A Phase I, Randomized, Double-Blind, Placebo-hydrochlorothiazide Parallel Controlled, Multiple-Ascending Dose Study to Evaluate the Safety, Efficacy of SHR 0532 Oral Tablets in Mild Hypertension Subjects
Overview
- Phase
- Phase 1
- Intervention
- SHR0532
- Conditions
- Hypertension
- Sponsor
- Jiangsu HengRui Medicine Co., Ltd.
- Enrollment
- 36
- Locations
- 1
- Primary Endpoint
- Adverse Events(AEs) and Serious Adverse Events （SAEs）
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
The study is being conducted to evaluate the safety and efficacy and Pharmacokinetics/Pharmacodynamics of SHR0532 in subjects with mild hypertension for 4 weeks.
Detailed Description
This is a randomized, double-blind, multiple ascending dose, placebo- and Hydrochlorothiazide-controlled study to evaluate the safety and tolerability, Pharmacokinetics and Pharmacodynamics and effect on blood pressure of SHR0532 tablets in patients with mild hypertension.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Males or females between 18 to 65 years old
- •Diagnosis of mild hypertension
- •18.5 kg/m2≤Body mass index (BMI) ≤35 kg/m\^2
- •Understand the study procedure and method, willing to participate the study and Informed consent form (ICF) signed in writing
Exclusion Criteria
- •History of significant drug allergy or allergic diseases (asthma, urticaria, eczematous dermatitis), or known allergy to anti hypertension drugs
- •Anti-hypertensive drugs were taken within 1 month before screening
- •History or at present patient has orthostatic hypotension
- •History or at screening Participant has plasma sodium lower than 135mmol/L
- •History or at screening visit/baseline patient has elevated serum uric acid (serum uric acid higher than ULN)
- •Patients with type 1 diabetes mellitus need insulin therapy or poor blood glucose control (HbA1c \> 9%, or oral anti diabetic drug dosage is not stable within 4 weeks before screening)
- •History of arrhythmia or patient has clinically significant abnormalities of 12-lead ECG or prolonged corrected QT (QTc) interval (male \> 450ms; female \> 460ms) at screening visit
- •History of New York Heart Association (NYHA) Definition II-IV Heart Failure
- •Severe cardiovascular diseases occurred within 6 months before screening, including ischemic heart disease, peripheral vascular disease, significant ventricular tachycardia, atrial fibrillation, atrial flutter or other serious arrhythmias, hypertrophic obstructive cardiomyopathy, severe obstructive coronary artery disease, aortic stenosis, aortic or mitral valve disease of great hemodynamic significance, and severe cerebrovascular disease
- •History of percutaneous intervention (PCI) or coronary artery bypass graft (CABG)
Arms & Interventions
SHR0532 tablet
up to 3 cohorts of subjects will receive multiple dose of oral tablets
Intervention: SHR0532
SHR0532 placebo
up to 3 cohorts of subjects will receive multiple dose of oral SHR0532 placebo
Intervention: SHR placebo
Hydrochlorothiazide
up to 3 cohorts of subjects will receive multiple dose of oral Hydrochlorothiazide 25mg
Intervention: Hydrochlorothiazide 25 mg
Outcomes
Primary Outcomes
Adverse Events(AEs) and Serious Adverse Events （SAEs）
Time Frame: from informed consent form signature to the end of the study (up to 2 months)
Incidence of AEs and SAEs, incidence of Treatment-Emergent Adverse Events, incidence of drug related adverse events (safety and tolrability)
Secondary Outcomes
- Change From Baseline in Clinic Systolic Blood Pressure (SBP) and Clinic Diastolic Blood Pressure (DBP)(Baseline to end of the study (up to 32 days))
- Change from baseline in 24h Urine sodium(from baseline to Day 8; from D28 to D32 (up to 32 days))
- Change from baseline in 24h Urine Volume(from baseline to Day 8; from D28 to D32 (up to 32 days))