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

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

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

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: SPH3127

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100029
      • The capital medical university affiliated Beijing anzhen hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Shanghai Pharmaceuticals Holding Co., Ltd
• Investigators: Principal Investigator: HONG MIAO, Shanghai Pharmaceuticals Holding Co., Ltd

Publications and helpful links

General Publications

• Jing S, Xu R, Yang K, Liu W, Zhang L, Ke Y, Xia G, Lin Y. Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of SPH3127: A Phase I, Randomized, Double-Blind, Placebo-Controlled Trial. Clin Ther. 2021 Apr;43(4):735.e1-735.e14. doi: 10.1016/j.clinthera.2021.01.025. Epub 2021 Feb 27.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2016
• Primary Completion (Actual): June 30, 2018
• Study Completion (Actual): July 30, 2018

Study Registration Dates

• First Submitted: January 5, 2017
• First Submitted That Met QC Criteria: April 24, 2017
• First Posted (Actual): April 25, 2017

Study Record Updates

• Last Update Posted (Actual): October 27, 2022
• Last Update Submitted That Met QC Criteria: October 26, 2022
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension
• Other Study ID Numbers: SPH3127-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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