Fibromyalgia syndrome (FMS) is a common systemic rheumatologic disorder estimated to affect 2 to 4% of the population. Fibromyalgia is associated with a reduced threshold for pain, generally identified by increased sensibility to pressure at particular points on the body, and is often accompanied by fatigue, sleep disturbance and morning stiffness. Other common symptoms include headhache, migraine, variable bowel habits, diffuse abdominal pain and urinary frequency. MedDRA version: 8.1 Level: L
Conditions
Interventions
Product Name: Milnacipran 25 mg
Product Code: F2207
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: MILNACIPRAN HYDROCHLORIDE
CAS Number: 101152947
Current Sponsor code: F2207
Concentration un
Sponsors
PIERRE FABRE MEDICAMENT
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: In order to be eligible to participate in the study, the Patient must fulfil the following criteria: · Has completed the 3-month F02207 GE 3 02 study, · Is able to give and has given her/his informed consent, · Is able to perform the Screening Visit (V1) on the day of F02207 GE 3 02 last visit (V10), · Had a diagnosis of FMS according to the American College of Rheumatology (ACR) 1990 at entry of F02207 GE3 02 study, · Is a male or female patient between the ages of 18 and 71 years, · (for women) Is either postmenopausal (no menses for at least 1 year) or has a post-hysterectomy, -oophorectomy (bilateral), or -tubal ligation status or, if of childbearing potential, has a negative urine pregnancy test at inclusion (V2/D1), and is currently using a medically acceptable form of contraception (e.g., hormonal birth control, IUD, double barrier [male condom, female condom, diaphragm] or a barrier method plus a spermicidal agent [contraceptive foam, jelly, or cream]). The Patient should be advised to continue the contraception one month (or two months for Denmark) after the intake of the last dose of study treatment, · Has a BDI £ 25 and BDI-item 9 £1 at Screening (V1/D-7) and Inclusion (V2/D1), · Is willing to carry on with withdrawal from CNS-active therapies commonly used for FMS, including anti-depressants, anti-convulsants, opioids whatever the route of administration, · Is willing to carry on with withdrawal from trigger point and tender point injections, acupuncture, and anaesthetics (ketamine). 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
Exclusion criteria: Psychological/ Psychiatric Criteria · With a major depressive episode, significant risk of suicide (“moderate” or “high”) or generalised anxiety disorder (GAD) at inclusion (V2/D1) according to the MINI (modules A, C and O) performed by a trained staff at Inclusion (V2/D1), · With a positive urine drug screen for benzodiazepines, opiates and cannabis at Screening (V1), · With a history or behaviour that would, in the Investigator’s opinion, prohibit compliance for the duration of the study. Somatic Criteria · With, within the past 6 months, a clinically significant cardiac disease on routine clinical examination (history, physical examination and ECG recording), or known congestive heart failure, myocardial infarction, clinically significant valvular heart disease (including patients with a prosthetic heart valve), and/or clinically significant cardiac rhythm or conduction abnormalities, and/or uncontrolled or unstable hypertension. · With pulmonary dysfunction or severe obstructive pulmonary disease that, in the Investigator’s judgment, could interfere with the study participation and completion. · With evidence of active liver disease (levels of AST, ALT and/or alkaline phosphatase > 1.5 x the upper limit of the normal range for the laboratory performing the test) or with a clinically significant laboratory abnormality. · With renal impairment (Cockroft creatinine clearance < 60 ml/min: adjustment for patient gender, age and weight). · With suspected rheumatoid arthritis or any other systemic autoimmune disease. · With current systemic infection. · Epileptic · With active cancer, (except basal cell carcinoma), or patients currently undergoing therapy for cancer. · With a current life expectancy less than one year. · With sleep apnoea severe enough that, in the Investigator’s opinion, would interfere with interpretation of changes in sleep habits. · With active peptic ulcer, inflammatory bowel disease. · With unstable endocrine disease, including unstable diabetes or thyroid disease. Disorders that have been stable under treatment for the preceding 6 months before inclusion will be acceptable. · (for men) With prostatic enlargement or other genito-urinary disorders, that might be at significant risk of dysuria and/or urinary retention when taking agents with noradrenaline re-uptake inhibition properties. · (for women) Pregnant or breastfeeding. Treatment-related Criteria · With a known hypersensitivity to milnacipran, · Has been receiving between screening and inclusion: MAO-A or -B inhibitors, tricyclics, tetracyclics, SSRIs agents, NARIs agents, SNRIs agents or alpha-agonists, anticonvulsants (phenytoine), phytotherapy with anxiolytic or anti-drepressive properties (e.g., hypericum), dopamine agonists, cholinesterase inhibitors (pyridostigmine, ambemonium) or muscle relaxants, · phenytoin and phenobarbital, oral anticoagulants (warfarin), carbamazepine and levomepromazine, · epinephrine, norepinephrine (alpha and beta sympathomimetics), · SAMe, melatonine or DHEA, · digitalis (digoxin) preparations, · centrally-acting class III analgesics, · trigger point and tender point injections, acupuncture, and anaesthetics (ketamine) · Has been receiving statines, except if stable, within 4 weeks before inclusion, · Is receiving concomitant therapy with long-term systemic corticosteroids except if stable and at low doses (equivalent to 10 mg of cortisone).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: To investigate the long-term efficacy (including the durability of efficacy) of milnacipran in treating FMS over 12 months of exposure at doses of 100, 150 and 200 mg daily.;Main Objective: To assess the long-term safety of milnacipran used for the treatment of FMS at doses of 100, 150 and 200 mg daily.;Primary end point(s): Safety:· Continuous adverse events report, · Vital signs, physical examination, weight at each scheduled and unscheduled visits, · ECG and clinical laboratory data at Screening Visit, End-of-Escalation Visit (V3/W4), V7/W28 and V10/W52 or PW (end of target dose phase) visits . Efficacy: - At each scheduled and unscheduled visit (from inclusion): · Last Week Pain VAS, last 24 h Pain VAS, Current Pain VAS and Patient Global Impression of Change (PGIC), · Last week sleep quality VAS and last week overall fatigue VAS. - At each scheduled visit: · Brief Pain Inventory Short Form (BPI-SF), State Trait Anxiety Inventory (STAI-S), · Fibromyalgia Impact Questionnaire (FIQ), Beck Depression Inventory (BDI), - At W0, W28, Week 52 (or PW) and Week 56: · Multi-dimensional Fatigue Inventory (MFI), Health Status (SF36), Multiple Ability Self-Report Questionnaire (MASQ). Specific Baseline Characteristics: · A, C, O MINI modules at V2 | — |
Countries
Czech Republic, Denmark, Germany, Italy, Portugal, Sweden, United Kingdom
Outcome results
None listed