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
This study will be conducted as a randomized, crossover study of 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).
- 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.
- 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
- 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.