Use of Duloxetine or Pregabalin in Monotherapy Versus Combination Therapy of Both Drugs in Patients With Painful Diabetic Neuropathy "The COMBO - DN (COmbination vs Monotherapy of pregaBalin and dulOxetine in Diabetic Neuropathy) Study"
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 811
- 试验地点
- 1
- 主要终点
- Change From Week 8 to Week 16 Endpoint in 24 Hour Average Pain Item Score on the Brief Pain Inventory (BPI) Modified Short Form
研究概览
简要总结
This study will investigate the efficacy of a combination treatment of duloxetine + pregabalin compared with the maximal dose of each drug in monotherapy, in patients with diabetic peripheral neuropathic pain (DPNP) who have not responded to the standard recommended dose of either drug. It will provide an answer to a common clinical question, namely, is it better to increase the dose of the current monotherapy or to combine both treatments early on, in patients who do not respond to standard doses of duloxetine or pregabalin.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Pain due to bilateral peripheral neuropathy (caused by type 1 or type 2 diabetes mellitus. Pain must begin in the feet, with relatively symmetrical onset. Daily pain should be present for more than 3 months [assessed by questioning patient]).
- •Score of at least 4 on the 24-hour average pain severity score on an 11-point Likert scale [on Brief Pain Inventory (BPI) Modified Short Form] at screening and at randomization.
- •Patient is currently not receiving treatment for diabetic peripheral neuropathic pain (DPNP) or was receiving treatment for DPNP, with a drug other than pregabalin or duloxetine, and completed the required washout
- •Patient has never received treatment with duloxetine or pregabalin. (However, a short course of less than 15 days of treatment, at any time previously, will be allowed.)
- •Stable glycemic control, as assessed by a physician investigator, and hemoglobin A1c (HbA1c) less than or equal to 12% at screening.
排除标准
- •Have a known hypersensitivity to duloxetine or pregabalin or any of the inactive ingredients or have any contraindication for the use of duloxetine or pregabalin.
- •Have uncontrolled narrow-angle glaucoma.
- •Have received treatment with a monoamine oxidase inhibitor (MAOI) within 14 days prior to randomization, or have a potential need to use a MAOI during the study or within 5 days after discontinuation of study drug.
- •Have received fluoxetine within 30 days prior to randomization.
- •Have acute liver injury (such as hepatitis) or severe cirrhosis (Child-Pugh Class C).
- •Have a serum creatinine greater than or equal to 1.5 milligram per deciliter (mg/dL) or a creatinine clearance less than 60 milliliter per minute (mL/min), at screening.
- •Are judged clinically by the investigator to be at suicidal risk or as defined by a score of 2 or greater on Question 9 of the Beck Depression Inventory-II (BDI-II), at screening or randomization
- •Have a historical exposure to drugs known to cause neuropathy (for example, vincristine), or a history of a medical condition, including pernicious anemia and hypothyroidism, that could have been responsible for neuropathy.
- •Have pain that cannot be clearly differentiated from or conditions that interfere with the assessment of the DPNP.
- •Have serious or unstable cardiovascular, hepatic, renal, respiratory or hematological illness; symptomatic peripheral vascular disease; a history of seizure disorder; or other medical (including unstable hypertension and not clinically euthyroid) or psychological conditions that, in the opinion of the investigator, would compromise participation or be likely to require hospitalization during the course of the study.
- •Have received non-pharmacological treatment for pain within 14 days prior to randomization, or do not agree to abstain from non-pharmacological treatment during the study.
- •Have a history of frequent and/or severe allergic reactions with multiple medications.
研究组 & 干预措施
Duloxetine
Initial Treatment:
Duloxetine 30 milligram (mg) daily for 1 week
Duloxetine 60 mg daily for 7 weeks
Intensive Treatment:
Duloxetine 90 mg (60 mg in the morning, 30 mg in the evening) daily for 1 week
Duloxetine 120 mg (60 mg twice daily) daily for 7 weeks
干预措施: Duloxetine (Drug)
Duloxetine
Initial Treatment:
Duloxetine 30 milligram (mg) daily for 1 week
Duloxetine 60 mg daily for 7 weeks
Intensive Treatment:
Duloxetine 90 mg (60 mg in the morning, 30 mg in the evening) daily for 1 week
Duloxetine 120 mg (60 mg twice daily) daily for 7 weeks
干预措施: Placebo (Drug)
Pregabalin+Duloxetine
Initial Treatment:
Pregabalin 150 mg daily for 1 week
Pregabalin 300 mg (150 mg twice daily) daily for 7 weeks
Intensive Treatment:
Pregabalin 300 mg (150 mg twice daily) daily for 8 weeks
Duloxetine 30 mg daily for 1 week
Duloxetine 60 mg daily for 7 weeks
干预措施: Duloxetine (Drug)
Pregabalin+Duloxetine
Initial Treatment:
Pregabalin 150 mg daily for 1 week
Pregabalin 300 mg (150 mg twice daily) daily for 7 weeks
Intensive Treatment:
Pregabalin 300 mg (150 mg twice daily) daily for 8 weeks
Duloxetine 30 mg daily for 1 week
Duloxetine 60 mg daily for 7 weeks
干预措施: Pregabalin (Drug)
Pregabalin+Duloxetine
Initial Treatment:
Pregabalin 150 mg daily for 1 week
Pregabalin 300 mg (150 mg twice daily) daily for 7 weeks
Intensive Treatment:
Pregabalin 300 mg (150 mg twice daily) daily for 8 weeks
Duloxetine 30 mg daily for 1 week
Duloxetine 60 mg daily for 7 weeks
干预措施: Placebo (Drug)
Pregabalin
Initial Treatment:
Pregabalin 150 mg daily for 1 week
Pregabalin 300 mg (150 mg twice daily) daily for 7 weeks
Intensive Treatment:
Pregabalin 450 mg (300 mg in the morning, 150 mg in the evening) daily for 1 week
Pregabalin 600 mg (300 mg twice daily) daily for 7 weeks
干预措施: Pregabalin (Drug)
Pregabalin
Initial Treatment:
Pregabalin 150 mg daily for 1 week
Pregabalin 300 mg (150 mg twice daily) daily for 7 weeks
Intensive Treatment:
Pregabalin 450 mg (300 mg in the morning, 150 mg in the evening) daily for 1 week
Pregabalin 600 mg (300 mg twice daily) daily for 7 weeks
干预措施: Placebo (Drug)
Duloxetine + Pregabalin
Initial Treatment:
Duloxetine 30 mg daily for 1 week
Duloxetine 60 mg daily for 7 weeks
Intensive Treatment:
Duloxetine 60 mg daily for 8 weeks
Pregabalin 150 mg daily for 1 week
Pregabalin 300 mg (150 mg twice daily) daily for 7 weeks
干预措施: Duloxetine (Drug)
Duloxetine + Pregabalin
Initial Treatment:
Duloxetine 30 mg daily for 1 week
Duloxetine 60 mg daily for 7 weeks
Intensive Treatment:
Duloxetine 60 mg daily for 8 weeks
Pregabalin 150 mg daily for 1 week
Pregabalin 300 mg (150 mg twice daily) daily for 7 weeks
干预措施: Pregabalin (Drug)
Duloxetine + Pregabalin
Initial Treatment:
Duloxetine 30 mg daily for 1 week
Duloxetine 60 mg daily for 7 weeks
Intensive Treatment:
Duloxetine 60 mg daily for 8 weeks
Pregabalin 150 mg daily for 1 week
Pregabalin 300 mg (150 mg twice daily) daily for 7 weeks
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Week 8 to Week 16 Endpoint in 24 Hour Average Pain Item Score on the Brief Pain Inventory (BPI) Modified Short Form
时间窗: Week 8, Week 16
BPI Modified Short Form 24-Hour average pain item score is a self-reported scale that measures 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). Mixed-effects model repeated measures (MMRM) analysis was used to calculate Least Squares (LS) Mean and 95% Confidence Interval (CI). LS Mean values are controlled for treatment, site, baseline value, visit, treatment\*visit, baseline\*visit and treatment in Study Period II.
次要结局
- Mean Change From Week 8 to Week 16 Endpoint in Items of the Brief Pain Inventory (BPI) Modified Short Form Worst Pain Score(Week 8, Week 16)
- Percentage of Participants With a Reduction of Greater Than or Equal to 30% on Brief Pain Inventory (BPI) Modified Short Form 24-Hour Average Pain Item Score at Week 16 Endpoint(Week 8 through Week 16)
- Percentage of Participants With a Reduction of Greater Than or Equal to 50% on Brief Pain Inventory (BPI) Modified Short Form 24-Hour Average Pain Item Score at Week 16 Endpoint(Week 8 through Week 16)
- Percentage of Participants With a Decrease of Greater Than or Equal to 2 Points on Brief Pain Inventory (BPI) Modified Short Form 24-Hour Average Pain Item Score at Week 16 Endpoint(Week 8 through Week 16)
- Clinical Global Impression of Improvement (CGI-I) at Week 16 Endpoint(Week 16)
- Mean Change From Week 8 to Week 16 Endpoint on the Neuropathic Pain Symptom Inventory (NPSI) Questionnaire(Week 8, Week 16)
- Mean Change From Week 8 to Week 16 Endpoint in Sheehan Disability Scale (SDS)(Week 8, Week 16)
- Mean Change From Week 8 to Week 16 Endpoint in Hospital Anxiety and Depression Scale (HADS)(Week 8, Week 16)
- Resource Utilization (Number of Days Hospitalized, Number of Days of Sick Leave) Week 8 Through Week 16(Week 8 through Week 16)
- Patient Global Impression of Improvement (PGI-I) Score at Week 16 Endpoint(Week 16)
- Mean Change in Blood Pressure (BP) From Week 8 to Week 16 Endpoint(Week 8, Week 16)
- Mean Change in Heart Rate From Week 8 to Week 16 Endpoint(Week 8, Week 16)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) Between Week 8 and Week 16 Endpoint(Week 8 through Week 16)
- Number of Participants Who Discontinued From Study Between Week 8 and Week 16 Endpoint(Week 8 through Week 16)