Official Title: “Randomized, Placebo-Controlled Multicenter Trial of the Effects of Orally Administered Xyrem (Sodium Oxybate) and Zolpidem on Sleep-Disordered Breathing in Obstructive Sleep Apnea Patients”

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).

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Placebo Control, Crossover Assignment, Safety/Efficacy Study

Study Primary Completion Date: June 2005

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).

Intervention(s) in this Clinical Trial

• Drug: Xyrem
  • Xyrem oral solution, 9 g per night in divided doses. 4.5 g at bedtime and 4.5 g given 2.5 to 4 hours later.
• Drug: Zolpidem + Xyrem Placebo
  • Zolpidem 10 mg oral tablets + Xyrem placebo were given at bedtime.
• Drug: Xyrem + modafinil
  • Xyrem oral solution 9 g per night in divided doses. 4.5 g at bedtime and 4.5 g given 2.5 to 4 hours later. Modafinil oral tablets was given at 8 am of the morning of Xyrem treatment.
• Drug: Placebo
  • Placebo oral solution was given at bedtime and 2.5 to 4 hours later.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Xyrem 9 grams given in a divided dose: 4.5 g at bedtime and 4.5 g given 2.5 to 4 hours later
• Active Comparator: 2
  • Zolpidem 10 mg + placebo were given at bedtime and placebo given 2.5 to 4 hours later.
• Experimental: 3
  • Xyrem 9 g + modafinil 200 mg (Xyrem 9 g was given in a divided dose: 4.5 g at bedtime and 4.5 g given 2.5 to 4 hours later; modafinil was given at 8 am on the morning of Xyrem treatment).
• Placebo Comparator: 4
  • Placebo was given at bedtime and again 2.5 to 4 hours later.

Primary Measures

• The primary efficacy variable was the AHI, determined from the polysomnogram (PSG). The AHI was defined as the incidence (events per hour) of apnea and hypopnea events associated with sleep.
  • Time Frame: One night of PSG during one night of treatment each per arm.
    Safety Issue?: Yes

Secondary Measures

• Duration and severity of oxygen desaturation.
  • Time Frame: One night of PSG during one night of treatment each per arm.
    Safety Issue?: Yes

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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Orphan Medical

Overall Clinical Trial Officials and Contacts

Yanping Zheng, MD Study Director Jazz Pharmaceuticals, Inc.  

Information obtained from ClinicalTrials.gov on November 19, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00086281

Study ID Number: OMC-SXB-23

ClinicalTrials.gov Identifier: NCT00086281

Health Authority: United States: Food and Drug Administration

Trial results