Randomized, Double-blind, Placebo-controlled, Multicenter Phase IIb Clinical Trial of Spray YJ001 for the Treatment of Diabetic Peripheral Neuropathic Pain

Inclusion Criteria:

• Male or female, between 18 to 75 years of age at screening
• The subject is diagnosed with Type 1 or Type 2 diabetes with a disease duration of at least 1 year
• The subject is diagnosed with diabetic peripheral neuropathic pain (DPNP, acceptable diagnostic certificates from other tertiary or higher-level hospitals.). Pain duration ≥ 3 months
• Glycated hemoglobin level (HbA1c) ≤ 9%
• At the screening visits, the score on the 11-point Numerical Rating Scale (NRS) must be ≥4.0. During the 1-week run-in period, subjects must complete at least 15 NRS scores, including 5 scores taken at 6 hours post-dose, and the mean pain score should have been ≥4.0
• Subjects are willing and able to participate in study visits, treatment plans, laboratory tests, and other study procedures
• Consented to participate in this study and signed the written informed consent form (ICF).

Exclusion Criteria:

• Subjects who are known or suspected to be allergic to or have had severe adverse reactions to the ingredients of YJ001 , the ingredients of YJ001 placebos for spray use, aspirin, salicylic acid, or YJ001-like drugs (such as 5-aminosalicylic acid, sulfasalazine, and salicylate esters)
• Subjects who participated in the YJ001 clinical study and received the investigational product before
• Subjects had widespread systemic pain that could affect the evaluation of pain at the administration site, as judged by the investigator; or the pain in the hand or more proximal area is more severe than in the foot
• Subjects with severe peripheral vascular disease (such as intermittent claudication) who were deemed by the investigator to be unsuitable for participation in the study at the time of screening
• Subjects have pain caused by non-diabetic peripheral neuropathy, such as active osteoarthritis, stage II or higher peripheral arterial disease, lumbar disc herniation, vitamin B deficiency, alcoholism, herpes neuralgia, vasculitis, and the somatoform pain caused by psychological disorders such as severe depression and anxiety, which may affect the investigator's score for DPNP
• Subjects had autoimmune diseases associated with elevated inflammatory factors at the time of screening, such as rheumatoid arthritis, inflammatory bowel disease, psoriasis, and atopic dermatitis
• Presence of a skin disease in the skin area where the drug is administered, in the investigator's judgment, may affect the score for diabetic peripheral neuropathic pain; or the skin at the administration site is redness, inflamed, damaged, or otherwise affected in a way that may interfere with drug absorption; or, in the investigator's judgment, the subject has tattoos or other skin abnormalities that may interfere with the study objectives
• The skin condition of the administration site scored >2
• Malignant tumors, except for non-metastatic basal cell carcinoma or squamous cell carcinoma of the skin that has been appropriately treated or surgically removed, or in situ cervical cancer
• Amputation of any part of the body other than the fingertips or toes
• Combined with diabetes-related foot ulcers, infections, or gangrene
• Acute diabetic metabolic complications, such as diabetic ketoacidosis, lactic acidosis, hyperosmolar hyperglycemic syndrome, or diabetic hyperosmolar coma
• One or more episodes of severe hypoglycemia (defined as requiring assistance from others to obtain carbohydrates, glucagon, or other rescue measures) during the 6 months prior to screening or during the run-in period
• During the one-week run-in period, the subject's NRS pain scores was <3 more than three times
• Subjects who have used transcutaneous electrical nerve stimulation (TENS), acupuncture, or other therapeutic measures within two weeks prior to inclusion, or who require combined transcutaneous electrical nerve stimulation (TENS) or acupuncture treatment during the treatment period
• Use of topical analgesics for the treatment of DPNP (such as capsaicin patches, lidocaine patches, etc.) within 2 weeks prior to inclusion
• Abnormal liver and kidney function: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 times the upper limit of normal values, creatinine > 1.5 times the upper limit of normal values
• Combined severe cardiovascular and cerebrovascular diseases (such as second- or third-degree cardiac conduction block, heart failure classified as New York Heart Association （NYHA） Functional Classification III-IV, myocardial infarction, acute stroke, etc.)
• Combined severe respiratory, blood, and hematopoietic system diseases
• Subjects with other neurological disorders (such as cognitive impairment) that the investigator think it might affect the evaluation of diabetic peripheral neuropathic pain or self-assessment, or psychiatric patients who, in the investigator's judgment, are not suitable for participation in this trial
• Subjects with a known or suspected history of alcohol abuse, drug abuse, or dependence within the past year
• Pregnant or lactating women; male subjects (including their female partner) and female subjects of childbearing potential who plan to become pregnant or cannot guarantee the use of one or more contraceptive methods (common contraceptive methods include tubal ligation intrauterine devices, birth control pills, condoms, etc.) from the start of screening until three months after the end of the trial
• Screen subjects who have participated in other clinical trials within the past 3 months
• Other situations where the investigator considers it inappropriate to participate in this trial