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

NCT02720744 | Completed Phase 3 Results DMC

• 1 other identifier: CLFT218-1501
• Study Type: interventional
• Target: 212
• Locations: 6 countries
• Sites: 57

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.

Conditions

Excessive Daytime Sleepiness; Cataplexy; Narcolepsy

Outcome Measures

Primary Outcomes (3)

• Maintenance of Wakefulness Test (MWT)

  Change from Baseline for MWT, which is the mean latency across 5 naps, averaged over the test day

  Study Visit 8 at 14 weeks

• 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

  Study Visit 8 at 14 weeks

• 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

  Visit 8 - Change from Baseline at 14 Weeks

Study Arms (2)

Sodium Oxybate

EXPERIMENTAL

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.

Drug: FT218

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

FT218 DRUG

Sodium Oxybate

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects 16 years of age or older
• 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
• 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.
• 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
• For NT1 only, current continuing presence of cataplexy as defined by subject report for the last 3 months
• Subjects may use concomitant stimulants, but must comply with the following:
• They must be on a stable dose of stimulants for at least 3 weeks prior to starting the screening process for this study; AND
• They must use the same stimulant regimen throughout the entire study period, including during screening and posttreatment periods
• They must discontinue all anti cataplexy drugs

You may not qualify if:

• Previous dosing must have been limited to no more than 4.5g per night
• Patient should not have taken sodium oxybate for more than 2 weeks.
• All previous dosing must not have occurred within the last year prior to entry to the study.
• Current use of sodium valproate
• Any use of the following prohibited medications for the duration of the clinical study:
• Anticonvulsants
• Clonidine
• SSRIs (selective serotonin re-uptake inhibitors) and serotonin and norepinephrine re-uptake inhibitors (SNRIs)
• MAOIs (monoamine oxidase inhibitors)
• TCAs (tricyclic antidepressants)
• Hypnotics
• Anxiolytics
• Sedating antihistamines
• Antipsychotics
• Other experimental medications designed to treat narcolepsy, cataplexy or any other condition

Sponsors & Collaborators

• Avadel: lead

Study Sites (57)

Pinnacle Research Group LLC

Anniston, Alabama, 36207, United States

Location

University Sleep Disorder Center

Auburn, Alabama, AL 36832, United States

Location

Sleep Disorders Center of Alabama

Birmingham, Alabama, 35213, United States

Location

Baptist Health Center for Clinical Research

Little Rock, Arkansas, 72205, United States

Location

California Center for Sleep Disorders

Alameda, California, 94501, United States

Location

Stanford Sleep Medicine

Redwood City, California, 94063, United States

Location

SDS Clinical Trials Inc

Santa Ana, California, CA 92705, United States

Location

Alpine Research Center

Boulder, Colorado, 80301, United States

Location

Yale-New Haven Hospital's Sleep Medicine Center

North Haven, Connecticut, 06473, United States

Location

Pulmonary Disease Specialist, PA

Kissimmee, Florida, 34741, United States

Location

Sleep Medicine Specialists of South Florida

Miami, Florida, 33176, United States

Location

Sleep Medicine Specialist of South Florida

Miami, Florida, FL 33126, United States

Location

NeuroMedical Research Institute/Global Research Holdings, LLC

Panama City, Florida, FL 32405, United States

Location

FL Pediatric REsearch Institute

Winter Park, Florida, 32789, United States

Location

Florida Pulmonary Research Institute LLC

Winter Park, Florida, 32789, United States

Location

NeuroTrials Research Inc

Atlanta, Georgia, 30342, United States

Location

Sleep Disorders Center of Georgia

Atlanta, Georgia, GA 30342, United States

Location

Clinical Research Institute

Stockbridge, Georgia, 30281, United States

Location

OSF Healthcare Saint Francis Medical Center

Peoria, Illinois, 61637, United States

Location

Fort Wayne Neurological Center

Fort Wayne, Indiana, IN 46804, United States

Location

Norton Clinical Research Group

Louisville, Kentucky, KY40218, United States

Location

Center for Sleep and Wake Disorders

Chevy Chase, Maryland, 20815, United States

Location

Infinity Medical Research

North Dartmouth, Massachusetts, MA 2747, United States

Location

Unknown Facility

Chesterfield, Missouri, 63017, United States

Location

Unknown Facility

St Louis, Missouri, 63143, United States

Location

Northwell Health

New Hyde Park, New York, NY 1040, United States

Location

Clinilabs Drug Development Corporation

New York, New York, NY10019, United States

Location

Montefiore Sleep-Wake Disorders Center

The Bronx, New York, 10467, United States

Location

Research Carolina of Huntersville

Huntersville, North Carolina, 28078, United States

Location

Wake Research Associates, LLC

Raleigh, North Carolina, NC 27612, United States

Location

Sleep Management Institute Intrepid Research

Cincinnati, Ohio, 45245, United States

Location

University Hospitals Case Medical Center

Cleveland, Ohio, 44106, United States

Location

Ohio Sleep Medicine Institute

Dublin, Ohio, 43017, United States

Location

Geisinger Medical Center

Danville, Pennsylvania, 17822, United States

Location

Medical University of South Carolina - Institute of Psychiatry

Charleston, South Carolina, SC 29425, United States

Location

SleepMed Of South Carolina

Columbia, South Carolina, 29201, United States

Location

Sleep and Neurology Consultants

Houston, Texas, 77063, United States

Location

Sleep Therapy Research Center

San Antonio, Texas, 78229, United States

Location

NHMRC CEntre for Translational Sleep and Circadian Neurobiology

Sydney, New South Wales, 2037, Australia

Location

Westmead Hospital

Sydney, New South Wales, NSW 2145, Australia

Location

Princess Alexandra Hospital

Brisbane, Queensland, QLD 4102, Australia

Location

Queen Elizabeth Hospital

Adelaide, South Australia, SA 5011, Australia

Location

Flinders Medical Centre

Adelaide, South Australia, SA 5042, Australia

Location

Melbourne Sleep Disorders Centre

Melbourne, Victoria, 3002, Australia

Location

Somni Research Inc. Calgary

Calgary, Alberta, T2X 2A8, Canada

Location

Okanagan Clinical Trials Ltd

Kelowna, British Columbia, BC V1Y 1Z9, Canada

Location

West Parry Sound Health Center

Parry Sound, Ontario, P2A 3A4, Canada

Location

Somni Research Inc

Toronto, Ontario, L3R 1A3, Canada

Location

Paediatric Sleep Research Inc

Toronto, Ontario, M5G 1N8, Canada

Location

CIUSS de Nord-de-I'ile-de- Montreal- Hopital de Sacre-Coeur de Montreal

Montreal, Quebec, 5400, Canada

Location

Vseobecna Facultni Nemocnice

Prague, 212821, Czechia

Location

CHU Michallon

Grenoble, 938043, France

Location

Hospital Gui-de-de-Chauliac

Montpellier, 34295, France

Location

INSERM - Centre d'Investigation Clinque Hopital Robert Debre

Paris, 75019, France

Location

Charit Universittsmedizin Berlin

Berlin, 10117, Germany

Location

Hephata Klinik

Schwalmstadt, 34131, Germany

Location

Somni bene GmbH

Schwerin, 19053, Germany

Location

Related Publications (7)

• Ortiz LE, Morse AM, Thorpy MJ, Kushida CA, Harsh J, Roth T, Gudeman J, Dauvilliers Y. Once-Nightly Sodium Oxybate Meets American Academy of Sleep Medicine Criteria for Treatment of Narcolepsy. J Sleep Res. 2025 Aug 25:e70189. doi: 10.1111/jsr.70189. Online ahead of print.

  PMID: 40851446 DERIVED

• Roth T, Thorpy MJ, Kushida CA, Gudeman J. Efficacy of Once-Nightly Sodium Oxybate in Patients with Narcolepsy: Post Hoc Analyses of Sensitivity, Effect Size, and Numbers Needed to Treat from the Phase 3 REST-ON Trial. CNS Drugs. 2025 Mar;39(Suppl 1):61-70. doi: 10.1007/s40263-025-01160-0. Epub 2025 Mar 20.

  PMID: 40111739 DERIVED

• Krahn L, Roy A, Winkelman JW, Morse AM, Gudeman J. Assessing Early Efficacy After Initiation of Once-Nightly Sodium Oxybate (ON-SXB; FT218) in Participants with Narcolepsy Type 1 or 2: A Post Hoc Analysis from the Phase 3 REST-ON Trial. CNS Drugs. 2025 Mar;39(Suppl 1):53-59. doi: 10.1007/s40263-024-01143-7. Epub 2025 Mar 20.

  PMID: 40111738 DERIVED

• Dauvilliers Y, Roth T, Bogan R, Thorpy MJ, Morse AM, Roy A, Gudeman J. Efficacy of once-nightly sodium oxybate (FT218) on daytime symptoms in individuals with narcolepsy with or without concomitant alerting agent use: A post hoc analysis from the phase 3 REST-ON trial. Sleep Med. 2024 Dec;124:209-216. doi: 10.1016/j.sleep.2024.09.024. Epub 2024 Sep 17.

  PMID: 39321628 DERIVED

• Roth T, Morse AM, Bogan R, Roy A, Gudeman J, Dauvilliers Y. Weight Loss With Once-nightly Sodium Oxybate for the Treatment of Narcolepsy: Analysis From the Phase III Randomized study Evaluating the efficacy and SafeTy of a ONce nightly formulation of sodium oxybate (REST-ON) Trial. Clin Ther. 2024 Oct;46(10):791-798. doi: 10.1016/j.clinthera.2024.07.010. Epub 2024 Aug 16.

  PMID: 39153911 DERIVED

• 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.

  PMID: 35380374 DERIVED

• 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.

  PMID: 34358324 DERIVED

MeSH Terms

Conditions

Disorders of Excessive Somnolence; Cataplexy; Narcolepsy

Condition Hierarchy (Ancestors)

Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders

Results Point of Contact

• Title: Jennifer Gudeman
• Organization: Flamel Ireland Limited

jgudeman@avadel.com

+1 (314) 750-2751

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 22, 2016
• First Posted: March 28, 2016
• Study Start: November 17, 2016
• Primary Completion: March 25, 2020
• Study Completion: March 25, 2020
• Last Updated: March 22, 2022
• Results First Posted: March 22, 2022

Record last verified: 2022-03

Locations

CZ (1); DE (3); CA (6); US (38); AU (6); FR (3)