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

Fibromyalgia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00087555
• Other study ID #: OMC-SXB-26
• Status: Completed
• Phase: Phase 2
• First received: July 12, 2004
• Last updated: January 20, 2012
• Start date: July 2004
• Est. completion date: January 2006

Study information

• Verified date: January 2012
• Source: Jazz Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 195
• Est. completion date: January 2006
• Est. primary completion date: April 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fibromyalgia
• Myofascial Pain Syndromes

Intervention

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.
• 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
Placebo one of two doses matching active treatment by volume for 8 weeks.

Locations

Country	Name	City	State
United States	Osteoporosis Medical Center	Beverly Hills	California
United States	Altoona Center for Clinical Research	Duncansville	Pennsylvania
United States	Duke University Medical Center	Durham	North Carolina
United States	Abigail Rebecca Neiman, MD	Katy	Texas
United States	Alvin Daughtridge Arthritis Center	Lenoir	North Carolina
United States	Central Kentucky Research Associates, Inc.	Lexington	Kentucky
United States	Wallace Rheumatic Study Center	Los Angeles	California
United States	Miami Research Associates	Miami	Florida
United States	Cleveland Sleep Center	Middlebrook Heights	Ohio
United States	Lynn Health Science Institute	Oklahoma City	Oklahoma
United States	Oregon Health and Science University	Portland	Oregon
United States	C.A.R.E. Center	Raleigh	North Carolina
United States	Pacific Rheumatology Research, Inc.	Renton	Washington
United States	The University of Texas Health Science Center	San Antonio	Texas
United States	Stress Medicine Clinic -- HealthSouth Rehabilitation Hospital	Sandy	Utah
United States	Radiant Research	Scottsdale	Arizona
United States	Seattle Rheumatology Associates	Seattle	Washington
United States	LSU Health Sciences Center	Shreveport	Louisiana
United States	Richard N. Podell, MD	Springfield	New Jersey
United States	Radiant Research, Inc.	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Jazz Pharmaceuticals

Country where clinical trial is conducted

United States, 

References & Publications (6)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

The abrupt cessation of therapeutically administered sodium oxybate (GHB) does not cause withdrawal symptoms. J Toxicol Clin Toxicol. 2003;41(2):131-5. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No