Victoria, Australia

West Parry Sound Health Center; 🇨🇦 Parry Sound, Ontario, Canada

Hephata Klinik; 🇩🇪 Schwalmstadt, Germany

Charit Universittsmedizin Berlin; 🇩🇪 Berlin, Germany

Somni bene GmbH; 🇩🇪 Schwerin, Germany

Fort Wayne Neurological Center; 🇺🇸 Fort Wayne, Indiana, United States

Center for Sleep and Wake Disorders; 🇺🇸 Chevy Chase, Maryland, United States

Clinilabs Drug Development Corporation; 🇺🇸 New York, New York, United States

SleepMed Of South Carolina; 🇺🇸 Columbia, South Carolina, United States

Research Carolina of Huntersville; 🇺🇸 Huntersville, North Carolina, United States

Westmead Hospital; 🇦🇺 Sydney, New South Wales, Australia

Flinders Medical Centre; 🇦🇺 Adelaide, South Australia, Australia

Paediatric Sleep Research Inc; 🇨🇦 Toronto, Ontario, Canada

Somni Research Inc; 🇨🇦 Toronto, Ontario, Canada

CHU Michallon; 🇫🇷 Grenoble, France

INSERM - Centre d'Investigation Clinque Hopital Robert Debre; 🇫🇷 Paris, France

Sleep Management Institute Intrepid Research; 🇺🇸 Cincinnati, Ohio, United States

Yale-New Haven Hospital's Sleep Medicine Center; 🇺🇸 North Haven, Connecticut, United States

Alpine Research Center; 🇺🇸 Boulder, Colorado, United States

OSF Healthcare Saint Francis Medical Center; 🇺🇸 Peoria, Illinois, United States

Hospital Gui-de-de-Chauliac; 🇫🇷 Montpellier, France

Norton Clinical Research Group; 🇺🇸 Louisville, Kentucky, United States

Montefiore Sleep-Wake Disorders Center; 🇺🇸 Bronx, New York, United States

Medical University of South Carolina - Institute of Psychiatry; 🇺🇸 Charleston, South Carolina, United States

NeuroMedical Research Institute/Global Research Holdings, LLC; 🇺🇸 Panama City, Florida, United States