Trial of Effects of Oral Xyrem and Zolpidem on Sleep-Disordered Breathing in Obstructive Sleep Apnea Patients
Condition: Obstructive Sleep Apnea Syndrome
MeSH terms: Apnea; Sleep Apnea Syndromes; Sleep Apnea, Obstructive
Intervention: Xyrem (X); Zolpidem (Z); Modafinil (M); Placebo (P)
Intervention description: Xyrem (Sodium Oxybate) Oral Solution; Zolpidem 10 mg oral tablets; Modafinil Oral Tablets; Placebo Oral Solution
Intervention MeSH terms: Zolpidem; Modafinil
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 60.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Sleep-disordered breathing; Obstructive sleep apnea syndrome

Summary:

      To study the effect of Xyrem (9 g), Xyrem (9 g) plus modafinil 200 mg administered the
      morning prior to Xyrem, positive control (zolpidem 10 mg), and placebo on the frequency and
      outcome of events of sleep-disordered breathing in patients with obstructive sleep apnea
      syndrome (OSAS).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Signed and dated an informed consent prior to beginning protocol required procedures.

          -  Willing and able to complete the entire trial as per the protocol including 6 nights
             in the sleep lab.

          -  18 years of age or older.

          -  Have a history of obstructive sleep apnea syndrome (as per American Academy of Sleep
             Medicine [AASM] Task Force 1999).

          -  Apnea-Hypopnea Index(AHI): 10 to 40 inclusive, lowest O2 saturation ≥75% (see AASM
             Task Force 1999 criteria)

          -  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:

          -  Have taken sodium oxybate (GHB) in the last 30 days.

          -  Have taken any investigational therapy within the 30-day period prior to the initial
             screening visit for this trial.

          -  Are routinely taking any stimulant medications, sedative hypnotics, tranquilizers,
             antihistamines (except for non-sedating antihistamines), benzodiazepines or clonidine
             at the start of the study. Patients taking anticonvulsants are not eligible to
             participate even if they are willing to washout anticonvulsants for the trial.

          -  Regularly consume alcohol and are unwilling or unable to totally abstain from alcohol
             use for the trial duration.

          -  Are experiencing any major illness, including unstable cardiovascular, endocrine,
             neoplastic, gastrointestinal, hematologic, hepatic, immunologic, metabolic,
             neurological, 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.