E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10048439 |
E.1.2 | Term | Fibromyalgia |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the safety and efficacy of Xyrem (sodium oxybate) oral solution at 4.5 g/night and 6 g/night compared to placebo for the treatment of fibromyalgia in a randomized, double-blind, placebo controlled, parallel-group trial. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
A subject will be eligible for trial participation if he/she meets the following criteria (see protocol section 8.1.1 for details): 1. Subject is able to understand the written informed consent and has signed and dated the consent prior to beginning protocol required procedures. 2. Subject is willing and able to complete the entire trial as described in the protocol. 3. Subject is male or female 18 years of age or older. 4. Subject meets the ACR criteria for fibromyalgia at screening and at baseline. 5. Subject has at least 5 out of 7 days with 100% compliance on the VAS self-rated pain scale in the week prior to Visit 4 and has an average VAS pain score of greater than or equal to 50 mm/100 mm as recorded in the subject diary on the 100% compliant days, defined as days that the morning, afternoon, and evening diaries were all completed. 6. Subject is willing to discontinue opiates, benzodiazepines, muscle relaxants (cyclobenzaprine [Flexeril]), anticonvulsants, antidepressants, dopamine agonists and/or tramadol (Ultram), or any other medications, herbal remedies, and/or devices being used to treat their fibromyalgia symptoms until trial completion. 7. Subjects who are on a consistent nutritional and/or exercise regimens and/or behavioral, massage, physical, or cognitive therapies for the last 3 months prior to baseline are willing to agree to remain on an unchanged regimen throughout the duration of the trial. 8. Subject agrees to use only acetaminophen (paracetamol) as rescue pain medication and to limit the dose to a maximum of 4 g/day throughout the course of the trial. Subjects may, for cardiac protection, take a single daily dose of 325 mg or less of aspirin. Any other use of aspirin is prohibited during this trial. 9. Subject is willing to discontinue the ingestion of alcohol for the duration of the trial. 10. Female subjects may be included if they are surgically sterile or 2 years post menopausal, but they must also have a negative pregnancy test. Female subjects of child bearing potential and peri-menopausal subjects may be included but must have a negative pregnancy test and agree to use a medically accepted method of birth control (eg, barrier method with spermicide, oral contraceptive, or abstinence) and agree to continue use of this method for the duration of the trial. 11. Subject has been screened for sleep apnea using the Berlin Questionnaire, and a determination of the subjects sleep apnea status has been made. |
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E.4 | Principal exclusion criteria |
A subject will be excluded from the trial if he/she meets any of the following criteria (see Protocol section 8.1.2 for details): 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 Painful osteoarthritis and symptomatic osteoarthritis that may interfere with the subjects or investigators ability to measure change on any outcome measures and/or compromise the objectives outlined in the protocol e.g. osteoarthritis associated with stiffness and muscle weakness Pain from traumatic injury Uncontrolled hypo- or hyperthyroidism of any type Autoimmune disease Multiple sclerosis Unstable cardiovascular, endocrine, gastrointestinal, hematologic, hepatic, immunologic, metabolic, neurological, pulmonary, and/or renal disease Neoplastic (excluding localized basal cell carcinoma) disease Systemic infection Any disease, disorder or condition that would place the subject at risk during the trial, interfere with the subjects or investigators 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 (TIA) or cerebrovascular accident (CVA). 3. Subject has a Major Depressive Disorder or is currently being treated for a Major Depressive Disorder or has a history of psychotic disorder and/or bipolar disorder. Subjects being considered for discontinuation of antidepressant medication require careful evaluation as to any risks from cessation of antidepressant therapy. If, in the opinion of the investigator, a reasonable risk of resultant subject harm exists, the subject will be excluded from study participation. 4. Subject has Generalized Anxiety Disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders IV, Text Revision (DSM IV-TR). 5. Subject has any other problems that, in the investigator's opinion, would preclude the subject's participation and completion of this trial or compromise reliable representation of subjective symptoms. 6. Subject has a MINI suicidality module score > 0 and/or subject who answers yes to the suicide question (A3-g) on the Major Depressive Episode module of the MINI and/or greater than or equal to 1 on Question 9 of the BDI-II. 7. Subject has a current or past history of a substance use disorder including alcohol abuse as defined by the Diagnostic and Statistical Manual of Mental Disorders IV, Text Revision (DSM IV-TR). 8. Subject has 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), chronic persistent migraine headaches, or past invasive intracranial surgery. 9. Subject has known succinic semialdehyde dehydrogenase deficiency. 10. Subject has participated in a previous Xyrem (sodium oxybate) clinical trial. 11. Subject has received acupuncture therapy intended for the treatment of fibromyalgia within 30 days prior to baseline. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Two primary efficacy parameters (1 and 2) will be evaluated. Primary efficacy parameter 1 is a composite parameter for the treatment of pain associated with fibromyalgia. The proportion of subjects in each treatment group that meet both of the following response criteria will be compared to assess the efficacy of Xyrem (sodium oxybate) in response to pain associated with fibromyalgia. Pain Severity: Overall pain severity will be assessed by pain VAS data recorded 3 times a day by the subject in an electronic diary. For pain VAS, a response is defined as a reduction in average pain of more than or equal to 20% from baseline to endpoint. Patient Global Impression of Change: The subjects perception of the overall improvement in their fibromyalgia symptoms will be assessed by means of the PGIc questionnaire completed at endpoint. A response to treatment is defined as a response of Very much better or Much better on the PGIc. Primary efficacy parameter 2 is a composite parameter for the treatment of fibromyalgia syndrome. The proportion of subjects in each treatment group that meet all 3 of the following response criteria will be compared to assess the efficacy of Xyrem (sodium oxybate) in response to fibromyalgia syndrome. Pain Severity: Overall pain severity will be assessed by pain VAS data recorded 3 times a day by the subject in an electronic diary. For pain VAS, a response will be defined as a reduction in average pain of more than or equal to 20% from baseline to endpoint. Functionality (Fibromyalgia Impact Questionnaire): Change from baseline to endpoint will be assessed. A response will be defined as a reduction of more than or equal to 20% in FIQ total score from baseline to endpoint. For example, if a subject has a baseline FIQ score of 40, they will need to have an FIQ score of 32 or less at endpoint, to be considered a responder. Patient Global Impression of Change: The subjects perception of the overall improvement in their fibromyalgia symptoms will be assessed by means of the PGIc questionnaire completed at endpoint. A response will be defined as a response of Very much better or Much better on the PGIc. Primary efficacy parameter 2 will not be tested unless primary efficacy parameter 1 demonstrates a significant treatment difference in favor of Xyrem (sodium oxybate). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |