A Randomized, Placebo-controlled, Double-blind, Parallel-group, Multicenter Combined Phase 2a/2b Study to Assess the Efficacy and Safety of BAY 1817080 in Patients With Diabetic Neuropathic Pain
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Bayer
- 入组人数
- 154
- 试验地点
- 42
- 主要终点
- Change in weekly mean 24-hour average pain intensity score using the 11-point Numeric Rating Scale (NRS) from baseline to the end of intervention
研究概览
简要总结
People suffering from diabetes often have high blood sugar levels. Over time this can affect many organs including the nerves in hands and feet and can cause a nerve pain called diabetic neuropathic pain (DNP). There are treatments for DNP but in many patients they do not reach a good pain reduction and have unwanted side effects.
In this trial, the researchers will look at how BAY1817080 works and how safe it is. They will compare it to a placebo or another treatment for DNP called pregabalin. A placebo looks like a treatment but does not have any medicine in it. The researchers will use a placebo to learn if the participants' results are due to BAY1817080 or if the results could be due to chance. The researchers will also learn more about the right dose of BAY1817080 for these participants.
The trial will include participants who have DNP and either type 1 or type 2 diabetes. It will include about 440 men and women who are at least 18 years old.
This trial will have 2 parts. In Part 1, the participants will take either BAY1817080 or the placebo. These treatments will be taken as a tablet by mouth twice a day for 8 weeks. In Part 2, participants will take BAY 1817080, pregabalin, or a matching placebo of either treatment. BAY1817080 and a placebo will be taken as a tablet by mouth twice a day for 12 weeks. Pregabalin and a placebo will be taken as a capsule by mouth twice a day for 12 weeks.
The participants in Part 1 will visit their trial site 6 times. The participants in Part 2 will visit their trial site 7 times. At these visits, the doctors will ask the participants if they have any health problems, take blood samples, and do a physical exam. They will also ask the participants to complete questionnaires about their pain and other symptoms.
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
- •Adults ≥ 18 years of age at the time of signing the informed consent.
- •At the time of screening, have documented diagnosis of type 1 OR type 2 diabetes mellitus (DM) with painful distal symmetrical sensorimotor neuropathy of more than 6 months duration according to modified Toronto Clinical Neuropathy Score.
- •Weekly mean 24-hour average pain NRS ≥ 4 with adequate variability (not the same score on all daily pain ratings) and compliance (non-missing pain score on at least 6 out of 7 consecutive days) in daily pain recording during the 7 day NRS baseline period.
- •Neuropathic pain according to the DN4 questionnaire (Douleur Neuropathique 4 Questions).
- •Women of childbearing potential must agree to use acceptable effective or highly effective birth control methods.
排除标准
- •Any differential diagnosis of peripheral diabetic neuropathy (PDN) including but not limited to other neuropathies (e.g. vitamin B12 deficiency, Chronic Inflammatory Demyelinating Polyneuropathy), polyradiculopathies, central disorders (e.g. demyelinating disease), or rheumatological disease (e.g. foot arthritis, plantar fasciitis).
- •Any other diseases or conditions that according to the investigator can compromise the function of the body systems and could result in altered absorption, excessive accumulation, impaired metabolism, or altered excretion of the study intervention (e.g. chronic bowel disease, Crohn's disease and ulcerative colitis).
- •Any serious or unstable diseases or conditions including psychiatric disorders that might interfere with the conduct of the study or the interpretation of the results.
- •Major surgery or radiological procedures (e.g. PTA (Percutaneous transluminal angioplasty) and stenting of peripheral vascular lesions in lower extremities) within 3 months before screening visit or scheduled during the study period, which might interfere pain response evaluation.
- •Symptomatic peripheral arterial disease in lower or upper extremities, including diabetic ulcers.
- •Previous use of strong opioids (e.g. oxymorphone, oxycodone) for neuropathic pain anytime, or topical use of capsaicin within 3 months prior to the screening visit.
- •History or current diagnosis of electrocardiogram (ECG) abnormalities indicating significant risk of safety for study participants.
- •Moderate-to-severe hepatic impairment defined as Child-Pugh Class B or C.
- •Have platelets ≤ 100 x 109/L, or neutrophil count < 1.2 x 109/L (or equivalent), hemoglobin ≤ 100 g/L for women or hemoglobin ≤ 110 g/L for men at screening.
- •Glycemic control unstable (hemoglobin HbA1c ≥11%) within 3 months prior to screening (e.g. ketoacidosis requiring hospitalization, any recent episode of hypoglycemia requiring assistance through medical intervention, uncontrolled hyperglycemia).
- •ALT >2xULN, or AST >2xULN, or total bilirubin greater than ULN, or alkaline phosphatase (AP) >2xULN, or INR greater than ULN (unless related to anticoagulation treatment) at screening.
- •Positive hepatitis B virus surface antigen (HBsAg) or positive hepatitis C virus antibodies (anti-HCV) and detection of mRNA (HCV-mRNA tested only if hepatitis C virus antibodies detected).
- •Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m^2 calculated by Modification of Diet in Renal Disease (MDRD) formula (local formulas will be used where applicable.
- •Uncontrolled hypertension despite optimal treatment with antihypertensive(s), indicated by a sitting systolic blood pressure ≥ 180 mmHg and/or diastolic blood pressure ≥ 110 mmHg.
研究组 & 干预措施
Part A: BAY1817080 150 mg BID
In Part A, Participants will be randomized to this arm with BAY1817080 150 mg BID.
干预措施: BAY1817080 (Drug)
Part A: Placebo BID
In Part A, Participants will be randomized to this arm with placebo for BAY1817080.
干预措施: Placebo for BAY1817080 (Drug)
Part B: BAY1817080 25 mg BID
In Part B, New participants will be screened for this part of the study and will be randomized to this arm with BAY1817080 25 mg BID and placebo for pregabalin.
干预措施: BAY1817080 (Drug)
Part B: BAY1817080 25 mg BID
In Part B, New participants will be screened for this part of the study and will be randomized to this arm with BAY1817080 25 mg BID and placebo for pregabalin.
干预措施: Placebo for Pregabalin (Drug)
Part B: BAY1817080 75 mg BID
In Part B, New participants will be screened for this part of the study and will be randomized to this arm with BAY1817080 75 mg BID and placebo for pregabalin.
干预措施: BAY1817080 (Drug)
Part B: BAY1817080 75 mg BID
In Part B, New participants will be screened for this part of the study and will be randomized to this arm with BAY1817080 75 mg BID and placebo for pregabalin.
干预措施: Placebo for Pregabalin (Drug)
Part B: BAY1817080 150 mg BID
In Part B, New participants will be screened for this part of the study and will be randomized to this arm with BAY1817080 150 mg BID and placebo for pregabalin.
干预措施: BAY1817080 (Drug)
Part B: BAY1817080 150 mg BID
In Part B, New participants will be screened for this part of the study and will be randomized to this arm with BAY1817080 150 mg BID and placebo for pregabalin.
干预措施: Placebo for Pregabalin (Drug)
Part B: Placebo BID
In Part B, New participants will be screened for this part of the study and will be randomized to this arm with placebo for BAY1817080 and placebo for pregabalin.
干预措施: Placebo for BAY1817080 (Drug)
Part B: Placebo BID
In Part B, New participants will be screened for this part of the study and will be randomized to this arm with placebo for BAY1817080 and placebo for pregabalin.
干预措施: Placebo for Pregabalin (Drug)
Part B: Pregabalin
In Part B, New participants will be screened for this part of the study and will be randomized to this arm with placebo for BAY1817080 and pregabalin.
干预措施: Placebo for BAY1817080 (Drug)
Part B: Pregabalin
In Part B, New participants will be screened for this part of the study and will be randomized to this arm with placebo for BAY1817080 and pregabalin.
干预措施: Pregabalin (Drug)
结局指标
主要结局
Change in weekly mean 24-hour average pain intensity score using the 11-point Numeric Rating Scale (NRS) from baseline to the end of intervention
时间窗: Part B: from baseline to end of intervention (in total up to 13 weeks)
NRS is an one-item assessment of average neuropathic pain intensity which is presented as an 11-point Likert scale with 0 as "no pain" and 10 as "worst imaginable pain".
次要结局
- Patient Global Impression of Change (PGI-C) at the end of intervention(Part A: at visit 5 (day 29 +/-2) and at end of intervention (day 57 +/- 2). Part B: at visit 5 (day 29 +/-2), at visit 7 (day 57 +/- 2) and at end of intervention (day 85 +/-2))
- Change in Neuropathic Pain Symptom Inventory (NPSI) score from baseline to the end of intervention(Part A: at visit 2, visit 4 (day 15 +/- 2), visit 5 (day 29 +/-2) and visit 7 EOI (day 57 +/-2). Part B: at visit 2, visit 4 (day 15 +/- 2), visit 5 (day 29 +/-2), visit 7 (day 57 +/-2) and visit 8 EOI (day 85 +/-2).)
- The proportion of participants achieving a ≥30% and a ≥50% reduction in weekly mean 24-hour average pain intensity score (i.e. responder rates using NRS)(Part A: from baseline to end of intervention (in total up to 9 weeks). Part B: from baseline to end of intervention (in total up to 13 weeks))
- Number of participants with treatment emergent adverse events (TEAE)(Start of intervention to 14 days after stop of treatment)