Study of Milnacipran for the Treatment of Fibromyalgia

Composite Pain Responder Status is the number of responders based on two domains: (1) 30% reduction in pain (as recorded in the Patient Experience Diary \[PED\], electronic diary, during the morning report; 24 hour recall); and (2) Patient Global Impression of Change (PGIC) score of very much improved or much improved.

Time frame: At the end of three-month stable dose treatment phase

Population: The primary efficacy analysis was performed based on intent-to-treat population defined as all randomized patients who took at least one dose of double-blind study medication. All subjects with missing assessments at the end of three-month stable dose treatment phase were considered non-responders (baseline value carried forward (BOCF)).

Composite Syndrome Responder Status is the number of responders based on 3 domains: (1) 30% reduction in pain (as recorded in the Patient Experience Diary \[PED\], electronic diary, during the morning report; 24 hour recall); (2) patient global impression of change (PGIC) score of very much improved and much improved; and (3) physical function improvement of 6 or more points on Short Form-36 Physical Component Summary (SF-36 PCS)

Time frame: At the end of the three-month stable dose treatment phase

Population: The primary efficacy analysis was performed based on intent-to-treat population defined as all randomized patients who took at least one dose of double-blind study medication. All subjects with missing assessments at the end of the three-month stable dose treatment phase were considered non-responders (baseline value carried forward (BOCF)).

Change from Baseline in the Multi-Dimensional Fatigue Inventory (MFI) total score at TX12. Negative differences indicate decrease of fatigue. MFI is a subjective report of fatigue symptoms consisting of 20 items that can be scored to produce 5 dimensions: general fatigue, physical fatigue, mental fatigue, reduced motivation, and reduced activity. The MFI is a 1-5 scale with 1=yes, that is true and 5=no, that is not true.

Time frame: Baseline through end of week 12 (Visit TX12)

Population: The analysis was performed based on intent-to-treat population defined as all randomized patients who took at least one dose of double-blind study medication. For all subjects with missing assessments at the end of week 12 (Visit TX12), values were imputed using Last Observation Carried Forward (LOCF).

Time-weighted average (area under the curve \[AUC\]) of the weekly average Patient Experience Diary (PED)-reported morning recall pain scores for weeks 1 through 12 of the stable dose treatment phase is the area under the Patient Experience Diary (PED)-time curve estimated using the trapezoidal method and normalized by time. PED is the Patient Experience Diary, an electronic diary system used for collection of patient self-reported pain data. Outcome measure is assessed using the VAS Pain Intensity Scale from 0-100 millimeters anchored at 0 mm (no pain) to 100 mm (worst possible pain).

Time frame: Weeks 1 through 12 of the stable dose treatment phase (Visit TX0-TX12)

Population: The analysis was performed based on intent-to-treat population defined as all randomized patients who took at least one dose of double-blind study medication. For all subjects with missing assessments for weeks 1-12 of the stable dose treatment phase, values were imputed using last observation carried forward (LOCF).

Time-weighted average (area under the curve \[AUC\]) for Patient Global Impression of Change (PGIC) from Visit TX0-TX12 is the area under the PGIC-time curve estimated using the trapezoidal method and normalized by time. PGIC is an efficacy assessment on a scale of 1-7 taken at visits TX0-TX12. The wording of the assessment is as follows: Since the start of the study, overall my fibromyalgia is: 1=Very Much Improved, 2=Much Improved, 3=Minimally Improved, 4=No Change, 5=Minimally Worse, 6=Much Worse, and 7-Very Much Worse.

Time frame: Weeks 1-12 (Visit TX0-TX12) of the stable dose treatment phase

Population: The analysis was performed based on intent-to-treat population defined as all randomized patients who took at least one dose of double-blind study medication. For all subjects with missing assessments from weeks 1-12 of the stable dose treatment phase, values were imputed using last observation carried forward (LOCF).

Short Form-36 (SF-36): pt. questionnaire (36 questions) which give rise to 8 domains & 2 component summaries (mental and physical); assessing quality of life, health & functional status. SF-36 PCS: weighted summary of physical function using all 8 domains. Scores are standardized so that the range for all domains and component summaries is 0 (worst possible score) to 100 (best possible score). Higher scores indicate better health or functional status. SF-36 PCS AUC (Area under the Curve): estimated using trapezoidal method, normalized by time.

Time frame: Weeks 1-12 (Visit TX0-TX12) of the stable dose treatment phase

Population: The analysis was performed based on intent-to-treat population defined as all randomized patients who took at least one dose of double-blind study medication. For all subjects with missing assessments from weeks 1-12 (Visit TX0-TX12) of the stable dose treatment phase, values were imputed using the Last Observation Carried Forward (LOCF) approach.