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

NCT00086281 | Completed Phase 4 Results

• 1 other identifier: OMC-SXB-23
• Study Type: interventional
• Target: 60
• Locations: 2 countries
• Sites: 2

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).

Conditions

Obstructive Sleep Apnea Syndrome

Keywords

Sleep-disordered breathing; Obstructive sleep apnea syndrome

Outcome Measures

Primary Outcomes (1)

• 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.

Study Arms (4)

1

EXPERIMENTAL

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)

2

ACTIVE COMPARATOR

Zolpidem 10 mg + placebo were given at bedtime and placebo given 2.5 to 4 hours later.

Drug: Zolpidem (Z); Drug: Placebo (P)

3

EXPERIMENTAL

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); Drug: Modafinil (M)

4

PLACEBO COMPARATOR

Placebo was given at bedtime and again 2.5 to 4 hours later.

Drug: Placebo (P)

Interventions

Xyrem (X) DRUG

Xyrem (Sodium Oxybate) Oral Solution

1; 3

Zolpidem (Z) DRUG

Zolpidem 10 mg oral tablets

Also known as: Ambien

2

Modafinil (M) DRUG

Modafinil Oral Tablets

Also known as: Provigil

3

Placebo (P) DRUG

Placebo Oral Solution

2; 4

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Jazz Pharmaceuticals: lead

Study Sites (2)

Clinical Research Group of St. Petersburg

St. Petersburg, Florida, 33707, United States

Location

London Health Sciences Centre, Victoria Campus

London, Ontario, N6A 4G5, Canada

Location

Related Publications (4)

• 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.

  PMID: 11833860 BACKGROUND

• 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.

  PMID: 12627729 BACKGROUND

• 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.

  PMID: 15033130 BACKGROUND

• 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.

  PMID: 12733850 BACKGROUND

MeSH Terms

Conditions

Sleep Apnea, Obstructive; Sleep Apnea Syndromes

Interventions

Sodium Oxybate; Zolpidem; Modafinil

Condition Hierarchy (Ancestors)

Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Hydroxybutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

• Title: Grace Wang, MD Director Clinical Development & Medical Monitor
• Organization: Jazz Pharmaceuticals, Inc.

650-496-3777

Study Officials

• Yanping Zheng, MD

  Jazz Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: June 29, 2004
• First Posted: July 1, 2004
• Study Start: November 1, 2003
• Primary Completion: June 1, 2005
• Study Completion: November 1, 2005
• Last Updated: February 24, 2012
• Results First Posted: February 24, 2012

Record last verified: 2012-01

Locations

US (1); CA (1)