Single Ascending Dose Study of Safety and Tolerability of SPH3127 Tablet in Chinese Healthy Volunteers

Study Overview
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Brief Summary
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To evaluate safety, tolerability and pharmacokinetics (PK) and pharmacodynamics (PD) characteristics of SPH3127 dose escalation, a single oral dose in Chines healthy volunteers. To explore the appropriate dose and provide the basis for the subsequent clinical trials.

Detailed Description
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48 healthy volunteers will participate in this trial. Participants will be divided into 6 group, 25mg，50mg，100mg，200mg，400mg and 800mg. In each group, 6 participants will take SPH3127 tablet, while 2 participants will take placebo randomly. Safety data and PK/PD data will be collected as protocol described.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Describe Pharmacokinetics/Pharmacodynamics, and the Safety and of SPH3127 Tablet in Chinese Healthy Volunteers

Conditions
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Hypertension

Intervention / Treatment
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* Drug: SPH3127


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adults,age >=18 years.Single gender should no less than a third of total subjects in each group. BMI should be18 to 24 kg/m2 (including threshold), allowing the lowest weight 50 kg (including threshold) for the male and 45 kg (including threshold) for the female. understand details of significance, benefit, inconvenience and potential danger of the research program, voluntarily signed informed consent. Exclusion Criteria: during pregnancy, nursing mothers, and plans to test in the first 6 months (grant) pregnant; abnormal results in physical examination, laboratory examination and have clinical significance (such as: liver function examination - aspartate aminotransferase (AST)/alanine aminotransferase (ALT) is more than 1.5 times of the upper limit of normal). with cardiovascular, liver, kidney, gastrointestinal, nervous system, blood system and familial blood disease, thyroid dysfunction or abnormal mental illness; has a history of drug allergy and allergic constitution; took birth control pills within 6 weeks; used any drugs (including Chinese herbal medicine) within 1 week; participated in blood donation within 2 months ; participated in any drug clinical trials (as subjects) within three months; any positive result in virus serology check: human immunodeficiency virus antigen antibody (HIV Ag/Ab) 、hepatitis c virus (HCV) - IgG antibody to IgG, hepatitis b surface antigen (HBsAg) and treponema pallidum antibody (TP); addicted to cigarettes, alcohol, drink coffee, strong tea and drug abuse; researchers think that exists any unfavorable factors to participate in the test.

Ages Eligible for Study
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Minimum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 25 mg SPH3127 tablet-Dose 1<br>6 Volunteers, Single dose of SPH3127 tablet, 25mg, po. 1 tablet. 2 Volunteers, Single dose of Placebo tablet, 25mg, po. 1 tablet. | Drug: SPH3127<br>* Drug: SPH3127 Tablet Drug: Placebo Tablet<br>|
| Experimental: 50 mg SPH3127 tablet-Dose 2<br>6 Volunteers, Single dose of SPH3127 tablet, 50mg, po. 1 tablet. 2 Volunteers, Single dose of Placebo tablet, 50mg, po. 1 tablet. | Drug: SPH3127<br>* Drug: SPH3127 Tablet Drug: Placebo Tablet<br>|
| Experimental: 100 mg SPH3127 tablet-Dose 3<br>6 Volunteers, Single dose of SPH3127 tablet, 100mg, po. 1 tablet. 2 Volunteers, Single dose of Placebo tablet, 100mg, po. 1 tablet. | Drug: SPH3127<br>* Drug: SPH3127 Tablet Drug: Placebo Tablet<br>|
| Experimental: 200 mg SPH3127 tablet-Dose 4<br>6 Volunteers, Single dose of SPH3127 tablet,100mg, po. 2 tablet. 2 Volunteers, Single dose of Placebo tablet, 100mg, po. 2 tablet. | Drug: SPH3127<br>* Drug: SPH3127 Tablet Drug: Placebo Tablet<br>|
| Experimental: 400 mg SPH3127 tablet-Dose 5<br>6 Volunteers, Single dose of SPH3127 tablet,100mg, po. 4 tablet. 2 Volunteers, Single dose of Placebo tablet, 100mg, po. 4 tablet. | Drug: SPH3127<br>* Drug: SPH3127 Tablet Drug: Placebo Tablet<br>|
| Experimental: 800 mg SPH3127 tablet-Dose 6<br>6 Volunteers, Single dose of SPH3127 tablet,100mg, po. 8 tablet. 2 Volunteers, Single dose of Placebo tablet, 100mg, po. 8 tablet. | Drug: SPH3127<br>* Drug: SPH3127 Tablet Drug: Placebo Tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of safety parameters [adverse events, laboratory data, vital signs, and ECG] | adverse events, laboratory data, vital signs, and ECG et al. | 10 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of PK parameter 1 [Cmax] | Peak plasma concentration (Cmax) | 2 days | 
| Assessment of PD parameter 1 [Inhibition of Renion Activity (%)] | Inhibition of Renion Activity (%) | 2 days | 
| Assessment of PD parameter 2 [Blood pressure (mmHg)] | Blood pressure (mmHg) | 2 days | 
| Assessment of PK parameter 2 [tmax] | time to peak plasma concentration (tmax) | 2 days | 
| Assessment of PK parameter 3 [AUC] | Area under the plasma concentration versus time curve (AUC) | 2 days |