Trial Comparing Effects of Xyrem Taken Orally and Modafinil With Placebo in Treating Daytime Sleepiness in Narcolepsy
Condition: Narcolepsy
MeSH terms: Narcolepsy; Disorders of Excessive Somnolence; Sleepiness
Intervention: Xyrem; Xyrem Placebo; Modafinil at established dose; Modafinil (Placebo)
Intervention description: Xyrem oral solution at 6 g/day for 4 weeks and 9 g/day for another 4 weeks.; Xyrem Placebo oral solution 12 ml per day for 4 weeks and 18 ml per day for another 4 weeks.; Modafinil oral capsules at 200 to 600 mg per day for 8 weeks.; Modafinil Placebo oral capsules 1 to 3 capsules per day for 8 weeks.
Intervention MeSH terms: Sodium Oxybate; Modafinil
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 231.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Narcolepsy; Daytime Sleepiness; Daytime sleepiness in narcolepsy

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.
    

Eligibility criteria:

        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.