Safety and Efficacy of SPH3127 on Treating Mild-moderate Essential Hypertension Patients

Study Overview
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Brief Summary
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SPH3127 tablet is a of renin inhibitor. It is expected to be a new drug for essential hypertension. This is a phase IIa trial which designed to evaluate its efficacy and safety on treating mild-moderate essential hypertension patients.

Detailed Description
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This is a dose finding trial. Totally 120 mild-moderate essential hypertension patients will be enrolled. All the patients will be randomized (1:1:1:1) into four groups (SPH3127 50mg, SPH3127 100mg, SPH3127 200mg and placebo). The trial has three phases: the screening phase, the leading phase and the treating phase. The primary endpoints are the changes of DBP and SBP compared to the baseline after 8 weeks of treatment. All the adverse events are required to be collected for safety analyzing.

Official Title
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To Evaluate the Safety and Efficacy of SPH3127 on Treating Mild-moderate Essential Hypertension Patients: A Randomized, Double-Blinded, Dose-Exploration and Placebo-Controlled Study

Conditions
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Hypertension,Essential

Intervention / Treatment
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* Drug: SPH3127 tablet Dose 1
* Drug: SPH3127 tablet Dose 2
* Drug: SPH3127 tablet Dose 3
* Drug: SPH3127 tablet Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female who is 18 - 65 years old. Subject who is meeting the diagnostic criteria of mild-moderate essential hypertension：mean seated Systolic Blood Pressure (SBP) (2 3 times average) ≥ 140 mmHg and ≤ 179 mmHg and mean seated Diastolic Blood Pressure (DBP) (2 3 times average)≥ 90 and ≤ 109 mmHg. Laboratory testing should: （1） GFR* ≥ 60mL/min （2） AST or ALT is less than 2 times upper limit of normal （3） Hemoglobin ≥ 90g/L （4） Serum potassium ≥ 3.5mmol/L and ≤ 5.5mmol/L *the conversion formulas for GFR* Male：GFR=186×（Scr)^-1.154×(age)^-0.203； Female：GFR=186×（Scr)^-1.154×(age)^-0.203×0.742； Serum creatinine(Scr) unit：µmol/L. Exclusion Criteria: Subject who is diagnosed as a secondary hypertension. Subject who is suspected to be malignant hypertension, hypertensive emergency, hypertensive urgencies patients. Subject who is at risk when the current anti-hypertensive therapy discontinued. Subject who is suffered by chronic congestive heart failure (NYHA III and IV) or myocardial infarction within 6 months. Subject has had or is currently suffered by serious heart disease, such as unstable angina, cardiogenic shock, arrhythmia to that needs treatment, heart valve disease, hypertrophic cardiomyopathy, rheumatic heart disease, etc. Subject who is suffered by severe cerebrovascular disease or shock within 6 months, such as hypertensive encephalopathy, cerebrovascular injury, cerebral hemorrhage, transient ischemic attack etc. Subject who is suffered by severe or malignant retinopathy. The severe lesions is defined as retinal hemorrhage, micro aneurysm, cotton wool patches, hard exudate or a combination of these symptoms. The malignant lesions defined as the combination of severe retinopathy and optic disc edema. Subject's medication compliance is not suitable for this trial (use of medication is <80% or >120% in the leading phase). Subject whose work is associated with such condition as work at height, motor driver or operating dangerous machine etc. Subject who is suffered by aorta-arteritis, large aneurysm or aortic dissection, severe subclavian artery stenosis in the past. Subject who had a gastrointestinal surgery history that may significantly alter drug absorption, distribution, metabolism and excretion（For example: gastroectomy, gastroenteroanastomosis or enterectomy, gastric bypass, gastrointestinal anastomosis, gastrointestinal band surgery, etc.). Subject who have drug allergy history and anaphylactic reaction. Subject who is lactating, or is planning to pregnant within six months after the trial. Subject whose diabetes is out of controlled. Defined as fasting blood-glucose is > 7.8 mmol/L or glycosylated hemoglobin is>7.5%. Subject who has a history of malignant tumor. Subject who has a history of mental disorders. Subject who has abnormal thyroid function examination or abnormal urine protein check value in urine routine(Urine protein test result is a + is considered abnormal). Subject who has participated clinical trials within past 3 months (as a subject). Subject who is planning or in use of other non-antihypertensive drugs which may affect blood pressure（for example: Monoamine oxidase inhibitors, anesthetics, tricyclic and tetracyclic antidepressants, non-steroidal anti-inflammatory drugs, reproductive oral contraceptive pills, thyroid hormones, adrenocortical hormones, etc.). Subject who is planning or in use of other antihypertensive drugs during the trial. Subject who is alcohol abuse （adult male/female consume more than 25g of alcohol per day: 25g of alcohol is equivalent to 200 mL of yellow rice wine/wine (15 degrees), 780mL of beer (4 degrees), 62 mL of liquor (50 degrees)） or drug abuse. Subject that investigators considered to be not suitable for this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SPH3127 tablet Dose 1<br>Low-dose group | Drug: SPH3127 tablet Dose 1<br>* Oral SPH3127 tablet, a kind of renion inhibitor, 50 mg, once daily for 8 weeks.<br>* Other names: renion inhibitor;|
| Experimental: SPH3127 tablet Dose 2<br>Mid-dose group | Drug: SPH3127 tablet Dose 2<br>* Oral SPH3127 tablet, a kind of renion inhibitor, 100 mg, once daily for 8 weeks.<br>* Other names: renion inhibitor;|
| Experimental: SPH3127 tablet Dose 3<br>High-dose group | Drug: SPH3127 tablet Dose 3<br>* Oral SPH3127 tablet, a kind of renion inhibitor, 200 mg, once daily for 8 weeks.<br>* Other names: renion inhibitor;|
| Placebo Comparator: SPH3127 tablet Placebo<br>Placebo Control group | Drug: SPH3127 tablet Placebo<br>* Oral SPH3127 tablet placebo, once daily for 8 weeks.<br>* Other names: renion inhibitor placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes From Baseline in Seated Systolic Blood Pressure (SBP) and Seated Diastolic Blood Pressure (DBP) After 8 Weeks of Treatment. | To compare the changes of SBP and DBP after 8 weeks of treatment between each group. | Baseline to 54-58 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from Baseline in Seated SBP and DBP after 2, 4 and 6 Weeks of Treatment. | To compare the changes of seated SBP and DBP after 2, 4 and 6 weeks of treatment between each group. | Baseline to 14±2, 28±2 and 42±2 days | 
| Changes from Baseline in 24-hour Ambulatory Blood Pressure after 8 Weeks of Treatment. | To compare the change from baseline in 24-hour ambulatory blood pressure in each group after 8 weeks of treatment. | Baseline to 54-58 days | 
| Effectiveness Rate after 4 and 8 Weeks of Treatment. | To compare the rates that SBP decreased more than 20 mmHg or DBP decreased more than 10 mmHg between each group after 4 and 8 weeks of treatment. | Baseline to 28±2 and 56±2 days | 
| Hypertension Controlled Rates after 4 and 8 Weeks of Treatment. | To compare the rates that seated SBP < 140 mmHg and DBP < 90 mmHg between each group after 4 and 8 weeks of treatment. | Baseline to 28±2 and 56±2 days | 
| Changes from Baseline in Plasma Renin Activity (PRA) Following 2, 4, 6 and 8 Weeks of Treatment. | To compare the changes of plasma renin activity (PRA) in each group after 2, 4, 6 and 8 weeks of treatment. | Baseline to 14±2, 28±2,42±2 and 56±2 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mild-moderate essential hypertension, SPH3127 tablet, renin inhibitor, efficacy, safety