Diabetic Neuropathies
Conditions
Brief summary
The purpose of the study is to determine if duloxetine can help patients with painful diabetic neuropathy.
Interventions
DRUGDuloxetine hydrochloride - 40 mg
duloxetine 40 mg taken orally every day
DRUGplacebo
placebo taken orally every day
DRUGDuloxetine hydrochloride - 60 mg
duloxetine 60 mg taken orally every day
Sponsors
Shionogi
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
20 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
* Patients with pain due to bilateral peripheral neuropathy induced by type 1 or 2 diabetes mellitus. The pain must have been present for at least 6 months and be evaluable in feet, legs, or hands. * Participants with hemoglobin A1c (HbA1c) less than or equal to 9.0 percent at Visit 1. * Participants in whom HbA1c had been measured 42-70 days before Visit 1 and subsequent HbA1c levels have been within +/- 1.0 percent of the level at Visit 1. * Participants with a mean of the 24-hour average pain severity scores (round off to a whole number) of 4 or higher, as calculated from the patient diary for 7 days immediately before Visit 2
Exclusion criteria
* Participants who have undergone renal transplant or who are currently on renal dialysis. * Participants who have a history requiring pharmacotherapy within the past year or current history of psychiatric disease, such as mania, bipolar disorder, depression, anxiety disorder, or eating disorder. * Participants with hypertension with poor control of blood pressure (systolic blood pressure greater than or equal to 180 millimeters of mercury (mmHg) or diastolic blood pressure greater than or equal to 110 mmHg * Participants with alanine transaminase (ALT) or aspartate transaminase (AST) greater than or equal to 100 Units per Liter (U/L) at Visit 1. * Participants unable to discontinue prohibited concomitant drugs or concomitant therapies after Visit 1.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline at Week 12 in Average Pain Severity Rating Using Diaries for the Combined Duloxetine Arms (40 mg + 60 mg) | Baseline, 12 weeks | Average pain severity was measured using an 11-point numerical rating scale, collected by diaries and expressed as weekly mean. The scale is a self-reported instrument that measures the severity of pain based on the average pain over the past 24-hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline at Week 12 in Worst Pain Severity Score and Night Pain Severity Score Using Diaries for the Combined Duloxetine Arms (40 mg + 60 mg) | Baseline, 12 weeks | Pain severity for worst pain and night pain as measured by an 11-point numerical rating scale, collected by diaries and expressed as weekly means. A self-reported scale that measures the severity of pain based on the worst pain and night pain experienced over the past 24-hours. The worst pain and night pain severity scores each range from 0 (no pain) to 10 (pain as severe as you can imagine). |
| Change From Baseline at Week 12 in Worst Pain Severity Score and Night Pain Severity Score Using Diaries | Baseline, Week 12 | Pain severity for worst pain and night pain as measured by an 11-point numerical rating scale, collected by diaries and expressed as weekly means. A self-reported scale that measures the severity of pain based on the worst pain and night pain experienced over the past 24-hours. The worst pain and night pain severity scores each range from 0 (no pain) to 10 (pain as severe as you can imagine). |
| Patient Global Impression of Improvement Scale at Week 12 in Combined Duloxetine Arms (40 mg + 60 mg) | Week 12 | A scale that measures the patient'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). |
| Patient Global Impression of Improvement Scale at Week 12 | Week 12 | A scale that measures the patient'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). |
| Change From Baseline in Brief Pain Inventory Severity Scores at Week 12 for the Combined Duloxetine Arms (40 mg + 60 mg) | Baseline, Week 12 | A self-reported scale that measures the severity of pain. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). There are 4 questions assessing worst pain, least pain, and average pain in the past 24 hours, and the pain right now. Each question has a total range of scores from 0 to 10. |
| Change From Baseline at Week 12 in Average Pain Severity Rating Score Using Diaries | Baseline, 12 weeks | Average pain severity was measured using an 11-point numerical rating scale, collected by diaries and expressed as weekly mean. The scale is a self-reported instrument that measures the severity of pain based on the average pain over the past 24-hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). |
| Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 for the Combined Duloxetine Arms (40 mg + 60 mg) | Baseline, Week 12 | The Interference scores range from 0 (does not interfere) to 10 (completely interferes). There are 7 questions assessing the interference of pain in the past 24 hours for general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. Each question has a total range of scores from 0 to 10. |
| Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 | Baseline, Week 12 | The Interference scores range from 0 (does not interfere) to 10 (completely interferes). There are 7 questions assessing the interference of pain in the past 24 hours for general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. Each question has a total range of scores from 0 to 10. |
| Change From Baseline in Beck Depression Inventory-II (BDI-II) Total Score at Week 12 for the Combined Duloxetine Arms (40 mg + 60 mg) | Baseline, Week 12 | A 21-item, patient-completed questionnaire to assess characteristics of depression. Each of the 21 items corresponding to a symptom of depression is summed to give a single score. There is a four-point scale for each item ranging from 0 to 3. Total score ranges from 0 (no depression) to 63 (severe depression). |
| Change From Baseline in Beck Depression Inventory-II (BDI-II) Total Score at Week 12 | Baseline, Week 12 | A 21-item, patient-completed questionnaire to assess characteristics of depression. Each of the 21 items corresponding to a symptom of depression is summed to give a single score. There is a four-point scale for each item ranging from 0 to 3. Total score ranges from 0 (no depression) to 63 (severe depression). |
| Change From Baseline in Brief Pain Inventory Severity Scores at Week 12 | Baseline, Week 12 | A self-reported scale that measures the severity of pain. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). There are 4 questions assessing worst pain, least pain, and average pain in the past 24 hours, and the pain right now. Each question has a total range of scores from 0 to 10. |
Countries
Japan
Participant flow
Pre-assignment details
Full Analysis Set Population consisted of all randomized patients who had at least one post-baseline measure of the primary efficacy variable.
Participants by arm
| Arm | Count |
|---|---|
| Placebo placebo comparator taken orally every day | 167 |
| Duloxetine 40 mg Duloxetine 40 milligrams (mg) taken orally every day | 85 |
| Duloxetine 60 mg Duloxetine 60 milligrams (mg) taken orally every day | 86 |
| Total | 338 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 9 | 9 | 10 |
| Overall Study | Entry Criteria Not Met | 1 | 1 | 0 |
| Overall Study | Lack of Efficacy | 2 | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
| Overall Study | Reason Not Specified | 3 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 2 | 1 |
Baseline characteristics
| Characteristic | Duloxetine 40 mg | Total | Placebo | Duloxetine 60 mg |
|---|---|---|---|---|
| Age Continuous | 62.1 years STANDARD_DEVIATION 9.3 | 60.8 years STANDARD_DEVIATION 10 | 60.8 years STANDARD_DEVIATION 9.2 | 59.7 years STANDARD_DEVIATION 12.1 |
| Beck Depression Inventory-II (BDI-II) | 9.4 units on a scale STANDARD_DEVIATION 8.8 | 9.1 units on a scale STANDARD_DEVIATION 7.4 | 8.8 units on a scale STANDARD_DEVIATION 6.8 | 9.4 units on a scale STANDARD_DEVIATION 7.2 |
| Body Mass Index (BMI) | 23.27 kilograms/square meters (kg/m^2) STANDARD_DEVIATION 3.67 | 23.82 kilograms/square meters (kg/m^2) STANDARD_DEVIATION 3.65 | 23.90 kilograms/square meters (kg/m^2) STANDARD_DEVIATION 3.7 | 24.20 kilograms/square meters (kg/m^2) STANDARD_DEVIATION 3.5 |
| Brief Pain Inventory (BPI) Interference Scores Average of Interference Scores | 3.88 units on a scale STANDARD_DEVIATION 2.25 | 3.87 units on a scale STANDARD_DEVIATION 2.17 | 3.75 units on a scale STANDARD_DEVIATION 2.15 | 4.09 units on a scale STANDARD_DEVIATION 2.13 |
| Brief Pain Inventory (BPI) Interference Scores Enjoyment of Life | 3.7 units on a scale STANDARD_DEVIATION 2.7 | 3.7 units on a scale STANDARD_DEVIATION 2.6 | 3.5 units on a scale STANDARD_DEVIATION 2.5 | 4.0 units on a scale STANDARD_DEVIATION 2.5 |
| Brief Pain Inventory (BPI) Interference Scores General Activity | 4.5 units on a scale STANDARD_DEVIATION 2.7 | 4.5 units on a scale STANDARD_DEVIATION 2.5 | 4.4 units on a scale STANDARD_DEVIATION 2.4 | 4.5 units on a scale STANDARD_DEVIATION 2.4 |
| Brief Pain Inventory (BPI) Interference Scores Mood | 3.9 units on a scale STANDARD_DEVIATION 2.5 | 4.1 units on a scale STANDARD_DEVIATION 2.5 | 4.2 units on a scale STANDARD_DEVIATION 2.4 | 4.2 units on a scale STANDARD_DEVIATION 2.5 |
| Brief Pain Inventory (BPI) Interference Scores Normal Work | 3.9 units on a scale STANDARD_DEVIATION 2.6 | 3.9 units on a scale STANDARD_DEVIATION 2.6 | 3.7 units on a scale STANDARD_DEVIATION 2.7 | 4.3 units on a scale STANDARD_DEVIATION 2.5 |
| Brief Pain Inventory (BPI) Interference Scores Relation to People | 2.7 units on a scale STANDARD_DEVIATION 2.7 | 2.7 units on a scale STANDARD_DEVIATION 2.5 | 2.6 units on a scale STANDARD_DEVIATION 2.5 | 2.9 units on a scale STANDARD_DEVIATION 2.4 |
| Brief Pain Inventory (BPI) Interference Scores Sleep | 4.0 units on a scale STANDARD_DEVIATION 2.8 | 4.0 units on a scale STANDARD_DEVIATION 2.7 | 3.9 units on a scale STANDARD_DEVIATION 2.7 | 4.3 units on a scale STANDARD_DEVIATION 2.7 |
| Brief Pain Inventory (BPI) Interference Scores Walking Ability | 4.4 units on a scale STANDARD_DEVIATION 2.8 | 4.2 units on a scale STANDARD_DEVIATION 2.6 | 4.0 units on a scale STANDARD_DEVIATION 2.6 | 4.3 units on a scale STANDARD_DEVIATION 2.5 |
| Brief Pain Inventory (BPI) Severity Scores Average Pain | 5.6 units on a scale STANDARD_DEVIATION 1.3 | 5.6 units on a scale STANDARD_DEVIATION 1.3 | 5.6 units on a scale STANDARD_DEVIATION 1.3 | 5.7 units on a scale STANDARD_DEVIATION 1.3 |
| Brief Pain Inventory (BPI) Severity Scores Least Pain | 4.0 units on a scale STANDARD_DEVIATION 1.8 | 4.1 units on a scale STANDARD_DEVIATION 1.8 | 4.1 units on a scale STANDARD_DEVIATION 1.8 | 4.2 units on a scale STANDARD_DEVIATION 1.6 |
| Brief Pain Inventory (BPI) Severity Scores Pain Right Now | 5.2 units on a scale STANDARD_DEVIATION 1.8 | 5.2 units on a scale STANDARD_DEVIATION 1.7 | 5.1 units on a scale STANDARD_DEVIATION 1.7 | 5.3 units on a scale STANDARD_DEVIATION 1.4 |
| Brief Pain Inventory (BPI) Severity Scores Worst Pain | 6.5 units on a scale STANDARD_DEVIATION 1.4 | 6.6 units on a scale STANDARD_DEVIATION 1.4 | 6.7 units on a scale STANDARD_DEVIATION 1.4 | 6.6 units on a scale STANDARD_DEVIATION 1.5 |
| Duration of Diabetes >= 10 years | 47 participants | 200 participants | 97 participants | 56 participants |
| Duration of Diabetes 5 - 10 years | 18 participants | 64 participants | 32 participants | 14 participants |
| Duration of Diabetes <5 years | 20 participants | 69 participants | 33 participants | 16 participants |
| Duration of Diabetes Unknown | 0 participants | 5 participants | 5 participants | 0 participants |
| Duration of Diabetic Neuropathy | 4.58 years STANDARD_DEVIATION 3.9 | 4.29 years STANDARD_DEVIATION 4.11 | 4.21 years STANDARD_DEVIATION 4.44 | 4.16 years STANDARD_DEVIATION 3.67 |
| Height | 163.63 centimeters (cm) STANDARD_DEVIATION 8.78 | 163.98 centimeters (cm) STANDARD_DEVIATION 8.34 | 164.13 centimeters (cm) STANDARD_DEVIATION 8.65 | 164.02 centimeters (cm) STANDARD_DEVIATION 7.32 |
| Race/Ethnicity, Customized Japanese | 85 participants | 338 participants | 167 participants | 86 participants |
| Region of Enrollment Japan | 85 participants | 338 participants | 167 participants | 86 participants |
| Sex: Female, Male Female | 20 Participants | 82 Participants | 38 Participants | 24 Participants |
| Sex: Female, Male Male | 65 Participants | 256 Participants | 129 Participants | 62 Participants |
| Type of Diabetes Type I | 5 participants | 17 participants | 8 participants | 4 participants |
| Type of Diabetes Type II | 80 participants | 321 participants | 159 participants | 82 participants |
| Weekly Means of 24-Hour Average Pain, Worst Pain, and Night Pain Diary Scores Average Pain Score | 5.79 units on a scale STANDARD_DEVIATION 1.23 | 5.78 units on a scale STANDARD_DEVIATION 1.18 | 5.78 units on a scale STANDARD_DEVIATION 1.17 | 5.76 units on a scale STANDARD_DEVIATION 1.17 |
| Weekly Means of 24-Hour Average Pain, Worst Pain, and Night Pain Diary Scores Night Pain Score | 5.55 units on a scale STANDARD_DEVIATION 1.64 | 5.56 units on a scale STANDARD_DEVIATION 1.54 | 5.5 units on a scale STANDARD_DEVIATION 1.49 | 5.69 units on a scale STANDARD_DEVIATION 1.54 |
| Weekly Means of 24-Hour Average Pain, Worst Pain, and Night Pain Diary Scores Worst Pain Score | 6.54 units on a scale STANDARD_DEVIATION 1.33 | 6.62 units on a scale STANDARD_DEVIATION 1.29 | 6.66 units on a scale STANDARD_DEVIATION 1.25 | 6.61 units on a scale STANDARD_DEVIATION 1.33 |
| Weight | 62.72 kilograms (kg) STANDARD_DEVIATION 13.35 | 64.21 kilograms (kg) STANDARD_DEVIATION 11.9 | 64.52 kilograms (kg) STANDARD_DEVIATION 11.93 | 65.08 kilograms (kg) STANDARD_DEVIATION 10.23 |
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 | 121 / 167 | 71 / 85 | 73 / 86 |
| serious Total, serious adverse events | 6 / 167 | 3 / 85 | 2 / 86 |
Outcome results
Primary
Change From Baseline at Week 12 in Average Pain Severity Rating Using Diaries for the Combined Duloxetine Arms (40 mg + 60 mg)
Average pain severity was measured using an 11-point numerical rating scale, collected by diaries and expressed as weekly mean. The scale is a self-reported instrument that measures the severity of pain based on the average pain over the past 24-hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine).
Time frame: Baseline, 12 weeks
Population: Patients in the Full Analysis Set Population who had a post-baseline measurement in the variable being presented.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline at Week 12 in Average Pain Severity Rating Using Diaries for the Combined Duloxetine Arms (40 mg + 60 mg) | -1.61 units on a scale | Standard Error 0.18 |
| Duloxetine 40 mg and 60 mg Combined | Change From Baseline at Week 12 in Average Pain Severity Rating Using Diaries for the Combined Duloxetine Arms (40 mg + 60 mg) | -2.47 units on a scale | Standard Error 0.18 |
Comparison: The primary objective and primary efficacy analysis for the study was the analysis between the combined duloxetine arms and placebo.p-value: <0.000195% CI: [-1.17, -0.56]Mixed Models Analysis
Secondary
Change From Baseline at Week 12 in Average Pain Severity Rating Score Using Diaries
Average pain severity was measured using an 11-point numerical rating scale, collected by diaries and expressed as weekly mean. The scale is a self-reported instrument that measures the severity of pain based on the average pain over the past 24-hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine).
Time frame: Baseline, 12 weeks
Population: Patients in the Full Analysis Set Population who had a post-baseline measurement in the variable being presented.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline at Week 12 in Average Pain Severity Rating Score Using Diaries | -1.61 units on a scale | Standard Error 0.19 |
| Duloxetine 40 mg and 60 mg Combined | Change From Baseline at Week 12 in Average Pain Severity Rating Score Using Diaries | -2.41 units on a scale | Standard Error 0.21 |
| Duloxetine 60 mg | Change From Baseline at Week 12 in Average Pain Severity Rating Score Using Diaries | -2.53 units on a scale | Standard Error 0.21 |
Secondary
Change From Baseline at Week 12 in Worst Pain Severity Score and Night Pain Severity Score Using Diaries
Pain severity for worst pain and night pain as measured by an 11-point numerical rating scale, collected by diaries and expressed as weekly means. A self-reported scale that measures the severity of pain based on the worst pain and night pain experienced over the past 24-hours. The worst pain and night pain severity scores each range from 0 (no pain) to 10 (pain as severe as you can imagine).
Time frame: Baseline, Week 12
Population: Patients in the Full Analysis Set Population who had a post-baseline measurement in the variable being presented.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline at Week 12 in Worst Pain Severity Score and Night Pain Severity Score Using Diaries | Worst Pain | -1.55 units on a scale | Standard Error 0.19 |
| Placebo | Change From Baseline at Week 12 in Worst Pain Severity Score and Night Pain Severity Score Using Diaries | Night Pain | -1.56 units on a scale | Standard Error 0.19 |
| Duloxetine 40 mg and 60 mg Combined | Change From Baseline at Week 12 in Worst Pain Severity Score and Night Pain Severity Score Using Diaries | Worst Pain | -2.42 units on a scale | Standard Error 0.22 |
| Duloxetine 40 mg and 60 mg Combined | Change From Baseline at Week 12 in Worst Pain Severity Score and Night Pain Severity Score Using Diaries | Night Pain | -2.33 units on a scale | Standard Error 0.22 |
| Duloxetine 60 mg | Change From Baseline at Week 12 in Worst Pain Severity Score and Night Pain Severity Score Using Diaries | Worst Pain | -2.59 units on a scale | Standard Error 0.22 |
| Duloxetine 60 mg | Change From Baseline at Week 12 in Worst Pain Severity Score and Night Pain Severity Score Using Diaries | Night Pain | -2.45 units on a scale | Standard Error 0.23 |
Comparison: Worst Pain analysis95% CI: [-1.26, -0.49]Mixed Models Analysis
Comparison: Worst Pain analysis95% CI: [-1.43, -0.66]Mixed Models Analysis
Comparison: Night Pain analysis95% CI: [-1.17, -0.39]Mixed Models Analysis
Comparison: Night Pain analysis95% CI: [-1.28, -0.5]Mixed Models Analysis
Secondary
Change From Baseline at Week 12 in Worst Pain Severity Score and Night Pain Severity Score Using Diaries for the Combined Duloxetine Arms (40 mg + 60 mg)
Pain severity for worst pain and night pain as measured by an 11-point numerical rating scale, collected by diaries and expressed as weekly means. A self-reported scale that measures the severity of pain based on the worst pain and night pain experienced over the past 24-hours. The worst pain and night pain severity scores each range from 0 (no pain) to 10 (pain as severe as you can imagine).
Time frame: Baseline, 12 weeks
Population: Patients in the Full Analysis Set Population who had a post-baseline measurement in the variable being presented.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline at Week 12 in Worst Pain Severity Score and Night Pain Severity Score Using Diaries for the Combined Duloxetine Arms (40 mg + 60 mg) | Worst Pain | -1.55 units on a scale | Standard Error 0.19 |
| Placebo | Change From Baseline at Week 12 in Worst Pain Severity Score and Night Pain Severity Score Using Diaries for the Combined Duloxetine Arms (40 mg + 60 mg) | Night Pain | -1.56 units on a scale | Standard Error 0.19 |
| Duloxetine 40 mg and 60 mg Combined | Change From Baseline at Week 12 in Worst Pain Severity Score and Night Pain Severity Score Using Diaries for the Combined Duloxetine Arms (40 mg + 60 mg) | Worst Pain | -2.51 units on a scale | Standard Error 0.19 |
| Duloxetine 40 mg and 60 mg Combined | Change From Baseline at Week 12 in Worst Pain Severity Score and Night Pain Severity Score Using Diaries for the Combined Duloxetine Arms (40 mg + 60 mg) | Night Pain | -2.39 units on a scale | Standard Error 0.19 |
p-value: <0.000195% CI: [-1.27, -0.64]Mixed Models Analysis
p-value: <0.000195% CI: [-1.15, -0.51]Mixed Models Analysis
Secondary
Change From Baseline in Beck Depression Inventory-II (BDI-II) Total Score at Week 12
A 21-item, patient-completed questionnaire to assess characteristics of depression. Each of the 21 items corresponding to a symptom of depression is summed to give a single score. There is a four-point scale for each item ranging from 0 to 3. Total score ranges from 0 (no depression) to 63 (severe depression).
Time frame: Baseline, Week 12
Population: Patients in the Full Analysis Set Population who had a post-baseline measurement in the variable being presented.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Beck Depression Inventory-II (BDI-II) Total Score at Week 12 | -3.28 units on a scale | Standard Error 0.65 |
| Duloxetine 40 mg and 60 mg Combined | Change From Baseline in Beck Depression Inventory-II (BDI-II) Total Score at Week 12 | -2.94 units on a scale | Standard Error 0.76 |
| Duloxetine 60 mg | Change From Baseline in Beck Depression Inventory-II (BDI-II) Total Score at Week 12 | -3.83 units on a scale | Standard Error 0.77 |
95% CI: [-1.03, 1.71]Mixed Models Analysis
95% CI: [-1.92, 0.81]Mixed Models Analysis
Secondary
Change From Baseline in Beck Depression Inventory-II (BDI-II) Total Score at Week 12 for the Combined Duloxetine Arms (40 mg + 60 mg)
A 21-item, patient-completed questionnaire to assess characteristics of depression. Each of the 21 items corresponding to a symptom of depression is summed to give a single score. There is a four-point scale for each item ranging from 0 to 3. Total score ranges from 0 (no depression) to 63 (severe depression).
Time frame: Baseline, Week 12
Population: Patients in the Full Analysis Set Population who had a post-baseline measurement in the variable being presented.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Beck Depression Inventory-II (BDI-II) Total Score at Week 12 for the Combined Duloxetine Arms (40 mg + 60 mg) | -3.27 units on a scale | Standard Error 0.64 |
| Duloxetine 40 mg and 60 mg Combined | Change From Baseline in Beck Depression Inventory-II (BDI-II) Total Score at Week 12 for the Combined Duloxetine Arms (40 mg + 60 mg) | -3.37 units on a scale | Standard Error 0.64 |
p-value: 0.851795% CI: [-1.22, 1.01]Mixed Models Analysis
Secondary
Change From Baseline in Brief Pain Inventory Interference Scores at Week 12
The Interference scores range from 0 (does not interfere) to 10 (completely interferes). There are 7 questions assessing the interference of pain in the past 24 hours for general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. Each question has a total range of scores from 0 to 10.
Time frame: Baseline, Week 12
Population: Patients in the Full Analysis Set Population who had a post-baseline measurement in the variable being presented.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 | General Activity | -1.88 units on a scale | Standard Error 0.24 |
| Placebo | Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 | Mood | -1.91 units on a scale | Standard Error 0.24 |
| Placebo | Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 | Walking Ability | -1.82 units on a scale | Standard Error 0.23 |
| Placebo | Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 | Normal Work | -1.49 units on a scale | Standard Error 0.23 |
| Placebo | Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 | Relation to People | -0.77 units on a scale | Standard Error 0.23 |
| Placebo | Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 | Sleep | -1.69 units on a scale | Standard Error 0.24 |
| Placebo | Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 | Enjoyment of Life | -1.59 units on a scale | Standard Error 0.23 |
| Placebo | Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 | Average of Interference Scores | -1.56 units on a scale | Standard Error 0.2 |
| Duloxetine 40 mg and 60 mg Combined | Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 | Walking Ability | -2.32 units on a scale | Standard Error 0.28 |
| Duloxetine 40 mg and 60 mg Combined | Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 | Enjoyment of Life | -1.96 units on a scale | Standard Error 0.28 |
| Duloxetine 40 mg and 60 mg Combined | Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 | Normal Work | -1.84 units on a scale | Standard Error 0.28 |
| Duloxetine 40 mg and 60 mg Combined | Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 | Relation to People | -1.16 units on a scale | Standard Error 0.27 |
| Duloxetine 40 mg and 60 mg Combined | Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 | Sleep | -2.26 units on a scale | Standard Error 0.29 |
| Duloxetine 40 mg and 60 mg Combined | Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 | General Activity | -2.48 units on a scale | Standard Error 0.29 |
| Duloxetine 40 mg and 60 mg Combined | Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 | Mood | -2.18 units on a scale | Standard Error 0.29 |
| Duloxetine 40 mg and 60 mg Combined | Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 | Average of Interference Scores | -2 units on a scale | Standard Error 0.24 |
| Duloxetine 60 mg | Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 | Walking Ability | -2.31 units on a scale | Standard Error 0.28 |
| Duloxetine 60 mg | Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 | Mood | -2.39 units on a scale | Standard Error 0.29 |
| Duloxetine 60 mg | Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 | General Activity | -2.1 units on a scale | Standard Error 0.29 |
| Duloxetine 60 mg | Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 | Normal Work | -1.9 units on a scale | Standard Error 0.28 |
| Duloxetine 60 mg | Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 | Enjoyment of Life | -2.35 units on a scale | Standard Error 0.28 |
| Duloxetine 60 mg | Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 | Sleep | -2.05 units on a scale | Standard Error 0.29 |
| Duloxetine 60 mg | Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 | Relation to People | -1.49 units on a scale | Standard Error 0.27 |
| Duloxetine 60 mg | Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 | Average of Interference Scores | -2.08 units on a scale | Standard Error 0.24 |
Comparison: General Activity score analysis95% CI: [-1.14, -0.06]Mixed Models Analysis
Comparison: General Activity score analysis95% CI: [-0.77, 0.32]Mixed Models Analysis
Comparison: Mood score analysis95% CI: [-0.8, 0.27]Mixed Models Analysis
Comparison: Mood score analysis95% CI: [-1.01, 0.05]Mixed Models Analysis
Comparison: Walking Ability score analysis95% CI: [-1.02, 0.02]Mixed Models Analysis
Comparison: Walking Ability score analysis95% CI: [-1.01, 0.03]Mixed Models Analysis
Comparison: Normal Work score analysis95% CI: [-0.86, 0.16]Mixed Models Analysis
Comparison: Normal Work score analysis95% CI: [-0.92, 0.11]Mixed Models Analysis
Comparison: Relation to People score analysis95% CI: [-0.89, 0.11]Mixed Models Analysis
Comparison: Relation to People score analysis95% CI: [-1.21, -0.22]Mixed Models Analysis
Comparison: Sleep score analysis95% CI: [-1.11, -0.03]Mixed Models Analysis
Comparison: Sleep score analysis95% CI: [-0.9, 0.18]Mixed Models Analysis
Comparison: Enjoyment of Life score analysis95% CI: [-0.88, 0.15]Mixed Models Analysis
Comparison: Enjoyment of Life score analysis95% CI: [-1.27, -0.24]Mixed Models Analysis
Comparison: Average of Interference scores analysis95% CI: [-0.9, 0]Mixed Models Analysis
Comparison: Average of Interference scores analysis95% CI: [-0.97, -0.07]Mixed Models Analysis
Secondary
Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 for the Combined Duloxetine Arms (40 mg + 60 mg)
The Interference scores range from 0 (does not interfere) to 10 (completely interferes). There are 7 questions assessing the interference of pain in the past 24 hours for general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. Each question has a total range of scores from 0 to 10.
Time frame: Baseline, Week 12
Population: Patients in the Full Analysis Set Population who had a post-baseline measurement in the variable being presented.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 for the Combined Duloxetine Arms (40 mg + 60 mg) | General Activity | -1.88 units on a scale | Standard Error 0.24 |
| Placebo | Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 for the Combined Duloxetine Arms (40 mg + 60 mg) | Mood | -1.91 units on a scale | Standard Error 0.24 |
| Placebo | Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 for the Combined Duloxetine Arms (40 mg + 60 mg) | Walking Ability | -1.82 units on a scale | Standard Error 0.23 |
| Placebo | Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 for the Combined Duloxetine Arms (40 mg + 60 mg) | Normal Work | -1.49 units on a scale | Standard Error 0.23 |
| Placebo | Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 for the Combined Duloxetine Arms (40 mg + 60 mg) | Relation to People | -0.77 units on a scale | Standard Error 0.23 |
| Placebo | Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 for the Combined Duloxetine Arms (40 mg + 60 mg) | Sleep | -1.69 units on a scale | Standard Error 0.24 |
| Placebo | Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 for the Combined Duloxetine Arms (40 mg + 60 mg) | Enjoyment of Life | -1.59 units on a scale | Standard Error 0.23 |
| Placebo | Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 for the Combined Duloxetine Arms (40 mg + 60 mg) | Average of Interference Scores | -1.56 units on a scale | Standard Error 0.2 |
| Duloxetine 40 mg and 60 mg Combined | Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 for the Combined Duloxetine Arms (40 mg + 60 mg) | Average of Interference Scores | -2.04 units on a scale | Standard Error 0.2 |
| Duloxetine 40 mg and 60 mg Combined | Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 for the Combined Duloxetine Arms (40 mg + 60 mg) | General Activity | -2.29 units on a scale | Standard Error 0.24 |
| Duloxetine 40 mg and 60 mg Combined | Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 for the Combined Duloxetine Arms (40 mg + 60 mg) | Relation to People | -1.32 units on a scale | Standard Error 0.23 |
| Duloxetine 40 mg and 60 mg Combined | Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 for the Combined Duloxetine Arms (40 mg + 60 mg) | Mood | -2.28 units on a scale | Standard Error 0.24 |
| Duloxetine 40 mg and 60 mg Combined | Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 for the Combined Duloxetine Arms (40 mg + 60 mg) | Enjoyment of Life | -2.15 units on a scale | Standard Error 0.23 |
| Duloxetine 40 mg and 60 mg Combined | Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 for the Combined Duloxetine Arms (40 mg + 60 mg) | Walking Ability | -2.31 units on a scale | Standard Error 0.23 |
| Duloxetine 40 mg and 60 mg Combined | Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 for the Combined Duloxetine Arms (40 mg + 60 mg) | Sleep | -2.15 units on a scale | Standard Error 0.24 |
| Duloxetine 40 mg and 60 mg Combined | Change From Baseline in Brief Pain Inventory Interference Scores at Week 12 for the Combined Duloxetine Arms (40 mg + 60 mg) | Normal Work | -1.86 units on a scale | Standard Error 0.23 |
p-value: 0.067695% CI: [-0.85, 0.03]Mixed Models Analysis
p-value: 0.093395% CI: [-0.8, 0.06]Mixed Models Analysis
p-value: 0.022895% CI: [-0.91, -0.07]Mixed Models Analysis
p-value: 0.078395% CI: [-0.8, 0.04]Mixed Models Analysis
p-value: 0.007695% CI: [-0.96, -0.15]Mixed Models Analysis
p-value: 0.037895% CI: [-0.9, -0.03]Mixed Models Analysis
p-value: 0.008995% CI: [-0.98, -0.14]Mixed Models Analysis
p-value: 0.009595% CI: [-0.85, -0.12]Mixed Models Analysis
Secondary
Change From Baseline in Brief Pain Inventory Severity Scores at Week 12
A self-reported scale that measures the severity of pain. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). There are 4 questions assessing worst pain, least pain, and average pain in the past 24 hours, and the pain right now. Each question has a total range of scores from 0 to 10.
Time frame: Baseline, Week 12
Population: Patients in the Full Analysis Set Population who had a post-baseline measurement in the variable being presented.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Brief Pain Inventory Severity Scores at Week 12 | Worst Pain | -1.62 units on a scale | Standard Error 0.21 |
| Placebo | Change From Baseline in Brief Pain Inventory Severity Scores at Week 12 | Least Pain | -1.13 units on a scale | Standard Error 0.21 |
| Placebo | Change From Baseline in Brief Pain Inventory Severity Scores at Week 12 | Average Pain | -1.55 units on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline in Brief Pain Inventory Severity Scores at Week 12 | Pain Right Now | -1.67 units on a scale | Standard Error 0.22 |
| Duloxetine 40 mg and 60 mg Combined | Change From Baseline in Brief Pain Inventory Severity Scores at Week 12 | Pain Right Now | -2.55 units on a scale | Standard Error 0.25 |
| Duloxetine 40 mg and 60 mg Combined | Change From Baseline in Brief Pain Inventory Severity Scores at Week 12 | Worst Pain | -2.51 units on a scale | Standard Error 0.25 |
| Duloxetine 40 mg and 60 mg Combined | Change From Baseline in Brief Pain Inventory Severity Scores at Week 12 | Average Pain | -2.53 units on a scale | Standard Error 0.23 |
| Duloxetine 40 mg and 60 mg Combined | Change From Baseline in Brief Pain Inventory Severity Scores at Week 12 | Least Pain | -1.92 units on a scale | Standard Error 0.25 |
| Duloxetine 60 mg | Change From Baseline in Brief Pain Inventory Severity Scores at Week 12 | Pain Right Now | -2.62 units on a scale | Standard Error 0.26 |
| Duloxetine 60 mg | Change From Baseline in Brief Pain Inventory Severity Scores at Week 12 | Least Pain | -2.04 units on a scale | Standard Error 0.25 |
| Duloxetine 60 mg | Change From Baseline in Brief Pain Inventory Severity Scores at Week 12 | Average Pain | -2.56 units on a scale | Standard Error 0.23 |
| Duloxetine 60 mg | Change From Baseline in Brief Pain Inventory Severity Scores at Week 12 | Worst Pain | -2.68 units on a scale | Standard Error 0.25 |
Comparison: Pain Right Now Score analysis95% CI: [-1.35, -0.41]Mixed Models Analysis
Comparison: Worst Pain Score analysis95% CI: [-1.34, -0.44]Mixed Models Analysis
Comparison: Worst Pain Score analysis95% CI: [-1.51, -0.62]Mixed Models Analysis
Comparison: Least Pain Score analysis95% CI: [-1.23, -0.33]Mixed Models Analysis
Comparison: Least Pain Score analysis95% CI: [-1.36, -0.46]Mixed Models Analysis
Comparison: Average Pain Score analysis95% CI: [-1.39, -0.58]Mixed Models Analysis
Comparison: Average Pain Score analysis95% CI: [-1.41, -0.61]Mixed Models Analysis
Comparison: Pain Right Now Score analysis95% CI: [-1.41, -0.48]Mixed Models Analysis
Secondary
Change From Baseline in Brief Pain Inventory Severity Scores at Week 12 for the Combined Duloxetine Arms (40 mg + 60 mg)
A self-reported scale that measures the severity of pain. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). There are 4 questions assessing worst pain, least pain, and average pain in the past 24 hours, and the pain right now. Each question has a total range of scores from 0 to 10.
Time frame: Baseline, Week 12
Population: Patients in the Full Analysis Set Population who had a post-baseline measurement in the variable being presented.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Brief Pain Inventory Severity Scores at Week 12 for the Combined Duloxetine Arms (40 mg + 60 mg) | Worst Pain | -1.62 units on a scale | Standard Error 0.21 |
| Placebo | Change From Baseline in Brief Pain Inventory Severity Scores at Week 12 for the Combined Duloxetine Arms (40 mg + 60 mg) | Least Pain | -1.13 units on a scale | Standard Error 0.21 |
| Placebo | Change From Baseline in Brief Pain Inventory Severity Scores at Week 12 for the Combined Duloxetine Arms (40 mg + 60 mg) | Average Pain | -1.54 units on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline in Brief Pain Inventory Severity Scores at Week 12 for the Combined Duloxetine Arms (40 mg + 60 mg) | Pain Right Now | -1.67 units on a scale | Standard Error 0.22 |
| Duloxetine 40 mg and 60 mg Combined | Change From Baseline in Brief Pain Inventory Severity Scores at Week 12 for the Combined Duloxetine Arms (40 mg + 60 mg) | Pain Right Now | -2.59 units on a scale | Standard Error 0.22 |
| Duloxetine 40 mg and 60 mg Combined | Change From Baseline in Brief Pain Inventory Severity Scores at Week 12 for the Combined Duloxetine Arms (40 mg + 60 mg) | Worst Pain | -2.59 units on a scale | Standard Error 0.21 |
| Duloxetine 40 mg and 60 mg Combined | Change From Baseline in Brief Pain Inventory Severity Scores at Week 12 for the Combined Duloxetine Arms (40 mg + 60 mg) | Average Pain | -2.54 units on a scale | Standard Error 0.2 |
| Duloxetine 40 mg and 60 mg Combined | Change From Baseline in Brief Pain Inventory Severity Scores at Week 12 for the Combined Duloxetine Arms (40 mg + 60 mg) | Least Pain | -1.98 units on a scale | Standard Error 0.21 |
p-value: <0.000195% CI: [-1.34, -0.61]Mixed Models Analysis
p-value: <0.000195% CI: [-1.21, -0.48]Mixed Models Analysis
p-value: <0.000195% CI: [-1.33, -0.67]Mixed Models Analysis
p-value: <0.000195% CI: [-1.29, -0.54]Mixed Models Analysis
Secondary
Patient Global Impression of Improvement Scale at Week 12
A scale that measures the patient'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).
Time frame: Week 12
Population: Patients in the Full Analysis Set Population who had a post-baseline measurement in the variable being presented.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Patient Global Impression of Improvement Scale at Week 12 | 3.18 units on a scale | Standard Error 0.12 |
| Duloxetine 40 mg and 60 mg Combined | Patient Global Impression of Improvement Scale at Week 12 | 2.53 units on a scale | Standard Error 0.14 |
| Duloxetine 60 mg | Patient Global Impression of Improvement Scale at Week 12 | 2.52 units on a scale | Standard Error 0.14 |
95% CI: [-0.9, -0.39]Mixed Models Analysis
95% CI: [-0.91, -0.4]Mixed Models Analysis
Secondary
Patient Global Impression of Improvement Scale at Week 12 in Combined Duloxetine Arms (40 mg + 60 mg)
A scale that measures the patient'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).
Time frame: Week 12
Population: Patients in the Full Analysis Set Population who had a post-baseline measurement in the variable being presented.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Patient Global Impression of Improvement Scale at Week 12 in Combined Duloxetine Arms (40 mg + 60 mg) | 3.18 units on a scale | Standard Error 0.12 |
| Duloxetine 40 mg and 60 mg Combined | Patient Global Impression of Improvement Scale at Week 12 in Combined Duloxetine Arms (40 mg + 60 mg) | 2.53 units on a scale | Standard Error 0.12 |
p-value: <0.000195% CI: [-0.85, -0.44]Mixed Models Analysis