A Japan Post-Marketing, Randomized, Double-Blind, Parallel-Group, Flexible Dose Comparative Study to Assess the Non-Inferiority of Duloxetine Compared With Pregabalin in Patients With Diabetic Peripheral Neuropathic Pain
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 304
- 主要终点
- Change From Baseline to 12 Weeks in the Weekly Mean of the 24-Hour Average Pain Score on the 11-Point Numeric Rating Scale (NRS)
研究概览
简要总结
The main purpose of this study is to evaluate the effectiveness and safety of the study drug known as duloxetine in participants with diabetic peripheral neuropathic pain.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 20 Years 至 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants present with pain due to bilateral, peripheral neuropathy
- •Participants who have hemoglobin A1c (HbA1c) ≤9.4% (National Glycohemoglobin Standardization Program [NGSP]) at screening
- •Participants who have HbA1c that has been measured 42 to 70 days prior to screening, and the range of variation in the values measured, thereafter, is within ±1.0% of the value measured at screening
- •Participants who have a score of at least 4 on the mean of the 24-hour average pain score measured using 11-point NRS (Numeric Rating Scale) in the daily diary (should be calculated from records 7 days immediately prior to randomization)
- •Participants who have made complete daily diary entries 80% or more of the time from screening to randomization
排除标准
- •Participants who have undergone renal transplant, or are currently undergoing renal dialysis
- •Participants who have uncontrolled narrow-angle glaucoma, history of uncontrolled seizures, or uncontrolled or poorly controlled hypertension
- •Participants whose glycemic control has been poor within 70 days immediately prior to screening (for example, ketoacidosis requiring hospitalization, or hypoglycemia that may cause consciousness disorder)
- •Pregnant or lactating female participants, or male participants who are planning for their partners to be or become pregnant during the timeframe of the study
- •Participants who have hypersensitivity to multiple medications
- •Participants who answered "yes" to either question 4 (active suicidal ideation with some intent to act, without specific plan) or question 5 (active suicidal ideation with specific plan and intent) on the "suicidal ideation" portion of the Columbia-Suicide Severity Rating Scale (C-SSRS) or answered "yes" to any of the suicide-related behaviors (actual attempt, interrupted attempt, aborted attempt, preparatory act or behavior) on the "suicidal behavior" portion of the C-SSRS; and the ideation or behavior occurred within the past month
- •Participants who have past history of psychiatric diseases, such as depression, anxiety disorder, eating disorder, etc., that required drug therapy in the past 1 year, or who are currently having complications of these diseases or any history of manic psychosis or bipolar disorder
- •Participants who have major depressive disorder as determined using the depression module of the Mini-International Neuropsychiatric Interview (MINI)
- •Participants who have complications of diseases that are considered to affect the assessment of diabetic peripheral neuropathic pain. For example, nerve diseases with pain other than diabetic peripheral neuropathic pain (cervical spondylosis, carpal tunnel syndrome, spinal canal stenosis, and post-herpetic pain), pain diseases other than nerve diseases (collagen diseases, gout, chronic obstructive arteriosclerosis, and arthritis), and other pain at the site of evaluation (skin diseases and traumatic injury) are excluded
- •Participants who have neuropathic pain suspected to be caused by alcohol
- •Participants who have been treated with a monoamine oxidase (MAO) inhibitor(s) within 14 days immediately prior to randomization. Participants who visited the investigator site 14 days prior to randomization, those who have been treated with MAO inhibitors(s), thereafter, are excluded
- •Participants who have alanine aminotransferase (ALT) and aspartate aminotransferase (AST) at a level ≥100 units/liter at screening
- •Participants who have total bilirubin at a level ≥1.5 milligrams/deciliter (mg/dL) at screening
- •Participants who have creatinine clearance (CrCL), calculated by Cockcroft-Gault, that is <1.0 milliliters/second (mL/s) (<60 mL/minute) at screening
- •Participants who have a white blood cell (WBC) value <2500/cubic millimeters (mm3), neutrophils <1500/mm3, or platelets <100×103/mm3 on their hematology tests at screening
- •Participants who are introduced to any treatments for diabetes, or a change in dosing regimen of any treatments for diabetes (exclude insulin treatment), or resumption of insulin treatment after screening
- •Participants who have been treated with prohibited concomitant drug(s), or who have undergone prohibited concomitant treatment(s) after screening
- •Participants who have taken restricted concomitant drugs 27 days immediately before screening, with continued use of the restricted concomitant drug prior to screening
- •Participants who have taken acetaminophen for 4 days or more 7 days immediately prior to randomization
研究组 & 干预措施
Duloxetine
20 milligrams (mg) duloxetine orally once a day (QD) for one week and then 40 mg duloxetine orally QD for 3 weeks. Duloxetine dosage may be increased up to 60 mg QD at week 4 or week 8. Placebo will be given with duloxetine for blinding. Dosage will be tapered down during the final week of the study.
干预措施: Duloxetine (Drug)
Duloxetine
20 milligrams (mg) duloxetine orally once a day (QD) for one week and then 40 mg duloxetine orally QD for 3 weeks. Duloxetine dosage may be increased up to 60 mg QD at week 4 or week 8. Placebo will be given with duloxetine for blinding. Dosage will be tapered down during the final week of the study.
干预措施: Placebo (Drug)
Pregabalin
150 mg pregabalin orally twice a day (BID) for 1 week and then 300 mg pregabalin orally BID for 3 weeks. Pregabalin dosage may be increased up to 450 mg BID at week 4 or 8, and increased up to 600 mg BID at week 8. Placebo will be given with pregabalin for blinding. Dosage will be tapered down during the final week of the study.
干预措施: Pregabalin (Drug)
Pregabalin
150 mg pregabalin orally twice a day (BID) for 1 week and then 300 mg pregabalin orally BID for 3 weeks. Pregabalin dosage may be increased up to 450 mg BID at week 4 or 8, and increased up to 600 mg BID at week 8. Placebo will be given with pregabalin for blinding. Dosage will be tapered down during the final week of the study.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline to 12 Weeks in the Weekly Mean of the 24-Hour Average Pain Score on the 11-Point Numeric Rating Scale (NRS)
时间窗: Baseline, Week 12
11-point NRS measures the severity of pain over the previous 24 hours. Participants were asked to provide 24-hour average pain scores in the daily Participant diary and among these, the weekly mean of the 24-hour average pain score was calculated. Scores range from 0 (no pain) to 10 (pain as bad as you can imagine). Mixed Model Repeated Measures (MMRM) model with baseline value, Duration of diabetic peripheral neuropathic pain (DPNP), treatment, week, treatment-by-week interaction as fixed effects was used to produce Least Square Mean (LS Mean).
次要结局
- Patient Global Impression of Improvement (PGI-I) at 12 Weeks(Week 12)
- Change From Baseline to 12 Weeks on the Brief Pain Inventory-Severity and Interference Rating Short Form (BPI-SF)(Baseline, Week 12)
- Change From Baseline to 12 Weeks on the Neuropathic Pain Symptom Inventory (NPSI)(Baseline, Week 12)
- Number of Participants With a 30% and 50% Reduction in the Weekly Mean of the 24-Hour Average Pain Score on the 11-Point NRS at 12 Weeks(Week 12)
- Change From Baseline to 12 Weeks in the Weekly Mean of Night Pain Scores on the 11-Point NRS(Baseline, Week 12)
- Change From Baseline to 12 Weeks in the Weekly Mean of the 24-Hour Worst Pain Scores on the 11-Point NRS(Baseline, Week 12)
- Clinical Global Impression of Improvement (CGI-I) at 12 Weeks(Week 12)
- Change From Baseline to 12 Weeks on the EuroQol 5 Dimension (EQ-5D)(Baseline, Week 12)
- Change From Baseline to 12 Weeks on the Beck Depression Inventory-II (BDI-II) Total Score(Baseline, Week 12)