A Long-Term, Open-Label Safety and Efficacy Study of Xyrem (sodium oxybate) in Subjects with Fibromyalgia

• Register: EUCTR
• Last refreshed on: 1 May 2012
• Main ID: EUCTR2006-006291-38-DE
• Date of registration: 01/04/2008
• Prospective Registration: Yes
• Primary sponsor: Jazz Pharmaceuticals, Inc.
• Public title: A Long-Term, Open-Label Safety and Efficacy Study of Xyrem (sodium oxybate) in Subjects with Fibromyalgia
• Scientific title: A Long-Term, Open-Label Safety and Efficacy Study of Xyrem (sodium oxybate) in Subjects with Fibromyalgia
• Target sample size: 1050
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-006291-38
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

France, Germany, Italy, Netherlands, Poland, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Subject has completed Jazz Pharmaceuticals, Inc., Study 06-009 within 7 days of entering Study 06-010. If subject has completed Study 06-009 more than 7 days before entering Study 06-010, subject is allowed into the study if their participation in 06-010 was postponed due to timing of approval of Study Protocol 06-010 by the German EC and BfArM.
2. Subject is able, in the opinion of the investigator, to take Xyrem® for approximately 9.5 months and complete all tests and visits described in this protocol.
3. Subject is able to understand the written informed consent and has signed and dated the consent prior to beginning protocol-required procedures.
4. Female subjects may be included if they have a negative urine pregnancy test at study entry.
5. Female subjects of child-bearing potential and peri-menopausal subjects must agree to use a medically acceptable method of birth control while enrolled in the study. Medically acceptable methods of birth control include implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence, and a vasectomised partner.
6. Subject must be willing to refrain from the use of any medications, herbal remedies, and/or devices being used to treat his/her fibromyalgia symptoms until trial completion. Such medications include but are not limited to: opiates, benzodiazepines, muscle relaxants, cyclobenzaprine, anticonvulsants, antidepressants, dopamine agonists and/or tramadol.
7. Subject agrees to use only ibuprofen (up to 1,200 mg/day), naproxen (up to 660 mg/day), or acetaminophen(paracetamol) (up to 4 g/day) as rescue pain medication. (Simultaneous use of acetaminophen(paracetamol) and either ibuprofen or naproxen is permitted. Simultaneous use of ibuprofen and naproxen will not be allowed on the same day during the study.)
8. Subject is willing to not drink alcohol for the duration of the trial.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Subject experienced any serious adverse event (SAE) that was related to study drug during participation in Jazz Pharmaceuticals, Inc., Protocol 06-008 or 06-009.
2. Subject, in the opinion of the investigator, experienced an AE in Protocol 06-008 or 06-009 that may prevent him/her from safely participating in and completing the current study.
3. Subject terminated early from Study 06-008 or 06-009.
4. Subject has any new condition, physical examination finding, or laboratory test result that, in the opinion of the investigator, could impact subject safety, could interfere with the evaluation of the subject, or affect subject’s compliance with the protocol requirements.
5. Subject developed a current primary diagnosis of major depressive disorder, psychotic disorder, and/or bipolar disorder (DSM-IV-TR).
6. Subject is, in the opinion of the investigator, a suicidal or homicidal risk; or subject scored =1 on Question 9 of the BDI-II at Visit 1 or any time during the 06-008 or 06 009 study.
7. Subject is pregnant, nursing, or lactating.
8. Subject has an abnormal pretrial (within 7 days of Visit 1 in this study) ECG result that in the opinion of the investigator is clinically significant.
9. Subject has a positive urine drug screen for benzodiazapines or other drugs of abuse and/or a positive alcohol test and/or a history of substance abuse.
10. Subject is diagnosed with sleep apnea and not currently on stable continuous positive airway pressure (CPAP) therapy, or the investigator judges that the subject’s risk of sleep apnea has increased during the double-blind study 06-008 or 06-009.
11. Subject has begun or plans to begin shift-work or another responsibility, activity, or schedule that, in the opinion of the investigator, could impact subject safety or affect the subject’s compliance with protocol requirements.
12. Subjects will be excluded at screening for Protocol 06-010 if they meet any of the
following medical and safety exclusion criteria specified in Protocol 06-009
Amendment 3G.
1) Subject has any of the following medical conditions:
• Rheumatic disease in addition to fibromyalgia, such as rheumatoid arthritis,
inflammatory arthritis, or systemic lupus erythematosus
• Symptoms of painful osteoarthritis or symptomatic osteoarthritis (e.g.
osteoarthritis associated with stiffness and muscle weakness) at screening
• Pain from traumatic injury
• Uncontrolled hypo- or hyperthyroidism of any type
• Autoimmune disease (with the exception of inactive Hashimoto's thyroiditis)
• Multiple sclerosis
• Unstable cardiovascular (eg, cardiac insufficiency, arterial hypertension),
endocrine, gastrointestinal, hematologic, hepatic, immunologic, metabolic,
neurological, pulmonary, and/or renal disease
• Current or recent neoplastic disease (ie, evaluable disease within the past 5
years), excluding localized basal cell carcinoma
• Systemic infection
• Any disease, disorder or condition that would place the subject at risk during the
trial, interfere with the subject’s or investigator’s ability to measure change on
any outcome measures and/or compromise the objectives outlined in the protocol
2) Subject has a history of myocardial infarction, transient ischemic attack or
cerebrovascular accident.
4) Subject has Generalized Anxiety Disorder as defined by the Diagnostic and
Statistical Manual of Mental Disorders IV
8) Subject has a clinically significant history of seizure disorder either past or present, a history of clinically significant head

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Fibromyalgia
MedDRA version: 8.1 Level: LLT Classification code 10048439 Term: Fibromyalgia

Intervention(s)

Trade Name: Xyrem(R)
Pharmaceutical Form: Oral solution
CAS Number: 502852
Current Sponsor code: n/a
Other descriptive name: SODIUM OXYBATE
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 500-

Primary Outcome(s)

Secondary Objective: Secondary objectives are to: 1) evaluate the long-term efficacy of open-label Xyrem in subjects with fibromyalgia, and 2) assess the long-term effects of open-label Xyrem on quality of life, social and occupational functioning, sleep, and daytime fatigue in subjects with fibromyalgia

Main Objective: The primary objective of this study is to assess the safety of Xyrem (sodium oxybate) in long term use (up to 38 weeks) in subjects completing a double-blind controlled trial of Xyrem for the treatment of fibromyalgia.

Primary end point(s): Two primary efficacy parameters (1 and 2) will be evaluated.
The first is a composite parameter for the treatment of pain associated with fibromyalgia. The proportion of subjects who meet both of the following response criteria will be summarized:
• Overall pain severity will be assessed by pain VAS data recorded each evening by the subject in an electronic diary. For pain VAS, a response is defined as a reduction in average pain of =20% from prior study baseline.
• Patient Global Impression of Change. The subject's perception of the overall improvement in his/her fibromyalgia symptoms compared to prior study baseline will be assessed by means of the PGIc questionnaire. A response to treatment is defined as a response of “Very much better” or “Much better” on the PGIc.

The second parameter is a composite parameter for the treatment of fibromyalgia syndrome. The proportion of subjects who meet all three of the following response criteria will be summarized.
• Overall pain severity will be assessed by pain VAS data recorded each evening by the subject in an electronic diary. For pain VAS, a response is defined as a reduction in average pain of = 20% from prior study baseline.
• Functionality (Fibromyalgia Impact Questionnaire). A response will be defined as a reduction of =20% in FIQ total score from prior study baseline. For example, if a subject has a prior study baseline FIQ score of 40, he/she will need to have an FIQ score of 32 or less to be considered a responder.
• Patient Global Impression of Change. The subject’s perception of the overall improvement in his/her fibromyalgia symptoms compared to prior study baseline will be assessed by means of the PGIc questionnaire. A response to treatment is defined as a response of “Very much better” or “Much better” on the PGIc

Secondary ID(s)

2006-006291-38-GB

06-010