The Tolerability and Pharmacokinetics of Multiple Doses of SPH3127 in Chinese Healthy People

Study Overview
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Brief Summary
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This study was a single center, parallel, randomized, double blind, placebo-controlled phase Ib clinical trial to to evaluate the safety and tolerability and pharmacokinetics of SPH3127 tablet in healthy subjects by increasing multiple dosing

Detailed Description
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Three panels(100mg, 200mg, 400mg), each consisting of eight participants (The number of individual subjects in each group was not less than 1/3 of the total number).Participants begin to receive the first dose of SPH3127 100mg. Then Participants begin to receive the second dose of SPH3127 200mg,after the researchers confirmed that the 100mg dose group was safe and well tolerated.Then the third dose of SPH3127 400mg must wait for the result of the second dose's safety and tolerability. If the subjects during escalating dose to the biggest tolerate dose group were not well tolerated, the study must adjust the maximum dose group and fall to a low dose group to conduct another test.

Official Title
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Multiple Doses Study to Evaluate the Tolerability and Pharmacokinetics of SPH3127 in Chinese Healthy People

Conditions
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Hypertension

Intervention / Treatment
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* Drug: SPH3127 50mg
* Drug: SPH3127 100mg
* Drug: Placebo matching to SPH3127 50mg
* Drug: Placebo matching to SPH3127 100mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The body mass index is 18-28kg/m2 (including the critical value), which allows the minimum weight of men to be 50kg (including the critical value) and 45kg for women (including the critical value). Before the study,participant has know about the significance , potential benefits, inconveniences and potential risks of the study Participant has understood the research's procedure and sign the informed consent . Exclusion Criteria: Participant who are Pregnancy, lactating women, and planned trials begin within six months of pregnancy Participant who has abnormal Physical examination, laboratory examination results and clinical significance (such as: liver function examination - aspartate aminotransferase (AST) and alanine aminotransferase (ALT) more than 1.5 times that of the upper limit of normal) Participant who has a history of cardiovascular, liver, kidney, digestive tract, nervous system, blood system, familial hematologic disease, abnormal thyroid function, or mental abnormality Participant who has drug allergy history and anaphylactic reaction Participant who took oral contraceptive in 6 months Participant who used any drug (including Chinese herbal medicine) within 1 week. Participant who donated blood within 2 months Participant who participated clinical trials of any drug in 3 months (as subjects) Participant who has any positive result of virus serology check: human immunodeficiency virus antigen antibody (HIV Ag/Ab) and hepatitis c virus (HCV) - immunoglobulin G(IgG) antibody to IgG, hepatitis b surface antigen (HBsAg) and treponema pallidum antibody (TP) Participant who are used to smoke, alcohol abuse, eat coffee and strong tea and drug abuse Participant who the researchers believe that there are volunteers who are not suitable for the study

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SPH3127 100mg<br>A single dose of SPH3127 50 mg*2 qd *7 days | Drug: SPH3127 50mg<br>* SPH3127 50mg<br>* Other names: SPH3127 is a new study drug for hypertension;|
| Placebo Comparator: Placebo to SPH3127 100mg<br>A single dose of placebo matching to SPH3127 50mg*2 qd *7 days | Drug: Placebo matching to SPH3127 50mg<br>* Placebo matching to SPH3127 50mg<br>* Other names: Placebo is oral tablet to matching to SPH3127 50mg;|
| Experimental: SPH3127 200mg<br>A single dose of SPH3127 100 mg*2 qd *7 days | Drug: SPH3127 100mg<br>* SPH3127 100mg<br>* Other names: SPH3127 is a new study drug for hypertension;|
| Placebo Comparator: Placebo to SPH3127 200mg<br>A single dose of placebo matching to SPH3127 100mg*2 qd *7 days | Drug: Placebo matching to SPH3127 100mg<br>* Placebo matching to SPH3127 100mg<br>* Other names: Placebo is oral tablet to matching to SPH3127 50mg;|
| Experimental: SPH3127 400mg<br>A single dose of SPH3127 100 mg*4 qd *7 days | Drug: SPH3127 100mg<br>* SPH3127 100mg<br>* Other names: SPH3127 is a new study drug for hypertension;|
| Placebo Comparator: Placebo to SPH3127 400mg<br>A single dose of placebo matching to SPH3127 100mg*4 qd *7 days | Drug: Placebo matching to SPH3127 100mg<br>* Placebo matching to SPH3127 100mg<br>* Other names: Placebo is oral tablet to matching to SPH3127 50mg;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events (AEs) | to assess incidence and intensity of Adverse Events according to Common Toxicity Criteria (CTC version 4.03) associated with increasing doses of SPH3127 | Baseline to 13-16 days post last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma area under curve (AUC)(0-∞) of SPH3127 | to evaluate Plasma AUC(0-∞) of SPH3127 | 10 minutes predose, 0.17hour, 0.33hour, 0.5hour, 0.75hour, 1hour, 1.25hour, 1.5hour, 2hour, 4hour, 6hour, 8hour, 12hour postdose at Day 1 and 7; 10 minutes predose at Day 2; 10 minutes predose, 1hour postdose at Day 5 or 6 | 
| Change from baseline in laboratory hematology values | to evaluate the Change from baseline in laboratory hematology values | Baseline to 13-16 days post last dose | 
| Change from baseline in laboratory chemistry values | to evaluate the Change from baseline in laboratory chemistry values | Baseline to 13-16 days post last dose | 
| Change from baseline in laboratory urinalysis values | to evaluate the Change from baseline in laboratory urinalysis values | Baseline to 13-16 days post last dose | 
| Change from baseline in ECG | to evaluate the Change from baseline in ECG | Baseline to 13-16 days post last dose | 
| Maximum Plasma Concentration (Cmax) of SPH3127 | to evaluate Plasma Cmax of SPH3127 | 10 minutes predose, 0.17hour, 0.33hour, 0.5hour, 0.75hour, 1hour, 1.25hour, 1.5hour, 2hour, 4hour, 6hour, 8hour, 12hour postdose at Day 1 and 7;10 minutes predose at Day 2; 10 minutes predose, 1hour postdose at Day 5 or 6 | 
| Plasma Maximum time to peak (Tmax) of SPH3127 | to evaluate Plasma Tmax of SPH3127 | 10 minutes predose, 0.17hour, 0.33hour, 0.5hour, 0.75hour, 1hour, 1.25hour, 1.5hour, 2hour, 4hour, 6hour, 8hour, 12hour postdose at Day 1 and 7;10 minutes predose at Day 2; 10 minutes predose, 1hour postdose at Day 5 or 6 | 
| Apparent terminal half-life of SPH3127 | to evaluate terminal half-life of SPH3127 | 10 minutes predose, 0.17hour, 0.33hour, 0.5hour, 0.75hour, 1hour, 1.25hour, 1.5hour, 2hour, 4hour, 6hour, 8hour, 12hour postdose at Day 1 and 7;10 minutes predose at Day 2; 10 minutes predose, 1hour postdose at Day 5 or 6 |