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

Obstructive Sleep Apnea Syndrome Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00086281
• Other study ID #: OMC-SXB-23
• Status: Completed
• Phase: Phase 4
• First received: June 29, 2004
• Last updated: January 20, 2012
• Start date: November 2003
• Est. completion date: November 2005

Study information

• Verified date: January 2012
• Source: Jazz Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: November 2005
• Est. primary completion date: June 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Apnea
• Obstructive Sleep Apnea Syndrome
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive

Intervention

Drug:
• Xyrem (X)
Xyrem (Sodium Oxybate) Oral Solution
• Zolpidem (Z)
Zolpidem 10 mg oral tablets
• Modafinil (M)
Modafinil Oral Tablets
• Placebo (P)
Placebo Oral Solution

Locations

Country	Name	City	State
Canada	London Health Sciences Centre, Victoria Campus	London	Ontario
United States	Clinical Research Group of St. Petersburg	St. Petersburg	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Jazz Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (4)

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. — View Citation

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. — View Citation

The abrupt cessation of therapeutically administered sodium oxybate (GHB) does not cause withdrawal symptoms. J Toxicol Clin Toxicol. 2003;41(2):131-5. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Primary Efficacy Variable Was the Mean Apnea-Hypopnea Index (AHI).	The AHI was defined as the incidence(events per hour) of apnea and hypopnea events associated with sleep, determined from the overnight polysomnogram (PSG). An apnea event is characterized by a cessation in airflow lasting >= 10 seconds, accompanied by oxygen desaturation of >3% or arousal. An Hyponea event is characterized by a transient reduction in breathing lasting >= 10 seconds, with clear decrease (>50%) from baseline in the amplitude of breathing or a decrease <50% in the amplitude of breathing accompanied by oxygen desaturation of >3% or arousal.	One night of PSG during one night of treatment each per arm.	Yes