Trial Comparing Effects of Xyrem Taken Orally and Modafinil With Placebo in Treating Daytime Sleepiness in Narcolepsy

Narcolepsy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00066170
• Other study ID #: OMC-SXB-22
• Status: Completed
• Phase: Phase 3
• First received: August 4, 2003
• Last updated: December 21, 2011
• Start date: April 2003
• Est. completion date: November 2004

Study information

• Verified date: December 2011
• Source: Jazz Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 231
• Est. completion date: November 2004
• Est. primary completion date: July 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Narcolepsy

Intervention

Drug:
• Xyrem
Xyrem oral solution at 6 g/day for 4 weeks and 9 g/day for another 4 weeks.
• Xyrem Placebo
Xyrem Placebo oral solution 12 ml per day for 4 weeks and 18 ml per day for another 4 weeks.
• Modafinil at established dose
Modafinil oral capsules at 200 to 600 mg per day for 8 weeks.
• Modafinil (Placebo)
Modafinil Placebo oral capsules 1 to 3 capsules per day for 8 weeks.

Locations

Country	Name	City	State
France	Centre du sommeil -- Hopital Gui de Chauliac	Montpellier	Cedex 5
France	Hopital Pitie Salpetriere -- Federation des Pathologies du sommeil	Paris	Cedex 13
Germany	Psychiatrische Universitatsklinik	Regensburg
Switzerland	Neurologische Poliklinik -- Universitats Spital Zurich	Zurich
United States	Lehigh Valley Hospital Sleep Disorders Center	Allentown	Pennsylvania
United States	Graves Gilbert Clinic	Bowling Green	Kentucky
United States	Capital Region Sleep Disorder Center	Carlisle	Pennsylvania
United States	Lowcountry Lung and Critical Care, PA	Charleston	South Carolina
United States	The Center for Sleep & Wake Disorders	Chevy Chase	Maryland
United States	Cincinnati Clinic & Sleep Management Institute	Cincinnati	Ohio
United States	Community Research Management Associates,Inc.	Cincinnati	Ohio
United States	SleepMed of South Carolina	Columbia	South Carolina
United States	Community Research & Sleep Management Institute	Crestview Hills	Kentucky
United States	The Center for Sleep and Wake Disorders/Midwest Neurology	Danville	Indiana
United States	Henry Ford Hospital	Detroit	Michigan
United States	New Jersey Neuroscience Institute at JFK Medical Center	Edison	New Jersey
United States	Sleep Disorders Center -- Union Hospital of Cecil County	Elkton	Maryland
United States	Vermont Medical Sleep Disorders Center, Inc.	Essex Junction	Vermont
United States	St. Jude Medical Center -- Sleep Disorders Institute	Fullerton	California
United States	CSC Research -- Grove City Sleep Diagnostic Center	Grove City	Ohio
United States	Center for Sleep Medicine	Lafayette Hill	Pennsylvania
United States	Pacific Sleep Medicine Services, Inc.	Los Angeles	California
United States	Chest Medicine Associates DBA -- Sleep Medicine Specialists	Louisville	Kentucky
United States	Bhupesh Dihenia, MD	Lubbock	Texas
United States	Neuro-Therapeutics, Inc.	Pasadena	California
United States	Peoria Pulmonary Associates, Ltd	Peoria	Illinois
United States	Pulmonary Associates, PA	Phoenix	Arizona
United States	Raleigh Neurology Associates	Raleigh	North Carolina
United States	Sleep Disorders Center of Rochester	Rochester	New York
United States	Strong Sleep Disorders Center	Rochester	New York
United States	SLEEP WALKER -- Sleep Disorders Center & Neurodiagnostics--Lung Diagnostics, Ltd.	San Antonio	Texas
United States	Pacific Sleep Medicine Services, Inc.	San Diego	California
United States	SDHRF Clinical Research Center	Sioux Falls	South Dakota
United States	Sioux Valley Clinic -- Pulmonary	Sioux Falls	South Dakota
United States	Sleep Disorders Center	Sioux Falls	South Dakota
United States	Washington University Sleep Center	St Louis	Missouri
United States	Clinical Research Group of St. Petersburg, Inc.	St. Petersburg	Florida
United States	Stanford Sleep Disorders Clinic	Stanford	California
United States	Sleep Medicine Associates of Maryland	Towson	Maryland
United States	ALL-TRIALS Clinical Research, LLC -- Summit Sleep Disorder	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Jazz Pharmaceuticals

Countries where clinical trial is conducted

United States,  France,  Germany,  Switzerland, 

References & Publications (6)

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

Black J, Houghton WC. Sodium oxybate improves excessive daytime sleepiness in narcolepsy. Sleep. 2006 Jul;29(7):939-46. — View 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. — 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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Daytime Sleep Latency as Measured by the Maintenance of Wakefulness Test (MWT)	The Maintenance of Wakefulness Test consisted of four 20 minute tests of the patient's ability to remain awake in soporific conditions. The Mean change from baseline to week 8 in the average MWT number of minutes until sleep onset was the primary endpoint.	Baseline to Week 8	No

External Links

•   Xyrem Informational website with the package insert