Clinical trial NCT03645278: The PK/PD Study of SHR0532 Tablets in Healthy Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Hypertension
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2018-08-24
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of subjects with adverse events and serious adverse events
timeFrame: Pre-dose to 5 days after dose administration
Secondary outcomes:
measure: Area under the plasma concentration versus time curve (AUC) of SHR-0532
timeFrame: Pre-dose to 5 days after dose administration
measure: Maximum observed serum concentration (Cmax) of SHR-0532
timeFrame: Pre-dose to 5 days after dose administration
measure: Time to maximum observed serum concentration (tmax) of SHR-0532
timeFrame: Pre-dose to 5 days after dose administration
measure: Time to elimination half-life (t1/2) of SHR-0532
timeFrame: Pre-dose to 5 days after dose administration
measure: Apparent total clearance of the drug from plasma after oral administration (CL/F) of SHR-0532
timeFrame: Pre-dose to 5 days after dose administration
measure: Apparent volume of distribution after non-intravenous administration (V/F) of SHR-0532
timeFrame: Pre-dose to 5 days after dose administration
measure: Renal clearance of the drug from plasma (CLR) of SHR-0532
timeFrame: Pre-dose to 5 days after dose administration
measure: Cumulative amount of unchanged drug excreted into the urine(Ae) of SHR-0532
timeFrame: Pre-dose to 5 days after dose administration
Other outcomes:
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