A Phase 2a, Randomized, Double-Blind, Placebo- and Active-Controlled, Parallel-Group, Multicenter Study to Assess the Safety and Efficacy of ADL5859 100 mg BID in Subjects With Neuropathic Pain Associated With Diabetic Peripheral Neuropathy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 226
- 试验地点
- 27
- 主要终点
- Change From Baseline in Mean Numeric Pain Rating Scale (NPRS) Score
研究概览
简要总结
The purpose of this study is to evaluate the effectiveness of ADL5859 in relieving the pain associated with diabetic peripheral neuropathy (DPN) compared with placebo and duloxetine (a marketed drug approved for the treatment of painful DPN). The pain symptoms of DPN are thought to be due to damage to nerves caused by the diabetes.
详细描述
Participants were permitted to take acetaminophen 650 to 975 mg every 4 to 6 hours (up to a total of 4 grams in 24 hours) as needed for 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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female participants between 18 and 75 years of age, inclusive
- •Body weight of at least 45 kilograms (kg)
- •Diabetes mellitus (type I or II) that is documented to be under stable glycemic control over a period of at least 3 months, as indicated by a glycosylated hemoglobin (HbgAIC) of less than or equal to 12% and a stable dose of insulin or oral diabetic medication for 90 days prior to starting study medication
- •No change in diabetic medications is planned for the duration of the study
- •Evidence of symmetrical, bilateral pain in the lower extremities due to diabetic peripheral neuropathy (DPN)
- •Presence of daily pain due to DPN for at least 3 months
- •Score greater than or equal to 3 on the physical examination portion of the Michigan Neuropathy Screening Instrument (MNSI)
- •Average weekly pain score of greater than or equal to 4 on the numeric pain rating scale (NPRS) for symmetrical neuropathic pain in the feet and legs
- •For male participants, be surgically sterile or agree to use an appropriate method of contraception
- •For female participants of childbearing potential, be surgically sterile or using an intrauterine device, or injectable, transdermal, or combination oral contraceptive deemed highly effective by the Food and Drug Administration (FDA)
- •Be willing and able to comply with the protocol requirements
- •Be able to understand and willing to provide written informed consent in English
排除标准
- •Presence of pain conditions that cannot be distinguished from DPN
- •Presence of significant renal disease, as indicated by a serum creatinine greater than or equal to 2.0 milligrams per deciliter (mg/dL), or presence of significant hepatic disease
- •Have a history of a seizure disorder
- •Presence of serious or unstable cardiovascular disease, respiratory disease, hematologic illness, or a psychiatric condition
- •History of evidence of symptomatic orthostatic hypotension
- •History of a major depressive disorder, generalized anxiety disorder, eating disorder, or substance abuse (including alcohol) within the past year
- •History or evidence of mania, bipolar disorder, or psychosis
- •History of allergy to acetaminophen or duloxetine
- •Score of greater than or equal to 18 on the Beck Depression Inventory II (BDI-II) or score of greater than zero on Item 9 of the BDI-II
- •Use of any of the following concomitant medications: fluvoxamine; quinolone antimicrobials (ciprofloxacin and enoxacin); selective serotonin reuptake inhibitors (SSRIs); serotonin norepinephrine reuptake inhibitors (SNRIs); tricyclic antidepressants; opioids; nonsteroidal anti-inflammatory drugs (NSAIDS); anticonvulsants; aspirin (with the exception of low-dose aspirin as cardiovascular prophylaxis); or cytochrome P4503A (CYP3A) and P-glycoprotein transporter inhibitors
- •Pregnant, lactating, or plans to become pregnant during the study
- •Presence of foot or toe amputation
- •Participation in another study with an investigational compound within the previous 30 days prior to study medication administration, or concurrent participation in another clinical study
研究组 & 干预措施
ADL5859
2 x 50 milligrams (mg) ADL5859 capsules administered orally once in the morning and once in the evening for 28 days
干预措施: ADL5859 (Drug)
Duloxetine
2 x 30 mg duloxetine capsules administered orally once in the morning and 2 placebo capsules filled with lactose administered orally once in the evening for 28 days
干预措施: Duloxetine (Drug)
Duloxetine
2 x 30 mg duloxetine capsules administered orally once in the morning and 2 placebo capsules filled with lactose administered orally once in the evening for 28 days
干预措施: Placebo (Drug)
Placebo
2 placebo capsules filled with lactose administered orally once in the morning and once in the evening for 28 days
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in Mean Numeric Pain Rating Scale (NPRS) Score
时间窗: Baseline, Week 4
The NPRS is an 11-point scale (0 to 10) with 0 indicating no pain and 10 indicating the worst possible pain. The mean of the daily average scores were calculated from the NPRS pain assessments obtained up to 3 times per day over a 7-day period. Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) with treatment group as a main factor and baseline NPRS score as a covariate. Change from Baseline = NPRS at baseline - NPRS at Week 4; a positive number in the LS mean indicates a reduction in pain intensity from baseline.
次要结局
- Change From Baseline in the Evening Assessment of the 24-hour Overall Mean Pain Intensity Score(Baseline, Week 4)
- Change in Sleep Interference Scale (SIS) From Baseline(Baseline, Week 4)
- Percentage of Responders(Baseline, Week 4)
- Patient Global Impression of Change (PGIC)(Week 4)
- Change From Baseline in NPRS at Rest in the Clinic(Baseline, Week 1, Week 2, Week 3, Week 4)
- Change From Baseline in NPRS After Walking 50 Feet in the Clinic(Baseline, Week 1, Week 2, Week 3, Week 4)