The Effect of YJ001 on Diabetic Peripheral Neuropathic Pain.

Study Overview
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Brief Summary
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In this study, a randomized, double-blind, placebo parallel-controlled design was used to evaluate the effectiveness and safety of YJ001 spray applied to local skin in patients with diabetic peripheral neuropathic pain, and to explore the best effective dose.

Detailed Description
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In this study, a randomized, double-blind, placebo parallel-controlled design was used to evaluate the effectiveness and safety of YJ001 spray applied to local skin in patients with diabetic peripheral neuropathic pain, and to explore the best effective dose.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Phase II Clinical Trial to Evaluate the Effectiveness and Safety of Spray YJ001 in the Treatment of Diabetic Peripheral Neuropathic Pain.

Conditions
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Diabetic Peripheral Neuropathic Pain

Intervention / Treatment
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* Drug: YJ001


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Subjects must meet all of the following criteria to be enrolled in this study. The age of screening was 18-75 years old, regardless of gender; Diagnosis of type 1 or type 2 diabetes for at least 1 years; Diabetic peripheral neuropathic pain was diagnosed and the duration of pain was 23 months. The level of glycosylated hemoglobin was less than 9%; At the screening visit, according to the 11 point digital pain intensity scale (NRS), the score was greater than or equal to 4; During the 1-week lead-in period, subjects completed at least 10 NRS pain scores, and the average pain score was greater than or equal to 4.0; The subjects are willing and able to comply with the study visit arrangement, treatment plan, laboratory examination and other study procedures; Those who agree to participate in the trial and sign the written informed consent. Exclusion Criteria: - Subjects meeting any one or more of the following criteria will not be allowed to participate in this study. Have known or suspected the ingredients of spray YJ001, the ingredients of YJ001 simulant, and ASA. Those who are allergic to aspirin, salicylic acid or yj001 (such as 5-aminosalicylic acid, sulfasalazine and salicylate) or have serious adverse reactions. Those who have participated in yj001 clinical study and received research drugs. The subjects have a wide range of systemic pain, which will affect the pain evaluation of the drug delivery site according to the judgment of the researchers; Or in the hand or more proximal area than the foot. The subjects with severe peripheral vascular disease (such as intermittent claudication) at the time of screening were not suitable for the trial according to the judgment of the researchers. Subjects suffered from nondiabetic peripheral neuropathy, such as osteoarthritis, II stage and above peripheral arterial disease, lumbar disc herniation, vitamin B deficiency, alcoholism, herpes neuralgia, vasculitis, and severe mental disorders such as depression and anxiety. It will also affect the researchers' evaluation of diabetic peripheral neuropathic pain. There is skin disease in the affected skin area. According to the judgement of the researcher, it may affect the evaluation of diabetic peripheral neuropathic pain. According to the judgment of the researcher, the subjects have tattoos or other skin abnormalities that may interfere with the purpose of the study. The score of skin condition evaluation of the administration site was more than 2. Patients with malignant tumors, but have received appropriate treatment or resection of non metastatic skin basal cell carcinoma or squamous cell carcinoma, or cervical cancer in situ. Amputation beyond the end of the fingers and toes. Diabetic foot ulcers, infection and gangrene were associated with diabetes. There are metabolic complications of acute diabetes, such as diabetic ketoacidosis or lactic acidosis or hyperosmolar hyperglycemia syndrome or hyperosmolar diabetic hyperglycemia. One or more severe hypoglycemia events occurred 6 months before screening or during the induction period (it means that the subjects need help from others to obtain carbohydrates, glucagon or other rescue measures). The NRS score of subjects with more than two pain scores was less than 3 points in the 1-week lead-in period. Patients who had used transcutaneous electrical nerve stimulation (TENS), acupuncture and other treatment measures within 2 weeks before entering the group, or during the treatment period, subjects need combined transcutaneous electrical nerve stimulation (TENS) or acupuncture treatment. Local analgesics (such as capsaicin patches and lidocaine patches) used in the treatment of diabetic peripheral neuropathic pain in the first 2 weeks. Abnormal liver and kidney function: ast or aut > 2.5 times the upper limit of normal value, creatinine > 1.5 times the upper limit of normal value. Complicated with severe cardiovascular and cerebrovascular diseases (such as degree II or III heart block, congestive heart failure with NYHA cardiac function grade III-IV, myocardial infarction, and acute stroke). Severe diseases of respiratory system, blood and hematopoietic system were found. There are other neurological diseases (such as cognitive impairment). The researchers believe that it may affect the evaluation of diabetic peripheral neuropathic pain or affect self ratings, or the psychiatric patients who are not suitable for the trial by the researchers. Patients with known or suspected history of alcohol abuse, drug abuse or dependence in the past year. Pregnant and lactating women; The male subjects (including their female partners) and the fertile female subjects had the intention of having children or could not guarantee the use of one or more contraceptives within 3 months from the beginning of screening to the end of the trial. Those who participated in other clinical trials within 3 months before screening. Other cases that the researcher considered unsuitable to participate in this trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| M1 Test group<br>YJ001 for spray, topical application on the skin, drug concentration 100mg/mL, 2 times/day (interval 11-13h), 8 sprays each time, a total of 12 weeks. | Drug: YJ001<br>* Skin spray<br>|
| M1 control group<br>YJ001 simulant for spray, topical application on the skin, drug concentration 100mg/mL, 2 times/day (interval 11-13h), 8 sprays each time, a total of 12 weeks. | |
| M2 Test group:<br>YJ001 for spray, topical application on the skin, drug concentration 150mg/mL, 2 times/day (interval 11-13h), 8 sprays each time, a total of 12 weeks. | Drug: YJ001<br>* Skin spray<br>|
| M2 control group:<br>YJ001 simulant for spray, topical application on the skin, drug concentration 150mg/mL, 2 times/day (interval 11-13h), 8 sprays each time, a total of 12 weeks. | |
| M3 Test group<br>YJ001 for spray, topical application on the skin, drug concentration 200mg/mL, 2 times/day (interval 11-13h), 8 sprays each time, a total of 12 weeks. | Drug: YJ001<br>* Skin spray<br>|
| M3 control group<br>YJ001 simulant for spray, topical application on the skin, drug concentration 200mg/mL, 2 times/day (interval 11-13h), 8 sprays each time, a total of 12 weeks. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change in the average weekly NRS score of pain from baseline | Numerical Rating Scale ：0-10 points, the greater the score, the more severe the pain. | at the twelfth week after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change in the average weekly NRS score of pain from the baseline | Numerical Rating Scale ：0-10 points, the greater the score, the more severe the pain. | 1-11 weeks after treatment | 
| Changes from baseline in the average sleep disturbance scores | sleep disturbance scores：0-10 points, the greater the score, the more severe the sleep disturbance. | each week and during the follow-up period from 1 to 12 weeks after treatment | 
| The change from baseline in the SF-36 Quality of Life Scale score | SF-36 Quality of Life Scale score：0-100 points, the smaller the score, the more severe the quality of life. | at the 12th week after treatment |