A Phase 2, Randomized, Double-Blind, Placebo Controlled, Dose-Ranging Study to Evaluate LY3556050 in Adult Participants With Diabetic Peripheral Neuropathic Pain
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 404
- 试验地点
- 133
- 主要终点
- Mean Change from Baseline for Average Pain Intensity Numeric Rating Scale (API-NRS)
研究概览
简要总结
The main purpose of this study is to determine the safety and efficacy of LY3556050 versus placebo in participants with diabetic peripheral neuropathic pain (DPNP). The study will lasts approximately 24 weeks, across 3 study periods.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have a history and current diagnosis of Type 1 Diabetes (T1D) or Type 2 Diabetes (T2D) diagnosed for at least 6 months prior to screening.
- •Have a stable glycemic control on stable diabetes treatment regimen for at least 90 days prior to day 1 with a hemoglobin A1c (HbA1c) ≤10 for T1D and HbA1c ≤11 for participants with T2D at time of screening.
- •Have a history of daily peripheral neuropathic pain for at least 12 weeks based on participant report or medical history.
- •Have a visual analog scale (VAS) pain value ≥40 and <95 during screening.
- •Have presence of diabetic peripheral neuropathy of symmetrical nature and in lower extremities for ≥6 months and diagnosed by a score of Part B ≥3 on Michigan Neuropathy Screening Instrument
- •Are willing to maintain a consistent regimen of any ongoing nonpharmacologic pain-relieving therapies (for example, physical therapy) and will not start any new nonpharmacologic pain-relieving therapies during study participation.
- •Are willing to discontinue all medications taken for chronic pain conditions, except allowed concomitant pain medication permitted per protocol, for the duration of the study
- •Have a body mass index ≤45 kilogram/square meter (kg/m²) (inclusive).
- •Are men, or women able to abide by reproductive and contraceptive requirements.
排除标准
- •History of other potentially causative and/or confounding sources of pain that may impair self-assessment of pain due to DPNP.
- •Have had a procedure within the past 6 months intended to produce permanent sensory loss in the target area of interest (for example, ablation techniques.
- •Have had cancer within 2 years of baseline, except for cutaneous basal cell or squamous cell carcinoma resolved by excision.
- •Are, in the judgment of the investigator, actively suicidal and therefore deemed to be at significant risk for suicide.
- •Have in the judgement of the investigator, an acute, serious, or unstable medical condition or a history or presence of any other medical illness that would preclude study participation.
- •Have a positive HIV test result at screening.
- •Have a surgery planned during the study for any reason.
- •Have a substance use disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders (5th edition; DSM-5; American Psychiatric Association)
研究组 & 干预措施
Placebo
Participants received a matching dose of placebo administered orally twice daily (BID) over a period of 12 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Mean Change from Baseline for Average Pain Intensity Numeric Rating Scale (API-NRS)
时间窗: Baseline, Week 12
Mean Change From Baseline in Average Pain Intensity (API) as Measured by Weekly Average of Numeric Rating Scale (NRS) - Bayesian Model Averaging (BMA) Dose-response Model
时间窗: Baseline, Week 12
* The NRS was a single-item numeric scale used to describe pain severity. Participants were asked to rate their average pain over the past 24 hours, on a scale of 0 to 10: 0 = no pain, and 10 = pain as bad as you can imagine; a higher score indicates worse outcome (greater pain severity). * The mixed-model repeated measures (MMRM) model included the fixed, centered, categorical effects of region, baseline NRS average pain score, as well as concurrent use of allowed concomitant medications (yes vs. no based on interactive web response system \[IWRS\]), and visit. The adjusted dose response value from the MMRM was used for fitting a Bayesian model averaging (BMA) dose-response model. * Posterior mean change from baseline, 95 percent (%) credible interval was derived using Bayesian mixed model repeated measures. Data presented were posterior mean with 95% credible interval.
Mean Change From Baseline in Average Pain Intensity (API) as Measured by Weekly Average of Numeric Rating Scale (NRS) - Frequentist Repeated Measures (FRM) Analysis
时间窗: Baseline, Week 12
* The NRS was a single-item numeric scale used to describe pain severity. Participants were asked to rate their average pain over the past 24 hours, on a scale of 0 to 10: 0 = no pain, and 10 = pain as bad as you can imagine; a higher score indicates worse outcome (greater pain severity). * The Least Squares (LS) Mean was calculated using a frequentist repeated measures (FRM) analysis, where Change = treatment, time interval, treatment \* time interval, region, average baseline pain severity category (mild or moderate versus \[vs.\] severe), concurrent use of allowed concomitant medication as entered in IWRS (yes versus no).
次要结局
- Mean Change from Baseline for Patient Reported Outcomes Measurement Information System (PROMIS) Pain Interference Short Form (SF)8a(Baseline, Week 12)
- Mean Change from Baseline for PROMIS Sleep Disturbance (SD)8b(Baseline, Week 12)
- Mean Change from Baseline for Patient's Global Impression of Illness (PGI) Severity as Measured by PGI-Severity(Baseline, Week 12)
- Mean Change from Baseline for Patient's Global Impression of Illness Status as Measured by PGI-Status(Baseline, Week 12)
- Mean Change from Baseline for Patient's Global Impression of Change as Measured by PGI-Change(Baseline, Week 12)
- Mean Change from Baseline for Neuropathy Total Symptom Score-6 (NTSS-6)(Baseline, Week 12)
- Summary of Frequency, Timing and Amount of Rescue Medication Used During the Treatment Period(Baseline to Week 12)
- Mean Change from Baseline for Worst Pain Intensity Numeric Rating Scale (WPI-NRS)(Baseline, Week 12)
- Mean Change from Baseline for Pain Interference with Sleep(Baseline, Week 12)
- Mean Change from Baseline for PROMIS Physical Functioning Short Form (SF)10a(Baseline, Week 12)
- Pharmacokinetics (PK): Plasma Concentration of LY3556050(Baseline to Week 12)
- Mean Change From Baseline in Worst Pain Intensity (WPI) as Measured by Weekly Average of Numeric Rating Scale (NRS)(Baseline, Week 12)
- Mean Change From Baseline in Patient-Reported Outcomes Measurement Information System Pain Interference Short Form 8a (PROMIS PI SF8a)(Baseline, Week 12)
- Mean Change From Baseline in Patient's Global Impression (PGI) of Illness Status as Measured by PGI-Status(Baseline, Week 12)
- Mean Change From Baseline in Pain Interference With Sleep(Baseline, Week 12)
- Mean Change From Baseline in Patient-Reported Outcomes Measurement Information System Physical Functioning Short Form 10a (PROMIS PF SF10a)(Baseline, Week 12)
- Mean Change From Baseline in Patient-Reported Outcomes Measurement Information System Sleep Disturbance Short Form 8b (PROMIS SD SF8b)(Baseline, Week 12)
- Mean Change From Baseline in Patient's Global Impression of Illness Severity as Measured by Patient's Global Impression-Severity (PGI-Severity)(Baseline, Week 12)
- Patient's Global Impression of Change as Measured by Patient's Global Impression-Change (PGI-Change)(Week 12)
- Mean Change From Baseline in Neuropathy Total Symptom Score-6 (NTSS-6)(Baseline, Week 12)
- Total Amount of Rescue Medication Use as Measured by Average Daily Dosage(Week 12)
- Percentage of Participants With at Least One Use of Rescue Medication(Week 12)
- Pharmacokinetics (PK): Plasma Concentration of Mazisotine(Postdose at Week 12)