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

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

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.

Study Overview

• Status: Completed
• Conditions: Hypertension,Essential
• Intervention / Treatment: Drug: SPH3127 tablet Dose 1; Drug: SPH3127 tablet Dose 2; Drug: SPH3127 tablet Dose 3; Drug: SPH3127 tablet Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Beijing Hospital
  • Beijing, China
    • Beijing Anzhen Hospital, Capital Medical University
  • Changsha, China
    • Xiangya Hospital Central South University
  • Changsha, China
    • The Second Xiangya Hospital of Central South University
  • Chengdu, China
    • West China Hospital of Sichuan University
  • Guangdong, China
    • Second People's Hospital of Guangdong Province
  • Hohhot, China
    • Inner Mongolia Medical University affiliated Hospital
  • Shanghai, China
    • Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
  • Wuhan, China
    • Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
  • Xuzhou, China
    • XuZhou Central Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female who is 18 - 65 years old.
2. 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.
3. 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:

1. Subject who is diagnosed as a secondary hypertension.
2. Subject who is suspected to be malignant hypertension, hypertensive emergency, hypertensive urgencies patients.
3. Subject who is at risk when the current anti-hypertensive therapy discontinued.
4. 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.
5. 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.
6. 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.
7. Subject's medication compliance is not suitable for this trial (use of medication is <80% or >120% in the leading phase).
8. Subject whose work is associated with such condition as work at height, motor driver or operating dangerous machine etc.
9. Subject who is suffered by aorta-arteritis, large aneurysm or aortic dissection, severe subclavian artery stenosis in the past.
10. 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.).
11. Subject who have drug allergy history and anaphylactic reaction.
12. Subject who is lactating, or is planning to pregnant within six months after the trial.
13. Subject whose diabetes is out of controlled. Defined as fasting blood-glucose is > 7.8 mmol/L or glycosylated hemoglobin is>7.5%.
14. Subject who has a history of malignant tumor.
15. Subject who has a history of mental disorders.
16. 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).
17. Subject who has participated clinical trials within past 3 months (as a subject).
18. 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.).
19. Subject who is planning or in use of other antihypertensive drugs during the trial.
20. 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.
21. Subject that investigators considered to be not suitable for this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Shanghai Pharmaceuticals Holding Co., Ltd
• Collaborators: R&G Pharma Studies Co.,Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): January 11, 2019
• Primary Completion (Actual): June 30, 2020
• Study Completion (Actual): June 30, 2020

Study Registration Dates

• First Submitted: November 16, 2018
• First Submitted That Met QC Criteria: November 26, 2018
• First Posted (Actual): November 28, 2018

Study Record Updates

• Last Update Posted (Actual): November 15, 2021
• Last Update Submitted That Met QC Criteria: November 11, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: safety; efficacy; mild-moderate essential hypertension; SPH3127 tablet; renin inhibitor
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Essential Hypertension
• Other Study ID Numbers: SPH3127-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No