A European Phase III, Multicentre, Double-blind, Randomised, Placebo-Controlled Monotherapy Study of Milnacipran for the Treatment of the Fibromyalgia Syndrome. - FMS Europe

INTERVENTION: Product Name: Milnacipran hydrochloride 25 mg Product Code: F02207 Pharmaceutical Form: Capsule, hard INN or Proposed INN: Milnacipran hydrochloride Current Sponsor code: F02207 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 25‐ Pharmaceutical form of the placebo: Capsule, hard Route of administration of the placebo: Oral use Product Name: Milnacipran hydrochloride 50 mg Product Code: F02207 Pharmaceutical Form: Capsule, hard INN or Proposed INN: Milnacipran hydrochloride Current Sponsor code: F02207 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 50‐ Pharmaceutical form of the placebo: Capsule, hard Route of administration of the placebo: Oral use CONDITION: Fibromyalgia, also known as 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 an increased sensitivity to pressure at particular points on the body, and is often accompanied by fatigue, sleep disturbance, and morning stiffness. Other common symptoms include headache, migraine, variable bowel habits, diffuse abdominal pain, and urinary frequency. PRIMARY OUTCOME: Main Objective: To demonstrate the efficacy of milnacipran 200 mg/day as compared to placebo in the treatment of the fibromyalgia syndrome in outpatients after a 12‐week period of fixed dose exposure through a primary composite criterion incorporating two domains: pain and patient global status, and key secondary criteria measuring physical and emotional functioning. Primary end point(s): Efficacy:; Primary parameter: responder status based on two patient self‐reported assessments (on the PED): Morning 24h Recall Pain Score and Patient Global Impression of Change (PGIC). ; Secondary parameters: ; Fibromyalgia Impact Questionnaire (FIQ total and FIQ‐PF), Brief Pain Inventory‐Short Form (BPI‐SF), 24h recall and weekly recall pain VAS (paper), Multiple Ability Self‐report Questionnaire (MASQ, cognitive function), the Multi‐dimensional Fatigue Inventory (MFI), SF‐36 Physical Component Summary (SF‐36 PCS), Beck Depression Inventory BDI, State Trait Anxiety Inventory (STAI), sleep quality scale (MOS).; Electronic diary assessments include morning report pain (current and 24‐hour recall,), evening report pain (current pain), overall pain last week (weekly report Friday evening), study medications taken (morning and evening report), concomitant treatment (evening report for the last 24 hours), overall fatigue VAS and sleep VAS in the last week (weekly report on Friday evening), PGIC and FIQ during on site visits.; ; Safety:; Adverse events, vital signs, ECG and clinical laboratory data.; ; Diagnosis:Psychological assessments: M.I.N.I. validated tool to exclude major depressive episode (MDE) and Generalized Anxiety Disorder (GAD) Secondary Objective: To compare the efficacy of 200 mg/day of milnacipran to placebo on a number of additional secondary criteria To establish the safety profile of 200 mg/day of milnacipran in patients with FMS INCLUSION CRITERIA: Female or male patient aged 18 ‐ 70 years with a diagnosis of fibromyalgia according to the 1990 ACR criteria. (for women) Either postmenopausal (no menses for at least 1 year) or ‐has a post‐hysterectomy, ‐oophorectomy (bilateral), ‐tubal ligation status or, if of childbearing potential, has a negative urine pregnancy test at BL1 Visit/V2/D‐14, and has been using a medically acceptable form of contraception for about two months before the inclusion in this study (i.e., 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 after the intake of the last dose of study treatment. Is able to give an informed consent. Is willing to withdraw from CNS‐active therapies commonly used for FMS, including anti‐depressants, anti‐convulsants, mood stabilizers, opioids and central anaest