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

Jazz Pharmaceuticals

Status and phase: Completed; Phase 4

Conditions: Obstructive Sleep Apnea Syndrome

Treatments: Drug: Xyrem (X); Drug: Placebo (P); Drug: Modafinil (M); Drug: Zolpidem (Z)

Study type: Interventional

Funder types: Industry

Identifiers

NCT00086281

OMC-SXB-23

Details and patient eligibility

About

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).

Full 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).

Enrollment: 60 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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60 participants in 4 patient groups, including a placebo group

1

Experimental group

Description:

Xyrem 9 grams given in a divided dose: 4.5 g at bedtime and 4.5 g given 2.5 to 4 hours later

Treatment:

Drug: Xyrem (X)

2

Active Comparator group

Description:

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

Treatment:

Drug: Zolpidem (Z)

Drug: Placebo (P)

3

Experimental group

Description:

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).

Treatment:

Drug: Modafinil (M)

Drug: Xyrem (X)

4

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo (P)