Multiple Sclerosis
Conditions
Keywords
Central Neuropathic Pain, Multiple Sclerosis
Brief summary
This study is designed to primarily assess the efficacy and safety of duloxetine 60-120 mg once daily (QD) compared with placebo on the reduction of pain severity in participants with central neuropathic pain due to Multiple Sclerosis.
Detailed description
Study is a multicenter, randomized, double-blind, parallel, placebo-controlled, 20-week trial with 4 study periods. Participants who screen successfully (Study Period I) will be randomized in a 1:1 fashion to duloxetine 60 mg QD or placebo. Starting with Study Period II, participants will be treated in a double-blind manner for 6 weeks. Participants who complete the 6-week, double-blind period will have the opportunity to participate in a 12-week, open-label, flexible-dose portion of the study (Study Period III). Study Period IV is a taper phase designed to reduce the occurrence of discontinuation adverse events. Participants may enter Study Period IV at any time after Visit 3.
Interventions
DRUGDuloxetine Hydrochloride (HCI)
Participants received 30 mg duloxetine (po, QD) for 1 week followed by 5 weeks at 60 mg in the acute placebo-controlled period. If the participant completes the double-blind portion of the trial, the participant will be offered the option to participate in the open-label extension period (given 60, 90, or 120 mg QD for 12 weeks).
DRUGPlacebo
Participants received placebo oral (po), once daily (QD) for 6 weeks (acute phase). If the participant completes the 6-week double-blind portion of the trial, the participant will be offered the option to participate in the open-label extension period (given 60, 90, or 120 milligrams \[mg\] QD for 12 weeks).
Sponsors
Eli Lilly and Company
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 No maximum
Healthy volunteers
No
Inclusion criteria
* Have central neuropathic pain due to multiple sclerosis (MS) based on the disease diagnostic criteria * Adult males or females * Have a score of 4 or greater on the daily 24-hour average pain score * Females must test negative for pregnancy at study entry * Complete the daily diaries for at least 70% of the days of the study * Participants may continue other prescription and nonprescription analgesic pain medications as long as the dose has been stable for 1 month prior to study entry, and they agree to maintain that stable dose throughout the study Disease Diagnostic Criteria: * Diagnosis of MS at least 1 year prior to study entry * No MS flares or change in disease treatment for the 3 months prior to study entry * Daily pain due to MS for a minimum of 3 months prior to study entry
Exclusion criteria
* Are currently in a clinical trial of MS disease-modifying therapy * Have pain that cannot be clearly differentiated from causes other than MS * Any current or historical diagnosis of mania, bipolar disorder, psychosis, or schizoaffective disorder * History of substance abuse or dependence * Are pregnant or breast-feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Weekly 24-Hour Average Pain Scores at Week 6 (Acute Phase) | Baseline, 6 weeks | 24-hour average pain severity scores recorded daily on an 11-point Likert scale, evaluated as a weekly mean, with scores ranging from 0 (no pain) to 10 (worst possible pain). Participants should complete electronic diary each day upon awakening. The 11-point Likert scale was used for assessment of 24-hour average pain and evaluated as weekly means. Scores range from 0 (no pain) to 10 (worst possible pain). The Least Squares Mean (LS Mean) Value was adjusted for investigative site and baseline severity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) Resulting in Discontinuation From Baseline During the Acute Phase | Baseline through 6 weeks | — |
| Change in the Weekly Mean of the Night Pain Scores From Week 6 Through Week 18 (Open-label Extension Phase) | Baseline (6 weeks) through Endpoint (18 weeks) | Weekly mean of the night pain severity scores recorded daily on an 11-point Likert scale, an ordinal scale ranging from 0 (no pain) to 10 (worst possible pain). Participants should complete the electronic diary each day upon awakening. Each weekly mean change represents change relative to week 6, the baseline of the extension phase. |
| Change From Baseline in Beck Depression Inventory II (BDI-II), Question #9 at Week 18 (Open-label Extension Phase) | Baseline (6 weeks), Endpoint (18 weeks) | The BDI-II is completed by the participant to rate the severity of depressive symptoms and any improvement during the course of the trial. The total score ranges from 0 to 63 with higher the score indicating more severe depressive symptoms. Question #9 is suicidal thoughts and wishes with the score ranging from 0 to 3. |
| Number of Participants Who Discontinued During the Open-label Extension Phase (by Week 18) | Baseline (6 weeks) through Endpoint (18 weeks) | — |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) During the Open-label Extension Phase | Baseline (6 weeks) through Endpoint (18 weeks) | Summary tables of serious adverse events (SAEs) and all other non-serious adverse events are located in the Reported Adverse Event Module. |
| Number of Participants With Adverse Events (AEs) Resulting in Discontinuation During the Open-label Extension Phase | Baseline (6 weeks) through Endpoint (18 weeks) | — |
| Change From Baseline in Blood Pressure at Week 18 (Open-label Extension Phase) | Baseline (6 weeks), Endpoint (18 weeks) | — |
| Change From Baseline in Pulse Rate at Week 18 (Open-label Extension Phase) | Baseline (6 weeks), endpoint (18 weeks) | — |
| Change From Baseline in Weight at Week 18 (Open-label Extension Phase) | Baseline (6 weeks), Endpoint (18 weeks) | — |
| Change From Baseline in the Weekly 24-Hour Average Pain Scores up to Week 6 (Acute Phase) | Baseline, 6 weeks | This is a nominal outcome reflecting whether or not a clinically-important efficacy outcome (≥30% or ≥50% pain reduction from baseline) was achieved at endpoint. It is based on a comparison between baseline and endpoint scores on an ordinal scale with scores from 0 (no pain) to 10 (worst possible pain). Used were the weekly mean of the scores of the average pain severity over the last 24 hours. The weekly averages were based on daily assessments recorded by participants in their diaries. |
| Patient Global Impressions of Improvement Scale (PGI-I) at 6 Weeks | 6 weeks | A scale that measures the participant's perception of improvement at the time of assessment compared with the start of treatment. The score ranges from 1 (very much better) to 7 (very much worse). The Least Squares (LS) Mean Value was adjusted for investigative site and baseline severity. |
| Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 6 (Acute Phase) | Baseline, 6 weeks | Measures pain severity and interference on function. Severity scores: 0 (no pain) to 10 (severe pain) on each question assessing worst, least, and average pain in past 24 hours, and pain right now. Interference scores: 0 (does not interfere) to 10 (completely interferes) on each question assessing pain interference in past 24 hours, such as general activity, mood, normal work, relations with other people, and sleep. Average interference=average of non-missing scores of individual interference items. Least Squares (LS) Mean Value was adjusted for investigative site and baseline severity. |
| Change From Baseline in the Clinical Global Impression of Severity Scale (CGI-S) at 6 Weeks (Acute Phase) | Baseline, 6 weeks | Measures severity of illness at the time of assessment compared with start of treatment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). The Least Squares (LS) Mean Value was adjusted for investigative site and baseline severity. |
| Change From Baseline in the Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at 6 Weeks (Acute Phase) | Baseline, 6 weeks | A 54 question measure covers 12 domains; assesses mental and physical health. Each domain score is converted into a 0-100 score based on individual item responses; higher scores=better health status. The physical health composite score is a weighted average of the physical health scales, such as physical function, health perceptions, and energy. The mental health composite score is a weighted average of the mental health scales, such as overall quality of life, cognitive function, and health distress. The Least Squares (LS) Mean Value was adjusted for investigative site and baseline severity. |
| Number of Participants With Suicidal Behaviors, Ideations, and Acts Based on The Columbia Suicide Severity Rating Scale (C-SSRS) at Week 6 | 6 weeks | C-SSRS scale captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Number of participants with suicidal behaviors, ideations, and acts are provided. Suicidal behavior: a yes answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation: a yes answer to any one of 5 suicidal ideation questions, which includes wish to be dead, and 4 different categories of active suicidal ideation. Suicidal act: a yes answer to actual attempt or completed suicide. |
| Change From Baseline in the Weekly Mean of Night Pain Scores at Week 6 (Acute Phase) | Baseline, 6 weeks | Weekly mean of the night pain severity scores recorded daily on an 11-point Likert scale, an ordinal scale ranging from 0 (no pain) to 10 (worst possible pain). Participants should complete the electronic diary each day upon awakening. The Least Squares (LS) Mean Value was adjusted for investigative site and baseline severity. |
| Change From Baseline in the Beck Depression Inventory II (BDI-II) Question #9 at Week 6 (Acute Phase) | Baseline, 6 weeks | The BDI-II is completed by the participant to rate the severity of depressive symptoms and any improvement during the course of the trial. The total score ranges from 0 to 63 with higher the score indicating more severe depressive symptoms. Question #9 is suicidal thoughts and wishes with a score ranging from 0 to 3. |
| Number of Participants Who Discontinued During the Acute Phase (by Week 6) | Baseline through 6 weeks | — |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) During the Acute Phase | Baseline through 6 weeks | Summary tables of serious adverse events (SAEs) and all other non-serious adverse events are located in the Reported Adverse Event Module. |
| Change From Baseline in Blood Pressure at Week 6 (Acute Phase) | Baseline, 6 weeks | — |
| Change From Baseline in Pulse Rate at Week 6 (Acute Phase) | Baseline, 6 weeks | — |
| Change From Baseline in Weight at Week 6 (Acute Phase) | Baseline, 6 weeks | — |
| Patient Global Impressions of Improvement Scale (PGI-I) Score at 18 Weeks | 18 weeks | A scale that measures the participant's perception of improvement at the time of assessment compared with the start of treatment. The scores range from 1 (very much better) to 7 (very much worse). |
| Change From Baseline in Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 18 | Baseline (end of acute phase/Week 6), Endpoint (Week 18) | BPI-S and BPI-I are self-reported scales measuring severity of pain and interference on function. Severity scores: 0 (no pain) to 10 (severe pain) on each question assessing worst pain, least pain, and average pain in past 24 hours, and pain right now. Interference scores: 0 (does not interfere) to 10 (completely interferes) on each question assessing interference of pain in past 24 hours for general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. Average interference = average of non-missing scores of individual interference items. |
| Change From Baseline in the Clinical Global Impression of Severity Scale (CGI-S) Score at Week 18 (Open-label Extension Phase) | Baseline (6 weeks), Endpoint (18 weeks) | Measures severity of illness at the time of assessment compared with start of treatment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). |
| Change From Baseline in Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at Week 18 (Open-label Extension Phase) | Baseline (6 weeks), Endpoint (18 weeks) | A 54 question measure covers 12 domains; assesses mental and physical health. Each domain score is converted into a 0-100 score based on individual item responses; higher scores=better health status. The physical health composite score is a weighted average of the physical health scales, such as physical function, health perceptions, and energy. The mental health composite score is a weighted average of the mental health scales, such as overall quality of life, cognitive function, and health distress. |
| Number of Participants With Suicidal Behaviors, Ideations, and Acts Based on The Columbia Suicide Severity Rating Scale (C-SSRS) at Week 18 | 18 weeks | C-SSRS scale captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Number of participants with suicidal behaviors, ideations, and acts are provided. Suicidal behavior: a yes answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation: a yes answer to any one of 5 suicidal ideation questions, which includes wish to be dead, and 4 different categories of active suicidal ideation. Suicidal act: a yes answer to actual attempt or completed suicide. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Platelet Count at Week 6 (Acute Phase) | Baseline, 6 weeks | Change from baseline to acute phase endpoint in laboratory assessment of platelet count. |
| Change From Baseline in Inorganic Phosphorus at Week 6 (Acute Phase) | Baseline, 6 weeks | Change from baseline to acute phase endpoint in laboratory assessment of inorganic phosphorus. |
| Change From Baseline in Uric Acid at Week 6 (Acute Phase) | Baseline, 6 weeks | Change from baseline to acute phase endpoint in laboratory assessment of uric acid. |
| Change From Baseline in Monocytes at Week 18 (Open-label Extension Phase) | Baseline (6 weeks), Endpoint (18 weeks) | — |
| Change From Baseline in Sodium at Week 18 (Open-label Extension Phase) | Baseline (6 weeks), Endpoint (18 weeks) | — |
| Change From Baseline in Total Protein at Week 18 (Open-label Extension Phase) | Baseline (6 weeks), Endpoint (18 weeks) | — |
| Change From Baseline in Bicarbonate (HCO3) at Week 6 (Acute Phase) | Baseline, 6 weeks | Change from baseline to acute phase endpoint in laboratory assessment for bicarbonate, HCO3. |
| Change From Baseline in Creatinine at Week 6 (Acute Phase) | Baseline, 6 weeks | Change from baseline to acute phase endpoint in laboratory assessment of creatinine. |
Countries
Belgium, Canada, Poland, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Duloxetine Participants received 30 milligrams (mg) duloxetine (oral \[po\], once daily \[QD\]) for 1 week followed by 5 weeks at 60 mg in the acute placebo-controlled period. If the participant completes the 6-week double-blind portion of the trial, the participant will be offered the option to participate in the open-label extension period (given 60, 90, or 120 mg QD for 12 weeks). | 118 |
| Placebo Participants received placebo po, QD for 6 weeks (acute phase). If the participant completes the 6-week double-blind portion of the trial, the participant will be offered the option to participate in the open-label extension period (given 60, 90, or 120 mg QD for 12 weeks). | 121 |
| Total | 239 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Acute Phase | Adverse Event | 16 | 5 |
| Acute Phase | Lack of Efficacy | 0 | 1 |
| Acute Phase | Physician Decision | 0 | 1 |
| Acute Phase | Protocol Violation | 1 | 3 |
| Acute Phase | Withdrawal by Subject | 1 | 2 |
| Open-label Extension Phase | Adverse Event | 7 | 7 |
| Open-label Extension Phase | Lack of Efficacy | 3 | 3 |
| Open-label Extension Phase | Lost to Follow-up | 2 | 0 |
| Open-label Extension Phase | Protocol Violation | 5 | 2 |
| Open-label Extension Phase | Sponsor Decision | 0 | 1 |
| Open-label Extension Phase | Withdrawal by Subject | 1 | 3 |
Baseline characteristics
| Characteristic | Placebo | Total | Duloxetine |
|---|---|---|---|
| Age Continuous | 52.67 years STANDARD_DEVIATION 9.07 | 51.73 years STANDARD_DEVIATION 9.4 | 50.77 years STANDARD_DEVIATION 9.67 |
| BPI Average Pain (Duloxetine n=116, Placebo n=119) | 5.91 units on a scale STANDARD_DEVIATION 1.33 | 6.00 units on a scale STANDARD_DEVIATION 1.42 | 6.09 units on a scale STANDARD_DEVIATION 1.5 |
| Brief Pain Inventory (BPI) Average Interference (Duloxetine n=116, Placebo n=119) | 5.24 Units on a scale STANDARD_DEVIATION 2.01 | 5.37 Units on a scale STANDARD_DEVIATION 2 | 5.50 Units on a scale STANDARD_DEVIATION 1.98 |
| Duration of central neuropathic pain (CNP) due to MS (n=118, 120) | 7.56 years STANDARD_DEVIATION 6.69 | 6.88 years STANDARD_DEVIATION 6.33 | 6.18 years STANDARD_DEVIATION 5.88 |
| Duration of MS | 11.40 years STANDARD_DEVIATION 8.49 | 11.23 years STANDARD_DEVIATION 7.99 | 11.05 years STANDARD_DEVIATION 7.48 |
| Expanded Disability Status Scale ([EDSS], n=118, 120) | 4.00 units on a scale STANDARD_DEVIATION 1.78 | 4.00 units on a scale STANDARD_DEVIATION 1.89 | 4.00 units on a scale STANDARD_DEVIATION 2.01 |
| Multiple Sclerosis (MS) Diagnosis Subtype Primary-Progressive | 16 participants | 26 participants | 10 participants |
| Multiple Sclerosis (MS) Diagnosis Subtype Progressive-Relapsing | 6 participants | 10 participants | 4 participants |
| Multiple Sclerosis (MS) Diagnosis Subtype Relapsing-Remitting | 72 participants | 153 participants | 81 participants |
| Multiple Sclerosis (MS) Diagnosis Subtype Secondary-Progressive | 27 participants | 50 participants | 23 participants |
| Multiple Sclerosis Quality of Life (MS-QOL-54) Overall Quality of Life Subsection | 61.78 units on a scale STANDARD_DEVIATION 18.8 | 59.94 units on a scale STANDARD_DEVIATION 18.76 | 58.06 units on a scale STANDARD_DEVIATION 18.61 |
| Race/Ethnicity, Customized African | 6 participants | 15 participants | 9 participants |
| Race/Ethnicity, Customized Caucasian | 112 participants | 221 participants | 109 participants |
| Race/Ethnicity, Customized Hispanic | 2 participants | 2 participants | 0 participants |
| Race/Ethnicity, Customized Native American | 1 participants | 1 participants | 0 participants |
| Region of Enrollment Belgium | 7 participants | 14 participants | 7 participants |
| Region of Enrollment Canada | 7 participants | 11 participants | 4 participants |
| Region of Enrollment Poland | 20 participants | 40 participants | 20 participants |
| Region of Enrollment United States | 87 participants | 174 participants | 87 participants |
| Sex: Female, Male Female | 93 Participants | 179 Participants | 86 Participants |
| Sex: Female, Male Male | 28 Participants | 60 Participants | 32 Participants |
| Weekly 24-Hour Average Pain | 6.31 units on a scale STANDARD_DEVIATION 1.33 | 6.40 units on a scale STANDARD_DEVIATION 1.37 | 6.49 units on a scale STANDARD_DEVIATION 1.41 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 70 / 118 | 59 / 121 | 130 / 209 |
| serious Total, serious adverse events | 4 / 118 | 0 / 121 | 7 / 209 |
Outcome results
Primary
Change From Baseline in the Weekly 24-Hour Average Pain Scores at Week 6 (Acute Phase)
24-hour average pain severity scores recorded daily on an 11-point Likert scale, evaluated as a weekly mean, with scores ranging from 0 (no pain) to 10 (worst possible pain). Participants should complete electronic diary each day upon awakening. The 11-point Likert scale was used for assessment of 24-hour average pain and evaluated as weekly means. Scores range from 0 (no pain) to 10 (worst possible pain). The Least Squares Mean (LS Mean) Value was adjusted for investigative site and baseline severity.
Time frame: Baseline, 6 weeks
Population: Number of randomized participants with baseline and at least 1 post-baseline value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine | Change From Baseline in the Weekly 24-Hour Average Pain Scores at Week 6 (Acute Phase) | -1.83 units on a scale | Standard Error 0.17 |
| Placebo | Change From Baseline in the Weekly 24-Hour Average Pain Scores at Week 6 (Acute Phase) | -1.07 units on a scale | Standard Error 0.16 |
Comparison: Null hypothesis: no difference between duloxetine and placebo on pain severity reduction as measured by weekly mean of the daily 24-hour average pain scores in participants assessed at 6 weeks. Sample size is determined using 2-sided t-test with significance level of 0.05, and 5% of randomized participants without post-baseline data due to very early discontinuation. With 119 participants per arm, study has approximately 80% power to detect an effect size of 0.375 on treatment group difference.p-value: 0.001Mixed Models Analysis
Secondary
Change From Baseline in Beck Depression Inventory II (BDI-II), Question #9 at Week 18 (Open-label Extension Phase)
The BDI-II is completed by the participant to rate the severity of depressive symptoms and any improvement during the course of the trial. The total score ranges from 0 to 63 with higher the score indicating more severe depressive symptoms. Question #9 is suicidal thoughts and wishes with the score ranging from 0 to 3.
Time frame: Baseline (6 weeks), Endpoint (18 weeks)
Population: Number of randomized participants who entered and had at least 1 non-missing value during extension phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine | Change From Baseline in Beck Depression Inventory II (BDI-II), Question #9 at Week 18 (Open-label Extension Phase) | -0.01 units on a scale | Standard Deviation 0.19 |
p-value: 0.706t-test, 2 sided
Secondary
Change From Baseline in Blood Pressure at Week 18 (Open-label Extension Phase)
Time frame: Baseline (6 weeks), Endpoint (18 weeks)
Population: Number of randomized participants who entered and had at least 1 non-missing value during extension phase.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine | Change From Baseline in Blood Pressure at Week 18 (Open-label Extension Phase) | Diastolic | -0.58 mm Hg | Standard Deviation 8.44 |
| Duloxetine | Change From Baseline in Blood Pressure at Week 18 (Open-label Extension Phase) | Systolic | -1.22 mm Hg | Standard Deviation 13.07 |
p-value: 0.32t-test, 2 sided
p-value: 0.182t-test, 2 sided
Secondary
Change From Baseline in Blood Pressure at Week 6 (Acute Phase)
Time frame: Baseline, 6 weeks
Population: Number of randomized participants with baseline and at least 1 post-baseline value.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine | Change From Baseline in Blood Pressure at Week 6 (Acute Phase) | Diastolic Blood Pressure | 1.34 mm Hg | Standard Error 0.66 |
| Duloxetine | Change From Baseline in Blood Pressure at Week 6 (Acute Phase) | Systolic Blood Pressure | 0.34 mm Hg | Standard Error 1.14 |
| Placebo | Change From Baseline in Blood Pressure at Week 6 (Acute Phase) | Diastolic Blood Pressure | 0.48 mm Hg | Standard Error 0.63 |
| Placebo | Change From Baseline in Blood Pressure at Week 6 (Acute Phase) | Systolic Blood Pressure | -0.06 mm Hg | Standard Error 1.09 |
p-value: 0.32295% CI: [-2.55, 0.84]ANCOVA
p-value: 0.78795% CI: [-3.32, 2.52]ANCOVA
Secondary
Change From Baseline in Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 18
BPI-S and BPI-I are self-reported scales measuring severity of pain and interference on function. Severity scores: 0 (no pain) to 10 (severe pain) on each question assessing worst pain, least pain, and average pain in past 24 hours, and pain right now. Interference scores: 0 (does not interfere) to 10 (completely interferes) on each question assessing interference of pain in past 24 hours for general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. Average interference = average of non-missing scores of individual interference items.
Time frame: Baseline (end of acute phase/Week 6), Endpoint (Week 18)
Population: Number of randomized participants who entered and had at least 1 non-missing value during extension phase.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine | Change From Baseline in Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 18 | BPI-S for Worst Pain | -1.27 units on a scale | Standard Deviation 2.07 |
| Duloxetine | Change From Baseline in Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 18 | BPI-S for Least Pain | -0.96 units on a scale | Standard Deviation 1.84 |
| Duloxetine | Change From Baseline in Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 18 | BPI-S for Average Pain | -1.26 units on a scale | Standard Deviation 1.76 |
| Duloxetine | Change From Baseline in Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 18 | BPI-S for Pain Right Now | -1.03 units on a scale | Standard Deviation 2.2 |
| Duloxetine | Change From Baseline in Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 18 | BPI-I for General Activity | -1.01 units on a scale | Standard Deviation 2.5 |
| Duloxetine | Change From Baseline in Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 18 | BPI-I for Mood | -1.08 units on a scale | Standard Deviation 2.56 |
| Duloxetine | Change From Baseline in Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 18 | BPI-I for Walking Ability | -0.84 units on a scale | Standard Deviation 2.62 |
| Duloxetine | Change From Baseline in Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 18 | BPI-I for Normal Work | -1.00 units on a scale | Standard Deviation 2.6 |
| Duloxetine | Change From Baseline in Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 18 | BPI-I for Relations With Others | -0.65 units on a scale | Standard Deviation 2.59 |
| Duloxetine | Change From Baseline in Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 18 | BPI-I for Sleep | -0.70 units on a scale | Standard Deviation 2.37 |
| Duloxetine | Change From Baseline in Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 18 | BPI-I for Enjoyment Of Life | -1.03 units on a scale | Standard Deviation 2.47 |
| Duloxetine | Change From Baseline in Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 18 | BPI for Mean Interference Score | -0.89 units on a scale | Standard Deviation 2.06 |
p-value: <0.001t-test, 2 sided
p-value: <0.001t-test, 2 sided
p-value: <0.001t-test, 2 sided
p-value: <0.001t-test, 2 sided
p-value: <0.001t-test, 2 sided
p-value: <0.001t-test, 2 sided
p-value: <0.001t-test, 2 sided
p-value: <0.001t-test, 2 sided
p-value: <0.001t-test, 2 sided
p-value: <0.001t-test, 2 sided
p-value: <0.001t-test, 2 sided
p-value: <0.001t-test, 2 sided
Secondary
Change From Baseline in Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at Week 18 (Open-label Extension Phase)
A 54 question measure covers 12 domains; assesses mental and physical health. Each domain score is converted into a 0-100 score based on individual item responses; higher scores=better health status. The physical health composite score is a weighted average of the physical health scales, such as physical function, health perceptions, and energy. The mental health composite score is a weighted average of the mental health scales, such as overall quality of life, cognitive function, and health distress.
Time frame: Baseline (6 weeks), Endpoint (18 weeks)
Population: Number of randomized participants who entered and had at least 1 non-missing value during extension phase.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine | Change From Baseline in Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at Week 18 (Open-label Extension Phase) | Physical Health Composite Section Score (N=198) | 2.70 units on a scale | Standard Deviation 12.32 |
| Duloxetine | Change From Baseline in Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at Week 18 (Open-label Extension Phase) | Mental Health Composite Section Score (N=201) | 1.97 units on a scale | Standard Deviation 14.45 |
| Duloxetine | Change From Baseline in Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at Week 18 (Open-label Extension Phase) | Physical Health Subsection Score (N=201) | 3.16 units on a scale | Standard Deviation 14.29 |
| Duloxetine | Change From Baseline in Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at Week 18 (Open-label Extension Phase) | Health Perceptions Subsection Score (N=201) | 2.24 units on a scale | Standard Deviation 14.04 |
| Duloxetine | Change From Baseline in Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at Week 18 (Open-label Extension Phase) | Energy Subsection Score (N=201) | 2.93 units on a scale | Standard Deviation 15.42 |
| Duloxetine | Change From Baseline in Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at Week 18 (Open-label Extension Phase) | Role Limitation Due to Physical Problems (N=201) | 0.50 units on a scale | Standard Deviation 39.29 |
| Duloxetine | Change From Baseline in Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at Week 18 (Open-label Extension Phase) | Pain Subsection Score (N=201) | 7.45 units on a scale | Standard Deviation 17.57 |
| Duloxetine | Change From Baseline in Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at Week 18 (Open-label Extension Phase) | Sexual Function Subsection Score (N=198) | 0.79 units on a scale | Standard Deviation 23.38 |
| Duloxetine | Change From Baseline in Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at Week 18 (Open-label Extension Phase) | Social Function Subsection Score (N=201) | 2.53 units on a scale | Standard Deviation 18.3 |
| Duloxetine | Change From Baseline in Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at Week 18 (Open-label Extension Phase) | Health Distress Subsection Score (N=201) | 1.44 units on a scale | Standard Deviation 18.51 |
| Duloxetine | Change From Baseline in Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at Week 18 (Open-label Extension Phase) | Overall Quality Of Life Subsection Score (N=201) | 1.47 units on a scale | Standard Deviation 11.04 |
| Duloxetine | Change From Baseline in Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at Week 18 (Open-label Extension Phase) | Emotional Well-being Subsection Score (N=201) | 2.63 units on a scale | Standard Deviation 13.61 |
| Duloxetine | Change From Baseline in Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at Week 18 (Open-label Extension Phase) | Role Limitation Due to Emotional Problems (N=201) | 3.15 units on a scale | Standard Deviation 38.96 |
| Duloxetine | Change From Baseline in Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at Week 18 (Open-label Extension Phase) | Cognitive Function Subsection Score (N=201) | -0.07 units on a scale | Standard Deviation 14.64 |
| Duloxetine | Change From Baseline in Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at Week 18 (Open-label Extension Phase) | Change in Health Subsection Score (N=201) | 4.35 units on a scale | Standard Deviation 25.3 |
| Duloxetine | Change From Baseline in Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at Week 18 (Open-label Extension Phase) | Satisfaction with Sexual Function Subsect (N=195) | 1.92 units on a scale | Standard Deviation 30.56 |
p-value: 0.002t-test, 2 sided
p-value: 0.054t-test, 2 sided
p-value: 0.002t-test, 2 sided
p-value: 0.025t-test, 2 sided
p-value: 0.008t-test, 2 sided
p-value: 0.858t-test, 2 sided
p-value: <0.001t-test, 2 sided
p-value: 0.637t-test, 2 sided
p-value: 0.051t-test, 2 sided
p-value: 0.27t-test, 2 sided
p-value: 0.061t-test, 2 sided
p-value: 0.007t-test, 2 sided
p-value: 0.253t-test, 2 sided
p-value: 0.942t-test, 2 sided
p-value: 0.016t-test, 2 sided
p-value: 0.381t-test, 2 sided
Secondary
Change From Baseline in Pulse Rate at Week 18 (Open-label Extension Phase)
Time frame: Baseline (6 weeks), endpoint (18 weeks)
Population: Number of randomized participants who entered and had at least 1 non-missing value during extension phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine | Change From Baseline in Pulse Rate at Week 18 (Open-label Extension Phase) | 1.47 beats per minute (bpm) | Standard Deviation 9.81 |
p-value: 0.032t-test, 2 sided
Secondary
Change From Baseline in Pulse Rate at Week 6 (Acute Phase)
Time frame: Baseline, 6 weeks
Population: Number of randomized participants with baseline and at least 1 post-baseline value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine | Change From Baseline in Pulse Rate at Week 6 (Acute Phase) | 1.76 beats per minute (bpm) | Standard Error 0.84 |
| Placebo | Change From Baseline in Pulse Rate at Week 6 (Acute Phase) | 0.22 beats per minute (bpm) | Standard Error 0.81 |
p-value: 0.1695% CI: [-3.7, 0.61]ANCOVA
Secondary
Change From Baseline in the Beck Depression Inventory II (BDI-II) Question #9 at Week 6 (Acute Phase)
The BDI-II is completed by the participant to rate the severity of depressive symptoms and any improvement during the course of the trial. The total score ranges from 0 to 63 with higher the score indicating more severe depressive symptoms. Question #9 is suicidal thoughts and wishes with a score ranging from 0 to 3.
Time frame: Baseline, 6 weeks
Population: Number of randomized participants with baseline and at least 1 post-baseline value.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine | Change From Baseline in the Beck Depression Inventory II (BDI-II) Question #9 at Week 6 (Acute Phase) | -0.04 units on a scale | Standard Deviation 0.39 |
| Placebo | Change From Baseline in the Beck Depression Inventory II (BDI-II) Question #9 at Week 6 (Acute Phase) | -0.03 units on a scale | Standard Deviation 0.21 |
p-value: 0.66295% CI: [-0.06, 0.04]ANCOVA
Secondary
Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 6 (Acute Phase)
Measures pain severity and interference on function. Severity scores: 0 (no pain) to 10 (severe pain) on each question assessing worst, least, and average pain in past 24 hours, and pain right now. Interference scores: 0 (does not interfere) to 10 (completely interferes) on each question assessing pain interference in past 24 hours, such as general activity, mood, normal work, relations with other people, and sleep. Average interference=average of non-missing scores of individual interference items. Least Squares (LS) Mean Value was adjusted for investigative site and baseline severity.
Time frame: Baseline, 6 weeks
Population: Number of randomized participants with baseline and at least 1 post-baseline value.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 6 (Acute Phase) | BPI Interference for Sleep | -2.01 units on a scale | Standard Error 0.22 |
| Duloxetine | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 6 (Acute Phase) | BPI Severity for Least Pain | -1.20 units on a scale | Standard Error 0.18 |
| Duloxetine | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 6 (Acute Phase) | BPI Severity for Pain Right Now | -1.91 units on a scale | Standard Error 0.21 |
| Duloxetine | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 6 (Acute Phase) | BPI Interference for General Activity | -1.81 units on a scale | Standard Error 0.23 |
| Duloxetine | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 6 (Acute Phase) | BPI Interference for Mood | -1.91 units on a scale | Standard Error 0.24 |
| Duloxetine | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 6 (Acute Phase) | BPI Interference for Walking Ability | -1.47 units on a scale | Standard Error 0.25 |
| Duloxetine | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 6 (Acute Phase) | BPI Interference for Normal Work | -1.51 units on a scale | Standard Error 0.24 |
| Duloxetine | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 6 (Acute Phase) | BPI Interference for Relations With Others | -1.72 units on a scale | Standard Error 0.22 |
| Duloxetine | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 6 (Acute Phase) | BPI Interference for Enjoyment Of Life | -1.82 units on a scale | Standard Error 0.24 |
| Duloxetine | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 6 (Acute Phase) | BPI Mean Interference Score | -1.77 units on a scale | Standard Error 0.19 |
| Duloxetine | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 6 (Acute Phase) | BPI Severity for Average Pain | -1.36 units on a scale | Standard Error 0.19 |
| Duloxetine | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 6 (Acute Phase) | BPI Severity for Worst Pain | -1.95 units on a scale | Standard Error 0.21 |
| Placebo | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 6 (Acute Phase) | BPI Interference for Enjoyment Of Life | -1.65 units on a scale | Standard Error 0.23 |
| Placebo | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 6 (Acute Phase) | BPI Severity for Worst Pain | -1.29 units on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 6 (Acute Phase) | BPI Interference for Normal Work | -1.18 units on a scale | Standard Error 0.22 |
| Placebo | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 6 (Acute Phase) | BPI Severity for Least Pain | -0.72 units on a scale | Standard Error 0.17 |
| Placebo | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 6 (Acute Phase) | BPI Severity for Average Pain | -0.84 units on a scale | Standard Error 0.17 |
| Placebo | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 6 (Acute Phase) | BPI Interference for General Activity | -1.29 units on a scale | Standard Error 0.22 |
| Placebo | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 6 (Acute Phase) | BPI Severity for Pain Right Now | -1.02 units on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 6 (Acute Phase) | BPI Interference for Relations With Others | -1.22 units on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 6 (Acute Phase) | BPI Interference for Sleep | -1.59 units on a scale | Standard Error 0.21 |
| Placebo | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 6 (Acute Phase) | BPI Interference for Mood | -1.25 units on a scale | Standard Error 0.22 |
| Placebo | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 6 (Acute Phase) | BPI Mean Interference Score | -1.32 units on a scale | Standard Error 0.18 |
| Placebo | Change From Baseline in the Brief Pain Inventory Severity and Interference Scores (BPI-S/BPI-I) at Week 6 (Acute Phase) | BPI Interference for Walking Ability | -0.91 units on a scale | Standard Error 0.24 |
p-value: 0.01695% CI: [0.12, 1.2]ANCOVA
p-value: 0.04395% CI: [0.02, 0.95]ANCOVA
p-value: 0.0395% CI: [0.05, 0.99]ANCOVA
p-value: 0.00195% CI: [0.36, 1.43]ANCOVA
p-value: 0.08395% CI: [-0.07, 1.11]ANCOVA
p-value: 0.03495% CI: [0.05, 1.27]ANCOVA
p-value: 0.08995% CI: [-0.08, 1.19]ANCOVA
p-value: 0.29195% CI: [-0.28, 0.93]ANCOVA
p-value: 0.07795% CI: [-0.06, 1.05]ANCOVA
p-value: 0.14895% CI: [-0.15, 0.97]ANCOVA
p-value: 0.58295% CI: [-0.45, 0.79]ANCOVA
p-value: 0.06795% CI: [-0.03, 0.94]ANCOVA
Secondary
Change From Baseline in the Clinical Global Impression of Severity Scale (CGI-S) at 6 Weeks (Acute Phase)
Measures severity of illness at the time of assessment compared with start of treatment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). The Least Squares (LS) Mean Value was adjusted for investigative site and baseline severity.
Time frame: Baseline, 6 weeks
Population: Number of randomized participants with baseline and at least 1 post-baseline value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine | Change From Baseline in the Clinical Global Impression of Severity Scale (CGI-S) at 6 Weeks (Acute Phase) | -0.67 units on a scale | Standard Error 0.09 |
| Placebo | Change From Baseline in the Clinical Global Impression of Severity Scale (CGI-S) at 6 Weeks (Acute Phase) | -0.44 units on a scale | Standard Error 0.08 |
p-value: 0.04195% CI: [0.01, 0.45]ANCOVA
Secondary
Change From Baseline in the Clinical Global Impression of Severity Scale (CGI-S) Score at Week 18 (Open-label Extension Phase)
Measures severity of illness at the time of assessment compared with start of treatment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill participants).
Time frame: Baseline (6 weeks), Endpoint (18 weeks)
Population: Number of randomized participants who entered and had at least 1 non-missing value during extension phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine | Change From Baseline in the Clinical Global Impression of Severity Scale (CGI-S) Score at Week 18 (Open-label Extension Phase) | -0.59 units on a scale | Standard Deviation 1.02 |
p-value: <0.001t-test, 2 sided
Secondary
Change From Baseline in the Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at 6 Weeks (Acute Phase)
A 54 question measure covers 12 domains; assesses mental and physical health. Each domain score is converted into a 0-100 score based on individual item responses; higher scores=better health status. The physical health composite score is a weighted average of the physical health scales, such as physical function, health perceptions, and energy. The mental health composite score is a weighted average of the mental health scales, such as overall quality of life, cognitive function, and health distress. The Least Squares (LS) Mean Value was adjusted for investigative site and baseline severity.
Time frame: Baseline, 6 weeks
Population: Number of randomized participants with baseline and at least 1 post-baseline value.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine | Change From Baseline in the Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at 6 Weeks (Acute Phase) | Physical Health Composite (N=106, 116) | 6.11 units on a scale | Standard Error 1.15 |
| Duloxetine | Change From Baseline in the Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at 6 Weeks (Acute Phase) | Mental Health Composite (N=106, 116) | 5.81 units on a scale | Standard Error 1.44 |
| Duloxetine | Change From Baseline in the Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at 6 Weeks (Acute Phase) | Physical Health (N=106, 116) | 3.35 units on a scale | Standard Error 1.51 |
| Duloxetine | Change From Baseline in the Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at 6 Weeks (Acute Phase) | Health Perceptions (N=106, 116) | 1.41 units on a scale | Standard Error 1.39 |
| Duloxetine | Change From Baseline in the Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at 6 Weeks (Acute Phase) | Energy Subsection Score (N=106, 116) | 6.54 units on a scale | Standard Error 1.6 |
| Duloxetine | Change From Baseline in the Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at 6 Weeks (Acute Phase) | Role Limitation Due to Physical (N=106, 116) | 11.73 units on a scale | Standard Error 3.17 |
| Duloxetine | Change From Baseline in the Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at 6 Weeks (Acute Phase) | Pain (N=106, 116) | 12.42 units on a scale | Standard Error 1.72 |
| Duloxetine | Change From Baseline in the Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at 6 Weeks (Acute Phase) | Sexual Function (N=106, 116) | 1.30 units on a scale | Standard Error 2.21 |
| Duloxetine | Change From Baseline in the Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at 6 Weeks (Acute Phase) | Social Function (N=106, 116) | 5.02 units on a scale | Standard Error 1.71 |
| Duloxetine | Change From Baseline in the Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at 6 Weeks (Acute Phase) | Health Distress (N=106, 116) | 8.96 units on a scale | Standard Error 1.76 |
| Duloxetine | Change From Baseline in the Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at 6 Weeks (Acute Phase) | Overall Quality Of Life (N=106, 116) | 3.66 units on a scale | Standard Error 1.34 |
| Duloxetine | Change From Baseline in the Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at 6 Weeks (Acute Phase) | Emotional Well-being Subsection Score (N=106, 116) | 4.59 units on a scale | Standard Error 1.37 |
| Duloxetine | Change From Baseline in the Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at 6 Weeks (Acute Phase) | Role Limitation Due to Emotional (N=106, 116) | 6.48 units on a scale | Standard Error 3.55 |
| Duloxetine | Change From Baseline in the Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at 6 Weeks (Acute Phase) | Cognitive Function (N=106, 116) | 6.38 units on a scale | Standard Error 1.45 |
| Duloxetine | Change From Baseline in the Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at 6 Weeks (Acute Phase) | Change in Health (N=106, 116) | 8.23 units on a scale | Standard Error 2.3 |
| Duloxetine | Change From Baseline in the Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at 6 Weeks (Acute Phase) | Satisfaction with Sexual Function (N=102, 112) | 2.66 units on a scale | Standard Error 2.82 |
| Placebo | Change From Baseline in the Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at 6 Weeks (Acute Phase) | Satisfaction with Sexual Function (N=102, 112) | -1.35 units on a scale | Standard Error 2.68 |
| Placebo | Change From Baseline in the Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at 6 Weeks (Acute Phase) | Physical Health Composite (N=106, 116) | 5.12 units on a scale | Standard Error 1.08 |
| Placebo | Change From Baseline in the Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at 6 Weeks (Acute Phase) | Social Function (N=106, 116) | 6.97 units on a scale | Standard Error 1.61 |
| Placebo | Change From Baseline in the Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at 6 Weeks (Acute Phase) | Mental Health Composite (N=106, 116) | 4.59 units on a scale | Standard Error 1.35 |
| Placebo | Change From Baseline in the Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at 6 Weeks (Acute Phase) | Role Limitation Due to Emotional (N=106, 116) | 1.58 units on a scale | Standard Error 3.33 |
| Placebo | Change From Baseline in the Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at 6 Weeks (Acute Phase) | Physical Health (N=106, 116) | 2.65 units on a scale | Standard Error 1.42 |
| Placebo | Change From Baseline in the Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at 6 Weeks (Acute Phase) | Health Distress (N=106, 116) | 9.34 units on a scale | Standard Error 1.66 |
| Placebo | Change From Baseline in the Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at 6 Weeks (Acute Phase) | Health Perceptions (N=106, 116) | 1.35 units on a scale | Standard Error 1.31 |
| Placebo | Change From Baseline in the Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at 6 Weeks (Acute Phase) | Change in Health (N=106, 116) | 6.25 units on a scale | Standard Error 2.16 |
| Placebo | Change From Baseline in the Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at 6 Weeks (Acute Phase) | Energy Subsection Score (N=106, 116) | 6.51 units on a scale | Standard Error 1.5 |
| Placebo | Change From Baseline in the Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at 6 Weeks (Acute Phase) | Overall Quality Of Life (N=106, 116) | 5.43 units on a scale | Standard Error 1.26 |
| Placebo | Change From Baseline in the Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at 6 Weeks (Acute Phase) | Role Limitation Due to Physical (N=106, 116) | 8.60 units on a scale | Standard Error 2.97 |
| Placebo | Change From Baseline in the Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at 6 Weeks (Acute Phase) | Cognitive Function (N=106, 116) | 5.57 units on a scale | Standard Error 1.36 |
| Placebo | Change From Baseline in the Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at 6 Weeks (Acute Phase) | Pain (N=106, 116) | 8.84 units on a scale | Standard Error 1.62 |
| Placebo | Change From Baseline in the Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at 6 Weeks (Acute Phase) | Emotional Well-being Subsection Score (N=106, 116) | 3.99 units on a scale | Standard Error 1.29 |
| Placebo | Change From Baseline in the Multiple Sclerosis Quality of Life-54 Instrument (MS-QOL-54) at 6 Weeks (Acute Phase) | Sexual Function (N=106, 116) | 1.12 units on a scale | Standard Error 2.09 |
p-value: 0.595% CI: [-3.9, 1.91]ANCOVA
p-value: 0.51295% CI: [-4.87, 2.44]ANCOVA
p-value: 0.7295% CI: [-4.51, 3.12]ANCOVA
p-value: 0.97395% CI: [-3.58, 3.46]ANCOVA
p-value: 0.99195% CI: [-4.07, 4.02]ANCOVA
p-value: 0.44195% CI: [-11.14, 4.87]ANCOVA
p-value: 0.10895% CI: [-7.94, 0.79]ANCOVA
p-value: 0.94895% CI: [-5.77, 5.39]ANCOVA
p-value: 0.37495% CI: [-2.37, 6.28]ANCOVA
p-value: 0.86795% CI: [-4.1, 4.87]ANCOVA
p-value: 0.30695% CI: [-1.63, 5.17]ANCOVA
p-value: 0.73395% CI: [-4.08, 2.88]ANCOVA
p-value: 0.28395% CI: [-13.88, 4.08]ANCOVA
p-value: 0.66495% CI: [-4.49, 2.86]ANCOVA
p-value: 0.50495% CI: [-7.81, 3.85]ANCOVA
p-value: 0.2795% CI: [-11.18, 3.14]ANCOVA
Secondary
Change From Baseline in the Weekly 24-Hour Average Pain Scores up to Week 6 (Acute Phase)
This is a nominal outcome reflecting whether or not a clinically-important efficacy outcome (≥30% or ≥50% pain reduction from baseline) was achieved at endpoint. It is based on a comparison between baseline and endpoint scores on an ordinal scale with scores from 0 (no pain) to 10 (worst possible pain). Used were the weekly mean of the scores of the average pain severity over the last 24 hours. The weekly averages were based on daily assessments recorded by participants in their diaries.
Time frame: Baseline, 6 weeks
Population: Number of randomized participants with baseline and at least 1 post-baseline value. Last-observation-carried-forward (LOCF) imputation was implemented for participants with early discontinuation. Baseline-observation-carried-forward (BOCF) imputation was implemented for participants with early discontinuation.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Duloxetine | Change From Baseline in the Weekly 24-Hour Average Pain Scores up to Week 6 (Acute Phase) | ≥30% Reduction (LOCF) | 47 participants |
| Duloxetine | Change From Baseline in the Weekly 24-Hour Average Pain Scores up to Week 6 (Acute Phase) | ≥50% Reduction (LOCF) | 26 participants |
| Duloxetine | Change From Baseline in the Weekly 24-Hour Average Pain Scores up to Week 6 (Acute Phase) | ≥30% Reduction (BOCF) | 44 participants |
| Duloxetine | Change From Baseline in the Weekly 24-Hour Average Pain Scores up to Week 6 (Acute Phase) | ≥50% Reduction (BOCF) | 24 participants |
| Placebo | Change From Baseline in the Weekly 24-Hour Average Pain Scores up to Week 6 (Acute Phase) | ≥50% Reduction (BOCF) | 16 participants |
| Placebo | Change From Baseline in the Weekly 24-Hour Average Pain Scores up to Week 6 (Acute Phase) | ≥30% Reduction (LOCF) | 32 participants |
| Placebo | Change From Baseline in the Weekly 24-Hour Average Pain Scores up to Week 6 (Acute Phase) | ≥30% Reduction (BOCF) | 29 participants |
| Placebo | Change From Baseline in the Weekly 24-Hour Average Pain Scores up to Week 6 (Acute Phase) | ≥50% Reduction (LOCF) | 19 participants |
p-value: 0.027Fisher Exact
p-value: 0.246Fisher Exact
p-value: 0.024Fisher Exact
p-value: 0.165Fisher Exact
Secondary
Change From Baseline in the Weekly Mean of Night Pain Scores at Week 6 (Acute Phase)
Weekly mean of the night pain severity scores recorded daily on an 11-point Likert scale, an ordinal scale ranging from 0 (no pain) to 10 (worst possible pain). Participants should complete the electronic diary each day upon awakening. The Least Squares (LS) Mean Value was adjusted for investigative site and baseline severity.
Time frame: Baseline, 6 weeks
Population: Number of randomized participants with baseline and at least 1 post-baseline value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine | Change From Baseline in the Weekly Mean of Night Pain Scores at Week 6 (Acute Phase) | -1.25 units on a scale | Standard Error 0.12 |
| Placebo | Change From Baseline in the Weekly Mean of Night Pain Scores at Week 6 (Acute Phase) | -0.74 units on a scale | Standard Error 0.12 |
p-value: 0.002Mixed Models Analysis
Secondary
Change From Baseline in Weight at Week 18 (Open-label Extension Phase)
Time frame: Baseline (6 weeks), Endpoint (18 weeks)
Population: Number of randomized participants who entered and had at least 1 non-missing value during extension phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine | Change From Baseline in Weight at Week 18 (Open-label Extension Phase) | -0.30 kilograms (kg) | Standard Deviation 2.84 |
p-value: 0.151t-test, 2 sided
Secondary
Change From Baseline in Weight at Week 6 (Acute Phase)
Time frame: Baseline, 6 weeks
Population: Number of randomized participants with baseline and at least 1 post-baseline value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine | Change From Baseline in Weight at Week 6 (Acute Phase) | -0.69 kilograms (kg) | Standard Error 0.2 |
| Placebo | Change From Baseline in Weight at Week 6 (Acute Phase) | 0.08 kilograms (kg) | Standard Error 0.18 |
p-value: 0.00395% CI: [0.27, 1.26]ANCOVA
Secondary
Change in the Weekly Mean of the Night Pain Scores From Week 6 Through Week 18 (Open-label Extension Phase)
Weekly mean of the night pain severity scores recorded daily on an 11-point Likert scale, an ordinal scale ranging from 0 (no pain) to 10 (worst possible pain). Participants should complete the electronic diary each day upon awakening. Each weekly mean change represents change relative to week 6, the baseline of the extension phase.
Time frame: Baseline (6 weeks) through Endpoint (18 weeks)
Population: Number of randomized participants who entered and had at least 1 non-missing value during extension phase.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine | Change in the Weekly Mean of the Night Pain Scores From Week 6 Through Week 18 (Open-label Extension Phase) | Week 7 (n=185) | -0.05 units on a scale | Standard Error 0.07 |
| Duloxetine | Change in the Weekly Mean of the Night Pain Scores From Week 6 Through Week 18 (Open-label Extension Phase) | Week 8 (n=205) | -0.31 units on a scale | Standard Error 0.07 |
| Duloxetine | Change in the Weekly Mean of the Night Pain Scores From Week 6 Through Week 18 (Open-label Extension Phase) | Week 9 (n=184) | -0.54 units on a scale | Standard Error 0.08 |
| Duloxetine | Change in the Weekly Mean of the Night Pain Scores From Week 6 Through Week 18 (Open-label Extension Phase) | Week 10 (n=197) | -0.62 units on a scale | Standard Error 0.08 |
| Duloxetine | Change in the Weekly Mean of the Night Pain Scores From Week 6 Through Week 18 (Open-label Extension Phase) | Week 11 (n=166) | -0.75 units on a scale | Standard Error 0.08 |
| Duloxetine | Change in the Weekly Mean of the Night Pain Scores From Week 6 Through Week 18 (Open-label Extension Phase) | Week 12 (n=192) | -0.89 units on a scale | Standard Error 0.09 |
| Duloxetine | Change in the Weekly Mean of the Night Pain Scores From Week 6 Through Week 18 (Open-label Extension Phase) | Week 13 (n=166) | -1.05 units on a scale | Standard Error 0.09 |
| Duloxetine | Change in the Weekly Mean of the Night Pain Scores From Week 6 Through Week 18 (Open-label Extension Phase) | Week 14 (n=177) | -0.98 units on a scale | Standard Error 0.1 |
| Duloxetine | Change in the Weekly Mean of the Night Pain Scores From Week 6 Through Week 18 (Open-label Extension Phase) | Week 15 (n=158) | -0.99 units on a scale | Standard Error 0.11 |
| Duloxetine | Change in the Weekly Mean of the Night Pain Scores From Week 6 Through Week 18 (Open-label Extension Phase) | Week 16 (n=176) | -1.04 units on a scale | Standard Error 0.11 |
| Duloxetine | Change in the Weekly Mean of the Night Pain Scores From Week 6 Through Week 18 (Open-label Extension Phase) | Week 17 (n=156) | -1.11 units on a scale | Standard Error 0.11 |
| Duloxetine | Change in the Weekly Mean of the Night Pain Scores From Week 6 Through Week 18 (Open-label Extension Phase) | Week 18 (n=175) | -1.04 units on a scale | Standard Error 0.11 |
p-value: 0.524Mixed Models Analysis
p-value: <0.001Mixed Models Analysis
p-value: <0.001Mixed Models Analysis
p-value: <0.001Mixed Models Analysis
p-value: <0.001Mixed Models Analysis
p-value: <0.001Mixed Models Analysis
p-value: <0.001Mixed Models Analysis
p-value: <0.001Mixed Models Analysis
p-value: <0.001Mixed Models Analysis
p-value: <0.001Mixed Models Analysis
p-value: <0.001Mixed Models Analysis
p-value: <0.001Mixed Models Analysis
Secondary
Number of Participants Who Discontinued During the Acute Phase (by Week 6)
Time frame: Baseline through 6 weeks
Population: All randomized participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Duloxetine | Number of Participants Who Discontinued During the Acute Phase (by Week 6) | Protocol Violation | 1 participants |
| Duloxetine | Number of Participants Who Discontinued During the Acute Phase (by Week 6) | Lack of Efficacy | 0 participants |
| Duloxetine | Number of Participants Who Discontinued During the Acute Phase (by Week 6) | Adverse Event (AE) | 16 participants |
| Duloxetine | Number of Participants Who Discontinued During the Acute Phase (by Week 6) | Physician Decision | 0 participants |
| Duloxetine | Number of Participants Who Discontinued During the Acute Phase (by Week 6) | Subject Decision | 1 participants |
| Duloxetine | Number of Participants Who Discontinued During the Acute Phase (by Week 6) | Discontinued Due to Any Reason | 18 participants |
| Placebo | Number of Participants Who Discontinued During the Acute Phase (by Week 6) | Subject Decision | 2 participants |
| Placebo | Number of Participants Who Discontinued During the Acute Phase (by Week 6) | Adverse Event (AE) | 5 participants |
| Placebo | Number of Participants Who Discontinued During the Acute Phase (by Week 6) | Protocol Violation | 3 participants |
| Placebo | Number of Participants Who Discontinued During the Acute Phase (by Week 6) | Discontinued Due to Any Reason | 12 participants |
| Placebo | Number of Participants Who Discontinued During the Acute Phase (by Week 6) | Lack of Efficacy | 1 participants |
| Placebo | Number of Participants Who Discontinued During the Acute Phase (by Week 6) | Physician Decision | 1 participants |
p-value: 0.244Fisher Exact
p-value: 0.012Fisher Exact
p-value: 0.622Fisher Exact
p-value: 1Fisher Exact
p-value: 1Fisher Exact
p-value: 1Fisher Exact
Secondary
Number of Participants Who Discontinued During the Open-label Extension Phase (by Week 18)
Time frame: Baseline (6 weeks) through Endpoint (18 weeks)
Population: All participants randomized to placebo in acute phase received duloxetine during the extension phase.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Duloxetine | Number of Participants Who Discontinued During the Open-label Extension Phase (by Week 18) | Discontinued Due to Any Reason | 34 participants |
| Duloxetine | Number of Participants Who Discontinued During the Open-label Extension Phase (by Week 18) | Adverse Event | 14 participants |
| Duloxetine | Number of Participants Who Discontinued During the Open-label Extension Phase (by Week 18) | Protocol Violation | 7 participants |
| Duloxetine | Number of Participants Who Discontinued During the Open-label Extension Phase (by Week 18) | Lack of Efficacy | 6 participants |
| Duloxetine | Number of Participants Who Discontinued During the Open-label Extension Phase (by Week 18) | Subject Decision | 4 participants |
| Duloxetine | Number of Participants Who Discontinued During the Open-label Extension Phase (by Week 18) | Lost to follow up | 2 participants |
| Duloxetine | Number of Participants Who Discontinued During the Open-label Extension Phase (by Week 18) | Sponsor Decision | 1 participants |
Secondary
Number of Participants With Adverse Events (AEs) Resulting in Discontinuation During the Open-label Extension Phase
Time frame: Baseline (6 weeks) through Endpoint (18 weeks)
Population: All randomized participants in the open-label extension phase.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Duloxetine | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation During the Open-label Extension Phase | Fatigue | 2 participants |
| Duloxetine | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation During the Open-label Extension Phase | Due to any AE | 14 participants |
| Duloxetine | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation During the Open-label Extension Phase | Somnolence | 2 participants |
| Duloxetine | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation During the Open-label Extension Phase | Alanine aminotransferase increased | 1 participants |
| Duloxetine | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation During the Open-label Extension Phase | Constipation | 1 participants |
| Duloxetine | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation During the Open-label Extension Phase | Diverticulitis | 1 participants |
| Duloxetine | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation During the Open-label Extension Phase | Dizziness | 1 participants |
| Duloxetine | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation During the Open-label Extension Phase | Fall | 1 participants |
| Duloxetine | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation During the Open-label Extension Phase | Hypertension | 1 participants |
| Duloxetine | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation During the Open-label Extension Phase | Insomnia | 1 participants |
| Duloxetine | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation During the Open-label Extension Phase | Multiple sclerosis relapse | 1 participants |
| Duloxetine | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation During the Open-label Extension Phase | Nausea | 1 participants |
| Duloxetine | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation During the Open-label Extension Phase | Rash pruritic | 1 participants |
Secondary
Number of Participants With Adverse Events (AEs) Resulting in Discontinuation From Baseline During the Acute Phase
Time frame: Baseline through 6 weeks
Population: All randomized participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Duloxetine | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation From Baseline During the Acute Phase | Any Adverse Event (AE) | 16 participants |
| Duloxetine | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation From Baseline During the Acute Phase | Dizziness | 3 participants |
| Duloxetine | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation From Baseline During the Acute Phase | Somnolence | 2 participants |
| Duloxetine | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation From Baseline During the Acute Phase | Abdominal discomfort | 1 participants |
| Duloxetine | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation From Baseline During the Acute Phase | Asthenia | 1 participants |
| Duloxetine | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation From Baseline During the Acute Phase | Back pain | 1 participants |
| Duloxetine | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation From Baseline During the Acute Phase | Balance disorder | 0 participants |
| Duloxetine | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation From Baseline During the Acute Phase | Fear | 1 participants |
| Duloxetine | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation From Baseline During the Acute Phase | Feeling jittery | 1 participants |
| Duloxetine | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation From Baseline During the Acute Phase | Headache | 0 participants |
| Duloxetine | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation From Baseline During the Acute Phase | Hypotension | 0 participants |
| Duloxetine | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation From Baseline During the Acute Phase | Libido decreased | 1 participants |
| Duloxetine | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation From Baseline During the Acute Phase | Mood altered | 0 participants |
| Duloxetine | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation From Baseline During the Acute Phase | Nausea | 1 participants |
| Duloxetine | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation From Baseline During the Acute Phase | Pain in extremity | 1 participants |
| Duloxetine | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation From Baseline During the Acute Phase | Rash maculo-papular | 1 participants |
| Duloxetine | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation From Baseline During the Acute Phase | Suicide attempt | 1 participants |
| Duloxetine | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation From Baseline During the Acute Phase | Throat irritation | 1 participants |
| Placebo | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation From Baseline During the Acute Phase | Nausea | 0 participants |
| Placebo | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation From Baseline During the Acute Phase | Any Adverse Event (AE) | 5 participants |
| Placebo | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation From Baseline During the Acute Phase | Headache | 1 participants |
| Placebo | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation From Baseline During the Acute Phase | Dizziness | 1 participants |
| Placebo | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation From Baseline During the Acute Phase | Throat irritation | 0 participants |
| Placebo | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation From Baseline During the Acute Phase | Somnolence | 0 participants |
| Placebo | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation From Baseline During the Acute Phase | Hypotension | 1 participants |
| Placebo | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation From Baseline During the Acute Phase | Abdominal discomfort | 0 participants |
| Placebo | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation From Baseline During the Acute Phase | Pain in extremity | 0 participants |
| Placebo | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation From Baseline During the Acute Phase | Asthenia | 0 participants |
| Placebo | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation From Baseline During the Acute Phase | Libido decreased | 0 participants |
| Placebo | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation From Baseline During the Acute Phase | Back pain | 0 participants |
| Placebo | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation From Baseline During the Acute Phase | Suicide attempt | 0 participants |
| Placebo | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation From Baseline During the Acute Phase | Balance disorder | 1 participants |
| Placebo | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation From Baseline During the Acute Phase | Mood altered | 1 participants |
| Placebo | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation From Baseline During the Acute Phase | Fear | 0 participants |
| Placebo | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation From Baseline During the Acute Phase | Rash maculo-papular | 0 participants |
| Placebo | Number of Participants With Adverse Events (AEs) Resulting in Discontinuation From Baseline During the Acute Phase | Feeling jittery | 0 participants |
Secondary
Number of Participants With Suicidal Behaviors, Ideations, and Acts Based on The Columbia Suicide Severity Rating Scale (C-SSRS) at Week 18
C-SSRS scale captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Number of participants with suicidal behaviors, ideations, and acts are provided. Suicidal behavior: a yes answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation: a yes answer to any one of 5 suicidal ideation questions, which includes wish to be dead, and 4 different categories of active suicidal ideation. Suicidal act: a yes answer to actual attempt or completed suicide.
Time frame: 18 weeks
Population: All randomized participants who entered the extension phase.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Duloxetine | Number of Participants With Suicidal Behaviors, Ideations, and Acts Based on The Columbia Suicide Severity Rating Scale (C-SSRS) at Week 18 | Suicidal Ideation | 1 participants |
| Duloxetine | Number of Participants With Suicidal Behaviors, Ideations, and Acts Based on The Columbia Suicide Severity Rating Scale (C-SSRS) at Week 18 | Suicidal Behavior | 0 participants |
| Duloxetine | Number of Participants With Suicidal Behaviors, Ideations, and Acts Based on The Columbia Suicide Severity Rating Scale (C-SSRS) at Week 18 | Suicidal Acts | 0 participants |
Secondary
Number of Participants With Suicidal Behaviors, Ideations, and Acts Based on The Columbia Suicide Severity Rating Scale (C-SSRS) at Week 6
C-SSRS scale captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Number of participants with suicidal behaviors, ideations, and acts are provided. Suicidal behavior: a yes answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation: a yes answer to any one of 5 suicidal ideation questions, which includes wish to be dead, and 4 different categories of active suicidal ideation. Suicidal act: a yes answer to actual attempt or completed suicide.
Time frame: 6 weeks
Population: All randomized participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Duloxetine | Number of Participants With Suicidal Behaviors, Ideations, and Acts Based on The Columbia Suicide Severity Rating Scale (C-SSRS) at Week 6 | Suicidal Ideation | 3 participants |
| Duloxetine | Number of Participants With Suicidal Behaviors, Ideations, and Acts Based on The Columbia Suicide Severity Rating Scale (C-SSRS) at Week 6 | Suicidal Behavior | 1 participants |
| Duloxetine | Number of Participants With Suicidal Behaviors, Ideations, and Acts Based on The Columbia Suicide Severity Rating Scale (C-SSRS) at Week 6 | Suicidal Acts | 1 participants |
| Placebo | Number of Participants With Suicidal Behaviors, Ideations, and Acts Based on The Columbia Suicide Severity Rating Scale (C-SSRS) at Week 6 | Suicidal Ideation | 0 participants |
| Placebo | Number of Participants With Suicidal Behaviors, Ideations, and Acts Based on The Columbia Suicide Severity Rating Scale (C-SSRS) at Week 6 | Suicidal Behavior | 0 participants |
| Placebo | Number of Participants With Suicidal Behaviors, Ideations, and Acts Based on The Columbia Suicide Severity Rating Scale (C-SSRS) at Week 6 | Suicidal Acts | 0 participants |
p-value: 0.119Fisher Exact
p-value: 0.494Fisher Exact
p-value: 0.494Fisher Exact
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) During the Acute Phase
Summary tables of serious adverse events (SAEs) and all other non-serious adverse events are located in the Reported Adverse Event Module.
Time frame: Baseline through 6 weeks
Population: All randomized participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Duloxetine | Number of Participants With Treatment Emergent Adverse Events (TEAEs) During the Acute Phase | Adverse Events (AEs) - Any Event | 70 participants |
| Duloxetine | Number of Participants With Treatment Emergent Adverse Events (TEAEs) During the Acute Phase | Serious Adverse Events (SAEs) - Any Event | 4 participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) During the Acute Phase | Adverse Events (AEs) - Any Event | 59 participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) During the Acute Phase | Serious Adverse Events (SAEs) - Any Event | 0 participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) During the Open-label Extension Phase
Summary tables of serious adverse events (SAEs) and all other non-serious adverse events are located in the Reported Adverse Event Module.
Time frame: Baseline (6 weeks) through Endpoint (18 weeks)
Population: All randomized participants in the open-label extension phase.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Duloxetine | Number of Participants With Treatment Emergent Adverse Events (TEAEs) During the Open-label Extension Phase | Adverse Events (AEs) - Any Event | 130 participants |
| Duloxetine | Number of Participants With Treatment Emergent Adverse Events (TEAEs) During the Open-label Extension Phase | Serious Adverse Events (SAEs) - Any Event | 7 participants |
Secondary
Patient Global Impressions of Improvement Scale (PGI-I) at 6 Weeks
A scale that measures the participant's perception of improvement at the time of assessment compared with the start of treatment. The score ranges from 1 (very much better) to 7 (very much worse). The Least Squares (LS) Mean Value was adjusted for investigative site and baseline severity.
Time frame: 6 weeks
Population: Number of randomized participants with at least 1 post-baseline value. Last-observation-carried-forward (LOCF) imputation was implemented.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine | Patient Global Impressions of Improvement Scale (PGI-I) at 6 Weeks | 3.27 units on a scale | Standard Error 0.11 |
| Placebo | Patient Global Impressions of Improvement Scale (PGI-I) at 6 Weeks | 3.48 units on a scale | Standard Error 0.1 |
p-value: 0.12195% CI: [-0.06, 0.49]ANOVA
Secondary
Patient Global Impressions of Improvement Scale (PGI-I) Score at 18 Weeks
A scale that measures the participant's perception of improvement at the time of assessment compared with the start of treatment. The scores range from 1 (very much better) to 7 (very much worse).
Time frame: 18 weeks
Population: Number of randomized participants who entered and had at least 1 non-missing value during extension phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine | Patient Global Impressions of Improvement Scale (PGI-I) Score at 18 Weeks | 2.67 units on a scale | Standard Deviation 1.25 |
p-value: <0.001t-test, 2 sided
Other Pre-specified
Change From Baseline in Bicarbonate (HCO3) at Week 6 (Acute Phase)
Change from baseline to acute phase endpoint in laboratory assessment for bicarbonate, HCO3.
Time frame: Baseline, 6 weeks
Population: Number of randomized participants with baseline and at least 1 post-baseline value.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine | Change From Baseline in Bicarbonate (HCO3) at Week 6 (Acute Phase) | Baseline | 22.43 milliEq/Liter | Standard Deviation 3.01 |
| Duloxetine | Change From Baseline in Bicarbonate (HCO3) at Week 6 (Acute Phase) | Change to Last Observation | 2.08 milliEq/Liter | Standard Deviation 2.91 |
| Placebo | Change From Baseline in Bicarbonate (HCO3) at Week 6 (Acute Phase) | Baseline | 23.23 milliEq/Liter | Standard Deviation 2.81 |
| Placebo | Change From Baseline in Bicarbonate (HCO3) at Week 6 (Acute Phase) | Change to Last Observation | 1.38 milliEq/Liter | Standard Deviation 2.97 |
p-value: 0.047ANOVA
Other Pre-specified
Change From Baseline in Creatinine at Week 6 (Acute Phase)
Change from baseline to acute phase endpoint in laboratory assessment of creatinine.
Time frame: Baseline, 6 weeks
Population: Number of randomized participants with baseline and at least 1 post-baseline value.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine | Change From Baseline in Creatinine at Week 6 (Acute Phase) | Baseline | 0.79 milligram/deciliter (mg/dL) | Standard Deviation 0.15 |
| Duloxetine | Change From Baseline in Creatinine at Week 6 (Acute Phase) | Change to Last Observation | -0.00 milligram/deciliter (mg/dL) | Standard Deviation 0.2 |
| Placebo | Change From Baseline in Creatinine at Week 6 (Acute Phase) | Baseline | 0.78 milligram/deciliter (mg/dL) | Standard Deviation 0.17 |
| Placebo | Change From Baseline in Creatinine at Week 6 (Acute Phase) | Change to Last Observation | 0.01 milligram/deciliter (mg/dL) | Standard Deviation 0.09 |
p-value: 0.033ANOVA
Other Pre-specified
Change From Baseline in Inorganic Phosphorus at Week 6 (Acute Phase)
Change from baseline to acute phase endpoint in laboratory assessment of inorganic phosphorus.
Time frame: Baseline, 6 weeks
Population: Number of randomized participants with baseline and at least 1 post-baseline value.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine | Change From Baseline in Inorganic Phosphorus at Week 6 (Acute Phase) | Baseline | 3.63 mg/dL | Standard Deviation 0.6 |
| Duloxetine | Change From Baseline in Inorganic Phosphorus at Week 6 (Acute Phase) | Change to Last Observation | -0.17 mg/dL | Standard Deviation 0.5 |
| Placebo | Change From Baseline in Inorganic Phosphorus at Week 6 (Acute Phase) | Baseline | 3.68 mg/dL | Standard Deviation 0.54 |
| Placebo | Change From Baseline in Inorganic Phosphorus at Week 6 (Acute Phase) | Change to Last Observation | 0.01 mg/dL | Standard Deviation 0.56 |
p-value: 0.007ANOVA
Other Pre-specified
Change From Baseline in Monocytes at Week 18 (Open-label Extension Phase)
Time frame: Baseline (6 weeks), Endpoint (18 weeks)
Population: Number of randomized participants who entered and had at least 1 non-missing value during extension phase.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine | Change From Baseline in Monocytes at Week 18 (Open-label Extension Phase) | Baseline | 0.38 Thousand/microliter | Standard Deviation 0.14 |
| Duloxetine | Change From Baseline in Monocytes at Week 18 (Open-label Extension Phase) | Change to Last Observation | 0.02 Thousand/microliter | Standard Deviation 0.14 |
p-value: 0.035Wilcoxon (Mann-Whitney)
Other Pre-specified
Change From Baseline in Sodium at Week 18 (Open-label Extension Phase)
Time frame: Baseline (6 weeks), Endpoint (18 weeks)
Population: Number of randomized participants who entered and had at least 1 non-missing value during extension phase.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine | Change From Baseline in Sodium at Week 18 (Open-label Extension Phase) | Baseline | 140.08 milliEq/Liter | Standard Deviation 3.04 |
| Duloxetine | Change From Baseline in Sodium at Week 18 (Open-label Extension Phase) | Change to Last Observation | -0.36 milliEq/Liter | Standard Deviation 2.76 |
p-value: 0.042Wilcoxon (Mann-Whitney)
Other Pre-specified
Change From Baseline in the Platelet Count at Week 6 (Acute Phase)
Change from baseline to acute phase endpoint in laboratory assessment of platelet count.
Time frame: Baseline, 6 weeks
Population: Number of randomized participants with baseline and at least 1 post-baseline value.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine | Change From Baseline in the Platelet Count at Week 6 (Acute Phase) | Baseline | 266.92 Thousand/microliter | Standard Deviation 77.19 |
| Duloxetine | Change From Baseline in the Platelet Count at Week 6 (Acute Phase) | Change to Last Observation | -2.20 Thousand/microliter | Standard Deviation 43.1 |
| Placebo | Change From Baseline in the Platelet Count at Week 6 (Acute Phase) | Baseline | 281.22 Thousand/microliter | Standard Deviation 66.78 |
| Placebo | Change From Baseline in the Platelet Count at Week 6 (Acute Phase) | Change to Last Observation | -11.00 Thousand/microliter | Standard Deviation 40.65 |
p-value: 0.034ANOVA
Other Pre-specified
Change From Baseline in Total Protein at Week 18 (Open-label Extension Phase)
Time frame: Baseline (6 weeks), Endpoint (18 weeks)
Population: Number of randomized participants who entered and had at least 1 non-missing value during extension phase.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine | Change From Baseline in Total Protein at Week 18 (Open-label Extension Phase) | Baseline | 7.04 gram/deciliter (g/dL) | Standard Deviation 0.43 |
| Duloxetine | Change From Baseline in Total Protein at Week 18 (Open-label Extension Phase) | Change to Last Observation | -0.06 gram/deciliter (g/dL) | Standard Deviation 0.36 |
p-value: 0.036Wilcoxon (Mann-Whitney)
Other Pre-specified
Change From Baseline in Uric Acid at Week 6 (Acute Phase)
Change from baseline to acute phase endpoint in laboratory assessment of uric acid.
Time frame: Baseline, 6 weeks
Population: Number of randomized participants with baseline and at least 1 post-baseline value.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine | Change From Baseline in Uric Acid at Week 6 (Acute Phase) | Baseline | 5.19 mg/dL | Standard Deviation 1.58 |
| Duloxetine | Change From Baseline in Uric Acid at Week 6 (Acute Phase) | Change to Last Observation | -0.23 mg/dL | Standard Deviation 0.67 |
| Placebo | Change From Baseline in Uric Acid at Week 6 (Acute Phase) | Baseline | 4.74 mg/dL | Standard Deviation 1.3 |
| Placebo | Change From Baseline in Uric Acid at Week 6 (Acute Phase) | Change to Last Observation | -0.04 mg/dL | Standard Deviation 0.6 |
p-value: 0.025ANOVA