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.

Study Overview

• Status: Completed
• Conditions: Fibromyalgia
• Intervention / Treatment: Drug: Xyrem (sodium oxybate) oral solution; Drug: Xyrem (sodium oxybate) oral solution; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 195
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85251
      • Radiant Research
  • California
    • Beverly Hills, California, United States, 90211
      • Osteoporosis Medical Center
    • Los Angeles, California, United States, 90048
      • Wallace Rheumatic Study Center
  • Florida
    • Miami, Florida, United States, 33173
      • Miami Research Associates
    • West Palm Beach, Florida, United States, 33407
      • Radiant Research, Inc.
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • Central Kentucky Research Associates, Inc.
  • Louisiana
    • Shreveport, Louisiana, United States, 71130-3932
      • LSU Health Sciences Center
  • New Jersey
    • Springfield, New Jersey, United States, 07081
      • Richard N. Podell, MD
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Lenoir, North Carolina, United States, 28645
      • Alvin Daughtridge Arthritis Center
    • Raleigh, North Carolina, United States, 27609
      • C.A.R.E. Center
  • Ohio
    • Middlebrook Heights, Ohio, United States, 44130
      • Cleveland Sleep Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Lynn Health Science Institute
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center for Clinical Research
  • Texas
    • Katy, Texas, United States, 77450
      • Abigail Rebecca Neiman, MD
    • San Antonio, Texas, United States, 78229
      • The University of Texas Health Science Center
  • Utah
    • Sandy, Utah, United States, 84094
      • Stress Medicine Clinic -- HealthSouth Rehabilitation Hospital
  • Washington
    • Renton, Washington, United States, 98055
      • Pacific Rheumatology Research, Inc.
    • Seattle, Washington, United States, 98104
      • Seattle Rheumatology Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 2; Sodium oxybate 6.0 g per day.	Drug: Xyrem (sodium oxybate) oral solution; Xyrem (sodium oxybate) oral solution 4.5 g per day in divided doses, 2.25 g at bedtime and another 2.5 g two and a half to four hours later for 8 weeks.; Drug: Xyrem (sodium oxybate) oral solution; Xyrem (sodium oxybate) oral solution 6.0 g per night in divided doses of 3 g at bedtime and 3 g at 2.5 to 4 hours later for 8 weeks.
Placebo Comparator: 3; Placebo (one of two doses matching active treatment by volume).	Drug: Placebo; Placebo one of two doses matching active treatment by volume for 8 weeks.
Experimental: 1; Sodium oxybate 4.5 g per day.	Drug: Xyrem (sodium oxybate) oral solution; Xyrem (sodium oxybate) oral solution 4.5 g per day in divided doses, 2.25 g at bedtime and another 2.5 g two and a half to four hours later for 8 weeks.; Drug: Xyrem (sodium oxybate) oral solution; Xyrem (sodium oxybate) oral solution 6.0 g per night in divided doses of 3 g at bedtime and 3 g at 2.5 to 4 hours later for 8 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Primary Outcome Measure Was a Composite of Changes From Baseline in Three Co-primary Self Report Measures: Pain Visual Analog Scale (PVAS, Electronic Diaries), Fibromyalgia Impact Questionnaire (FIQ), and Patient Global Impression of Change (PGI-C).	The percentage of participants who met all 3 of the following criteria: Reduction of >=20% from baseline to week 8 in both PVAS & FIQ total score and PGI-C response of "very much better" or "much better". Analysis was based on LOCF (Last Observation Carried Forward) data. The PVAS ranges from 0 (no pain) to 100 (worst imaginable pain). The FIQ ranges from 0 (best function) to 100 (worst function). PGI-C is a 7 point likert scale measuring change in the participant's fibromyalgia symptoms that ranges from "very much worse" to "very much better"	Baseline to week 8

Collaborators and Investigators

• Sponsor: Jazz Pharmaceuticals
• Investigators: Study Director: Yanping Zheng, MD, Jazz Pharmaceuticals, Inc

Publications and helpful links

General 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.
• Scharf MB, Baumann M, Berkowitz DV. The effects of sodium oxybate on clinical symptoms and sleep patterns in patients with fibromyalgia. J Rheumatol. 2003 May;30(5):1070-4.
• Russell IJ, Perkins AT, Michalek JE; Oxybate SXB-26 Fibromyalgia Syndrome Study Group. Sodium oxybate relieves pain and improves function in fibromyalgia syndrome: a randomized, double-blind, placebo-controlled, multicenter clinical trial. Arthritis Rheum. 2009 Jan;60(1):299-309. doi: 10.1002/art.24142.

Study record dates

Study Major Dates

• Study Start: July 1, 2004
• Primary Completion (Actual): April 1, 2005
• Study Completion (Actual): January 1, 2006

Study Registration Dates

• First Submitted: July 12, 2004
• First Submitted That Met QC Criteria: July 13, 2004
• First Posted (Estimate): July 14, 2004

Study Record Updates

• Last Update Posted (Estimate): January 24, 2012
• Last Update Submitted That Met QC Criteria: January 20, 2012
• Last Verified: January 1, 2012

More Information

Terms related to this study

• Keywords: Pain; Fibromyalgia
• Additional Relevant MeSH Terms: Nervous System Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Muscular Diseases; Neuromuscular Diseases; Fibromyalgia; Myofascial Pain Syndromes; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Adjuvants, Anesthesia; Pharmaceutical Solutions; Sodium Oxybate
• Other Study ID Numbers: OMC-SXB-26