Trial Comparing the Effects of Xyrem (Sodium Oxybate) With Placebo for the Treatment of Fibromyalgia

Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multi-Center Trial Comparing the Effects of Orally Administered Xyrem(R) (Sodium Oxybate) With Placebo for the Treatment of Fibromyalgia

The purpose of this study is to determine whether Xyrem (sodium oxybate) is effective when used alone to treat the pain and sleep disturbances of fibromyalgia.

Fibromyalgia affects millions of Americans, yet there are no FDA approved drugs to treat this debilitating condition. Besides causing pain, it also disrupts normal sleep patterns in many of its victims. Pain and lack of sleep reinforce each other, making patients progressively more miserable. Xyrem is a potent hypnotic that induces and consolidates sleep. In a few small studies Xyrem has been reported to offer relief to some fibromyalgia patients. This trial is designed to test this hypothesis. Patients who enroll in this study will stop taking any prescription medications for fibromyalgia (over-the-counter pain relievers will be permitted). They will then take either Xyrem alone or placebo alone. Patients will be followed for eight weeks to evaluate any relief of the pain or functional impairment of fibromyalgia from their study treatment. Sleep characteristics will also be assessed subjectively and by polysomnographic recordings at baseline and twice during the treatment phase.

Inclusion Criteria

• Sign & date informed consent
• Willing & able to complete trial as described in protocol
• > 18 years of age
• Meet American College of Rheumatology criteria for Fibromyalgia [Widespread pain for at least 3 months, including all of the following: (1) Pain on right & left sides of body; (2) Pain above & below waist; (3) Pain in axial skeleton; 4) Pain on digital palpation with approximately 4kg force in at least 11 of 18 tender point sites]
• (Study continuation) Have an average VAS pain score > 4 on a scale of 0 to 10 as recorded in patient diary the last week before Visit 4.
• Discontinue all prescription medication taken for fibromyalgia, including opiates, benzodiazepines, anticonvulsants taken for pain, antidepressants, cyclobenzaprine (Flexeril), and/or tramadol (Ultram) until study completion
• Continue all pre-existing nutritional and/or exercise regimens and/or behavioral, massage, acupuncture, physical or cognitive therapies on an unchanged, consistent & regular schedule throughout study
• Use only acetaminophen or over-the-counter non-steroidal anti-inflammatory drugs as rescue pain medications & to limit dose to the labeled over-the-counter maximum. Aspirin may only be used as a cardiac protectant; formulations with caffeine are excluded.
• Forego ingestion of alcohol for duration of study.
• Fertile females must use a medically accepted method of birth control (e.g., barrier method with spermicide, oral contraceptive, or abstinence) for duration of trial.

Exclusion Criteria

1. Have any of the following medical conditions:

   • Other rheumatic disease, such as rheumatoid arthritis, osteoarthritis, or systemic lupus erythematosis
   • Uncontrolled hypo- or hyper-thyroidism of any type
   • Unstable cardiovascular, endocrine, neoplastic (excluding localized basal cell carcinoma), gastrointestinal, hematologic, hepatic, immunologic, metabolic, neurological, pulmonary, and/or renal disease which would place patient at risk during trial or compromise objectives outlined in protocol
   • Myocardial infarction within last six months
   • On their screening PSG (polysomnogram) have an Apnea Index greater than 10 per hour or an Apnea Hypopnea Index greater than 15 per hour. Note: patients with sleep apnea are not excluded if their indices are below these thresholds while sleeping with CPAP (Continuous Positive Airway Pressure) and they are compliant with CPAP therapy.
   • 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.
   • If a patient will have to discontinue antidepressant medication taken for depression, the investigator must make an evaluation as to any risks from cessation of anti-depressant therapy. If, in the opinion of the investigator, a reasonable risk of resultant patient harm exists, patient is excluded from study participation
   • Current or recent history of substance abuse including alcohol abuse
   • History of seizure disorder, history of head trauma, migraine headaches or intracranial surgery, & are taking anticonvulsants
   • Succinic semialdehyde dehydrogenase deficiency

2. Have taken any of these therapies:

   • gamma-hydroxybutyrate (sodium oxybate) in 30 days prior to signing informed consent
   • any investigational therapy in 30 days prior to signing informed consent
   • ever taken anticonvulsants to treat epilepsy or any other convulsions

3. Unwilling to stop these therapies during course of trial:

   • anticonvulsants prescribed solely for pain
   • all antidepressants
   • medication for sleep

4. Have any of the following clinical laboratory results:

   • Serum creatinine > 2.0 mg/dL
   • TSH (Thyroid Stimulating Hormone) < 0.3 μU/mL OR TSH > 6 μU/mL
   • abnormal liver function tests (SGOT [AST] or SGPT [ALT] more than twice the upper limit of normal)
   • elevated serum bilirubin (more than 1.5 times the upper limit of normal)
   • pre-trial ECG with arrhythmia, greater than a first degree AV block
   • positive pregnancy test at any time during trial

5. Have any of the following socio-economic factors:

   • Pending worker's compensation litigation or related other monetary settlements
   • Have an occupation that requires variable shift work or routine night shifts