YJ001 Spray for Diabetic Peripheral Neuropathic Pain

Inclusion Criteria:

• Aged ≥18 years, of either gender
• Diagnosed with type 1 or type 2 diabetes for at least 1 year
• Diagnosed with diabetic peripheral neuropathic pain (DPNP, other tertiary hospitals' diagnostic certificates are acceptable), with pain duration ≥6 months, and the most painful area being the foot
• Stable blood glucose control within 3 months prior to screening, i.e., glycated hemoglobin (HbA1c) ≤9.0% at screening. If the patient has been receiving hypoglycemic drug treatment at screening, stable treatment for at least 30 days is required;
• If the patient has been receiving neurotrophic, circulation-improving, and metabolic drug treatments at screening, stable dosing for at least 30 days is required. If the patient has discontinued neurotrophic, circulation-improving, and metabolic drug treatments at screening, the duration of drug withdrawal must meet at least 7 drug half-lives as determined by the investigator;
• If the patient has been receiving non-pharmacological treatments (including physiotherapy, massage, chiropractic treatment, psychological therapy, etc.) at screening, stable treatment for at least 12 weeks is required, and the treatment regimen must not be changed during the trial
• If the patient has not been receiving stable non-pharmacological treatments (including physiotherapy, massage, chiropractic treatment, psychological therapy, etc.), non-pharmacological treatment must be discontinued for at least 1 week prior to screening, and no additional non-pharmacological treatments are planned to be added during the trial
• Pain NRS score ≥4.0 and <9.0 at screening
• After the run-in period and before randomization, the trial participant meets all inclusion criteria and does not meet any exclusion criteria
• The ADPS score during the run-in period [defined as the average of the daily pain NRS scores calculated based on the patient diary card records excluding the day of randomization] is ≥4, and the trial participant completes at least 10 pain assessments during the run-in period (excluding the day of randomization); - Both pain VAS scores at screening and during the 2-day visit before randomization are ≥40mm and <90mm
• Medication adherence to the study drug during the run-in period is 80-120% (inclusive)
• The trial participant is willing and able to adhere to study visit schedules, treatment plans, laboratory tests, and other research procedures, agrees to participate in this trial, and signs a written informed consent form.

Participants in the second part of the trial must meet all the following criteria to be eligible for enrollment in the second part of this study.

• Trial participants who have completed the double-blind treatment period;
• Trial participants who are willing and capable of adhering to the study visit schedule, treatment plan, laboratory tests, and other research procedures.

Exclusion Criteria:

Experiment Part One

• Known or suspected to be allergic to or have serious adverse reactions to the active ingredients of Kligabalin Benzenesulfonate Capsules or any excipient ingredients, or allergic to or have serious adverse reactions to the ingredients of YJ001 Spray, the ingredients of YJ001 Spray Simulant, paracetamol, aspirin, salicylic acid or similar drugs of YJ001 (such as 5-aminosalicylic acid, sulfasalazine and salicylate);

• Previous use of calcium channel modulators such as pregabalin, gabapentin, krigabalin, and melogabalin without improvement in pain (reported by the patient);

• Those who have participated in the clinical study of YJ001 spray and received the study drug in the past;

• According to the research, the test participants are in the acute stage of diabetes peripheral neuropathic pain, or need surgery for focal compression neuropathy, or have widespread systemic pain that will affect the evaluation of pain at the drug delivery site. According to the judgment of the researchers, the evaluation of pain at the drug delivery site will be affected; Or more severe in the hands or closer areas than in the feet; Or the test participants have pain caused by non diabetes peripheral neuropathy, such as active osteoarthritis, lumbar disc herniation, vitamin B deficiency (vitamin B12, folic acid), alcoholism, herpetic neuralgia, vasculitis, and serious depression, anxiety and other psychological diseases, which will affect the researchers' evaluation of diabetes peripheral neuropathic pain;

• Participants who have severe peripheral vascular disease (such as intermittent claudication and lower limb arterial occlusion) during screening and are deemed unsuitable by the researchers to participate in the trial;

• Abnormal skin conditions at the site of administration can affect the determination of test results, such as:

  1. Those with a skin condition evaluation score greater than 2 points at the site of administration;
  2. There is skin disease in the affected skin area, which affects the investigator's evaluation of diabetes related peripheral neuropathic pain, or the skin at the administration site is red, swollen, inflamed, damaged or other conditions that affect drug absorption, or according to the investigator's judgment, the test participants have tattoos that may interfere with the research purpose;
  3. Patients with foot ulcers, infections and gangrene related to diabetes that have not recovered.

• Malignant tumor patients, except for non metastatic skin basal cell carcinoma or squamous cell carcinoma that has received appropriate treatment or resection, or cervical cancer in situ;

• Amputation of limbs other than the tips of fingers and toes;

• Complicated with acute metabolic complications of diabetes, such as diabetes ketoacidosis or lactic acidosis or hyperosmolar hyperglycemia syndrome or diabetes hyperosmolar coma;

• Within the 6 months prior to screening or during the introduction period, there has been one or more severe hypoglycemic events (referring to trial participants requiring assistance from others to obtain carbohydrates, glucagon, or other rescue measures);

• When comparing and screening, the ADPS scores of the experimental participants during the introduction period decreased by ≥ 30%; When comparing and screening, the VAS scores of the trial participants decreased by ≥ 30% during the first 2 days of random visits;

• Those who have been used within 2 weeks before screening or need to be combined with the following treatments during the planned trial: 1) transcutaneous electrical nerve stimulation (TENS), acupuncture and moxibustion treatment, infrared ray, laser, etc; 2) Local analgesics (such as NSAIDs, peppermint ointment, capsaicin patch, lidocaine patch, etc.) and opioid analgesics (such as morphine, tramadol, etc.);

• During the trial period, it is planned to add and combine non pharmacological treatments such as physical therapy, massage, spinal acupressure therapy, psychological therapy, etc;

• Before screening, within 7 drug half lives [14 hours for oral ibuprofen tablets and diclofenac sodium tablets, 5 days for naproxen tablets; 2 days for pregabalin capsules and gabapentin tablets, 7 days for krigabalin, 7 days for melogabalin, 4 days for carbamazepine; 2 days for venlafaxine tablets, 4 days for duloxetine, 12 days for amitriptyline, 2 weeks for traditional Chinese medicine], have received analgesic drugs [such as oral NSAIDs, calcium channel modulators (pregabalin, gabapentin, krigabalin, melogabalin) Participants in the trial of SNRIs drugs (such as duloxetine, venlafaxine, etc.), tricyclic antidepressants (such as amitriptyline, etc.), carbamazepine, oxcarbazepine, traditional Chinese medicine, etc.), or those who purchase and use the above drugs themselves during the trial, or those who need to add and use the above analgesic drugs for treatment during the trial (except for Clegabalin);

• During screening, test participants were associated with the following active infections with abnormal clinical significance, including hepatitis B (HBV), hepatitis C (HCV), syphilis, and human immunodeficiency virus (HIV):

Active hepatitis B is defined as: hepatitis B surface antigen positive and HBV-DNA detection value exceeding the upper limit of normal; Active hepatitis C is defined as: positive hepatitis C antibodies and HCV-RNA detection values exceeding the upper limit of normal; Positive for Treponema pallidum antibody (TP Ab) and positive for syphilis non-specific antibody titers; Known as a human immunodeficiency virus infection, or HIV antibody test result positive.

• Abnormal liver and kidney function during screening: AST or ALT ≥ 2.5 times the upper limit of normal value, creatinine ≥ 1.5 times the upper limit of normal value; Or accompanied by thyroid dysfunction that cannot be controlled with stable drug doses, or clinically significant abnormalities in thyroid function test results during screening that require treatment initiation; Or combined with severe cardiovascular and cerebrovascular diseases (such as grade II or III heart block, NYHA heart failure classified as III-IV, myocardial infarction, acute stroke, etc.), unstable diseases (such as cerebral infarction, acute coronary syndrome), severe respiratory, blood and hematopoietic system diseases;
• Those who have suicidal behaviors or suicidal tendencies in the past, or who are complicated with pernicious anemia, untreated hypothyroidism, or have other nervous system diseases (such as cognitive impairment), the researchers think that it may affect the evaluation of diabetes related peripheral neuropathic pain or affect the self rating, or the mental patients who are judged by the researchers to be not suitable for this trial;
• Known history of drug abuse, drug dependence, and/or alcohol abuse within the past year [drinking more than 14 servings per week (1 serving is equivalent to 360mL of beer, 45mL of 40% alcohol strong liquor, or 150mL of wine)]; 19.Pregnant and lactating women; Male trial participants (including their female partners) and female trial participants with fertility, who have planned to have children or cannot guarantee the use of one or more contraceptive measures (commonly used contraceptive measures include sterilization surgery, intrauterine devices, birth control pills, condoms, etc.) within 3 months after the end of the trial from screening;
• During the trial period, participants engaged in driving, operating complex machinery, or other potentially hazardous activities; 21.For patients with a bipedal administration area of less than 450cm^2[bipedal administration area (cm2)=0.00718 × W ^ 0.425 × H ^ 0.725 × 5% × 10000, where W is weight (kg) and H is height (cm)];
• Screening participants who have participated in other interventional clinical trials within the previous 3 months;
• Researchers believe that other situations are not suitable for participation in this experiment.

The second part of the experiment

• Medication adherence < 80% or > 120% in double-blind studies;
• Major safety issues occur in the double-blind study or there are unresolved serious adverse events before the medication administration in the second part of this study;
• Pregnant and lactating women; male trial participants (including their female partners) and female trial participants who are capable of reproduction, and who intend to conceive or cannot ensure the use of one or more contraceptive measures (common contraceptive measures include sterilization surgery, intrauterine devices, contraceptive pills, condoms, etc.) from the screening phase until 3 months after the end of the trial;
• Other situations where the researcher deems it inappropriate to participate in this trial.