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

This study has been completed.
Sponsor:
Information provided by:
Jazz Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00086281
First received: June 29, 2004
Last updated: January 20, 2012
Last verified: January 2012
  Purpose

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 Intervention Phase
Obstructive Sleep Apnea Syndrome
Drug: Xyrem (X)
Drug: Zolpidem (Z)
Drug: Modafinil (M)
Drug: Placebo (P)
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, 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

Resource links provided by NLM:


Further study details as provided by Jazz Pharmaceuticals:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 60
Study Start Date: November 2003
Study Completion Date: November 2005
Primary Completion Date: June 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00086281

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:
Responsible Party: Senior Director Clinical Development, Jazz Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT00086281     History of Changes
Other Study ID Numbers: OMC-SXB-23
Study First Received: June 29, 2004
Results First Received: November 11, 2011
Last Updated: January 20, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Jazz Pharmaceuticals:
Sleep-disordered breathing
Obstructive sleep apnea syndrome

Additional relevant MeSH terms:
Apnea
Respiratory Aspiration
Sleep Apnea Syndromes
Sleep Apnea, Obstructive
Syndrome
Disease
Dyssomnias
Nervous System Diseases
Pathologic Processes
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms
Signs and Symptoms, Respiratory
Sleep Disorders
Sleep Disorders, Intrinsic
Armodafinil
Modafinil
Zolpidem
Central Nervous System Agents
Central Nervous System Depressants
Central Nervous System Stimulants
GABA Agents
GABA Agonists
GABA-A Receptor Agonists
Hypnotics and Sedatives
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014