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

NCT ID: NCT00066170

Last Updated: 2011-12-29

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

231 participants

Study Classification

INTERVENTIONAL

Study Start Date

2003-04-30

Study Completion Date

2004-11-30

Brief Summary

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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.

Detailed Description

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Conditions

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Narcolepsy

Keywords

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Narcolepsy Daytime Sleepiness Daytime sleepiness in narcolepsy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Group 1.

Xyrem + Modafinil Placebo

Group Type EXPERIMENTAL

Xyrem

Intervention Type DRUG

Xyrem oral solution at 6 g/day for 4 weeks and 9 g/day for another 4 weeks.

Modafinil (Placebo)

Intervention Type DRUG

Modafinil Placebo oral capsules 1 to 3 capsules per day for 8 weeks.

Group 2:

Xyrem Placebo + Modafinil Placebo

Group Type PLACEBO_COMPARATOR

Xyrem Placebo

Intervention Type DRUG

Xyrem Placebo oral solution 12 ml per day for 4 weeks and 18 ml per day for another 4 weeks.

Modafinil (Placebo)

Intervention Type DRUG

Modafinil Placebo oral capsules 1 to 3 capsules per day for 8 weeks.

Group 3

Xyrem Placebo + Modafinil at established dose

Group Type ACTIVE_COMPARATOR

Xyrem Placebo

Intervention Type DRUG

Xyrem Placebo oral solution 12 ml per day for 4 weeks and 18 ml per day for another 4 weeks.

Modafinil at established dose

Intervention Type DRUG

Modafinil oral capsules at 200 to 600 mg per day for 8 weeks.

Group 4:

Xyrem + Modafinil at established dose

Group Type EXPERIMENTAL

Xyrem

Intervention Type DRUG

Xyrem oral solution at 6 g/day for 4 weeks and 9 g/day for another 4 weeks.

Modafinil at established dose

Intervention Type DRUG

Modafinil oral capsules at 200 to 600 mg per day for 8 weeks.

Interventions

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Xyrem

Xyrem oral solution at 6 g/day for 4 weeks and 9 g/day for another 4 weeks.

Intervention Type DRUG

Xyrem Placebo

Xyrem Placebo oral solution 12 ml per day for 4 weeks and 18 ml per day for another 4 weeks.

Intervention Type DRUG

Modafinil at established dose

Modafinil oral capsules at 200 to 600 mg per day for 8 weeks.

Intervention Type DRUG

Modafinil (Placebo)

Modafinil Placebo oral capsules 1 to 3 capsules per day for 8 weeks.

Intervention Type DRUG

Other Intervention Names

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Sodium Oxybate Sodium Oxybate Placebo Provigil Provigil Placebo

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Jazz Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Jazz Pharmaceuticals, Inc.

Principal Investigators

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Yanping Zheng, MD

Role: STUDY_DIRECTOR

Jazz Pharmaceuticals, Inc

Locations

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Pulmonary Associates, PA

Phoenix, Arizona, United States

Site Status

St. Jude Medical Center -- Sleep Disorders Institute

Fullerton, California, United States

Site Status

Pacific Sleep Medicine Services, Inc.

Los Angeles, California, United States

Site Status

Neuro-Therapeutics, Inc.

Pasadena, California, United States

Site Status

Pacific Sleep Medicine Services, Inc.

San Diego, California, United States

Site Status

Stanford Sleep Disorders Clinic

Stanford, California, United States

Site Status

Clinical Research Group of St. Petersburg, Inc.

St. Petersburg, Florida, United States

Site Status

Peoria Pulmonary Associates, Ltd

Peoria, Illinois, United States

Site Status

The Center for Sleep and Wake Disorders/Midwest Neurology

Danville, Indiana, United States

Site Status

Graves Gilbert Clinic

Bowling Green, Kentucky, United States

Site Status

Community Research & Sleep Management Institute

Crestview Hills, Kentucky, United States

Site Status

Chest Medicine Associates DBA -- Sleep Medicine Specialists

Louisville, Kentucky, United States

Site Status

The Center for Sleep & Wake Disorders

Chevy Chase, Maryland, United States

Site Status

Sleep Disorders Center -- Union Hospital of Cecil County

Elkton, Maryland, United States

Site Status

Sleep Medicine Associates of Maryland

Towson, Maryland, United States

Site Status

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

Washington University Sleep Center

St Louis, Missouri, United States

Site Status

New Jersey Neuroscience Institute at JFK Medical Center

Edison, New Jersey, United States

Site Status

Sleep Disorders Center of Rochester

Rochester, New York, United States

Site Status

Strong Sleep Disorders Center

Rochester, New York, United States

Site Status

Raleigh Neurology Associates

Raleigh, North Carolina, United States

Site Status

ALL-TRIALS Clinical Research, LLC -- Summit Sleep Disorder

Winston-Salem, North Carolina, United States

Site Status

Cincinnati Clinic & Sleep Management Institute

Cincinnati, Ohio, United States

Site Status

Community Research Management Associates,Inc.

Cincinnati, Ohio, United States

Site Status

CSC Research -- Grove City Sleep Diagnostic Center

Grove City, Ohio, United States

Site Status

Lehigh Valley Hospital Sleep Disorders Center

Allentown, Pennsylvania, United States

Site Status

Capital Region Sleep Disorder Center

Carlisle, Pennsylvania, United States

Site Status

Center for Sleep Medicine

Lafayette Hill, Pennsylvania, United States

Site Status

Lowcountry Lung and Critical Care, PA

Charleston, South Carolina, United States

Site Status

SleepMed of South Carolina

Columbia, South Carolina, United States

Site Status

SDHRF Clinical Research Center

Sioux Falls, South Dakota, United States

Site Status

Sioux Valley Clinic -- Pulmonary

Sioux Falls, South Dakota, United States

Site Status

Sleep Disorders Center

Sioux Falls, South Dakota, United States

Site Status

Bhupesh Dihenia, MD

Lubbock, Texas, United States

Site Status

SLEEP WALKER -- Sleep Disorders Center & Neurodiagnostics--Lung Diagnostics, Ltd.

San Antonio, Texas, United States

Site Status

Vermont Medical Sleep Disorders Center, Inc.

Essex Junction, Vermont, United States

Site Status

Hopital Pitie Salpetriere -- Federation des Pathologies du sommeil

Paris, Cedex 13, France

Site Status

Centre du sommeil -- Hopital Gui de Chauliac

Montpellier, Cedex 5, France

Site Status

Psychiatrische Universitatsklinik

Regensburg, , Germany

Site Status

Neurologische Poliklinik -- Universitats Spital Zurich

Zurich, , Switzerland

Site Status

Countries

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United States France Germany Switzerland

References

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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.

Reference Type BACKGROUND
PMID: 11833860 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 2281247 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8506453 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12627729 (View on PubMed)

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.

Reference Type RESULT
PMID: 16895262 (View on PubMed)

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.

Reference Type RESULT
PMID: 21206549 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32356515 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29221779 (View on PubMed)

Related Links

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http://www.xyrem.com

Xyrem Informational website with the package insert

Other Identifiers

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OMC-SXB-22

Identifier Type: -

Identifier Source: org_study_id