NCT03645278UnknownPhase 1
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
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 1
- Enrollment
- 50
- Primary Endpoint
- Number of subjects with adverse events and serious adverse events
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 45 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •males or females, aged 18-45
- •subjects have no cardiovascular disease, with sitting blood pressure: 90mmHg ≤SBP<140mmHg and 60mmHg ≤DBP<90mmHg;
- •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
- •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
- •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or total bilirubin > 1.5 x ULN during screening/baseline;
- •Serum creatinine>ULN)during screening/baseline;
- •Human immunodeficiency virus antibody (HIV-ab), syphilis serological examination, hepatitis b virus surface antigen (HBsAg), hepatitis c virus antibody (HCV-ab) test positive;
- •Known postural hypotension; the numeric difference of systolic blood pressure between both upper limbs >20mmHg；
- •A clinical history of arrhythmia；subjects with Electrocardiogram QTc prolongation（male>450ms；female>460ms）during screening；
- •A clinical history of hyperuricemia；serum uric acid > the upper limit of normal value (ULN) during screening;
- •A clinical history of diabetes；fasting plasma glucose or hemoglobin A1c exceeded the upper limit of normal value (ULN) during screening;
- •Subjects with previous GI discomfort -abdominal pain, diarrhea, and nausea 3 months prior to screening；
- •A clinical history of acute or chronic kidney disease;
- •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.
Arms & Interventions
SHR0532
Experimental
Up to 5 cohorts of healthy subjects will receive a single dose of oral SHR0532 tablet.
Intervention: SHR0532 (Drug)
Placebo
Experimental
Up to 5 cohorts of healthy subjects will receive a single dose of oral placebo.
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Number of subjects with adverse events and serious adverse events
Time Frame: Pre-dose to 5 days after dose administration
Secondary Outcomes
- Maximum observed serum concentration (Cmax) of SHR-0532(Pre-dose to 5 days after dose administration)
- Area under the plasma concentration versus time curve (AUC) 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 volume of distribution after non-intravenous administration (V/F) 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)
- 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)
- Apparent total clearance of the drug from plasma after oral administration (CL/F) of SHR-0532(Pre-dose to 5 days after dose administration)
Investigators
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