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

NCT00066170 | Completed Phase 3 Results

• 1 other identifier: OMC-SXB-22
• Study Type: interventional
• Target: 231
• Locations: 4 countries
• Sites: 40

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.

Conditions

Narcolepsy

Keywords

Narcolepsy; Daytime Sleepiness; Daytime sleepiness in narcolepsy

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (4)

Group 1.

EXPERIMENTAL

Xyrem + Modafinil Placebo

Drug: Xyrem; Drug: Modafinil (Placebo)

Group 2:

PLACEBO COMPARATOR

Xyrem Placebo + Modafinil Placebo

Drug: Xyrem Placebo; Drug: Modafinil (Placebo)

Group 3

ACTIVE COMPARATOR

Xyrem Placebo + Modafinil at established dose

Drug: Xyrem Placebo; Drug: Modafinil at established dose

Group 4:

EXPERIMENTAL

Xyrem + Modafinil at established dose

Drug: Xyrem; Drug: Modafinil at established dose

Interventions

Xyrem DRUG

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

Also known as: Sodium Oxybate

Group 1.; Group 4:

Xyrem Placebo DRUG

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

Also known as: Sodium Oxybate Placebo

Group 2:; Group 3

Modafinil at established dose DRUG

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

Also known as: Provigil

Group 3; Group 4:

Modafinil (Placebo) DRUG

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

Also known as: Provigil Placebo

Group 1.; Group 2:

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Jazz Pharmaceuticals: lead

Study Sites (40)

Pulmonary Associates, PA

Phoenix, Arizona, 85006, United States

Location

St. Jude Medical Center -- Sleep Disorders Institute

Fullerton, California, 92835, United States

Location

Pacific Sleep Medicine Services, Inc.

Los Angeles, California, 90048, United States

Location

Neuro-Therapeutics, Inc.

Pasadena, California, 91105, United States

Location

Pacific Sleep Medicine Services, Inc.

San Diego, California, 92121, United States

Location

Stanford Sleep Disorders Clinic

Stanford, California, 94305, United States

Location

Clinical Research Group of St. Petersburg, Inc.

St. Petersburg, Florida, 33707, United States

Location

Peoria Pulmonary Associates, Ltd

Peoria, Illinois, 61603, United States

Location

The Center for Sleep and Wake Disorders/Midwest Neurology

Danville, Indiana, 46122, United States

Location

Graves Gilbert Clinic

Bowling Green, Kentucky, 42101, United States

Location

Community Research & Sleep Management Institute

Crestview Hills, Kentucky, 41017, United States

Location

Chest Medicine Associates DBA -- Sleep Medicine Specialists

Louisville, Kentucky, 40217, United States

Location

The Center for Sleep & Wake Disorders

Chevy Chase, Maryland, 20815, United States

Location

Sleep Disorders Center -- Union Hospital of Cecil County

Elkton, Maryland, 21921, United States

Location

Sleep Medicine Associates of Maryland

Towson, Maryland, 21204, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Washington University Sleep Center

St Louis, Missouri, 63108, United States

Location

New Jersey Neuroscience Institute at JFK Medical Center

Edison, New Jersey, 08818, United States

Location

Sleep Disorders Center of Rochester

Rochester, New York, 14618, United States

Location

Strong Sleep Disorders Center

Rochester, New York, 14618, United States

Location

Raleigh Neurology Associates

Raleigh, North Carolina, 27607, United States

Location

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

Winston-Salem, North Carolina, 27103, United States

Location

Cincinnati Clinic & Sleep Management Institute

Cincinnati, Ohio, 45219, United States

Location

Community Research Management Associates,Inc.

Cincinnati, Ohio, 45219, United States

Location

CSC Research -- Grove City Sleep Diagnostic Center

Grove City, Ohio, 43123, United States

Location

Lehigh Valley Hospital Sleep Disorders Center

Allentown, Pennsylvania, 18105, United States

Location

Capital Region Sleep Disorder Center

Carlisle, Pennsylvania, 17013, United States

Location

Center for Sleep Medicine

Lafayette Hill, Pennsylvania, 19444, United States

Location

Lowcountry Lung and Critical Care, PA

Charleston, South Carolina, 29406-7108, United States

Location

SleepMed of South Carolina

Columbia, South Carolina, 29220, United States

Location

SDHRF Clinical Research Center

Sioux Falls, South Dakota, 57104, United States

Location

Sioux Valley Clinic -- Pulmonary

Sioux Falls, South Dakota, 57105, United States

Location

Sleep Disorders Center

Sioux Falls, South Dakota, 57105, United States

Location

Bhupesh Dihenia, MD

Lubbock, Texas, 79410, United States

Location

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

San Antonio, Texas, 78229, United States

Location

Vermont Medical Sleep Disorders Center, Inc.

Essex Junction, Vermont, 05452, United States

Location

Hopital Pitie Salpetriere -- Federation des Pathologies du sommeil

Paris, Cedex 13, 75651, France

Location

Centre du sommeil -- Hopital Gui de Chauliac

Montpellier, Cedex 5, 34295, France

Location

Psychiatrische Universitatsklinik

Regensburg, 93042, Germany

Location

Neurologische Poliklinik -- Universitats Spital Zurich

Zurich, CH-8091, Switzerland

Location

Related Publications (8)

• 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.

  PMID: 11833860 BACKGROUND

• 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.

  PMID: 2281247 BACKGROUND

• 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.

  PMID: 8506453 BACKGROUND

• 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.

  PMID: 12627729 BACKGROUND

• 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.

  PMID: 16895262 RESULT

• 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.

  PMID: 21206549 RESULT

• 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.

  PMID: 32356515 DERIVED

• 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.

  PMID: 29221779 DERIVED

Related Links

• Xyrem Informational website with the package insert

MeSH Terms

Conditions

Narcolepsy; Disorders of Excessive Somnolence

Interventions

Sodium Oxybate; Modafinil

Condition Hierarchy (Ancestors)

Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders

Intervention Hierarchy (Ancestors)

Hydroxybutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

• Title: Grace Wang, MD Director of Clinical Development & Medical Monitor
• Organization: Jazz Pharmaceuticals, Inc

650-496-3777

Study Officials

• Yanping Zheng, MD

  Jazz Pharmaceuticals, Inc

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: August 4, 2003
• First Posted: August 6, 2003
• Study Start: April 1, 2003
• Primary Completion: July 1, 2004
• Study Completion: November 1, 2004
• Last Updated: December 29, 2011
• Results First Posted: November 30, 2011

Record last verified: 2011-12

Locations

US (36); CH (1); FR (2); DE (1)