Fibromyalgia
Conditions
Keywords
Milnacipran, Duloxetine, Switch, Forest Research Institute
Brief summary
The objective of this study is to evaluate the safety, tolerability and efficacy of milnacipran in patients with an inadequate response to duloxetine for the treatment of fibromyalgia.
Detailed description
* Two weeks Duloxetine 60 mg Open-Label Period * Randomization to Double-Blind Treatment Period: 10 weeks Milnacipran (direct switch) or 10 weeks placebo (one week blinded 30 mg duloxetine) * One week Double-Blind Down-Taper Period
Interventions
DRUGPlacebo
* Placebo tablets, oral administration, twice daily for 10 weeks during randomized, double-blind treatment period. Duloxetine capsules, oral administration, 30 mg/day for 1 week after randomization to effect a duloxetine down-taper. * Placebo tablets, twice daily for 1 week during double-blind down-taper treatment period.
DRUGMilnacipran
* Milnacipran tablets, 100 to 200 mg/day, oral administration, twice daily in divided doses for 10 weeks during randomized, double-blind treatment period. Placebo capsules, 1 capsule/day administered for 1 week after randomization to maintain double-blind duloxetine down-taper. * Milnacipran tablets, 100 to 0 mg/day, oral administration, twice daily in divided doses for 1 week during double-blind down-taper treatment period.
Sponsors
Cypress Bioscience, Inc.
Forest Laboratories
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of fibromyalgia * Have been treated with a stable dosage of duloxetine (60 mg/day) for ≥ 4 weeks immediately before Screening (Visit 1) * Duloxetine must have been prescribed for the treatment of Fibromyalgia * Have a VAS 1-week pain recall score ≥ 40 mm and ≤ 90 mm * At Visit 2, to be eligible to enter the randomized treatment period, must continue to have a VAS 1-week pain recall score ≥ 40 mm and be dissatisfied with current Duloxetine treatment.
Exclusion criteria
* Suicidal risk * History of mania, bipolar disorder, psychotic disorder, schizophrenia, or a current episode of major depressive disorder * Myocardial infarction and/or stroke within the prior 6 months * Systolic blood pressure \> 160 mm Hg or mean diastolic blood pressure \> 100 mm Hg at Screening (Visit 1) * Substance abuse * Pulmonary dysfunction * Severe renal impairment * Active cardiac disease * Liver disease * Uncontrolled narrow-angle glaucoma * Autoimmune disease * Cancer * Inflammatory bowel disease * Unstable endocrine disease * Prostatic enlargement * Female patients who are pregnant or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Responder Status Based on Patient Global Impression of Change (PGIC) Score at Visit 5 (Week 13) | Assessed at Visit 4 (Week 9) and Visit 5 (Week 13) or early termination. Presented results generated via LOCF approach. | The PGIC is a patient-reported measure of improvement in pain sensation and quality of life scored on a scale from 1 (very much improved) to 7 (very much worse). To meet the criteria for a responder in this study, patients must report a score of 1 (very much improved) or 2 (much improved) on the PGIC. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Visit 5 (Week 13) in the Visual Analog Scale (VAS) 1-week Pain Recall Score | Change from Baseline (Week 3) to Visit 5 (Week 13) | The VAS assessment ranges from a scale of 0 (no pain) to 100 (worst possible pain). |
Countries
United States
Participant flow
Recruitment details
Recruitment occurred over an 8 month period from February 2010 to September 2010 at 25 study centers in the United States. Last patient last visit occurred on December 22nd, 2010.
Pre-assignment details
All participants were given an open-label treatment of duloxetine 60 mg once daily for a two week period before randomization. Patients randomized to placebo received 1 week of duloxetine 30 mg to effect a duloxetine down-taper. Patients randomized to milnacipran received 1 week of placebo capsules to maintain the blind.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Double-blind Safety Population: Placebo treatment assignment, dose-matched placebo tablets, twice a day, oral administration. | 21 |
| Milnacipran Double-blind Safety Population: milnacipran treatment assignment, 100 to 200 md/day, twice a day in divided doses, oral administration.
One patient randomized to the milnacipran treatment group did not take at least one dose of double-blind study drug and was therefore not included in the Double-blind Safety Population. | 85 |
| Total | 106 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 15 |
| Overall Study | Lack of Efficacy | 6 | 8 |
| Overall Study | Lost to Follow-up | 2 | 5 |
| Overall Study | Other Reason | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 6 |
Baseline characteristics
| Characteristic | Placebo | Milnacipran | Total |
|---|---|---|---|
| Age Continuous | 48.5 years STANDARD_DEVIATION 11.3 | 48.5 years STANDARD_DEVIATION 10.5 | 48.5 years STANDARD_DEVIATION 10.6 |
| Age, Customized 18 to 59 | 17 participants | 77 participants | 94 participants |
| Age, Customized 60 to 70 | 4 participants | 8 participants | 12 participants |
| Region of Enrollment United States | 21 participants | 85 participants | 106 participants |
| Sex: Female, Male Female | 19 Participants | 79 Participants | 98 Participants |
| Sex: Female, Male Male | 2 Participants | 6 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 16 / 21 | 63 / 85 |
| serious Total, serious adverse events | 0 / 21 | 2 / 85 |
Outcome results
Primary
Responder Status Based on Patient Global Impression of Change (PGIC) Score at Visit 5 (Week 13)
The PGIC is a patient-reported measure of improvement in pain sensation and quality of life scored on a scale from 1 (very much improved) to 7 (very much worse). To meet the criteria for a responder in this study, patients must report a score of 1 (very much improved) or 2 (much improved) on the PGIC.
Time frame: Assessed at Visit 4 (Week 9) and Visit 5 (Week 13) or early termination. Presented results generated via LOCF approach.
Population: ITT Population: patients in the Double-blind Safety Population with ≥ 1 PGIC post-baseline assessment. Double-blind Safety Population includes 6 patients who were not included in ITT population. Presented results generated via LOCF approach. No statistical comparisons between groups are presented; study was exploratory, not hypothesis-testing.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Responder Status Based on Patient Global Impression of Change (PGIC) Score at Visit 5 (Week 13) | 5 participants |
| Milnacipran | Responder Status Based on Patient Global Impression of Change (PGIC) Score at Visit 5 (Week 13) | 26 participants |
Secondary
Change From Baseline to Visit 5 (Week 13) in the Visual Analog Scale (VAS) 1-week Pain Recall Score
The VAS assessment ranges from a scale of 0 (no pain) to 100 (worst possible pain).
Time frame: Change from Baseline (Week 3) to Visit 5 (Week 13)
Population: ITT Population: patients in the Double-blind Safety Population with ≥ 1 PGIC post-baseline assessment. Double-blind Safety Population includes 6 patients who were not included in ITT population. Presented results generated via LOCF approach. No statistical comparisons between groups are presented; study was exploratory, not hypothesis-testing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Visit 5 (Week 13) in the Visual Analog Scale (VAS) 1-week Pain Recall Score | -1.3 Units on a scale | Standard Deviation 22.5 |
| Milnacipran | Change From Baseline to Visit 5 (Week 13) in the Visual Analog Scale (VAS) 1-week Pain Recall Score | -12.3 Units on a scale | Standard Deviation 27.3 |