A Randomized, Double-Blind, Placebo and Active Comparator-Controlled Study of DS-5565 for Treatment of Neuropathic Pain Associated With Diabetic Peripheral Neuropathy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 452
- 主要终点
- Mean Change From Baseline to Week 5 in Average Daily Pain Score (ADPS) Following Treatment With DS-5565 Compared to Pregabalin and Placebo
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability and effectiveness of DS-5565 compared to placebo (inactive substance) and pregabalin in diabetic subjects with DPN.
详细描述
Diabetic peripheral neuropathy (DPN) affects up to 50% of patients who have diabetes for at least 25 years. Up to 26% of all patients with DPN experience neuropathic pain. DPN pain contributes to sleep disorders, depression, and anxiety, which together may have an impact on a patient's well-being and quality of life.
There are currently several drugs used to treat painful DPN. For example, Lyrica® (pregabalin) is approved by the United States Food and Drug Administration (FDA) to treat neuropathic pain associated with DPN and is commonly prescribed. The dosage of the FDA-approved drugs is limited by side-effects such as dizziness, sleepiness, weight gain and swelling of the hands, legs, and feet. As a result, many patients suffering from DPN pain do not get satisfactory pain relief.
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
- •Age > 18 years of age
- •Able to give informed consent and willing to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures
- •Type 1 or type 2 diabetes with a hemoglobin A1c (HbA1c) ≤ 10% at Screening and on a stable antidiabetic medication regimen for at least 30 days prior to Screening (insulin therapy is acceptable)
- •Painful distal symmetrical sensorimotor polyneuropathy (as per American Society of Pain Educators guidelines ) diagnosed for at least 6 months, based on neurological history and/or examination; diagnosis includes absent or reduced deep tendon reflexes at both ankles
- •At Screening, a pain score of ≥ 40 mm on the SF-MPQ VAS
- •At Randomization, a pain score of ≥ 40 mm on the SF-MPQ VAS and an ADPS of ≥ 4 on the 11-point NRS, the latter calculated from a minimum of 4 pain ratings in daily diaries obtained during the 1-week Baseline Period (prior to randomization)
- •Creatinine clearance > 60 mL/min (estimated using the Cockcroft-Gault equation)
- •Antidiabetic and other medications anticipated to remain stable and constant during the study period
- •Women of child bearing potential (WOCBP) must be using an adequate method of contraception as detailed in the protocol to avoid pregnancy during the study and for 4 weeks after study completion
排除标准
- •Diagnosis of mononeuropathy
- •Use of concomitant medications that may confound assessments of efficacy and/or safety (see Section 5.2)
- •Major psychiatric disorders
- •Have had a malignancy other than basal cell carcinoma within the past 2 years
- •At Visit 1, have a white blood cell count < 2500/mm3, neutrophil count < 1500/mm3, or platelet count < 100 x 103/mm3
- •Clinically significant unstable diabetes mellitus, unstable hepatic, respiratory, or hematologic illness, unstable cardiovascular disease (including myocardial infarction in the 3 months prior to Visit 1), or symptomatic peripheral vascular disease
- •Clinically significant findings on the Screening ECG
- •History of pernicious anemia, untreated hypothyroidism, chronic hepatitis B, hepatitis B within the past 3 months, or human immunodeficiency virus infection
- •Amputations of body parts other than toes
- •Prior therapeutic failure of pregabalin or gabapentin (considered unresponsive or intolerant to treatment); therapeutic failure implies lack of efficacy following full titration to effective doses (eg, 300 mg/day for pregabalin)
- •Known hypersensitivity to pregabalin or gabapentin
- •Requirement for concomitant anticonvulsant and antidepressant therapy, with the exception of stable doses of SSRIs
- •Neurologic disorders unrelated to DPN that may confound the assessment of pain associated with DPN
- •Skin conditions that could alter sensation
- •Other sources of pain that may confound assessment or self-evaluation of the pain due to DPN
- •Abuse of prescription medications, street drugs or alcohol (including alcohol dependence) within the last 1 year
- •Current enrollment in another investigational study, participation in another investigational study with the past 30 days, or other current or recent use of any investigational drug
- •Pregnancy (as based on lab test results) or breast feeding
- •Laboratory values exceeding limits listed in Table 4.1 of the protocol
研究组 & 干预措施
DS-5565 20 mg total per day
DS-5565 20 mg/day (one 10 mg tablet in the morning and one 10 mg tablet at bedtime)
干预措施: DS-5565 tablet (Drug)
DS-5565 20 mg total per day
DS-5565 20 mg/day (one 10 mg tablet in the morning and one 10 mg tablet at bedtime)
干预措施: placebo capsule (Drug)
DS-5565 5mg nighttime
DS-5565 5 mg/day (one 5 mg tablet at bedtime)
干预措施: DS-5565 tablet (Drug)
DS-5565 5mg nighttime
DS-5565 5 mg/day (one 5 mg tablet at bedtime)
干预措施: placebo capsule (Drug)
DS-5565 10 mg at bedtime
DS-5565 10 mg/day (one 10 mg tablet at bedtime)
干预措施: DS-5565 tablet (Drug)
DS-5565 10 mg at bedtime
DS-5565 10 mg/day (one 10 mg tablet at bedtime)
干预措施: placebo capsule (Drug)
DS-5565 15 mg at bedtime
DS-5565 15 mg/day (one 5 mg tablet plus one 10 mg tablet at bedtime)
干预措施: DS-5565 tablet (Drug)
DS-5565 15 mg at bedtime
DS-5565 15 mg/day (one 5 mg tablet plus one 10 mg tablet at bedtime)
干预措施: placebo capsule (Drug)
DS-5565 30 mg total per day
DS-5565 30 mg/day (one 5 mg tablet plus one 10 mg tablet in the morning and one 5 mg tablet plus one 10 mg tablet at bedtime)
干预措施: DS-5565 tablet (Drug)
DS-5565 30 mg total per day
DS-5565 30 mg/day (one 5 mg tablet plus one 10 mg tablet in the morning and one 5 mg tablet plus one 10 mg tablet at bedtime)
干预措施: placebo capsule (Drug)
Pregabalin 300 mg total per day
Pregabalin 300 mg/day (two 150 mg capsules, in the morning and at bedtime)
干预措施: pregabalin capsule (Drug)
Pregabalin 300 mg total per day
Pregabalin 300 mg/day (two 150 mg capsules, in the morning and at bedtime)
干预措施: Placebo tablet (Drug)
结局指标
主要结局
Mean Change From Baseline to Week 5 in Average Daily Pain Score (ADPS) Following Treatment With DS-5565 Compared to Pregabalin and Placebo
时间窗: Baseline up to Week 5 postdose, up to 10 months total follow up
Average daily pain score (ADPS) is a participant-reported instrument that measures pain intensity using an 11-point numeric rating scale (NRS) where 0 is defined as no pain and 10 is defined as worst possible pain. Higher scores indicate worse pain intensity level. The change from baseline to Week 5 is reported where a negative value is considered an improvement in pain intensity. A minimally meaningful effect was defined as a decrease of at least 1.0 point \[scale of 0 to 10\] versus placebo).
次要结局
- Average Daily Pain Score Responder Rates Based on ≥30% and ≥50% Decrease From Baseline at Endpoint) Following Treatment With DS-5565 or Placebo Compared to Pregabalin(Baseline up to Week 5 postdose, up to 10 months total follow up)
- Short-Form McGill Pain Questionnaire (SF-MPQ) Sensory and Affective Scores Change From Baseline to Endpoint Following Treatment With DS-5565 Compared to Pregabalin and Placebo(Baseline up to Week 5 postdose, up to 10 months total follow up)
- Mean Change From Baseline to End-of-Treatment in Average Daily Sleep Interference Score Following Treatment With DS-5565 Compared to Pregabalin and Placebo(Baseline up to Week 5 postdose, up to 10 months total follow up)
- Least Square Means of Average Daily Pain Score by Week Mixed Effects Model for Repeated Measures (MMRM) Following Treatment With DS-5565 Compared to Pregabalin and Placebo(Baseline up to Week 5 postdose, up to 10 months total follow up)
- Short-Form McGill Pain Questionnaire (SF-MPQ) Total Score and Visual Analog Scale Change From Baseline to Endpoint Following Treatment With DS-5565 Compared to Pregabalin and Placebo(Baseline up to Week 5 postdose, up to 10 months total follow up)
- Short-Form McGill Pain Questionnaire (SF-MPQ) Present Pain Intensity Change From Baseline to Endpoint Following Treatment With DS-5565 Compared to Pregabalin and Placebo(Baseline up to Week 5 postdose, up to 10 months total follow up)
- Mean Change From Baseline to Endpoint of Modified Brief Pain Inventory (BPI) Subscale, Interference With Daily Functions, Following Treatment With DS-5565 Compared to Pregabalin and Placebo(Baseline up to Week 5 postdose, up to 10 months total follow up)
- Mean Change From Baseline to Endpoint of Modified BPI Subscales, Worst, Least and Average Pain Intensity, Following Treatment With DS-5565 Compared to Pregabalin and Placebo(Baseline up to Week 5 postdose, up to 10 months total follow up)
- Mean Change From Baseline to Endpoint of Modified BPI Subscale, Pain Right Now, Following Treatment With DS-5565 Compared to Pregabalin and Placebo(Baseline up to Week 5 postdose, up to 10 months total follow up)
- Mean Change From Baseline to Endpoint of Modified BPI Subscale, Relief From Pain, Following Treatment With DS-5565 Compared to Pregabalin and Placebo(Baseline up to Week 5 postdose, up to 10 months total follow up)
- Patient Global Impression of Change at End-of-Treatment or Early Termination Following Treatment With DS-5565 Compared to Pregabalin and Placebo(Baseline up to Week 5 postdose, up to 10 months total follow up)
- Drug-related Treatment-Emergent Adverse Events (n ≥2 Participants in Any Treatment Group) Following Treatment With DS-5565 Compared to Pregabalin and Placebo(From the time of signing the informed consent form (ICF) up to 10 months postdose)