Fibromyalgia
Conditions
Keywords
fibromyalgia, milnacipran, pregabalin, treatment, Forest Research Institute
Brief summary
To evaluate the safety, tolerability, and efficacy of milnacipran when taken with another drug called pregabalin in people with fibromyalgia.
Interventions
No added treatment
DRUGMilnacipran Added
Milnacipran 100 mg/d added
Sponsors
Forest Laboratories
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* diagnosis of fibromyalgia defined by 1990 American College of Rheumatology (ACR) Criteria * tolerate at least 300 mg/day of pregabalin * have an incomplete response to pregabalin treatment
Exclusion criteria
* suicidal risk * substance abuse * pulmonary dysfunction * renal impairment * active cardiac disease * liver disease * narrow angle glaucoma * autoimmune disease * cancer * inflammatory bowel disease * unstable endocrine disease * prostatic enlargement
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Patient Global Impression of Change (PGIC) Responder Rate at End of Study | End of Randomized treatment period (11 weeks) | The primary efficacy parameter was the PGIC responder rate, defined as the percentage of patients who rated themselves as very much improved or much improved (ie, having a score of 1 or 2 on the 7-point scale) for the PGIC at end of study (Visit 6 or Early Termination) compared to Visit 1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Visual Analog Scale (VAS) 1-week Pain Recall at End of Study | Baseline (0 weeks) and End of Randomized Treatment Period (11 weeks) | The secondary efficacy measure was the change from Visit 2 (Week 0) in the 1-week pain recall at Visit 6 (Week 11) or End of Study, measured using a 100-mm VAS assessment of pain (0 indicating no pain and 100 indicating the worst possible pain). |
Countries
United States
Participant flow
Recruitment details
Participants were recruited and enrolled in this study within the US from December 2008 to June 2009.
Pre-assignment details
Participants entered an open label pregabalin period concurrent with prohibited medication washout. Incomplete responders to pregabalin were randomized to receive either milnacipran (100 mg/d) or no added treatment for 11 weeks. All participant continued background stable dose pregabalin (300 or 450 mg/d) throughout the randomized treatment period.
Participants by arm
| Arm | Count |
|---|---|
| No Treatment Added No treatment added for 11 weeks of randomized treatment period | 178 |
| Milnacipran Added Milnacipran (100 mg/day) added for 11 weeks of randomized treatment period | 184 |
| Total | 362 |
Baseline characteristics
| Characteristic | No Treatment Added | Milnacipran Added | Total |
|---|---|---|---|
| Age Categorical >=60 years | 27 participants | 38 participants | 65 participants |
| Age Categorical Between 18 and 60 years | 151 participants | 146 participants | 297 participants |
| Age Continuous | 48.8 years STANDARD_DEVIATION 10.4 | 49.8 years STANDARD_DEVIATION 10.3 | 49.3 years STANDARD_DEVIATION 10.3 |
| Region of Enrollment United States | 178 participants | 184 participants | 362 participants |
| Sex: Female, Male Female | 159 Participants | 170 Participants | 329 Participants |
| Sex: Female, Male Male | 19 Participants | 14 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 38 / 178 | 90 / 184 |
| serious Total, serious adverse events | 6 / 178 | 5 / 184 |
Outcome results
Primary
Patient Global Impression of Change (PGIC) Responder Rate at End of Study
The primary efficacy parameter was the PGIC responder rate, defined as the percentage of patients who rated themselves as very much improved or much improved (ie, having a score of 1 or 2 on the 7-point scale) for the PGIC at end of study (Visit 6 or Early Termination) compared to Visit 1.
Time frame: End of Randomized treatment period (11 weeks)
Population: All efficacy analyses are based on the Intent-to-Treat population, defined as all randomized patients who received at least one dose of randomized study drug and had at least one post-baseline PGIC assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| No Treatment Added | Patient Global Impression of Change (PGIC) Responder Rate at End of Study | Responder | 36 participants |
| No Treatment Added | Patient Global Impression of Change (PGIC) Responder Rate at End of Study | Non-Responder | 137 participants |
| Milnacipran Added | Patient Global Impression of Change (PGIC) Responder Rate at End of Study | Responder | 83 participants |
| Milnacipran Added | Patient Global Impression of Change (PGIC) Responder Rate at End of Study | Non-Responder | 96 participants |
Comparison: The responder rates between 'No Treatment Added' and 'Milnacipran Added' groups were compared using a logistic regression model.p-value: <0.001Regression, Logistic
Secondary
Change From Baseline in Visual Analog Scale (VAS) 1-week Pain Recall at End of Study
The secondary efficacy measure was the change from Visit 2 (Week 0) in the 1-week pain recall at Visit 6 (Week 11) or End of Study, measured using a 100-mm VAS assessment of pain (0 indicating no pain and 100 indicating the worst possible pain).
Time frame: Baseline (0 weeks) and End of Randomized Treatment Period (11 weeks)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| No Treatment Added | Change From Baseline in Visual Analog Scale (VAS) 1-week Pain Recall at End of Study | -6.43 mm | Standard Error 1.93 |
| Milnacipran Added | Change From Baseline in Visual Analog Scale (VAS) 1-week Pain Recall at End of Study | -20.77 mm | Standard Error 1.92 |
Comparison: This parameter was analyzed using an ANCOVA model with treatment group and study center as factors and baseline value as a covariate.95% CI: [-18.99, -9.71]ANCOVA