Safety and Efficacy of Xyrem Oral Solution (Sodium Oxybate) Compared With Placebo in Narcoleptic Patients

Narcolepsy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00049803
• Other study ID #: OMC-SXB-15
• Status: Completed
• Phase: Phase 3
• First received: November 13, 2002
• Last updated: June 23, 2005
• Start date: December 2000
• Est. completion date: April 2004

Study information

• Verified date: July 2004
• Source: Orphan Medical
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: April 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Narcolepsy

Intervention

Drug:
• sodium oxybate

Locations

Country	Name	City	State
Canada	Canadian Sleep Institute	Calgary	Alberta
Canada	Sleep Disorder Centre -- Hopital du Sacre-Coeur	Montreal	Quebec
Canada	The Ottawa Hospital Sleep Centre -- Ottawa Hospital -- Civic Campus -- Sleep Laboratory	Ottawa	Ontario
Canada	Saint John Regional Hospital -- Somnology Program	Saint John	New Brunswick
Canada	Brain & Sleep Diagnostic Center	Toronto	Ontario
Canada	The Sleep Disorders Clinic of the Centre for Sleep and Chronobiology	Toronto	Ontario
Canada	Vancouver Hospital -- Sleep Disorders Clinic	Vancouver	British Columbia
Switzerland	Neurologische Poliklinik - Universitats Spital Zurich	Zurich
United States	Sleep Disorders Center of Georgia	Atlanta	Georgia
United States	Sleep Disorders Center of Alabama, Inc.	Birmingham	Alabama
United States	Charleston Pulmonary Associates PA	Charleston	South Carolina
United States	Low Country Lung and Critical Care PA	Charleston	South Carolina
United States	Center for Sleep and Wake Disorders	Chevy Chase	Maryland
United States	Palmetto Baptist Medical Center Sleep Disorders Center	Columbia	South Carolina
United States	The Center for Sleep and Wake Disorders/Midwest Neurology	Danville	Indiana
United States	Duke University Medical Center	Durham	North Carolina
United States	Sleep Disorders Center--Division of Neurology	Evanston	Illinois
United States	Fort Wayne Neurological Center	Fort Wayne	Indiana
United States	Fort Wayne Neurological Center	Fort Wayne	Indiana
United States	CSC Research -- Grove City Sleep Diagnostic Center	Grove City	Ohio
United States	Sleep Medicine Assoc PLLC -- Summit Medical Center	Hermitage	Tennessee
United States	The Houston Sleep Center	Houston	Texas
United States	Pacific Sleep Medicine Services	La Jolla	California
United States	Chest Medicine Associates DBA/Sleep Medicine Specialists	Louisville	Kentucky
United States	Southwest Cleveland Sleep Center	Middleburg Heights	Ohio
United States	Charleston Pulmonary Associates PA	Mount Pleasant	South Carolina
United States	Sleep/Wake Center 7N2 -- Bellevue Hospital Center	New York	New York
United States	Center for Sleep Diagnostics	Newton	Massachusetts
United States	Sleep Disorders Center -- Eastern Virginia Medical School -- Sentara General Hospital	Norfolk	Virginia
United States	Lynn Health Science Institute	Oklahoma City	Oklahoma
United States	Peoria Pulmonary Associates, Ltd.	Peoria	Illinois
United States	Sleep Medicine Associates of Texas	Plano	Texas
United States	Miriam Hospital	Providence	Rhode Island
United States	Rhode Island Hospital - Division of Pulmonary, Sleep and Critical Care Medicine	Providence	Rhode Island
United States	Raleigh Neurology Associates	Raleigh	North Carolina
United States	VCU Health System MCV Hospitals - Sleep Disorders Center	Richmond	Virginia
United States	Washington University -- Sleep Medicine Center	Saint Louis	Missouri
United States	Central Carolina Neurology & Sleep	Salisbury	North Carolina
United States	Swedish Sleep Medicine Institute	Seattle	Washington
United States	LSU Health Science Center	Shreveport	Louisiana
United States	St. Petersburg Sleep Disorders Center	St. Petersburg	Florida
United States	Stanford Sleep Disorders Clinic	Stanford	California
United States	The Sleep Center - Community General Hospital	Syracuse	New York
United States	Clinical Pharmaceutical Trials, Inc.	Tulsa	Oklahoma
United States	Department of Neurology	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Orphan Medical

Countries where clinical trial is conducted

United States,  Canada,  Switzerland, 

References & Publications (4)

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. — View 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. — View 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. — View 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. — View Citation