Fibromyalgia
Conditions
Brief summary
The purpose of the study is to assess the effectiveness and safety of duloxetine in participants with fibromyalgia.
Interventions
DRUGDuloxetine 60 mg
Duloxetine 60 mg taken orally once every day for 15 weeks
DRUGPlacebo
Placebo taken orally once every day for 15 weeks
Sponsors
Shionogi
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
* Participants fulfilling the following criteria in the American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia * Participants with pain rated severity 4 or over by Brief Pain Inventory (BPI) - average pain severity item (Question 3)
Exclusion criteria
* Participants with serious cardiovascular, hepatic, renal, respiratory, or hematological disease, or clinically significant laboratory or electrocardiogram abnormality which indicate a serious medical problem or require significant intervention in the judgment of the investigators * Participants with alanine aminotransferase/aspartate aminotransferase of not less than 100 international units per liter (IU/L) or total bilirubin of not less than 1.6 milligrams per deciliter (mg/dL) * Participants with serum creatinine level of not less than 2.0 mg/dL, participant who has undergone kidney transplantation or hemodialysis * Participants with pain difficult to discriminate from pain associated with fibromyalgia or disease which disturbs the assessment * Participants with treatment-refractory fibromyalgia * Participants with thyroidal dysfunction, excluding those assessed by the investigator that the disorder is controlled as appropriate by 3-month or longer drug therapy * Participants with present or past history of rheumatoid arthritis, inflammatory arthritis, infectious arthritis, or auto immune disease rather than thyroid deficiency * Participants with an axis I condition according to Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV), currently or within the past year, except for major depressive disorders * Participants with a lifetime diagnosis of bipolar disorder or schizoaffective disorder; or any other disorder with psychotic symptoms - based on the clinical opinion of the investigator * Participants with personality disorder or mental retardation * Participants with uncontrolled angle closure glaucoma * Participants with present or past history of uncontrolled seizures or convulsion disorders * Participants with suicidal ideation within past 6 months, with suicidal attempt within past 1 year * Participants answering yes to any of the questions about active suicidal ideation/intent/behaviors occurring within the past 6 months (Columbia Suicide Severity Rating Scale, Suicide Ideation section - Questions 4 and 5; Suicidal Behavior section) * Participants with past history of multiple episodes of drug allergy * Female participants who are pregnant, lactating, or who want to get pregnant during the study period. Male participants who want his partner to get pregnant * Females of child-bearing potential who can't agree to utilize medically. acceptable and reliable means of birth control during the study and for 1 month following the last dose of the study * Participants with a history of alcohol or any psychoactive substance abuse or dependence (including alcohol, but excluding nicotine and caffeine) within the past 1 year * Participants who have a positive urine drug screen for any substance of abuse (phencyclidine, cocaine, antihypnotic agent, or cannabis) * Participants previously treated with duloxetine
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to 14-Week Endpoint in the BPI 24-Hour Average Pain Severity Item of the BPI-Modified Short Form Score (MMRM) | Baseline, 14 weeks | BPI 24-hour average pain severity is a self-reported scale that measures the severity of pain based on the average pain over the past 24-hours. Severity scores ranged from 0 (no pain) to 10 (severe pain). Least squares (LS) mean was calculated using a mixed-effects model repeated measures (MMRM) approach including administration groups, observation points, and interaction between the administration groups as fixed effects, and BPI average pain severity at baseline and the presence or absence of major depressive disorder as covariates; a linear model with unstructured error variance was applied. |
| Change From Baseline to 2 Weeks in the BPI 24-Hour Average Pain Severity Item of the BPI-Modified Short Form Score (MMRM) | Baseline, 2 weeks | BPI 24-hour average pain severity is a self-reported scale that measures the severity of pain based on the average pain over the past 24-hours. Severity scores ranged from 0 (no pain) to 10 (severe pain). LS mean was calculated using an MMRM approach including administration groups, observation points, and interaction between the administration groups as fixed effects, and BPI average pain severity at baseline and the presence or absence of major depressive disorder as covariates; a linear model with unstructured error variance was applied. |
| Change From Baseline to 4 Weeks in the BPI 24-Hour Average Pain Severity Item of the BPI-Modified Short Form Score (MMRM) | Baseline, 4 weeks | BPI 24-hour average pain severity is a self-reported scale that measures the severity of pain based on the average pain over the past 24-hours. Severity scores ranged from 0 (no pain) to 10 (severe pain). LS mean was calculated using an MMRM approach including administration groups, observation points, and interaction between the administration groups as fixed effects, and BPI average pain severity at baseline and the presence or absence of major depressive disorder as covariates; a linear model with unstructured error variance was applied. |
| Change From Baseline to 6 Weeks in the BPI 24-Hour Average Pain Severity Item of the BPI-Modified Short Form Score (MMRM) | Baseline, 6 weeks | BPI 24-hour average pain severity is a self-reported scale that measures the severity of pain based on the average pain over the past 24-hours. Severity scores ranged from 0 (no pain) to 10 (severe pain). LS mean was calculated using an MMRM approach including administration groups, observation points, and interaction between the administration groups as fixed effects, and BPI average pain severity at baseline and the presence or absence of major depressive disorder as covariates; a linear model with unstructured error variance was applied. |
| Change From Baseline to 10 Weeks in the BPI 24-Hour Average Pain Severity Item of the BPI-Modified Short Form Score (MMRM) | Baseline, 10 weeks | BPI 24-hour average pain severity is a self-reported scale that measures the severity of pain based on the average pain over the past 24-hours. Severity scores ranged from 0 (no pain) to 10 (severe pain). LS mean was calculated using an MMRM approach including administration groups, observation points, and interaction between the administration groups as fixed effects, and BPI average pain severity at baseline and the presence or absence of major depressive disorder as covariates; a linear model with unstructured error variance was applied. |
| Change From Baseline up to 14-Week Endpoint in the BPI 24-Hour Average Pain Severity Item of the BPI-Modified Short Form Score (ANCOVA) | Baseline, up to 14 weeks | BPI 24-hour average pain severity is a self-reported scale that measures the severity of pain based on the average pain over the past 24-hours. Severity scores ranged from 0 (no pain) to 10 (severe pain). LS mean was calculated using an analysis of covariance (ANCOVA) approach including administration groups as fixed effects, and BPI average pain severity at baseline and the presence or absence of major depressive disorder as covariates. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to 14-Week Endpoint in Average Pain and Worst Pain Severity Score Within 24-Hours in Participant Diary | Baseline, 14 weeks | Each morning participants rated their average pain and worst pain within the past 24 hours on separate 11-point Likert scales with scores ranging from 0 (no pain) through 10 (worst possible pain). These scores were then averaged for the week and compared to baseline. LS mean was calculated using an MMRM approach including administration groups, observation points, and interaction between the administration groups as fixed effects, and baseline as well as the presence or absence of major depressive disorder as covariates; a linear model with unstructured error variance was applied. |
| Patients Global Impression of Improvement (PGI-I) at Endpoint | 14 weeks | PGI-I measures the participant's perception of improvement at the time of assessment compared with the start of treatment. Scores ranged from 1 (very much better) to 7 (very much worse). LS mean was calculated using an MMRM approach including administration groups, observation points, and interaction between the administration groups as fixed effects, and the presence or absence of major depressive disorder as covariates; a linear model with unstructured error variance was applied. |
| Change From Baseline to 14-Week Endpoint in Brief Pain Inventory-Severity (BPI-S) and Brief Pain Inventory-Interference (BPI-I) Scores on the BPI-Modified Short Form | Baseline, 14 weeks | BPI-S and BPI-I are self-reported scales measuring severity of pain and interference on function, respectively. Severity scores ranged from 0 (no pain) to 10 (severe pain) for each question assessing worst pain, least pain, and pain right now. Interference scores ranged from 0 (does not interfere) to 10 (completely interferes) for each question assessing interference of pain in past 24 hours with general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. Average interference was the average of non-missing scores of individual interference items. LS mean was calculated using an MMRM approach including administration groups, observation points, and interaction between the administration groups as fixed effects, and baseline as well as the presence or absence of major depressive disorder as covariates; a linear model with unstructured error variance was applied. |
| Clinical Global Impression of Improvement (CGI-I) at Endpoint | 14 weeks | CGI-I measures the clinician's perception of participant improvement at the time of assessment (compared with the start of treatment). Scores ranged from 1 (very much better) to 7 (very much worse). LS mean was calculated using an MMRM approach including administration groups, observation points, and interaction between the administration groups as fixed effects, and the presence or absence of major depressive disorder as covariates; a linear model with unstructured error variance was applied. |
| Change From Baseline to 14-Week Endpoint in Fibromyalgia Impact Questionnaire (FIQ) | Baseline, 14 weeks | FIQ is a 20-item, self-administered questionnaire using Likert-type scales to measure participant (pt) outcomes over the past week. Items 1 through 11 measured physical functioning on 4-point scales. Items 12 and 13 measured the number of days a pt felt well and days a pt was unable to work due to fibromyalgia symptoms. Items 14 through 20 were 11-point scales on which a pt rated work difficulty, pain, fatigue, morning tiredness, stiffness, anxiety, and depression. If a pt did not do all the tasks listed, those items were deleted from scoring. Algorithms were used to determine total FIQ scores which ranged from 0 to 100; higher scores indicated a more negative impact. LS mean was calculated using an MMRM approach including administration groups, observation points, and interaction between administration groups as fixed effects, and baseline as well as the presence or absence of major depressive disorder as covariates; a linear model with unstructured error variance was applied. |
| Change From Baseline to 14-Week Endpoint in 36-Item Short-Form (SF-36) Health Survey Domain Scores | Baseline, up to 14 weeks | The SF-36 Health Survey is a generic, health-related survey assessing the participant's quality of life on 8 domains: physical functioning, daily functioning (physical), bodily pain, general health, vitality, social functioning, daily functioning (emotional), and mental health. Each domain was scored by summing individual items pertaining to that domain and transforming scores into a 0 to 100 scale, with higher scores indicating better health status or functioning. LS mean was calculated using an ANCOVA approach including administration groups as fixed effects, and baseline as well as the presence or absence of complication by major depressive disorder as covariates. |
| Change From Baseline to 14-Week Endpoint in Beck Depression Inventory-II (BDI-II) | Baseline, 14 weeks | The BDI-II is a 21-item self-administered questionnaire designed to assess the characteristics of depression. Each item was scored on a 4-point scale ranging from 0 (not present) to 3 (present in the extreme) and was summed to give a total BDI-II score. A total BDI-II score of 0 through 13 was considered minimal, 14 through 19 was mild, 20 through 28 was moderate, and 29 through 63 was severe depression symptoms. LS mean was calculated using an MMRM approach including administration groups, observation points, and interaction between the administration groups and as fixed effects, and baseline as well as the presence or absence of major depressive disorder as covariates; a linear model with unstructured error variance was applied. |
| Change From Baseline to 14-Week Endpoint in Widespread Pain Index (WPI) and Symptom Severity (SS) in American College of Rheumatology (ACR) Fibromyalgia Diagnostic Criteria 2010 | Baseline, 14 weeks | WPI: Participant-reported areas (out of 19 points on the body) in which the participant had pain in the past week. WPI scores ranged from 0 (no areas) to 19 (all areas). SS: The sum of severity scores for fatigue, waking unrefreshed, and cognitive symptoms \[each rated from 0 (no problem) to 3 (severe; life-disturbing problems)\] plus the severity of somatic symptoms in general \[rated from 0 (no symptoms) to 3 (a great deal of symptoms)\]. The total SS score ranged from 0 and 12. LS mean was calculated using an MMRM approach including administration groups, observation points, interaction between the administration groups and the observation points as fixed effects, and baseline as well as the presence or absence of major depressive disorder as covariates; a linear model with unstructured error variance was applied. |
Countries
Japan
Participant flow
Pre-assignment details
Randomized participants who completed the 14-week treatment period were considered to have completed the study. After study completion or early discontinuation, participants completed a 1-week taper and were observed 1 week post-treatment for safety.
Participants by arm
| Arm | Count |
|---|---|
| Duloxetine 60 mg Treatment Period: Up to 60-mg dose of duloxetine administered orally once daily for 14 weeks. During the first 2 weeks of treatment, participants gradually increased their dosage. Week 1: 20-mg dose of duloxetine (one 20-mg capsule, and 2 placebo capsules), Week 2: 40-mg dose of duloxetine (two 20-mg capsules and 1 placebo capsule), Weeks 3 to 14: 60-mg dose of duloxetine (three 20-mg capsules).
During the 1-week taper, the daily dosage was gradually reduced. For the first 3 days: 40-mg dose of duloxetine (two 20-mg capsules) administered orally once daily. For the remaining 4 days: 20-mg dose of duloxetine (one 20-mg capsule) administered orally once daily. | 191 |
| Placebo Treatment Period: 3 placebo capsules administered orally once daily for 14 weeks.
During the 1-week taper, the number of placebo capsules was gradually reduced. For the first 3 days: 2 placebo capsules administered orally once daily. For the remaining 4 days: 1 placebo capsule administered orally once daily. | 195 |
| Total | 386 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 14 | 15 |
| Overall Study | Entry Criteria Not Met | 2 | 2 |
| Overall Study | Lack of Efficacy | 8 | 23 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 5 | 8 |
Baseline characteristics
| Characteristic | Placebo | Total | Duloxetine 60 mg |
|---|---|---|---|
| Age, Continuous | 49.5 years STANDARD_DEVIATION 11.7 | 48.7 years STANDARD_DEVIATION 11.9 | 47.8 years STANDARD_DEVIATION 12 |
| Race/Ethnicity, Customized Japanese | 195 participants | 386 participants | 191 participants |
| Region of Enrollment Japan | 195 participants | 386 participants | 191 participants |
| Sex: Female, Male Female | 164 Participants | 321 Participants | 157 Participants |
| Sex: Female, Male Male | 31 Participants | 65 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 147 / 194 | 122 / 196 |
| serious Total, serious adverse events | 1 / 194 | 1 / 196 |
Outcome results
Primary
Change From Baseline to 10 Weeks in the BPI 24-Hour Average Pain Severity Item of the BPI-Modified Short Form Score (MMRM)
BPI 24-hour average pain severity is a self-reported scale that measures the severity of pain based on the average pain over the past 24-hours. Severity scores ranged from 0 (no pain) to 10 (severe pain). LS mean was calculated using an MMRM approach including administration groups, observation points, and interaction between the administration groups as fixed effects, and BPI average pain severity at baseline and the presence or absence of major depressive disorder as covariates; a linear model with unstructured error variance was applied.
Time frame: Baseline, 10 weeks
Population: Randomized participants who received at least 1 dose of study drug and had at least 1 post-baseline measurement of primary efficacy (BPI 24-hour average pain severity).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine 60 mg | Change From Baseline to 10 Weeks in the BPI 24-Hour Average Pain Severity Item of the BPI-Modified Short Form Score (MMRM) | -1.85 units on a scale | Standard Error 0.23 |
| Placebo | Change From Baseline to 10 Weeks in the BPI 24-Hour Average Pain Severity Item of the BPI-Modified Short Form Score (MMRM) | -1.41 units on a scale | Standard Error 0.23 |
p-value: 0.022695% CI: [-0.82, -0.06]MMRM
Primary
Change From Baseline to 14-Week Endpoint in the BPI 24-Hour Average Pain Severity Item of the BPI-Modified Short Form Score (MMRM)
BPI 24-hour average pain severity is a self-reported scale that measures the severity of pain based on the average pain over the past 24-hours. Severity scores ranged from 0 (no pain) to 10 (severe pain). Least squares (LS) mean was calculated using a mixed-effects model repeated measures (MMRM) approach including administration groups, observation points, and interaction between the administration groups as fixed effects, and BPI average pain severity at baseline and the presence or absence of major depressive disorder as covariates; a linear model with unstructured error variance was applied.
Time frame: Baseline, 14 weeks
Population: Randomized participants who received at least 1 dose of study drug and had at least 1 post-baseline measurement of primary efficacy (BPI 24-hour average pain severity).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine 60 mg | Change From Baseline to 14-Week Endpoint in the BPI 24-Hour Average Pain Severity Item of the BPI-Modified Short Form Score (MMRM) | -1.90 units on a scale | Standard Error 0.23 |
| Placebo | Change From Baseline to 14-Week Endpoint in the BPI 24-Hour Average Pain Severity Item of the BPI-Modified Short Form Score (MMRM) | -1.58 units on a scale | Standard Error 0.23 |
p-value: 0.098895% CI: [-0.7, 0.06]MMRM
Primary
Change From Baseline to 2 Weeks in the BPI 24-Hour Average Pain Severity Item of the BPI-Modified Short Form Score (MMRM)
BPI 24-hour average pain severity is a self-reported scale that measures the severity of pain based on the average pain over the past 24-hours. Severity scores ranged from 0 (no pain) to 10 (severe pain). LS mean was calculated using an MMRM approach including administration groups, observation points, and interaction between the administration groups as fixed effects, and BPI average pain severity at baseline and the presence or absence of major depressive disorder as covariates; a linear model with unstructured error variance was applied.
Time frame: Baseline, 2 weeks
Population: Randomized participants who received at least 1 dose of study drug and had at least 1 post-baseline measurement of primary efficacy (BPI 24-hour average pain severity).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine 60 mg | Change From Baseline to 2 Weeks in the BPI 24-Hour Average Pain Severity Item of the BPI-Modified Short Form Score (MMRM) | -1.00 units on a scale | Standard Error 0.21 |
| Placebo | Change From Baseline to 2 Weeks in the BPI 24-Hour Average Pain Severity Item of the BPI-Modified Short Form Score (MMRM) | -0.60 units on a scale | Standard Error 0.22 |
p-value: 0.011395% CI: [-0.71, -0.09]MMRM
Primary
Change From Baseline to 4 Weeks in the BPI 24-Hour Average Pain Severity Item of the BPI-Modified Short Form Score (MMRM)
BPI 24-hour average pain severity is a self-reported scale that measures the severity of pain based on the average pain over the past 24-hours. Severity scores ranged from 0 (no pain) to 10 (severe pain). LS mean was calculated using an MMRM approach including administration groups, observation points, and interaction between the administration groups as fixed effects, and BPI average pain severity at baseline and the presence or absence of major depressive disorder as covariates; a linear model with unstructured error variance was applied.
Time frame: Baseline, 4 weeks
Population: Randomized participants who received at least 1 dose of study drug and had at least 1 post-baseline measurement of primary efficacy (BPI 24-hour average pain severity).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine 60 mg | Change From Baseline to 4 Weeks in the BPI 24-Hour Average Pain Severity Item of the BPI-Modified Short Form Score (MMRM) | -1.55 units on a scale | Standard Error 0.22 |
| Placebo | Change From Baseline to 4 Weeks in the BPI 24-Hour Average Pain Severity Item of the BPI-Modified Short Form Score (MMRM) | -0.94 units on a scale | Standard Error 0.22 |
p-value: 0.000595% CI: [-0.94, -0.27]MMRM
Primary
Change From Baseline to 6 Weeks in the BPI 24-Hour Average Pain Severity Item of the BPI-Modified Short Form Score (MMRM)
BPI 24-hour average pain severity is a self-reported scale that measures the severity of pain based on the average pain over the past 24-hours. Severity scores ranged from 0 (no pain) to 10 (severe pain). LS mean was calculated using an MMRM approach including administration groups, observation points, and interaction between the administration groups as fixed effects, and BPI average pain severity at baseline and the presence or absence of major depressive disorder as covariates; a linear model with unstructured error variance was applied.
Time frame: Baseline, 6 weeks
Population: Randomized participants who received at least 1 dose of study drug and had at least 1 post-baseline measurement of primary efficacy (BPI 24-hour average pain severity).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine 60 mg | Change From Baseline to 6 Weeks in the BPI 24-Hour Average Pain Severity Item of the BPI-Modified Short Form Score (MMRM) | -1.81 units on a scale | Standard Error 0.22 |
| Placebo | Change From Baseline to 6 Weeks in the BPI 24-Hour Average Pain Severity Item of the BPI-Modified Short Form Score (MMRM) | -1.09 units on a scale | Standard Error 0.23 |
p-value: <0.000195% CI: [-1.07, -0.37]MMRM
Primary
Change From Baseline up to 14-Week Endpoint in the BPI 24-Hour Average Pain Severity Item of the BPI-Modified Short Form Score (ANCOVA)
BPI 24-hour average pain severity is a self-reported scale that measures the severity of pain based on the average pain over the past 24-hours. Severity scores ranged from 0 (no pain) to 10 (severe pain). LS mean was calculated using an analysis of covariance (ANCOVA) approach including administration groups as fixed effects, and BPI average pain severity at baseline and the presence or absence of major depressive disorder as covariates.
Time frame: Baseline, up to 14 weeks
Population: Randomized participants who received at least 1 dose of study drug and had at least 1 post-baseline measurement of primary efficacy (BPI 24-hour average pain severity); Last Observation Carried Forward (LOCF) values were used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine 60 mg | Change From Baseline up to 14-Week Endpoint in the BPI 24-Hour Average Pain Severity Item of the BPI-Modified Short Form Score (ANCOVA) | -1.60 units on a scale | Standard Error 0.26 |
| Placebo | Change From Baseline up to 14-Week Endpoint in the BPI 24-Hour Average Pain Severity Item of the BPI-Modified Short Form Score (ANCOVA) | -1.22 units on a scale | Standard Error 0.26 |
p-value: 0.040895% CI: [-0.74, -0.02]ANCOVA
Secondary
Change From Baseline to 14-Week Endpoint in 36-Item Short-Form (SF-36) Health Survey Domain Scores
The SF-36 Health Survey is a generic, health-related survey assessing the participant's quality of life on 8 domains: physical functioning, daily functioning (physical), bodily pain, general health, vitality, social functioning, daily functioning (emotional), and mental health. Each domain was scored by summing individual items pertaining to that domain and transforming scores into a 0 to 100 scale, with higher scores indicating better health status or functioning. LS mean was calculated using an ANCOVA approach including administration groups as fixed effects, and baseline as well as the presence or absence of complication by major depressive disorder as covariates.
Time frame: Baseline, up to 14 weeks
Population: Randomized participants who received at least 1 dose of study drug and had at least 1 post-baseline measurement of primary efficacy (BPI 24-hour average pain severity); LOCF values were used.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine 60 mg | Change From Baseline to 14-Week Endpoint in 36-Item Short-Form (SF-36) Health Survey Domain Scores | Physical Functioning | 7.40 units on a scale | Standard Error 2.13 |
| Duloxetine 60 mg | Change From Baseline to 14-Week Endpoint in 36-Item Short-Form (SF-36) Health Survey Domain Scores | Role-Physical | 8.20 units on a scale | Standard Error 2.96 |
| Duloxetine 60 mg | Change From Baseline to 14-Week Endpoint in 36-Item Short-Form (SF-36) Health Survey Domain Scores | Bodily Pain | 10.95 units on a scale | Standard Error 2.07 |
| Duloxetine 60 mg | Change From Baseline to 14-Week Endpoint in 36-Item Short-Form (SF-36) Health Survey Domain Scores | General Health | 6.55 units on a scale | Standard Error 1.92 |
| Duloxetine 60 mg | Change From Baseline to 14-Week Endpoint in 36-Item Short-Form (SF-36) Health Survey Domain Scores | Vitality | 10.05 units on a scale | Standard Error 2.51 |
| Duloxetine 60 mg | Change From Baseline to 14-Week Endpoint in 36-Item Short-Form (SF-36) Health Survey Domain Scores | Social Functioning | 10.32 units on a scale | Standard Error 3.04 |
| Duloxetine 60 mg | Change From Baseline to 14-Week Endpoint in 36-Item Short-Form (SF-36) Health Survey Domain Scores | Role-Emotional | 5.50 units on a scale | Standard Error 3.35 |
| Duloxetine 60 mg | Change From Baseline to 14-Week Endpoint in 36-Item Short-Form (SF-36) Health Survey Domain Scores | Mental Health | 5.91 units on a scale | Standard Error 2.51 |
| Placebo | Change From Baseline to 14-Week Endpoint in 36-Item Short-Form (SF-36) Health Survey Domain Scores | Mental Health | -2.00 units on a scale | Standard Error 2.52 |
| Placebo | Change From Baseline to 14-Week Endpoint in 36-Item Short-Form (SF-36) Health Survey Domain Scores | Physical Functioning | 3.06 units on a scale | Standard Error 2.15 |
| Placebo | Change From Baseline to 14-Week Endpoint in 36-Item Short-Form (SF-36) Health Survey Domain Scores | Vitality | 3.35 units on a scale | Standard Error 2.53 |
| Placebo | Change From Baseline to 14-Week Endpoint in 36-Item Short-Form (SF-36) Health Survey Domain Scores | Role-Physical | 0.44 units on a scale | Standard Error 2.98 |
| Placebo | Change From Baseline to 14-Week Endpoint in 36-Item Short-Form (SF-36) Health Survey Domain Scores | Role-Emotional | -3.63 units on a scale | Standard Error 3.36 |
| Placebo | Change From Baseline to 14-Week Endpoint in 36-Item Short-Form (SF-36) Health Survey Domain Scores | Bodily Pain | 5.28 units on a scale | Standard Error 2.08 |
| Placebo | Change From Baseline to 14-Week Endpoint in 36-Item Short-Form (SF-36) Health Survey Domain Scores | Social Functioning | 3.28 units on a scale | Standard Error 3.06 |
| Placebo | Change From Baseline to 14-Week Endpoint in 36-Item Short-Form (SF-36) Health Survey Domain Scores | General Health | 3.31 units on a scale | Standard Error 1.94 |
Comparison: Physical Functioningp-value: 0.004995% CI: [1.32, 7.35]ANCOVA
Comparison: Role-Physicalp-value: 0.000395% CI: [3.57, 11.94]ANCOVA
Comparison: Bodily Painp-value: 0.000295% CI: [2.76, 8.59]ANCOVA
Comparison: General Healthp-value: 0.019295% CI: [0.53, 5.96]ANCOVA
Comparison: Vitalityp-value: 0.000295% CI: [3.15, 10.25]ANCOVA
Comparison: Social Functioningp-value: 0.001495% CI: [2.74, 11.34]ANCOVA
Comparison: Role-Emotionalp-value: 0.000295% CI: [4.41, 13.83]ANCOVA
Comparison: Mental Healthp-value: <0.000195% CI: [4.39, 11.43]ANCOVA
Secondary
Change From Baseline to 14-Week Endpoint in Average Pain and Worst Pain Severity Score Within 24-Hours in Participant Diary
Each morning participants rated their average pain and worst pain within the past 24 hours on separate 11-point Likert scales with scores ranging from 0 (no pain) through 10 (worst possible pain). These scores were then averaged for the week and compared to baseline. LS mean was calculated using an MMRM approach including administration groups, observation points, and interaction between the administration groups as fixed effects, and baseline as well as the presence or absence of major depressive disorder as covariates; a linear model with unstructured error variance was applied.
Time frame: Baseline, 14 weeks
Population: Randomized participants who received at least 1 dose of study drug and had at least 1 post-baseline measurement of primary efficacy (BPI 24-hour average pain severity).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine 60 mg | Change From Baseline to 14-Week Endpoint in Average Pain and Worst Pain Severity Score Within 24-Hours in Participant Diary | Average Pain | -1.82 units on a scale | Standard Error 0.18 |
| Duloxetine 60 mg | Change From Baseline to 14-Week Endpoint in Average Pain and Worst Pain Severity Score Within 24-Hours in Participant Diary | Worst Pain | -1.81 units on a scale | Standard Error 0.19 |
| Placebo | Change From Baseline to 14-Week Endpoint in Average Pain and Worst Pain Severity Score Within 24-Hours in Participant Diary | Average Pain | -1.48 units on a scale | Standard Error 0.18 |
| Placebo | Change From Baseline to 14-Week Endpoint in Average Pain and Worst Pain Severity Score Within 24-Hours in Participant Diary | Worst Pain | -1.34 units on a scale | Standard Error 0.19 |
Comparison: Average Painp-value: 0.075595% CI: [-0.7, 0.03]MMRM
Comparison: Worst Painp-value: 0.023295% CI: [-0.88, -0.06]MMRM
Secondary
Change From Baseline to 14-Week Endpoint in Beck Depression Inventory-II (BDI-II)
The BDI-II is a 21-item self-administered questionnaire designed to assess the characteristics of depression. Each item was scored on a 4-point scale ranging from 0 (not present) to 3 (present in the extreme) and was summed to give a total BDI-II score. A total BDI-II score of 0 through 13 was considered minimal, 14 through 19 was mild, 20 through 28 was moderate, and 29 through 63 was severe depression symptoms. LS mean was calculated using an MMRM approach including administration groups, observation points, and interaction between the administration groups and as fixed effects, and baseline as well as the presence or absence of major depressive disorder as covariates; a linear model with unstructured error variance was applied.
Time frame: Baseline, 14 weeks
Population: Randomized participants who received at least 1 dose of study drug and had at least 1 post-baseline measurement of primary efficacy (BPI 24-hour average pain severity).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine 60 mg | Change From Baseline to 14-Week Endpoint in Beck Depression Inventory-II (BDI-II) | -4.07 units on a scale | Standard Error 0.84 |
| Placebo | Change From Baseline to 14-Week Endpoint in Beck Depression Inventory-II (BDI-II) | -1.22 units on a scale | Standard Error 0.85 |
p-value: 0.000295% CI: [-4.32, -1.38]MMRM
Secondary
Change From Baseline to 14-Week Endpoint in Brief Pain Inventory-Severity (BPI-S) and Brief Pain Inventory-Interference (BPI-I) Scores on the BPI-Modified Short Form
BPI-S and BPI-I are self-reported scales measuring severity of pain and interference on function, respectively. Severity scores ranged from 0 (no pain) to 10 (severe pain) for each question assessing worst pain, least pain, and pain right now. Interference scores ranged from 0 (does not interfere) to 10 (completely interferes) for each question assessing interference of pain in past 24 hours with general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. Average interference was the average of non-missing scores of individual interference items. LS mean was calculated using an MMRM approach including administration groups, observation points, and interaction between the administration groups as fixed effects, and baseline as well as the presence or absence of major depressive disorder as covariates; a linear model with unstructured error variance was applied.
Time frame: Baseline, 14 weeks
Population: Randomized participants who received at least 1 dose of study drug and had at least 1 post-baseline measurement of primary efficacy (BPI 24-hour average pain severity).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine 60 mg | Change From Baseline to 14-Week Endpoint in Brief Pain Inventory-Severity (BPI-S) and Brief Pain Inventory-Interference (BPI-I) Scores on the BPI-Modified Short Form | Interference With General Activity | -2.22 units on a scale | Standard Error 0.31 |
| Duloxetine 60 mg | Change From Baseline to 14-Week Endpoint in Brief Pain Inventory-Severity (BPI-S) and Brief Pain Inventory-Interference (BPI-I) Scores on the BPI-Modified Short Form | Interference With Normal Work | -2.18 units on a scale | Standard Error 0.31 |
| Duloxetine 60 mg | Change From Baseline to 14-Week Endpoint in Brief Pain Inventory-Severity (BPI-S) and Brief Pain Inventory-Interference (BPI-I) Scores on the BPI-Modified Short Form | Pain Right Now | -1.77 units on a scale | Standard Error 0.26 |
| Duloxetine 60 mg | Change From Baseline to 14-Week Endpoint in Brief Pain Inventory-Severity (BPI-S) and Brief Pain Inventory-Interference (BPI-I) Scores on the BPI-Modified Short Form | Interference With Relations With Other People | -1.09 units on a scale | Standard Error 0.3 |
| Duloxetine 60 mg | Change From Baseline to 14-Week Endpoint in Brief Pain Inventory-Severity (BPI-S) and Brief Pain Inventory-Interference (BPI-I) Scores on the BPI-Modified Short Form | Interference With Mood | -2.17 units on a scale | Standard Error 0.32 |
| Duloxetine 60 mg | Change From Baseline to 14-Week Endpoint in Brief Pain Inventory-Severity (BPI-S) and Brief Pain Inventory-Interference (BPI-I) Scores on the BPI-Modified Short Form | Interference With Sleep | -1.82 units on a scale | Standard Error 0.35 |
| Duloxetine 60 mg | Change From Baseline to 14-Week Endpoint in Brief Pain Inventory-Severity (BPI-S) and Brief Pain Inventory-Interference (BPI-I) Scores on the BPI-Modified Short Form | Least Pain | -1.72 units on a scale | Standard Error 0.22 |
| Duloxetine 60 mg | Change From Baseline to 14-Week Endpoint in Brief Pain Inventory-Severity (BPI-S) and Brief Pain Inventory-Interference (BPI-I) Scores on the BPI-Modified Short Form | Interference With Enjoyment of Life | -1.90 units on a scale | Standard Error 0.31 |
| Duloxetine 60 mg | Change From Baseline to 14-Week Endpoint in Brief Pain Inventory-Severity (BPI-S) and Brief Pain Inventory-Interference (BPI-I) Scores on the BPI-Modified Short Form | Interference With Walking Ability | -1.67 units on a scale | Standard Error 0.29 |
| Duloxetine 60 mg | Change From Baseline to 14-Week Endpoint in Brief Pain Inventory-Severity (BPI-S) and Brief Pain Inventory-Interference (BPI-I) Scores on the BPI-Modified Short Form | Average Interference | -1.95 units on a scale | Standard Error 0.27 |
| Duloxetine 60 mg | Change From Baseline to 14-Week Endpoint in Brief Pain Inventory-Severity (BPI-S) and Brief Pain Inventory-Interference (BPI-I) Scores on the BPI-Modified Short Form | Worst Pain | -1.91 units on a scale | Standard Error 0.26 |
| Placebo | Change From Baseline to 14-Week Endpoint in Brief Pain Inventory-Severity (BPI-S) and Brief Pain Inventory-Interference (BPI-I) Scores on the BPI-Modified Short Form | Average Interference | -1.44 units on a scale | Standard Error 0.27 |
| Placebo | Change From Baseline to 14-Week Endpoint in Brief Pain Inventory-Severity (BPI-S) and Brief Pain Inventory-Interference (BPI-I) Scores on the BPI-Modified Short Form | Worst Pain | -1.35 units on a scale | Standard Error 0.26 |
| Placebo | Change From Baseline to 14-Week Endpoint in Brief Pain Inventory-Severity (BPI-S) and Brief Pain Inventory-Interference (BPI-I) Scores on the BPI-Modified Short Form | Least Pain | -1.23 units on a scale | Standard Error 0.22 |
| Placebo | Change From Baseline to 14-Week Endpoint in Brief Pain Inventory-Severity (BPI-S) and Brief Pain Inventory-Interference (BPI-I) Scores on the BPI-Modified Short Form | Pain Right Now | -1.20 units on a scale | Standard Error 0.26 |
| Placebo | Change From Baseline to 14-Week Endpoint in Brief Pain Inventory-Severity (BPI-S) and Brief Pain Inventory-Interference (BPI-I) Scores on the BPI-Modified Short Form | Interference With General Activity | -1.76 units on a scale | Standard Error 0.32 |
| Placebo | Change From Baseline to 14-Week Endpoint in Brief Pain Inventory-Severity (BPI-S) and Brief Pain Inventory-Interference (BPI-I) Scores on the BPI-Modified Short Form | Interference With Mood | -1.42 units on a scale | Standard Error 0.33 |
| Placebo | Change From Baseline to 14-Week Endpoint in Brief Pain Inventory-Severity (BPI-S) and Brief Pain Inventory-Interference (BPI-I) Scores on the BPI-Modified Short Form | Interference With Walking Ability | -1.29 units on a scale | Standard Error 0.3 |
| Placebo | Change From Baseline to 14-Week Endpoint in Brief Pain Inventory-Severity (BPI-S) and Brief Pain Inventory-Interference (BPI-I) Scores on the BPI-Modified Short Form | Interference With Normal Work | -1.76 units on a scale | Standard Error 0.32 |
| Placebo | Change From Baseline to 14-Week Endpoint in Brief Pain Inventory-Severity (BPI-S) and Brief Pain Inventory-Interference (BPI-I) Scores on the BPI-Modified Short Form | Interference With Relations With Other People | -0.53 units on a scale | Standard Error 0.3 |
| Placebo | Change From Baseline to 14-Week Endpoint in Brief Pain Inventory-Severity (BPI-S) and Brief Pain Inventory-Interference (BPI-I) Scores on the BPI-Modified Short Form | Interference With Sleep | -1.57 units on a scale | Standard Error 0.36 |
| Placebo | Change From Baseline to 14-Week Endpoint in Brief Pain Inventory-Severity (BPI-S) and Brief Pain Inventory-Interference (BPI-I) Scores on the BPI-Modified Short Form | Interference With Enjoyment of Life | -1.24 units on a scale | Standard Error 0.32 |
Comparison: Worst Painp-value: 0.012695% CI: [-0.99, -0.12]MMRM
Comparison: Least Painp-value: 0.009295% CI: [-0.87, -0.12]MMRM
Comparison: Pain Right Nowp-value: 0.008395% CI: [-1, -0.15]MMRM
Comparison: Interference With General Activityp-value: 0.080795% CI: [-0.98, 0.06]MMRM
Comparison: Interference With Moodp-value: 0.005795% CI: [-1.29, -0.22]MMRM
Comparison: Interference With Walking Abilityp-value: 0.111495% CI: [-0.84, 0.09]MMRM
Comparison: Interference With Normal Workp-value: 0.108195% CI: [-0.94, 0.09]MMRM
Comparison: Interference With Relationships With Other Peoplep-value: 0.026495% CI: [-1.04, -0.07]MMRM
Comparison: Interference With Sleepp-value: 0.395995% CI: [-0.81, 0.32]MMRM
Comparison: Interference With Enjoyment of Lifep-value: 0.011995% CI: [-1.18, -0.15]MMRM
Comparison: Average Interferencep-value: 0.022295% CI: [-0.96, -0.07]MMRM
Secondary
Change From Baseline to 14-Week Endpoint in Fibromyalgia Impact Questionnaire (FIQ)
FIQ is a 20-item, self-administered questionnaire using Likert-type scales to measure participant (pt) outcomes over the past week. Items 1 through 11 measured physical functioning on 4-point scales. Items 12 and 13 measured the number of days a pt felt well and days a pt was unable to work due to fibromyalgia symptoms. Items 14 through 20 were 11-point scales on which a pt rated work difficulty, pain, fatigue, morning tiredness, stiffness, anxiety, and depression. If a pt did not do all the tasks listed, those items were deleted from scoring. Algorithms were used to determine total FIQ scores which ranged from 0 to 100; higher scores indicated a more negative impact. LS mean was calculated using an MMRM approach including administration groups, observation points, and interaction between administration groups as fixed effects, and baseline as well as the presence or absence of major depressive disorder as covariates; a linear model with unstructured error variance was applied.
Time frame: Baseline, 14 weeks
Population: Randomized participants who received at least 1 dose of study drug and had at least 1 post-baseline measurement of primary efficacy (BPI 24-hour average pain severity).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine 60 mg | Change From Baseline to 14-Week Endpoint in Fibromyalgia Impact Questionnaire (FIQ) | -18.41 units on a scale | Standard Error 2.57 |
| Placebo | Change From Baseline to 14-Week Endpoint in Fibromyalgia Impact Questionnaire (FIQ) | -13.05 units on a scale | Standard Error 2.65 |
p-value: 0.007395% CI: [-9.26, -1.45]MMRM
Secondary
Change From Baseline to 14-Week Endpoint in Widespread Pain Index (WPI) and Symptom Severity (SS) in American College of Rheumatology (ACR) Fibromyalgia Diagnostic Criteria 2010
WPI: Participant-reported areas (out of 19 points on the body) in which the participant had pain in the past week. WPI scores ranged from 0 (no areas) to 19 (all areas). SS: The sum of severity scores for fatigue, waking unrefreshed, and cognitive symptoms \[each rated from 0 (no problem) to 3 (severe; life-disturbing problems)\] plus the severity of somatic symptoms in general \[rated from 0 (no symptoms) to 3 (a great deal of symptoms)\]. The total SS score ranged from 0 and 12. LS mean was calculated using an MMRM approach including administration groups, observation points, interaction between the administration groups and the observation points as fixed effects, and baseline as well as the presence or absence of major depressive disorder as covariates; a linear model with unstructured error variance was applied.
Time frame: Baseline, 14 weeks
Population: Randomized participants who received at least 1 dose of study drug and had at least 1 post-baseline measurement of primary efficacy (BPI 24-hour average pain severity).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine 60 mg | Change From Baseline to 14-Week Endpoint in Widespread Pain Index (WPI) and Symptom Severity (SS) in American College of Rheumatology (ACR) Fibromyalgia Diagnostic Criteria 2010 | WPI | -2.34 units on a scale | Standard Error 0.58 |
| Duloxetine 60 mg | Change From Baseline to 14-Week Endpoint in Widespread Pain Index (WPI) and Symptom Severity (SS) in American College of Rheumatology (ACR) Fibromyalgia Diagnostic Criteria 2010 | SS | -1.37 units on a scale | Standard Error 0.27 |
| Placebo | Change From Baseline to 14-Week Endpoint in Widespread Pain Index (WPI) and Symptom Severity (SS) in American College of Rheumatology (ACR) Fibromyalgia Diagnostic Criteria 2010 | WPI | -1.06 units on a scale | Standard Error 0.6 |
| Placebo | Change From Baseline to 14-Week Endpoint in Widespread Pain Index (WPI) and Symptom Severity (SS) in American College of Rheumatology (ACR) Fibromyalgia Diagnostic Criteria 2010 | SS | -1.00 units on a scale | Standard Error 0.28 |
Comparison: WPIp-value: 0.002995% CI: [-2.12, -0.44]MMRM
Comparison: Symptom Severityp-value: 0.090695% CI: [-0.79, 0.06]MMRM
Secondary
Clinical Global Impression of Improvement (CGI-I) at Endpoint
CGI-I measures the clinician's perception of participant improvement at the time of assessment (compared with the start of treatment). Scores ranged from 1 (very much better) to 7 (very much worse). LS mean was calculated using an MMRM approach including administration groups, observation points, and interaction between the administration groups as fixed effects, and the presence or absence of major depressive disorder as covariates; a linear model with unstructured error variance was applied.
Time frame: 14 weeks
Population: Randomized participants who received at least 1 dose of study drug and had at least 1 post-baseline measurement of primary efficacy (BPI 24-hour average pain severity).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine 60 mg | Clinical Global Impression of Improvement (CGI-I) at Endpoint | 2.83 units on a scale | Standard Error 0.15 |
| Placebo | Clinical Global Impression of Improvement (CGI-I) at Endpoint | 3.27 units on a scale | Standard Error 0.16 |
p-value: 0.001295% CI: [-0.71, -0.18]MMRM
Secondary
Patients Global Impression of Improvement (PGI-I) at Endpoint
PGI-I measures the participant's perception of improvement at the time of assessment compared with the start of treatment. Scores ranged from 1 (very much better) to 7 (very much worse). LS mean was calculated using an MMRM approach including administration groups, observation points, and interaction between the administration groups as fixed effects, and the presence or absence of major depressive disorder as covariates; a linear model with unstructured error variance was applied.
Time frame: 14 weeks
Population: Randomized participants who received at least 1 dose of study drug and had at least 1 post-baseline measurement of primary efficacy (BPI 24-hour average pain severity).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine 60 mg | Patients Global Impression of Improvement (PGI-I) at Endpoint | 2.83 units on a scale | Standard Error 0.16 |
| Placebo | Patients Global Impression of Improvement (PGI-I) at Endpoint | 3.32 units on a scale | Standard Error 0.16 |
p-value: 0.000395% CI: [-0.76, -0.22]MMRM