E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
pain and associated symptoms in patients with fibromyalgia. |
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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 assess the long-term safety and tolerability of [S,S]-reboxetine (QD) in patients with fibromyalgia |
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E.2.2 | Secondary objectives of the trial |
To assess the long-term efficacy of [S,S]-reboxetine (QD) in the management of fibromyalgia |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female of any race, at least 18 years of age; 2. Female patients must be non-pregnant and non-lactating, and be either postmenopausal, surgically sterilized, or using an appropriate method of contraception. Prior to starting the trial, it is strongly recommended that women of childbearing potential use two of the following methods of birth control for at least one month or for whatever amount of time prescribing doctor determines it will take for the methods of birth control to be fully effective: oral birth control pills, diaphragms, progesterone implanted rods, medroxyprogesterone acetate, Depo-Provera, or condoms. Women of childbearing potential must have a confirmed negative serum pregnancy test at the Screening visit (Visit 1); 3. Patients must have personally signed and dated a legally effective written informed consent prior to admission to the study; 4. At screening (V1), patients must meet the ACR criteria for fibromyalgia (ie, widespread pain present for at least 3 months, and pain in at least 11 of 18 specific tender point sites); 5. At screening (V1), patients must have a score of ≥40 mm on the Pain Visual Analog Scale (VAS); 6. Patients must be willing and able to understand and cooperate with study procedures. |
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E.4 | Principal exclusion criteria |
1. Patients with other severe pain (e.g., DPN and PHN) that may confound assessment or selfevaluation of the pain associated with fibromyalgia; 2. Patients with any inflammatory musculoskeletal disorders, rheumatic diseases other than fibromyalgia, active infections, or untreated endocrine disorders; 3. Previous participation in a clinical trial with [S,S]-reboxetine or currently receiving treatment with Edronax® for any condition; 4. Any patients judged clinically to be at risk of suicide based on Beck’s Scale for Suicide Ideation (BSS) and clinical judgement; 5. Patients who have a history of a seizure disorder including alcoholic seizures, a family history of seizures or a history of head trauma that resulted in loss of consciousness or concussion; 6. History of uncontrolled narrow angle glaucoma; 7. History of recurrent syncope or evidence of low blood pressure (<90 mm Hg systolic or <40 mm Hg diastolic); 8. Evidence of postural hypotension e. g. falls in systolic blood pressure of >20 mm Hg or diastolic blood pressure >10 mm Hg on standing (from supine); 9. Patients with a history of transient ischemic attacks, stroke, or the presence of a carotid bruit (unless significant carotid stenosis (>70%) has been ruled out by appropriate investigation); 10. History of chronic hepatitis B or C, acute hepatitis A, B or C within the past 3 months, or HIV infection; 11. Patients with serious hepatic, respiratory, haematologic, renal or immunologic illnesses, or unstable cardiovascular disease; 12. Malignancy within the past 2 years with the exception of basal cell carcinoma; 13. Patients with a history of illicit drug or alcohol abuse within the last 2 years; 14. Patients with significant hepatic impairment (i.e. AST, ALT or total bilirubin >1.5 × ULN); 15. Platelet count <100 × 109/L; white blood cell (WBC) count <2.5 × 109/L; neutrophil count <1.5 × 109/L; 16. Westergren erythrocyte sedimentation rate (ESR) >40 mm/hr; 17. Abnormal antinuclear antibody (ANA ≥1:160 titre), or rheumatoid factor (RF >80 IU/mL); 18. Abnormal (clinically relevant) 12-lead electrocardiogram (ECG). See Appendix 8 of the protocol; 19. Patients taking any other experimental drugs within 30 days prior to screening (V1), or according to local regulation if greater than 30 days; 20. Patients with active GI disease including any GI surgery that in the opinion of the investigator would interfere with the absorption of study medication; 21. Patients with difficulties swallowing tablets or unable to tolerate oral medication; 22. Use of prohibited pain/sleep medications (including antidepressants, sedatives, hypnotics, opiates, muscle relaxants) in the absence of appropriate washout periods); 23. Clinically significant or unstable medical or psychological conditions that, in the opinion of the investigator, would compromise participation in the trial; 24. Patients with pending Worker’s Compensation, Workman’s Compensation, civil litigation or disability claims pertinent to the patient’s fibromyalgia; current involvement in out-of-court settlements for claims pertinent to the patient’s fibromyalgia; or currently receiving monetary compensation as a result of any of the above (USA only; for non-US centers-patients involved in legal cases related to fibromyalgia). 25. A current or recent diagnosis (last 6 months), or episode of major depressive disorder, dysthymia (as diagnosed by M.I.N.I) and/or uncontrolled depression; 26. History of mania, hypomania, other psychotic disorder, or current mood disorder with psychotic features, as diagnosed by the M.I.N.I.; 27. History of urinary retention; |
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E.5 End points |
E.5.1 | Primary end point(s) |
The following parameters will be obtained in order to determine the safety and tolerability of [S,S]-reboxetine in patients with fibromyalgia. 1. Vital signs (supine/standing blood pressure and pulse) 2. Physical examination 3. 12-lead ECG 4. Hematology/Biochemistry 5. Adverse events |
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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 | No |
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 | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 35 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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The End of Trial will be the Last Subject Last Visit date |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |