Primary Fibromyalgia
Conditions
Keywords
Fibromyalgia, Pediatric Fibromyalgia, Adolescent Fibromyalgia, milnacipran, Savella, loss of therapeutic response, Forest Research Institute, Pain, Fatigue, Serotonin Norepinephrine Reuptake Inhibitors
Brief summary
The purpose of this study is to evaluate the long-term safety and efficacy of milnacipran in pediatric patients aged 13 to 17 years with primary fibromyalgia.
Interventions
DRUGMilnacipran
maximum tolerated dose (50, 75, or 100 mg/day tablets); for 52 weeks.
Sponsors
Cypress Bioscience, Inc.
Forest Laboratories
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
13 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Patients must have completed or discontinued prematurely from lead-in study, MLN-MD-14, tolerating a minimum daily dose of 50mg milnacipran
Exclusion criteria
* Can not tolerate a minimum daily dose of 50mg milnacipran * Significant risk of suicidality * Pregnant or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | Baseline (Visit 1) to Week 53 (Visit 9) | Number of Patients who experience one or more treatment emergent adverse event (TEAE) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Who Experienced Level 4 Suicidal Ideation, as Assessed by the Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS). | Baseline (Visit 1) to Week 53 (Visit 9) | The electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) is a validated, self-rated version of the C-SSRS designed to uniquely assess both suicidal behavior and ideation. Suicidal ideation is assessed at 5 distinct levels of increasing severity: * Level 1: Wish to be Dead * Level 2: Non-Specific Active Suicidal Thoughts * Level 3: Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act * Level 4: Active Suicidal Ideation with Some Intent to Act, without Specific Plan * Level 5: Active Suicidal Ideation with Specific Plan and Intent |
| Number of Patients Who Experienced Level 3 Suicidal Ideation, as Assessed by the Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS). | Baseline (Visit 1) to Week 53 (Visit 9) | The electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) is a validated, self-rated version of the C-SSRS designed to uniquely assess both suicidal behavior and ideation. Suicidal ideation is assessed at 5 distinct levels of increasing severity: * Level 1: Wish to be Dead * Level 2: Non-Specific Active Suicidal Thoughts * Level 3: Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act * Level 4: Active Suicidal Ideation with Some Intent to Act, without Specific Plan * Level 5: Active Suicidal Ideation with Specific Plan and Intent |
| Number of Patients Who Experienced Level 5 Suicidal Ideation, as Assessed by the Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS). | Baseline (Visit 1) to Week 53 (Visit 9) | The electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) is a validated, self-rated version of the C-SSRS designed to uniquely assess both suicidal behavior and ideation. Suicidal ideation is assessed at 5 distinct levels of increasing severity: * Level 1: Wish to be Dead * Level 2: Non-Specific Active Suicidal Thoughts * Level 3: Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act * Level 4: Active Suicidal Ideation with Some Intent to Act, without Specific Plan * Level 5: Active Suicidal Ideation with Specific Plan and Intent |
| Number of Patients Who Experienced Level 1 Suicidal Ideation, as Assessed by the Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS). | Baseline (Visit 1) to Week 53 (Visit 9) | The electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) is a validated, self-rated version of the C-SSRS designed to uniquely assess both suicidal behavior and ideation. Suicidal ideation is assessed at 5 distinct levels of increasing severity: * Level 1: Wish to be Dead * Level 2: Non-Specific Active Suicidal Thoughts * Level 3: Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act * Level 4: Active Suicidal Ideation with Some Intent to Act, without Specific Plan * Level 5: Active Suicidal Ideation with Specific Plan and Intent |
| Number of Patients Who Experienced Any Suicidal Behavior as Assessed by the Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) | Baseline (Visit 1) to Week 53 (Visit 9) | The electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) is a validated, self-rated version of the C-SSRS designed to uniquely assess both suicidal behavior and ideation. Suicidal behaviors as defined by the eC-SSRS are: * Preparatory acts or behavior * Aborted attempt * Interrupted attempt * Actual attempt * Completed suicide attempt |
| Number of Patients Who Experienced Level 2 Suicidal Ideation, as Assessed by the Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS). | Baseline (Visit 1) to Week 53 (Visit 9) | The electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) is a validated, self-rated version of the C-SSRS designed to uniquely assess both suicidal behavior and ideation. Suicidal ideation is assessed at 5 distinct levels of increasing severity: * Level 1: Wish to be Dead * Level 2: Non-Specific Active Suicidal Thoughts * Level 3: Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act * Level 4: Active Suicidal Ideation with Some Intent to Act, without Specific Plan * Level 5: Active Suicidal Ideation with Specific Plan and Intent |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Milnacipran oral administration, twice daily dosing
Milnacipran : maximum tolerated dose (50, 75, or 100 mg/day tablets); for 52 weeks. | 57 |
| Total | 57 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 6 |
| Overall Study | Lack of Efficacy | 2 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Protocol Violation | 3 |
| Overall Study | Study Terminated by Sponsor | 38 |
| Overall Study | Withdrawal by Subject | 7 |
Baseline characteristics
| Characteristic | Milnacipran |
|---|---|
| Age Continuous | 15.4 years STANDARD_DEVIATION 1.35 |
| Age, Customized 13 years old | 5 participants |
| Age, Customized 14 years old | 12 participants |
| Age, Customized 15 years old | 11 participants |
| Age, Customized 16 years old | 12 participants |
| Age, Customized 17 years old | 17 participants |
| Maximum Tolerated Dose of Milnacipran 100mg | 46 participants |
| Maximum Tolerated Dose of Milnacipran 50 mg | 3 participants |
| Maximum Tolerated Dose of Milnacipran 75 mg | 8 participants |
| Maximum Tolerated Dose of Milnacipran Less than 50mg | 0 participants |
| Region of Enrollment United States | 57 participants |
| Sex: Female, Male Female | 50 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 28 / 57 |
| serious Total, serious adverse events | 2 / 57 |
Outcome results
Primary
Adverse Events
Number of Patients who experience one or more treatment emergent adverse event (TEAE)
Time frame: Baseline (Visit 1) to Week 53 (Visit 9)
Population: 57 patients who took at least 1 dose of open-label milnacipran were included in the safety population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Milnacipran | Adverse Events | 42 participants |
Other Pre-specified
Number of Patients Who Experienced Any Suicidal Behavior as Assessed by the Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS)
The electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) is a validated, self-rated version of the C-SSRS designed to uniquely assess both suicidal behavior and ideation. Suicidal behaviors as defined by the eC-SSRS are: * Preparatory acts or behavior * Aborted attempt * Interrupted attempt * Actual attempt * Completed suicide attempt
Time frame: Baseline (Visit 1) to Week 53 (Visit 9)
Population: 57 patients who took at least 1 dose of open-label milnacipran were included in the safety population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Milnacipran | Number of Patients Who Experienced Any Suicidal Behavior as Assessed by the Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) | 0 participants |
Other Pre-specified
Number of Patients Who Experienced Level 1 Suicidal Ideation, as Assessed by the Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS).
The electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) is a validated, self-rated version of the C-SSRS designed to uniquely assess both suicidal behavior and ideation. Suicidal ideation is assessed at 5 distinct levels of increasing severity: * Level 1: Wish to be Dead * Level 2: Non-Specific Active Suicidal Thoughts * Level 3: Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act * Level 4: Active Suicidal Ideation with Some Intent to Act, without Specific Plan * Level 5: Active Suicidal Ideation with Specific Plan and Intent
Time frame: Baseline (Visit 1) to Week 53 (Visit 9)
Population: 57 patients who took at least 1 dose of open-label milnacipran were included in the safety population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Milnacipran | Number of Patients Who Experienced Level 1 Suicidal Ideation, as Assessed by the Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS). | 3 participants |
Other Pre-specified
Number of Patients Who Experienced Level 2 Suicidal Ideation, as Assessed by the Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS).
The electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) is a validated, self-rated version of the C-SSRS designed to uniquely assess both suicidal behavior and ideation. Suicidal ideation is assessed at 5 distinct levels of increasing severity: * Level 1: Wish to be Dead * Level 2: Non-Specific Active Suicidal Thoughts * Level 3: Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act * Level 4: Active Suicidal Ideation with Some Intent to Act, without Specific Plan * Level 5: Active Suicidal Ideation with Specific Plan and Intent
Time frame: Baseline (Visit 1) to Week 53 (Visit 9)
Population: 57 patients who took at least 1 dose of open-label milnacipran were included in the safety population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Milnacipran | Number of Patients Who Experienced Level 2 Suicidal Ideation, as Assessed by the Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS). | 0 participants |
Other Pre-specified
Number of Patients Who Experienced Level 3 Suicidal Ideation, as Assessed by the Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS).
The electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) is a validated, self-rated version of the C-SSRS designed to uniquely assess both suicidal behavior and ideation. Suicidal ideation is assessed at 5 distinct levels of increasing severity: * Level 1: Wish to be Dead * Level 2: Non-Specific Active Suicidal Thoughts * Level 3: Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act * Level 4: Active Suicidal Ideation with Some Intent to Act, without Specific Plan * Level 5: Active Suicidal Ideation with Specific Plan and Intent
Time frame: Baseline (Visit 1) to Week 53 (Visit 9)
Population: 57 patients who took at least 1 dose of open-label milnacipran were included in the safety population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Milnacipran | Number of Patients Who Experienced Level 3 Suicidal Ideation, as Assessed by the Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS). | 1 participants |
Other Pre-specified
Number of Patients Who Experienced Level 4 Suicidal Ideation, as Assessed by the Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS).
The electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) is a validated, self-rated version of the C-SSRS designed to uniquely assess both suicidal behavior and ideation. Suicidal ideation is assessed at 5 distinct levels of increasing severity: * Level 1: Wish to be Dead * Level 2: Non-Specific Active Suicidal Thoughts * Level 3: Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act * Level 4: Active Suicidal Ideation with Some Intent to Act, without Specific Plan * Level 5: Active Suicidal Ideation with Specific Plan and Intent
Time frame: Baseline (Visit 1) to Week 53 (Visit 9)
Population: 57 patients who took at least 1 dose of open-label milnacipran were included in the safety population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Milnacipran | Number of Patients Who Experienced Level 4 Suicidal Ideation, as Assessed by the Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS). | 1 participants |
Other Pre-specified
Number of Patients Who Experienced Level 5 Suicidal Ideation, as Assessed by the Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS).
The electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) is a validated, self-rated version of the C-SSRS designed to uniquely assess both suicidal behavior and ideation. Suicidal ideation is assessed at 5 distinct levels of increasing severity: * Level 1: Wish to be Dead * Level 2: Non-Specific Active Suicidal Thoughts * Level 3: Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act * Level 4: Active Suicidal Ideation with Some Intent to Act, without Specific Plan * Level 5: Active Suicidal Ideation with Specific Plan and Intent
Time frame: Baseline (Visit 1) to Week 53 (Visit 9)
Population: 57 patients who took at least 1 dose of open-label milnacipran were included in the safety population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Milnacipran | Number of Patients Who Experienced Level 5 Suicidal Ideation, as Assessed by the Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS). | 0 participants |