Clinical trial NCT00049803: Safety and Efficacy of Xyrem Oral Solution (Sodium Oxybate) Compared With Placebo in Narcoleptic Patients
Official title: Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multi-Center Trial Comparing the Effects of Orally Administered Xyrem (Sodium Oxybate) With Placebo for the Treatment of Narcolepsy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Narcolepsy
Keywords: Narcolepsy
Sodium Oxybate
Cataplexy
Excessive Daytime Sleepiness
GHB
Gamma Hydroxybutyric Acid
Orphan Medical
Orphan Drug
Lead sponsor: Orphan Medical
Sponsor class: INDUSTRY
First posted: 2002-11-15
Enrollment: 200
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 initial portion of the protocol involves discontinuing any medications for cataplexy that the patient may be taking. Subsequently, the patient is prescribed a dose of oral solution of study drug or placebo over a 10-11 week period. During the trial, narcolepsy symptoms will be evaluated. Participants are allowed to continue using stimulant medications at constant doses during the study. A total of 1 to 3 daytime visits in addition to 4 overnight visits to the sleep center will be required to complete the study.


Eligibility criteria: INCLUSION CRITERIA

* Have signed \& dated informed consent before beginning protocol procedures.
* Willing \& able to complete entire trial as described in protocol.
* 16 years of age or older.
* Have a history and presenting symptoms of excessive daytime sleepiness.
* Have a history of cataplexy localizable to a specific muscle group(s) or part(s) of body during which the patient is lucid (not experiencing an inadvertent nap or micro sleep).
* Have valid PSG \& MSLT scores (collected during an overnight test) within last five years and a current diagnosis of narcolepsy according to the following criteria established by the American Sleep Disorders Association: (1) Recurrent daytime naps or lapses into sleep occur almost daily for at least 3 months; (2) Sudden bilateral loss of postural muscle tone occurs in association with intense emotion (cataplexy); (3) Polysomnography demonstrates one or more of the following: (a) Sleep latency less than 10 minutes; (b) REM sleep latency less than 20 minutes; (c) An MSLT that demonstrates a mean sleep latency of less than 5 minutes; (d) Two or more sleep-onset REM periods
* Females who are surgically sterile, two years post-menopausal, or if of child-bearing potential, using a medically accepted method of birth control 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 trial to include transportation to and from 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

* Received gamma-hydroxybutyrate in the last 30 days.
* Have taken any investigational therapy within 30-day period prior to initial screening visit for this trial.
* Patients taking fluoxetine (Prozac).
* Have been diagnosed with sleep apnea syndrome, defined as an Apnea Index \> 10 per hour or an 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.
* 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 even if willing to washout anticonvulsants for the trial.
* Experiencing unstable cardiovascular, endocrine, neoplastic (excluding localized basal cell carcinoma), 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 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 current or recent (within one year) history of a substance use disorder including alcohol abuse as defined by DSM-IV.
* 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 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 last six months.
* Have an occupation that requires variable shift work or routine night shift.
* Have a clinically significant history of seizure disorder, 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:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Sleep Disorders Center of Alabama, Inc.
state: Alabama
city: La Jolla
country: United States
facility: Pacific Sleep Medicine Services
state: California
city: Stanford
country: United States
facility: Stanford Sleep Disorders Clinic
state: California
city: St. Petersburg
country: United States
facility: St. Petersburg Sleep Disorders Center
state: Florida
city: Atlanta
country: United States
facility: Sleep Disorders Center of Georgia
state: Georgia
city: Evanston
country: United States
facility: Sleep Disorders Center--Division of Neurology
state: Illinois
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: Fort Wayne
country: United States
facility: Fort Wayne Neurological Center
state: Indiana
city: Fort Wayne
country: United States
facility: Fort Wayne Neurological Center
state: Indiana
city: Louisville
country: United States
facility: Chest Medicine Associates DBA/Sleep Medicine Specialists
state: Kentucky
city: Shreveport
country: United States
facility: LSU Health Science Center
state: Louisiana
city: Chevy Chase
country: United States
facility: Center for Sleep and Wake Disorders
state: Maryland
city: Newton
country: United States
facility: Center for Sleep Diagnostics
state: Massachusetts
city: Worcester
country: United States
facility: Department of Neurology
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University -- Sleep Medicine Center
state: Missouri
city: New York
country: United States
facility: Sleep/Wake Center 7N2 -- Bellevue Hospital Center
state: New York
city: Syracuse
country: United States
facility: The Sleep Center - Community General Hospital
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Raleigh
country: United States
facility: Raleigh Neurology Associates
state: North Carolina
city: Salisbury
country: United States
facility: Central Carolina Neurology & Sleep
state: North Carolina
city: Grove City
country: United States
facility: CSC Research -- Grove City Sleep Diagnostic Center
state: Ohio
city: Middleburg Heights
country: United States
facility: Southwest Cleveland Sleep Center
state: Ohio
city: Oklahoma City
country: United States
facility: Lynn Health Science Institute
state: Oklahoma
city: Tulsa
country: United States
facility: Clinical Pharmaceutical Trials, Inc.
state: Oklahoma
city: Providence
country: United States
facility: Rhode Island Hospital - Division of Pulmonary, Sleep and Critical Care Medicine
state: Rhode Island
city: Providence
country: United States
facility: Miriam Hospital
state: Rhode Island
city: Charleston
country: United States
facility: Charleston Pulmonary Associates PA
state: South Carolina
city: Charleston
country: United States
facility: Low Country Lung and Critical Care PA
state: South Carolina
city: Columbia
country: United States
facility: Palmetto Baptist Medical Center Sleep Disorders Center
state: South Carolina
city: Mount Pleasant
country: United States
facility: Charleston Pulmonary Associates PA
state: South Carolina
city: Hermitage
country: United States
facility: Sleep Medicine Assoc PLLC -- Summit Medical Center
state: Tennessee
city: Houston
country: United States
facility: The Houston Sleep Center
state: Texas
city: Plano
country: United States
facility: Sleep Medicine Associates of Texas
state: Texas
city: Norfolk
country: United States
facility: Sleep Disorders Center -- Eastern Virginia Medical School -- Sentara General Hospital
state: Virginia
city: Richmond
country: United States
facility: VCU Health System MCV Hospitals - Sleep Disorders Center
state: Virginia
city: Seattle
country: United States
facility: Swedish Sleep Medicine Institute
state: Washington
city: Calgary
country: Canada
facility: Canadian Sleep Institute
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver Hospital -- Sleep Disorders Clinic
state: British Columbia
city: Saint John
country: Canada
facility: Saint John Regional Hospital -- Somnology Program
state: New Brunswick
city: Ottawa
country: Canada
facility: The Ottawa Hospital Sleep Centre -- Ottawa Hospital -- Civic Campus -- Sleep Laboratory
state: Ontario
city: Toronto
country: Canada
facility: The Sleep Disorders Clinic of the Centre for Sleep and Chronobiology
state: Ontario
city: Toronto
country: Canada
facility: Brain & Sleep Diagnostic Center
state: Ontario
city: Montreal
country: Canada
facility: Sleep Disorder Centre -- Hopital du Sacre-Coeur
state: Quebec
city: Zurich
country: Switzerland
facility: Neurologische Poliklinik - Universitats Spital Zurich
Study officials:
affiliation: Orphan Medical
name: William Houghton, MD
role: STUDY_CHAIR
affiliation: Orphan Medical
name: Harry N Cook, MBA, RPh
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: 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: Roth T, Dauvilliers Y, Guinta D, Alvarez-Horine S, Dynin E, Black J. Effect of sodium oxybate on disrupted nighttime sleep in patients with narcolepsy. J Sleep Res. 2017 Aug;26(4):407-414. doi: 10.1111/jsr.12468. Epub 2016 Nov 3.
citation: Bogan R, Swick T, Mamelak M, Kovacevic-Ristanovic R, Lai C, Black J, Villa KF, Montplaisir J. Evaluation of Quality of Life in Patients With Narcolepsy Treated With Sodium Oxybate: Use of the 36-Item Short-Form Health Survey in a Clinical Trial. Neurol Ther. 2016 Dec;5(2):203-213. doi: 10.1007/s40120-016-0053-5. Epub 2016 Oct 24.