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| ID | Type | Description | Link |
|---|---|---|---|
| F1J-MC-HMGV | Other Identifier | Eli Lilly and Company |
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The purpose of this trial is to assess the efficacy of duloxetine 60 milligrams (mg) once daily (QD) compared with placebo, on the change in pain severity from baseline to 12 weeks as measured by the weekly mean of the daily pain scores recorded in the participant's diary in participants with diabetic peripheral neuropathic pain.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Duloxetine | Experimental |
| |
| Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Duloxetine | Drug | 30 mg administered orally (po), QD for 1 week; 60 mg administered po, QD for remaining 11 weeks; 30 mg administered po, QD for 1 week during taper period |
|
| Measure | Description | Time Frame |
|---|---|---|
| Mean Change From Baseline at 12-Week Endpoint in the Weekly Mean of Pain Severity Score | 24-hour average pain severity scores were recorded daily by the participant on an 11-point Likert scale, an ordinal scale, with scores ranging from 0 (no pain) to 10 (worst possible pain). The weekly mean was calculated. A negative change indicated an improvement in participant's condition. Least squares (LS) mean was calculated using mixed model repeating measures (MMRM) and adjusted for treatment, pooled investigator, visit, and treatment-by-visit interaction, as well as baseline score and baseline score-by-visit interaction. | Baseline, 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Mean Change From Baseline at 12-Week Endpoint in Weekly Mean of Night Pain and Worst Pain | 24-hour average night pain and worst pain severity scores were recorded daily on an 11-point Likert scale, an ordinal scale, with scores ranging from 0 (no pain) to 10 (worst possible pain). A negative change indicated an improvement in the participant's condition. LS mean was calculated using MMRM and adjusted for treatment, pooled investigator, visit, and treatment-by-visit interaction, as well as the baseline score and baseline score-by-visit interaction. |
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Inclusion Criteria:
Present with pain due to bilateral peripheral neuropathy
Females must test negative for a serum pregnancy test at Screening. Females of child-bearing potential (who are not surgically sterilized and between menarche and 1 year postmenopause) must agree to use a medically acceptable and reliable means of birth control, during the study and for 1 month following the last study dose.
Stable glycemic control as assessed by a physician investigator and a glycosylated hemoglobin (HbA1c) <12% before randomization
Score of greater than or equal to 4 on the Brief Pain Inventory (BPI) 24-hour average pain item at Screening.
Full completion of the daily diaries for at least 80% of the days between the second and third time you come to the hospital (Screening).
Exclusion Criteria:
Currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational drug or device or off-label use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
Current (less than or equal to 1 year) Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) Axis I diagnosis of major depressive disorder, dysthymia, anxiety disorders (excluding phobias), alcohol or eating disorders as determined by the Mini-International Neuropsychiatric Interview (MINI) or a previous diagnosis
DSM-IV diagnosis of mania, bipolar disorder, or psychosis determined either by participant history or by diagnosis using specific MNSI modules
Serious or unstable cardiovascular, hepatic, renal, respiratory, or hematologic illness, symptomatic peripheral vascular disease, or other medical condition or psychological conditions that in the opinion of investigator would compromise participation or be likely to lead to hospitalization during the course of the study.
At Screening alanine transaminase (ALT) greater than 2 times upper limit of normal (ULN), based on central laboratory reference ranges times ULN, based on central laboratory reference ranges
Prior renal transplant, current renal dialysis, or serum creatinine laboratory value >1.5 times ULN, based on central laboratory reference ranges at Screening.
Historical exposure to drugs known to cause neuropathy, or a history of a medical condition, including pernicious anemia and hypothyroidism, that could have been responsible for neuropathy
Pain that cannot be clearly differentiated from or conditions that interfere with the assessment of the diabetic neuropathy pain. Examples of painful conditions that could be confused with diabetic neuropathy pain include peripheral vascular disease, neurological disorders unrelated to diabetic neuropathy, skin condition in the area of the neuropathy that could alter sensation, other painful conditions
Participants who have previously completed or withdrawn from this study or have been previously treated with duloxetine, including participants who participated in study F1J-MC-HMEQ (NCT00408993), even those in the placebo arm
Participants taking excluded medications that cannot be stopped at Screening
Treatment with a monoamine oxidase inhibitor (MAOI) or fluoxetine within 30 days of the third Screening
Participants with a positive Hepatitis B surface antigen and/or Hepatitis C antibody are to be excluded if they have any of the following:
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| Name | Affiliation | Role |
|---|---|---|
| Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) | Eli Lilly and Company | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Beijing | 100730 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25939897 | Derived | Gao Y, Guo X, Han P, Li Q, Yang G, Qu S, Yue L, Wang CN, Skljarevski V, Duenas H, Raskin J, Gu L. Treatment of patients with diabetic peripheral neuropathic pain in China: a double-blind randomised trial of duloxetine vs. placebo. Int J Clin Pract. 2015 Sep;69(9):957-66. doi: 10.1111/ijcp.12641. Epub 2015 May 4. |
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Participants tapered off study drug after either completing the 12 weeks of treatment or discontinued treatment early.
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| ID | Title | Description |
|---|---|---|
| FG000 | Duloxetine | 30 milligrams (mg) duloxetine capsule administered orally, once daily (QD) during Week 1 then 60 mg duloxetine capsule orally, QD for the remaining 11 weeks of treatment. After a total 12 weeks of treatment or early discontinuation participants tapered off study drug (30 mg duloxetine capsule QD) for 1 week during taper. |
| FG001 | Placebo | Placebo administered orally, QD for 12 weeks of the treatment and orally, QD for 1 week during taper. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
All randomized participants.
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| ID | Title | Description |
|---|---|---|
| BG000 | Duloxetine | 30 mg duloxetine capsule administered orally, QD during Week 1 then 60 mg duloxetine capsule orally, QD for remaining 11 weeks of the treatment. After a total 12 weeks of treatment or early discontinuation, participants tapered off study drug (30 mg duloxetine capsule orally, QD) for 1 week during taper. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Mean Change From Baseline at 12-Week Endpoint in the Weekly Mean of Pain Severity Score | 24-hour average pain severity scores were recorded daily by the participant on an 11-point Likert scale, an ordinal scale, with scores ranging from 0 (no pain) to 10 (worst possible pain). The weekly mean was calculated. A negative change indicated an improvement in participant's condition. Least squares (LS) mean was calculated using mixed model repeating measures (MMRM) and adjusted for treatment, pooled investigator, visit, and treatment-by-visit interaction, as well as baseline score and baseline score-by-visit interaction. | Intent-to-treat (ITT) principle was applied: All participants with a baseline and 12-week 24-hour average pain score based on the randomized group were analyzed. | Least Squares Mean | Standard Error | units on a scale | Baseline, 12 weeks |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Duloxetine Treatment | 30 mg duloxetine capsule administered orally, QD during Week 1 of the treatment; 60 mg capsule administered orally, QD for remaining 11 weeks of the treatment; |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Coronary artery disease | Cardiac disorders | MedDRA 16.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 16.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | Eli Lilly and Company | 800-545-5979 |
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| ID | Term |
|---|---|
| D003929 | Diabetic Neuropathies |
| ID | Term |
|---|---|
| D010523 | Peripheral Nervous System Diseases |
| D009468 | Neuromuscular Diseases |
| D009422 | Nervous System Diseases |
| D048909 | Diabetes Complications |
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| ID | Term |
|---|---|
| D000068736 | Duloxetine Hydrochloride |
| ID | Term |
|---|---|
| D013876 | Thiophenes |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D006573 | Heterocyclic Compounds, 1-Ring |
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|
| Placebo | Drug | Administered po, QD for 12 weeks; administered po, QD for 1 week during taper period |
|
| Baseline, 12 weeks |
| Mean Change From Baseline at 12-Week Endpoint in the BPI-Severity Scale | BPI-Severity Scale was a self-reported scale that measured 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). A negative change indicated an improvement in the participant's condition. LS mean was calculated using MMRM and adjusted for treatment, pooled investigator, visit, and treatment-by-visit interaction, as well as baseline score and baseline score-by-visit interaction. | Baseline, 12 weeks |
| Mean Change From Baseline at 12-Week Endpoint in the CGI-S Scale | CGI-S was administered by the investigator in the presence of the participant and measured the severity of illness at the time of assessment compared with start of treatment; CGI-S scores ranged from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). A negative change indicated an improvement in the participant's condition. LS mean was calculated using MMRM and adjusted for treatment, pooled investigator, visit, and treatment-by-visit interaction, as well as baseline score and baseline score-by-visit interaction. | Baseline, 12 weeks |
| Patient Global Impression of Improvement (PGI-I) Scale at 12-Week Endpoint | PGI-I was self-reported and measured a participant's perception of improvement at the time of assessment compared with the start of treatment. Scores ranged from 1 (very much better) to 7 (very much worse). LS mean was calculated using MMRM and adjusted for treatment, pooled investigator, visit, and treatment-by-visit interaction, as well as baseline score and baseline score-by-visit interaction. | 12 weeks |
| Mean Change From Baseline at 12-Week Endpoint in the Sensory Subscale of the SF-MPQ | SF-MPQ was a self-reported instrument that consisted of 11 sensory descriptors describing pain. The descriptors were rated on an intensity scale from 0 (none), 1 (mild), 2 (moderate) or 3 (severe). Three (3) pain scores were derived from the sum of the intensity rank values of the words chosen for sensory descriptors. The SF-MPQ sensory subscale was the sum of the 11 scores (ranged from 0 to 33, with 33 being the worst pain). A negative change indicates an improvement. LS mean was calculated using analysis of covariance (ANCOVA) adjusted for treatment, pooled investigator and baseline. | Baseline, 12 weeks |
| Percentage of Participants Who Experience Equal to or Greater Than 30%, 50% or 75% Reduction From Baseline at 12-Week Endpoint in Weekly Mean of Average Daily Pain | 24-hour self-assessment of average daily pain was recorded in the participants diary based on an 11 point Likert scale with scores ranging from 0 (no pain) to 10 (worst possible pain). Percentage of participants was calculated as: (number of participants with 30% [or 50% or 75%] reduction in average daily pain) divided by (number of participants) multiplied by 100. | Baseline, 12 weeks |
| Percentage of Participants Who Experienced Equal to or Greater Than 30%, 50% or 75% Reduction From Baseline at 12-week Endpoint in BPI-Severity Average Pain Score | BPI-Severity scale was a self-reported scale that measured the severity of pain based on the average pain experienced over the past 24 hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). A negative change indicated an improvement in the participant's condition. Percentage of participants was calculated as: (number of participants with 30% [or 50% or 75%] reduction in BPI-Severity average pain) divided by (number of participants) multiplied by 100. | Baseline, 12 weeks |
| Mean Change From Baseline at 12-week Endpoint in the BPI Interference Score | BPI-Interference Score was a self-reported scale that measured the interference of pain based on the average of the 7 questions assessing the interference of pain for general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. The average interference scores ranged from 0 (does not interfere) to 10 (completely interferes). A negative change indicates an improvement in the participant's condition. LS means was calculated using MMRM and adjusted treatment, pooled investigator, visit, and treatment-by-visit interaction, baseline score and baseline score-by-visit interaction. | Baseline, 12 weeks |
| Mean Change From Baseline at 12 Week Endpoint in the SDS Total Score | SDS was self-reported and used to assess the effect of the participant's symptoms on their work (Item 1), social life (Item 2), and family life (Item 3). Each item was measured on a 0 (not at all) to 10 (extremely) point scale with higher values indicating greater disruption. SDS total score was the sum of the 3 items and ranged from 0 to 30, with higher values indicating greater disruption in the participant's work/social/family life. Scores ≥5 were associated with significant functional impairment. A negative change indicated an improvement in the participant's condition. LS mean was adjusted using MMRM and adjusted for treatment, pooled investigator, visit, and treatment-by-visit interaction, baseline score and baseline score-by-visit interaction. | Baseline, 12 weeks |
| China |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Bengbu | 233004 | China |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Changchun | 130021 | China |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Chengdu | 610072 | China |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Chongqing | China |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Guangzhou | 510515 | China |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Jinan | 250001 | China |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Nanjin | 210006 | China |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Qingdao | 266003 | China |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Shanghai | 200040 | China |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Shantou | 515041 | China |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Shijiazhuang | 050051 | China |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Tianjin | 300211 | China |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Xi'an | 710061 | China |
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Yueyang | 414000 | China |
| Entry Criteria Not Met |
|
| Lost to Follow-up |
|
| Protocol Violation |
|
| Physician Decision |
|
| Placebo |
Placebo administered orally, QD for 12 weeks of the treatment and orally, QD for 1 week during taper. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Diabetes Disease Characteristics-Types of Diabetes | Number | participants |
|
| Diabetes Disease Characteristics | Mean | Standard Deviation | years |
|
| Weekly Mean of 24-Hour Average Pain | Participants measured their pain on an 11-point Likert scale that was completed daily. The scale ranged from 0 (no pain) to 10 (worst possible pain). The participant-recorded average pain due to diabetic neuropathy over the previous 24 hours. | Mean | Standard Deviation | units on a scale |
|
| Brief Pain Inventory (BPI)-Severity Average Pain in the Last Week | BPI-Severity Modified Short Form Severity was a self-reported scale that measured the severity of pain. Severity scores ranged from 0 (no pain) to 10 (pain as bad as you could imagine). There were 4 questions assessing the severity for worst pain, least pain, average pain, and the pain right now. | Mean | Standard Deviation | units on a scale |
|
| Clinical Global Impression of Severity (CGI-S) | Number of participants analyzed was: Duloxetine treatment =126 and Placebo=136. Data from 9 sites were not included in baseline analysis due to wrong questionnaire used. CSI-S was administered by the investigator in the presence of the participant and measured severity of illness at baseline with scores ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). | Mean | Standard Deviation | units on a scale |
|
| Short Form-McGill Pain Questionnaire (SF-MPQ), Sensory Portion Total Score | SF-MPQ sensory portion was a self-reported instrument consisting of 11 sensory descriptors describing pain, each rated on an intensity scale from 0 (none) to 3 (severe). Total scores ranged from 0 to 33. | Mean | Standard Deviation | units on a scale |
|
| BPI-Interference Average Score | BPI-Interference Score was self-reported scale that measured interference of pain based on the average of the 7 questions assessing the interference of pain for general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. The average interference scores ranged from 0 (does not interfere) to 10 (completely interferes). | Mean | Standard Deviation | units on a scale |
|
| Sheehan Disability Scale (SDS) Total Score | SDS was self-reported and used to assess the effect of the participant's symptoms on their work (Item 1), social life (Item 2), and family life (Item 3). Each item was measured on a 0 (not at all) to 10 (extremely) point scale with higher values indicating greater disruption. SDS Total Score was the sum of the 3 items and ranged from 0 to 30 with higher values indicating greater disruption in the participant's work/social/family life. Scores ≥5 were associated with significant functional impairment. | Mean | Standard Deviation | units on a scale |
|
| OG001 | Placebo | Placebo administered orally, QD for 12 weeks of the treatment and orally, QD for 1 week during taper. |
|
|
|
| Secondary | Mean Change From Baseline at 12-Week Endpoint in Weekly Mean of Night Pain and Worst Pain | 24-hour average night pain and worst pain severity scores were recorded daily on an 11-point Likert scale, an ordinal scale, with scores ranging from 0 (no pain) to 10 (worst possible pain). A negative change indicated an improvement in the participant's condition. LS mean was calculated using MMRM and adjusted for treatment, pooled investigator, visit, and treatment-by-visit interaction, as well as the baseline score and baseline score-by-visit interaction. | ITT principle was applied: All participants with a baseline and 12-week 24-hour night pain score and worst pain score based on the randomized group were analyzed. | Least Squares Mean | Standard Error | units on a scale | Baseline, 12 weeks |
|
|
|
|
| Secondary | Mean Change From Baseline at 12-Week Endpoint in the BPI-Severity Scale | BPI-Severity Scale was a self-reported scale that measured 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). A negative change indicated an improvement in the participant's condition. LS mean was calculated using MMRM and adjusted for treatment, pooled investigator, visit, and treatment-by-visit interaction, as well as baseline score and baseline score-by-visit interaction. | ITT principle was applied: All participants with a baseline and 12-week, 24-hour BPI-Severity score based on the randomized group were analyzed. | Least Squares Mean | Standard Error | units on a scale | Baseline, 12 weeks |
|
|
|
|
| Secondary | Mean Change From Baseline at 12-Week Endpoint in the CGI-S Scale | CGI-S was administered by the investigator in the presence of the participant and measured the severity of illness at the time of assessment compared with start of treatment; CGI-S scores ranged from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). A negative change indicated an improvement in the participant's condition. LS mean was calculated using MMRM and adjusted for treatment, pooled investigator, visit, and treatment-by-visit interaction, as well as baseline score and baseline score-by-visit interaction. | ITT principle was applied: All participants with a baseline and 12-week CGI-S score based on the randomized group were analyzed. Data from 9 sites was not included in analysis due to wrong questionnaire used. | Least Squares Mean | Standard Error | units on a scale | Baseline, 12 weeks |
|
|
|
|
| Secondary | Patient Global Impression of Improvement (PGI-I) Scale at 12-Week Endpoint | PGI-I was self-reported and measured a participant's perception of improvement at the time of assessment compared with the start of treatment. Scores ranged from 1 (very much better) to 7 (very much worse). LS mean was calculated using MMRM and adjusted for treatment, pooled investigator, visit, and treatment-by-visit interaction, as well as baseline score and baseline score-by-visit interaction. | All participants with a baseline and 12-week PGI-I score. | Least Squares Mean | Standard Error | units on a scale | 12 weeks |
|
|
|
|
| Secondary | Mean Change From Baseline at 12-Week Endpoint in the Sensory Subscale of the SF-MPQ | SF-MPQ was a self-reported instrument that consisted of 11 sensory descriptors describing pain. The descriptors were rated on an intensity scale from 0 (none), 1 (mild), 2 (moderate) or 3 (severe). Three (3) pain scores were derived from the sum of the intensity rank values of the words chosen for sensory descriptors. The SF-MPQ sensory subscale was the sum of the 11 scores (ranged from 0 to 33, with 33 being the worst pain). A negative change indicates an improvement. LS mean was calculated using analysis of covariance (ANCOVA) adjusted for treatment, pooled investigator and baseline. | ITT principle was applied: All participants with a baseline and 12 weeks SF-MPQ score based on the randomized group were analyzed; last observation carried forward (LOCF). | Least Squares Mean | Standard Error | units on a scale | Baseline, 12 weeks |
|
|
|
|
| Secondary | Percentage of Participants Who Experience Equal to or Greater Than 30%, 50% or 75% Reduction From Baseline at 12-Week Endpoint in Weekly Mean of Average Daily Pain | 24-hour self-assessment of average daily pain was recorded in the participants diary based on an 11 point Likert scale with scores ranging from 0 (no pain) to 10 (worst possible pain). Percentage of participants was calculated as: (number of participants with 30% [or 50% or 75%] reduction in average daily pain) divided by (number of participants) multiplied by 100. | All participants with a baseline and postbaseline 24-hour average pain score. | Number | percentage of participants | Baseline, 12 weeks |
|
|
|
|
| Secondary | Percentage of Participants Who Experienced Equal to or Greater Than 30%, 50% or 75% Reduction From Baseline at 12-week Endpoint in BPI-Severity Average Pain Score | BPI-Severity scale was a self-reported scale that measured the severity of pain based on the average pain experienced over the past 24 hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). A negative change indicated an improvement in the participant's condition. Percentage of participants was calculated as: (number of participants with 30% [or 50% or 75%] reduction in BPI-Severity average pain) divided by (number of participants) multiplied by 100. | All participants with a baseline and postbaseline BPI-Severity average pain scores. | Number | percentage of participants | Baseline, 12 weeks |
|
|
|
|
| Secondary | Mean Change From Baseline at 12-week Endpoint in the BPI Interference Score | BPI-Interference Score was a self-reported scale that measured the interference of pain based on the average of the 7 questions assessing the interference of pain for general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. The average interference scores ranged from 0 (does not interfere) to 10 (completely interferes). A negative change indicates an improvement in the participant's condition. LS means was calculated using MMRM and adjusted treatment, pooled investigator, visit, and treatment-by-visit interaction, baseline score and baseline score-by-visit interaction. | All participants with non-missing BPI-Interference score at baseline and 12 weeks. | Least Squares Mean | Standard Error | units on a scale | Baseline, 12 weeks |
|
|
|
|
| Secondary | Mean Change From Baseline at 12 Week Endpoint in the SDS Total Score | SDS was self-reported and used to assess the effect of the participant's symptoms on their work (Item 1), social life (Item 2), and family life (Item 3). Each item was measured on a 0 (not at all) to 10 (extremely) point scale with higher values indicating greater disruption. SDS total score was the sum of the 3 items and ranged from 0 to 30, with higher values indicating greater disruption in the participant's work/social/family life. Scores ≥5 were associated with significant functional impairment. A negative change indicated an improvement in the participant's condition. LS mean was adjusted using MMRM and adjusted for treatment, pooled investigator, visit, and treatment-by-visit interaction, baseline score and baseline score-by-visit interaction. | All participants with non-missing SDS Total Score at baseline and 12 weeks. | Least Squares Mean | Standard Error | units on a scale | Baseline, 12 weeks |
|
|
|
|
| 4 |
| 202 |
| 93 |
| 202 |
| EG001 | Placebo Treatment | Placebo administered orally, QD for 12 weeks of the treatment. | 3 | 202 | 71 | 202 |
| EG002 | Duloxetine Taper | After 12 weeks of treatment or early discontinuation, 30 mg duloxetine capsule administered orally, QD for 1 week during taper. | 3 | 181 | 8 | 181 |
| EG003 | Placebo Taper | After 12 weeks of treatment or early discontinuation, placebo administered orally, QD for 1 week during taper. | 1 | 177 | 5 | 177 |
| Nodal arrhythmia | Cardiac disorders | MedDRA 16.0 | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA 16.0 | Systematic Assessment |
|
| Cholecystitis chronic | Hepatobiliary disorders | MedDRA 16.0 | Systematic Assessment |
|
| Diabetes mellitus | Metabolism and nutrition disorders | MedDRA 16.0 | Systematic Assessment |
|
| Non-hodgkin's lymphoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 16.0 | Systematic Assessment |
|
| Cerebral infarction | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
|
| Diabetic neuropathy | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA 16.0 | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA 16.0 | Systematic Assessment |
|
| Coronary artery disease | Cardiac disorders | MedDRA 16.0 | Systematic Assessment |
|
| Palpitations | Cardiac disorders | MedDRA 16.0 | Systematic Assessment |
|
| Hypoacusis | Ear and labyrinth disorders | MedDRA 16.0 | Systematic Assessment |
|
| Tinnitus | Ear and labyrinth disorders | MedDRA 16.0 | Systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | MedDRA 16.0 | Systematic Assessment |
|
| Amaurosis | Eye disorders | MedDRA 16.0 | Systematic Assessment |
|
| Diabetic retinopathy | Eye disorders | MedDRA 16.0 | Systematic Assessment |
|
| Photophobia | Eye disorders | MedDRA 16.0 | Systematic Assessment |
|
| Vision blurred | Eye disorders | MedDRA 16.0 | Systematic Assessment |
|
| Visual impairment | Eye disorders | MedDRA 16.0 | Systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| Epigastric discomfort | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| Eructation | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| Faeces hard | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| Gastric ulcer | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| Gastritis | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| Gastrointestinal disorder | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| Hiatus hernia | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| Hypoaesthesia oral | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| Infrequent bowel movements | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| Regurgitation | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| Tongue discolouration | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA 16.0 | Systematic Assessment |
|
| Chest discomfort | General disorders | MedDRA 16.0 | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA 16.0 | Systematic Assessment |
|
| Chills | General disorders | MedDRA 16.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 16.0 | Systematic Assessment |
|
| Hunger | General disorders | MedDRA 16.0 | Systematic Assessment |
|
| Malaise | General disorders | MedDRA 16.0 | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 16.0 | Systematic Assessment |
|
| Sluggishness | General disorders | MedDRA 16.0 | Systematic Assessment |
|
| Thirst | General disorders | MedDRA 16.0 | Systematic Assessment |
|
| Fatty liver alcoholic | Hepatobiliary disorders | MedDRA 16.0 | Systematic Assessment |
|
| Hepatic function abnormal | Hepatobiliary disorders | MedDRA 16.0 | Systematic Assessment |
|
| Hepatic lesion | Hepatobiliary disorders | MedDRA 16.0 | Systematic Assessment |
|
| Liver injury | Hepatobiliary disorders | MedDRA 16.0 | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
|
| Head injury | Injury, poisoning and procedural complications | MedDRA 16.0 | Systematic Assessment |
|
| Joint dislocation | Injury, poisoning and procedural complications | MedDRA 16.0 | Systematic Assessment |
|
| Spinal cord injury cauda equina | Injury, poisoning and procedural complications | MedDRA 16.0 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 16.0 | Systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA 16.0 | Systematic Assessment |
|
| Blood bicarbonate decreased | Investigations | MedDRA 16.0 | Systematic Assessment |
|
| Blood cholesterol decreased | Investigations | MedDRA 16.0 | Systematic Assessment |
|
| Blood creatine phosphokinase increased | Investigations | MedDRA 16.0 | Systematic Assessment |
|
| Blood potassium decreased | Investigations | MedDRA 16.0 | Systematic Assessment |
|
| Blood potassium increased | Investigations | MedDRA 16.0 | Systematic Assessment |
|
| Blood pressure increased | Investigations | MedDRA 16.0 | Systematic Assessment |
|
| Blood triglycerides increased | Investigations | MedDRA 16.0 | Systematic Assessment |
|
| Blood uric acid increased | Investigations | MedDRA 16.0 | Systematic Assessment |
|
| Gamma-glutamyltransferase increased | Investigations | MedDRA 16.0 | Systematic Assessment |
|
| Transaminases increased | Investigations | MedDRA 16.0 | Systematic Assessment |
|
| Weight increased | Investigations | MedDRA 16.0 | Systematic Assessment |
|
| White blood cell count decreased | Investigations | MedDRA 16.0 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 16.0 | Systematic Assessment |
|
| Dyslipidaemia | Metabolism and nutrition disorders | MedDRA 16.0 | Systematic Assessment |
|
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA 16.0 | Systematic Assessment |
|
| Hypercholesterolaemia | Metabolism and nutrition disorders | MedDRA 16.0 | Systematic Assessment |
|
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 16.0 | Systematic Assessment |
|
| Hyperlipidaemia | Metabolism and nutrition disorders | MedDRA 16.0 | Systematic Assessment |
|
| Hypertriglyceridaemia | Metabolism and nutrition disorders | MedDRA 16.0 | Systematic Assessment |
|
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA 16.0 | Systematic Assessment |
|
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA 16.0 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 16.0 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Systematic Assessment |
|
| Fasciitis | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Systematic Assessment |
|
| Osteoporosis | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Systematic Assessment |
|
| Autonomic neuropathy | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
|
| Cerebral infarction | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
|
| Clonus | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
|
| Convulsion | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
|
| Diabetic autonomic neuropathy | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
|
| Disturbance in attention | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
|
| Dreamy state | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
|
| Formication | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
|
| Hypersomnia | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
|
| Lacunar infarction | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
|
| Lethargy | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
|
| Memory impairment | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
|
| Poor quality sleep | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
|
| Sciatica | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
|
| Tremor | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
|
| Agitation | Psychiatric disorders | MedDRA 16.0 | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA 16.0 | Systematic Assessment |
|
| Dysphoria | Psychiatric disorders | MedDRA 16.0 | Systematic Assessment |
|
| Fear | Psychiatric disorders | MedDRA 16.0 | Systematic Assessment |
|
| Food aversion | Psychiatric disorders | MedDRA 16.0 | Systematic Assessment |
|
| Illusion | Psychiatric disorders | MedDRA 16.0 | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA 16.0 | Systematic Assessment |
|
| Mutism | Psychiatric disorders | MedDRA 16.0 | Systematic Assessment |
|
| Nervousness | Psychiatric disorders | MedDRA 16.0 | Systematic Assessment |
|
| Nightmare | Psychiatric disorders | MedDRA 16.0 | Systematic Assessment |
|
| Panic attack | Psychiatric disorders | MedDRA 16.0 | Systematic Assessment |
|
| Sleep disorder | Psychiatric disorders | MedDRA 16.0 | Systematic Assessment |
|
| Tic | Psychiatric disorders | MedDRA 16.0 | Systematic Assessment |
|
| Dysuria | Renal and urinary disorders | MedDRA 16.0 | Systematic Assessment |
|
| Nephrolithiasis | Renal and urinary disorders | MedDRA 16.0 | Systematic Assessment |
|
| Pollakiuria | Renal and urinary disorders | MedDRA 16.0 | Systematic Assessment |
|
| Renal failure chronic | Renal and urinary disorders | MedDRA 16.0 | Systematic Assessment |
|
| Urinary retention | Renal and urinary disorders | MedDRA 16.0 | Systematic Assessment |
|
| Urine flow decreased | Renal and urinary disorders | MedDRA 16.0 | Systematic Assessment |
|
| Benign prostatic hyperplasia | Reproductive system and breast disorders | MedDRA 16.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| Dry throat | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| Dermatitis allergic | Skin and subcutaneous tissue disorders | MedDRA 16.0 | Systematic Assessment |
|
| Diabetic foot | Skin and subcutaneous tissue disorders | MedDRA 16.0 | Systematic Assessment |
|
| Eczema | Skin and subcutaneous tissue disorders | MedDRA 16.0 | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 16.0 | Systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA 16.0 | Systematic Assessment |
|
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA 16.0 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 16.0 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 16.0 | Systematic Assessment |
|
| Skin swelling | Skin and subcutaneous tissue disorders | MedDRA 16.0 | Systematic Assessment |
|
| Haemorrhoid operation | Surgical and medical procedures | MedDRA 16.0 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 16.0 | Systematic Assessment |
|
Not provided
| D003920 | Diabetes Mellitus |
| D004700 | Endocrine System Diseases |
| D006571 |
| Heterocyclic Compounds |
| 0.017 |
P-value is for mean change from baseline to 12 week endpoint in worst pain. |
| Mean Difference (Final Values) |
| -0.55 |
| 2-Sided |
| 95 |
| -1.00 |
| -0.10 |
| No |
| Superiority or Other |
| ≥75% Reduction |
|
Cochran-Mantel-Haenszel test was stratified by pooled investigator. |
| 0.006 |
P-value is for ≥50% reduction in 24-hour average pain. |
| No |
| Superiority or Other |
| Cochran-Mantel-Haenszel | Cochran-Mantel-Haenszel test was stratified by pooled investigator. | 0.193 | P-value is for ≥75% reduction in 24-hour average pain. | No | Superiority or Other |
| ≥75% Reduction |
|
Cochran-Mantel-Haenszel test was stratified by pooled investigator. |
| 0.001 |
P-value is for ≥50% reduction in 24-hour BPI-Severity average pain. |
| No |
| Superiority or Other |
| Cochran-Mantel-Haenszel | Cochran Mantel Haenszel test was stratified by pooled investigator. | 0.168 | P-value is for ≥75% reduction in 24-hour BPI-Severity average pain. | No | Superiority or Other |