Alprostadil Liposomes for Injection for Lower Extremity Arteriosclerosis Obliteran

Study Overview
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Brief Summary
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This is a randomized, positive-control, multicenter, multiple-dose, dose-escalation phase II trial

Detailed Description
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A randomized, positive-control, multicenter, multiple-dose, dose-escalation phase II trial. The trial was divided into 4 dose groups: the positive drug Kaishi 10 μg group and the alprostadil liposome for injection 40μg, 80μg, 120μg group.

Official Title
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Alprostadil Liposomes for Injection for Lower Extremity Arteriosclerosis Obliteran of Phase II Clinical Trial

Conditions
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Peripheral Artery Disease

Intervention / Treatment
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* Drug: Alprostadil liposomes for injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 40 <age ≤ 80 years ，regardless of gender; Agree to participate in this clinical trial and sign the informed consent voluntarily; Meet the diagnostic criteria of lower extremity arteriosclerosis obliteran (lower extremity ASO) (according to the definition of the 2015 Chinese lower extremity arteriosclerosis obliteran diagnosis and treatment guidelines), which are: age> 40 years; have clinical manifestations of lower extremity arteriosclerosis obliteran ; Weakness or disappearance of distal arterial pulsation in ischemic limbs; Ankle-brachial index (ABI) <0.9; Fontaine stage II or III. For subjects with Fontaine stage II, intermittent claudication distance is between 50m and 800m (fixed plate speed 3km / h, slope 12%); and at least 2 tests with difference of ≤25% (comparison based on the first measurement value, the second measurement is performed after the subject is fully rested the next day and after); Imaging examinations such as color Doppler ultrasound, CTA, MRA, or DSA within 1 month before enrollment revealed lesions such as stenosis or occlusion of the corresponding lower limb arteries. Exclusion Criteria: Patients with pre-existing cardiac dysfunction, such as untreated heart failure, arrhythmia, coronary heart disease, mitral or aortic stenosis, or a history of myocardial infarction within the last 6 months; Combining a history of stroke or cerebral hemorrhage, the judgment of researchers will affect the safety evaluation of efficacy; Patients diagnosed or suspected of having pulmonary edema, pulmonary infiltration, or interstitial pneumonia through clinical or related examinations, or those with severe chronic obstructive ventilation disorder or respiratory insufficiency; Obesity (BMI≥40); Fontaine stage is IV, or patients with severe resting pain need to use strong analgesics or surgical amputation; Hepatic impairment (ALT or AST ≥ 3 times ULN) or primary liver disease; Renal dysfunction, SCr> 1.5 times the upper limit of normal value; Poorly controlled hypertension (systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥110 mmHg); Diabetic patients with poor control (HbA1c> 9%); Patients with a history of interventional or bypass surgery or endovascular treatment in the past 3 months; or those who have stopped using prostaglandins for less than 5 half-life of the corresponding drugs; Elderly within 5 half-life of the corresponding drug (such as naphthylamine, pentoxifylline, butrodil, cilostazol, etc.); Patients who have successfully received walking rehabilitation training in the past 6 months; There are other diseases that significantly affect the walking distance, such as lower extremity joint disease, spinal disease, neuropathyt; Patients with inflammatory vascular diseases, such as multiple arteritis, peripheral edema, thrombo-occlusive vasculitis, etc .; Patients with total femoral or above, femoropopliteal artery occlusion, or above groin artery occlusion; Patients with active peptic ulcer or bleeding tendency; Glaucoma or hypertensive patients; Patients who have used powerful analgesics (such as morphine) in the nearly a month; Patients with mental illness or dementia; Patients with malignant tumors; Patients with previous allergies to similar products; Those who have participated in drug clinical trials in the past 3 months; Patients who are pregnant or nursing, or patients who are unable to perform effective contraception during the study period; Active hepatitis B virus infection (HBV surface antigen positive and (HBVDNA quantification ≥1 × 103copies / mL), hepatitis C virus, syphilis antibody and HIV antibody positive; Other patients considered by investigators to be unsuitable for this trial.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alprostadil liposomes for injection<br> | Drug: Alprostadil liposomes for injection<br>* 40ug,once a day,continuous administration for 2 weeks<br>|
| Active Comparator: KAISHI for injection<br> | Drug: Alprostadil liposomes for injection<br>* 40ug,once a day,continuous administration for 2 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| intermittent claudication distance | Change of intermittent claudication distance from baseline after 2 weeks | After 2 weeks of treatment |