Phase I Study of Continuous Administration of Salvianolic Acid A Tablet

Study Overview
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Brief Summary
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Salvianolic acid A has a variety of pharmacological effects, such as: anti-oxidation, scavenging oxygen free radicals, anti-fibrosis, anti-myocardial ischemia, anti-coagulation, anti-thrombosis, anti-tumor, etc. Professor Du Guanhua, at Institue of Materia Medica, Chinese Academy of Medical Sciences, first discovered that salvianolic acid A can alleviate diabetic complications and improve patients' quality of life. With the support of major national science and technology projects, the preclinical research work of salvianolic acid A was completed, and the application was approved by the State Food and Drug Administration (Clinical Approval No.: 2016L06293).The purpose of this study is to assess the safety,tolerability, and pharmacokinetics (PK) of an extended dosing regimen ofsalvianolic acid A: open label, continuous subcutaneous infusion for 7 days were tested as ascending doses of salvianolic acid A from 90mg up to 180 mg.

Detailed Description
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This was a Phase I repeated incremental doses study in healthy volunteers. A total of 24 subjects was planned to be enrolled. This was performed according to a double blind, randomized, placebo controlled design and included two sequential dose groups of repeat doses. Each group enrolled 12 subjects on salvianolic acid A or placebo (ratio 9 experimental: 3 placebo) and received salvianolic acid A or placebo twice daily (90mg) or daily (180mg) for 7 days, and follow-up to 3 or 4 days.

Official Title
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Randomized, Double-blind, Placebo-controlled, Continuous Dosing, Single-center, Evaluation of Safety, Tolerability, and Pharmacokinetic Properties of Salvianolic Acid A Tablets in Healthy Volunteers

Conditions
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Diabetes

Intervention / Treatment
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* Drug: salvianolic acid A
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1) Gender: male or female, healthy volunteers; 2) Age: 18 45 years old; 3) Weight: Male subjects need to weigh ≥ 50kg, female subjects should have ≥ 45kg, body mass index [BMI = weight (kg) / height 2 (m2)] in the range of 19   25 kg / m2; 4) Subjects must give informed consent to the trial prior to the trial and voluntarily sign a written informed consent form; 5) The subject is able to communicate well with the investigator and is able to complete the trial in accordance with the protocol. Exclusion Criteria: (1) Hepatitis B surface antigen, hepatitis C virus, human immunodeficiency virus and syphilis positive; (2) alcoholics; (3) subjects who took any drug or long-term use of drugs within 2 weeks before screening (4) Blood donors within 3 months prior to the trial; (5) participated in any drug clinical trial within 3 months prior to screening; (6) had a clear history of allergic disease; (7) had central nervous system, cardiovascular Systematic, kidney, liver, digestive tract, lung disease, metabolic and skeletal muscle system with a clear history or other significant disease; (8) pregnant, lactating women; (9) other factors not suitable for participation in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Salvianolic Acid A<br>2 anticipated doses are 90 mg and 180 mg. | Drug: salvianolic acid A<br>* salvianolic acid A/Placebo 90 mg bid; salvianolic acid A/Placebo 180 mg qd<br>|
| Placebo Comparator: Placebo Oral Tablet<br>Placebo tablets containing no salvianolic acid A will be given to healthy subjects. | Drug: Placebo<br>* salvianolic acid A/Placebo 90 mg bid; salvianolic acid A/Placebo 180 mg qd<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subject incidence of treatment-emergent adverse events |  | 10 or 11 days | 
| Percentage of participants with change from baseline in vital signs | Heart rate, Blood Pressure，auxillary temperature | 10 or 11 days | 
| Change from baseline in electrocardiograms (ECGs) | PR interval, QT interval, QTc interval, QTcF, and rhythm abnormalities | 10 or 11 days | 
| Percentage of participants with change from baseline in clinical laboratory parameters | blood routine, urine routine, biochemical parameters of blood and urine，coagulation tests | 10 or 11 days | 
| Plasma concentrations of salvianolic acid A | To investigate the pharmacokinetics (PK) profile of multiple ascending doses of salvianolic acid A | 8 days |