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

• ClinicalTrials.gov Identifier: NCT00086281
• Recruitment Status: Completed
• First Posted: July 1, 2004
• Results First Posted: February 24, 2012
• Last Update Posted: February 24, 2012
• Sponsor: Jazz Pharmaceuticals
• Information provided by: Jazz Pharmaceuticals

Study Description

Brief 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).

Condition or disease	Intervention/treatment	Phase
Obstructive Sleep Apnea Syndrome	Drug: Xyrem (X); Drug: Zolpidem (Z); Drug: Modafinil (M); Drug: Placebo (P)	Phase 4

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).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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 Start Date: November 2003
• Actual Primary Completion Date: June 2005
• Actual Study Completion Date: November 2005

Arms and Interventions

Arm	Intervention/treatment
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	Drug: Xyrem (X); Xyrem (Sodium Oxybate) Oral Solution
Active Comparator: 2; Zolpidem 10 mg + placebo were given at bedtime and placebo given 2.5 to 4 hours later.	Drug: Zolpidem (Z); Zolpidem 10 mg oral tablets; Other Name: Ambien; Drug: Placebo (P); Placebo Oral Solution
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).	Drug: Xyrem (X); Xyrem (Sodium Oxybate) Oral Solution; Drug: Modafinil (M); Modafinil Oral Tablets; Other Name: Provigil
Placebo Comparator: 4; Placebo was given at bedtime and again 2.5 to 4 hours later.	Drug: Placebo (P); Placebo Oral Solution

Outcome Measures

Primary Outcome Measures :

1. The Primary Efficacy Variable Was the Mean Apnea-Hypopnea Index (AHI). [ Time Frame: One night of PSG during one night of treatment each per arm. ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Florida

Clinical Research Group of St. Petersburg

St. Petersburg, Florida, United States, 33707

Canada, Ontario

London Health Sciences Centre, Victoria Campus

London, Ontario, Canada, N6A 4G5

Sponsors and Collaborators

Jazz Pharmaceuticals

Investigators

• Study Director: Yanping Zheng, MD; Jazz Pharmaceuticals, Inc.

More Information

Publications:

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.

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. doi: 10.1016/j.sleep.2003.11.002.

The abrupt cessation of therapeutically administered sodium oxybate (GHB) does not cause withdrawal symptoms. J Toxicol Clin Toxicol. 2003;41(2):131-5. doi: 10.1081/clt-120019128.

• Responsible Party: Senior Director Clinical Development, Jazz Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT00086281
• Other Study ID Numbers: OMC-SXB-23
• First Posted: July 1, 2004
• Results First Posted: February 24, 2012
• Last Update Posted: February 24, 2012
• Last Verified: January 2012

Keywords provided by Jazz Pharmaceuticals:

Sleep-disordered breathing; Obstructive sleep apnea syndrome

Additional relevant MeSH terms:

Apnea; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Zolpidem; Modafinil; Central Nervous System Stimulants; Physiological Effects of Drugs; Wakefulness-Promoting Agents; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 Enzyme Inducers; Molecular Mechanisms of Pharmacological Action; Sleep Aids, Pharmaceutical; Hypnotics and Sedatives; Central Nervous System Depressants; GABA-A Receptor Agonists; GABA Agonists; GABA Agents; Neurotransmitter Agents