Clinical trial NCT00066170: Trial Comparing Effects of Xyrem Taken Orally and Modafinil With Placebo in Treating Daytime Sleepiness in Narcolepsy
Official title: Randomized, Double-Blind, Double-Dummy, Placebo-Controlled, Parallel-Group, Multi-Center Trial Comparing the Effects of Orally Administered Xyrem (Sodium Oxybate) and Modafinil With Placebo in Treatment of Daytime Sleepiness in Narcolepsy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Narcolepsy
Keywords: Narcolepsy
Daytime Sleepiness
Daytime sleepiness in narcolepsy
Lead sponsor: Jazz Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2003-08-06
Enrollment: 231
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will be conducted as a randomized, double blind, double-dummy, placebo-controlled, parallel-group trial in patients diagnosed with narcolepsy. Volunteers for this trial will be required to make 5 visits over up to 14 weeks to a participating expert physician practitioner for various sleep and narcolepsy evaluations and diaries will also be collected. Participants will take assigned medications during the course of the trial. Subjects will have a 25% probability of receiving placebo for both drugs (modafinil and Xyrem). All subject volunteers must meet criteria for narcolepsy and have evidence of daytime sleepiness. Patients will not incur any personal medical expenses due to participation in this trial. The sponsor is covering all visit costs not covered by insurance and there are some funds for patient expenses such as travel.


Eligibility criteria: INCLUSION CRITERIA

Patients will be included in the trial if they:

* Have signed and dated an informed consent prior to beginning protocol required procedures.
* Are willing and able to complete the entire trial as described in the protocol.
* Are 18 years of age or older.
* Fulfill the International Classification of Sleep Disorders criteria for the diagnosis of narcolepsy.
* Are taking stable doses of modafinil (200 to 600 mg/day) for the treatment of daytime sleepiness for a period of three months or greater and the modafinil dose has been stable for at least 1 month prior to entering this trial
* Females may be included who are surgically sterile, two years post-menopausal, or if of child-bearing potential, using a medically accepted method of birth control (e.g., barrier method with spermicide, oral contraceptive, or abstinence) and agree to continue use of this method for the duration of the trial.
* In the opinion of the investigator have adequate support for the duration of the trial to include transportation to and from the trial site. In addition, if in the investigator's assessment it is clinically indicated, the patient is willing to not operate a car or heavy machinery for the duration of the trial or for as long as the investigator deems clinically indicated.

EXCLUSION CRITERIA

Patients will be excluded from the trial if they:

* Have received gamma-hydroxybutyrate in the last 30 days.
* Have taken any investigational therapy within the 30-day period prior to the initial screening visit (Visit 1) for this trial.
* Have sleep apnea syndrome, defined as an Apnea Index \> 10 per hour or an AHI (Apnea Hypopnea Index) greater than 15 per hour, or have any other cause of daytime sleepiness, and have any other disorder(s) that can be considered a primary cause of excessive daytime sleepiness (e.g., severe periodic leg movement syndrome as determined by the investigator, sleep apnea, sleep deprivation).
* Are taking hypnotics, tranquilizers, antihistamines (except for non-sedating antihistamines), benzodiazepines or clonidine at the start of the baseline period. Patients taking anticonvulsants are not eligible to participate event if they are willing to washout anticonvulsants for the trial.
* Are experiencing any major illness, including unstable cardiovascular, endocrine, neoplastic, gastrointestinal, hematologic, hepatic, immunologic, metabolic, neurological (other than narcolepsy/cataplexy), pulmonary, and/or renal disease which would place the patient at risk during the trial or compromise the objectives outlined in the protocol.
* Have psychiatric disorders, major affective or psychotic disorders, or other problems that, in the investigator's opinion, would preclude the patient's participation and completion of this trial or compromise reliable representation of subjective symptoms.
* Have a current or recent (within one year) history of a substance use disorder including alcohol abuse as defined by the DSM-IV.
* Have a serum creatinine greater than 2.0 mg/dL, abnormal liver function tests (SGOT \[AST\] or SGPT \[ALT\] more than twice the upper limit of normal), or elevated serum bilirubin (more than 1.5 times the upper limit of normal), or pre-trial ECG results demonstrating clinically significant arrhythmias, greater than a first degree AV block or a history of myocardial infarction within the last six months.
* Have an occupation that requires variable shift work or routine night shift.
* Have a clinically significant history of seizure disorder either past or present, a history of clinically significant head trauma (i.e., concussion resulting in clinically significant loss of consciousness) or past invasive intracranial surgery, and are taking anticonvulsant medications.

Primary outcomes:
measure: Daytime Sleep Latency as Measured by the Maintenance of Wakefulness Test (MWT)
timeFrame: Baseline to Week 8
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Pulmonary Associates, PA
state: Arizona
city: Fullerton
country: United States
facility: St. Jude Medical Center -- Sleep Disorders Institute
state: California
city: Los Angeles
country: United States
facility: Pacific Sleep Medicine Services, Inc.
state: California
city: Pasadena
country: United States
facility: Neuro-Therapeutics, Inc.
state: California
city: San Diego
country: United States
facility: Pacific Sleep Medicine Services, Inc.
state: California
city: Stanford
country: United States
facility: Stanford Sleep Disorders Clinic
state: California
city: St. Petersburg
country: United States
facility: Clinical Research Group of St. Petersburg, Inc.
state: Florida
city: Peoria
country: United States
facility: Peoria Pulmonary Associates, Ltd
state: Illinois
city: Danville
country: United States
facility: The Center for Sleep and Wake Disorders/Midwest Neurology
state: Indiana
city: Bowling Green
country: United States
facility: Graves Gilbert Clinic
state: Kentucky
city: Crestview Hills
country: United States
facility: Community Research & Sleep Management Institute
state: Kentucky
city: Louisville
country: United States
facility: Chest Medicine Associates DBA -- Sleep Medicine Specialists
state: Kentucky
city: Chevy Chase
country: United States
facility: The Center for Sleep & Wake Disorders
state: Maryland
city: Elkton
country: United States
facility: Sleep Disorders Center -- Union Hospital of Cecil County
state: Maryland
city: Towson
country: United States
facility: Sleep Medicine Associates of Maryland
state: Maryland
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: St Louis
country: United States
facility: Washington University Sleep Center
state: Missouri
city: Edison
country: United States
facility: New Jersey Neuroscience Institute at JFK Medical Center
state: New Jersey
city: Rochester
country: United States
facility: Sleep Disorders Center of Rochester
state: New York
city: Rochester
country: United States
facility: Strong Sleep Disorders Center
state: New York
city: Raleigh
country: United States
facility: Raleigh Neurology Associates
state: North Carolina
city: Winston-Salem
country: United States
facility: ALL-TRIALS Clinical Research, LLC -- Summit Sleep Disorder
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Clinic & Sleep Management Institute
state: Ohio
city: Cincinnati
country: United States
facility: Community Research Management Associates,Inc.
state: Ohio
city: Grove City
country: United States
facility: CSC Research -- Grove City Sleep Diagnostic Center
state: Ohio
city: Allentown
country: United States
facility: Lehigh Valley Hospital Sleep Disorders Center
state: Pennsylvania
city: Carlisle
country: United States
facility: Capital Region Sleep Disorder Center
state: Pennsylvania
city: Lafayette Hill
country: United States
facility: Center for Sleep Medicine
state: Pennsylvania
city: Charleston
country: United States
facility: Lowcountry Lung and Critical Care, PA
state: South Carolina
city: Columbia
country: United States
facility: SleepMed of South Carolina
state: South Carolina
city: Sioux Falls
country: United States
facility: SDHRF Clinical Research Center
state: South Dakota
city: Sioux Falls
country: United States
facility: Sioux Valley Clinic -- Pulmonary
state: South Dakota
city: Sioux Falls
country: United States
facility: Sleep Disorders Center
state: South Dakota
city: Lubbock
country: United States
facility: Bhupesh Dihenia, MD
state: Texas
city: San Antonio
country: United States
facility: SLEEP WALKER -- Sleep Disorders Center & Neurodiagnostics--Lung Diagnostics, Ltd.
state: Texas
city: Essex Junction
country: United States
facility: Vermont Medical Sleep Disorders Center, Inc.
state: Vermont
city: Paris
country: France
facility: Hopital Pitie Salpetriere -- Federation des Pathologies du sommeil
state: Cedex 13
city: Montpellier
country: France
facility: Centre du sommeil -- Hopital Gui de Chauliac
state: Cedex 5
city: Regensburg
country: Germany
facility: Psychiatrische Universitatsklinik
city: Zurich
country: Switzerland
facility: Neurologische Poliklinik -- Universitats Spital Zurich
Study officials:
affiliation: Jazz Pharmaceuticals, Inc
name: Yanping Zheng, MD
role: STUDY_DIRECTOR
References:
citation: A randomized, double blind, placebo-controlled multicenter trial comparing the effects of three doses of orally administered sodium oxybate with placebo for the treatment of narcolepsy. Sleep. 2002 Feb 1;25(1):42-9.
citation: Scrima L, Hartman PG, Johnson FH Jr, Thomas EE, Hiller FC. The effects of gamma-hydroxybutyrate on the sleep of narcolepsy patients: a double-blind study. Sleep. 1990 Dec;13(6):479-90. doi: 10.1093/sleep/13.6.479.
citation: Lammers GJ, Arends J, Declerck AC, Ferrari MD, Schouwink G, Troost J. Gammahydroxybutyrate and narcolepsy: a double-blind placebo-controlled study. Sleep. 1993 Apr;16(3):216-20. doi: 10.1093/sleep/16.3.216.
citation: A 12-month, open-label, multicenter extension trial of orally administered sodium oxybate for the treatment of narcolepsy. Sleep. 2003 Feb 1;26(1):31-5.
citation: Black J, Houghton WC. Sodium oxybate improves excessive daytime sleepiness in narcolepsy. Sleep. 2006 Jul;29(7):939-46. doi: 10.1093/sleep/29.7.939.
citation: Black J, Pardi D, Hornfeldt CS, Inhaber N. The nightly use of sodium oxybate is associated with a reduction in nocturnal sleep disruption: a double-blind, placebo-controlled study in patients with narcolepsy. J Clin Sleep Med. 2010 Dec 15;6(6):596-602.
citation: Husain AM, Bujanover S, Ryan R, Scheckner B, Black J, Profant J. Incidence and duration of common, early-onset adverse events occurring during 2 randomized, placebo-controlled, phase 3 studies of sodium oxybate in participants with narcolepsy. J Clin Sleep Med. 2020 Sep 15;16(9):1469-1474. doi: 10.5664/jcsm.8530.
citation: Dauvilliers Y, Roth T, Guinta D, Alvarez-Horine S, Dynin E, Black J. Effect of sodium oxybate, modafinil, and their combination on disrupted nighttime sleep in narcolepsy. Sleep Med. 2017 Dec;40:53-57. doi: 10.1016/j.sleep.2017.07.030. Epub 2017 Oct 7.