Trial of Effects of Oral Xyrem and Zolpidem on Sleep-Disordered Breathing in Obstructive Sleep Apnea Patients

Condition(s) targeted: Obstructive Sleep Apnea Syndrome

Intervention: Xyrem (Drug); Zolpidem + Xyrem Placebo (Drug); Xyrem + modafinil (Drug); Placebo (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: Orphan Medical

Official(s) and/or principal investigator(s):
Yanping Zheng, MD, Study Director, Affiliation: Jazz Pharmaceuticals, Inc.

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).

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

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

Primary outcome: 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.

Secondary outcome: Duration and severity of oxygen desaturation.

Detailed description: 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).

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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.

Clinical Research Group of St. Petersburg, St. Petersburg, Florida 33707, United States

London Health Sciences Centre, Victoria Campus, London, Ontario N6A 4G5, Canada

Trial results

Related publications:

[No authors listed] 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.

[No authors listed] 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.

U.S. Xyrem Multicenter Study Group. Sodium oxybate demonstrates long-term efficacy for the treatment of cataplexy in patients with narcolepsy. Sleep Med. 2004 Mar;5(2):119-23.

[No authors listed] The abrupt cessation of therapeutically administered sodium oxybate (GHB) does not cause withdrawal symptoms. J Toxicol Clin Toxicol. 2003;41(2):131-5.

Starting date: November 2003
Ending date: November 2005
Last updated: May 22, 2008