A 2-part trial to learn more about how BAY1817080 works, how safe it is, and what the right dose is for participants with diabetic neuropathic pai

Phase 1

• Conditions: europathic pain associated with diabetic peripheral neuropathy; MedDRA version: 21.1Level: LLTClassification code 10067547Term: Diabetic peripheral neuropathic painSystem Organ Class: 100000004852; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2020-002066-14-FI
• Lead Sponsor: Bayer AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-10-02
• Last Update Posted: 4 January 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 440

Inclusion Criteria

1. Adults = 18 years of age at the time of signing the informed consent.

2. 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.

3. 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.

4. Neuropathic pain according to the DN4 questionnaire.

5. Women of childbearing potential must agree to use acceptable effective or highly effective birth control methods.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 300
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 140

Exclusion Criteria

1. 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).

2. 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).

3. 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.

4. Major surgery or radiological procedures (e.g. PTA 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.

5. Symptomatic peripheral arterial disease in lower or upper extremities, including diabetic ulcers.

6. 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.

7. History or current diagnosis of electrocardiogram (ECG) abnormalities indicating significant risk of safety for study participants.

8. Moderate-to-severe hepatic impairment defined as Child-Pugh Class B or C.

9. 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.

10. 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).

11. ALT >2xULN, or AST >2xULN, or total bilirubin greater than ULN, or alkaline phosphatase (AP) >2x ULN, or INR greater than ULN (unless related to

anticoagulation treatment) at screening.

12. 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).

13. 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.

14. Uncontrolled hypertension despite optimal treatment with antihypertensive(s), indicated by a sitting systolic blood pressure = 180 mmHg and/or diastolic blood pressure = 110 mmHg.

15. Any other disease or condition 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., excessively low body weight, chronic bowel diseases, Crohn's disease and ulcerative colitis)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Part A: to evaluate the efficacy of BAY1817080 on the treatment of pain associated with DNP as compared with placebo <br><br><br><br>Part B: to describe the dose-response relationship and evaluate the efficacy of BAY1817080 on the treatment of pain associated with DNP as compared with placebo (and active comparator);Secondary Objective: To further evaluate the efficacy of BAY1817080 on pain and associated symptoms<br><br><br><br>To evaluate the safety and tolerability of BAY1817080 on the treatment of pain associated with DNP as compared with placebo in Part A and placebo as well as active comparator in Part B;Primary end point(s): 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;Timepoint(s) of evaluation of this end point: Part A: from baseline to end of intervention (in total up to 9 weeks)<br><br>Part B: from baseline to end of intervention (in total up to 13 weeks)