The PK/PD Study of SHR0532 Tablets in Healthy Subjects

A Phase I, Randomized, Double-Blind, Placebo-Controlled, Single-Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of SHR0532 Tablets in Healthy Subjects

In the last four decades, several classes of diuretics have been the first line option for the therapy of widespread hypertension. However, all the classes of diuretics cause alteration of potassium homeostasis. The primary objective of this study is to assess the safety and tolerability of SHR0532 tablets in healthy subjects. In addition, this study will provide information on Pharmacokinetics and Pharmacodynamics of SHR0532 tablets in healthy subjects.

Study Overview

• Status: Unknown
• Conditions: Hypertension
• Intervention / Treatment: Drug: SHR0532; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 1

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. males or females, aged 18-45
2. subjects have no cardiovascular disease, with sitting blood pressure: 90mmHg ≤SBP<140mmHg and 60mmHg ≤DBP<90mmHg;
3. body mass index (BMI) between 19 to 26, and a total body weight: male ≥50.0 kg and <90.0 kg; female ≥45.0 kg and <90.0 kg
4. Participant in general good health. No clinically significant findings in laboratory parameters or clinically significant abnormality on electrocardiogram, X-ray, Echocardiograph and B-type ultrasonic

Exclusion Criteria:

1. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or total bilirubin > 1.5 x ULN during screening/baseline;
2. Serum creatinine>ULN)during screening/baseline;
3. Human immunodeficiency virus antibody (HIV-ab), syphilis serological examination, hepatitis b virus surface antigen (HBsAg), hepatitis c virus antibody (HCV-ab) test positive;
4. Known postural hypotension; the numeric difference of systolic blood pressure between both upper limbs >20mmHg；
5. A clinical history of arrhythmia；subjects with Electrocardiogram QTc prolongation（male>450ms；female>460ms）during screening；
6. A clinical history of hyperuricemia；serum uric acid > the upper limit of normal value (ULN) during screening;
7. A clinical history of diabetes；fasting plasma glucose or hemoglobin A1c exceeded the upper limit of normal value (ULN) during screening;
8. Subjects with previous GI discomfort -abdominal pain, diarrhea, and nausea 3 months prior to screening；
9. A clinical history of acute or chronic kidney disease;
10. Subjects with severe trauma or surgery within 3 months prior to the screening； 11.3 months prior to screening involved in any drug or medical device clinical subjects, or within 5 half-life of drugs (test drug half-life more than 3 months) before screening;

12.Pregnant or Serum β-hCG > 5mIU/mL at baseline or women who are breastfeeding; etc.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SHR0532; Up to 5 cohorts of healthy subjects will receive a single dose of oral SHR0532 tablet.	Drug: SHR0532; Ascending dose oral adminstration
Experimental: Placebo; Up to 5 cohorts of healthy subjects will receive a single dose of oral placebo.	Drug: Placebo; Ascending dose oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of subjects with adverse events and serious adverse events	Pre-dose to 5 days after dose administration

Secondary Outcome Measures

Outcome Measure	Time Frame
Area under the plasma concentration versus time curve (AUC) of SHR-0532	Pre-dose to 5 days after dose administration
Maximum observed serum concentration (Cmax) of SHR-0532	Pre-dose to 5 days after dose administration
Time to maximum observed serum concentration (tmax) of SHR-0532	Pre-dose to 5 days after dose administration
Time to elimination half-life (t1/2) of SHR-0532	Pre-dose to 5 days after dose administration
Apparent total clearance of the drug from plasma after oral administration (CL/F) of SHR-0532	Pre-dose to 5 days after dose administration
Apparent volume of distribution after non-intravenous administration (V/F) of SHR-0532	Pre-dose to 5 days after dose administration
Renal clearance of the drug from plasma (CLR) of SHR-0532	Pre-dose to 5 days after dose administration
Cumulative amount of unchanged drug excreted into the urine(Ae) of SHR-0532	Pre-dose to 5 days after dose administration

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): August 24, 2018
• Primary Completion (Anticipated): December 15, 2018
• Study Completion (Anticipated): April 30, 2019

Study Registration Dates

• First Submitted: August 12, 2018
• First Submitted That Met QC Criteria: August 22, 2018
• First Posted (Actual): August 24, 2018

Study Record Updates

• Last Update Posted (Actual): August 24, 2018
• Last Update Submitted That Met QC Criteria: August 22, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension
• Other Study ID Numbers: SHR0532-101

Drug and device information, study documents

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