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出境医 / 临床实验 / Safety and Effect Study of SHR0532 (Drug Code) Tablets in Patients With Mild Hypertension

Safety and Effect Study of SHR0532 (Drug Code) Tablets in Patients With Mild Hypertension

Study Description
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.

Condition or disease Intervention/treatment Phase
Hypertension Drug: SHR0532 Drug: SHR placebo Drug: Hydrochlorothiazide 25 mg Phase 1

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.
Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: 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
Estimated Study Start Date : June 2019
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019
Arms and Interventions
Arm Intervention/treatment
Experimental: SHR0532 tablet
up to 3 cohorts of subjects will receive multiple dose of oral tablets
Drug: SHR0532
once daily(QD) for 4weeks

Placebo Comparator: SHR0532 placebo
up to 3 cohorts of subjects will receive multiple dose of oral SHR0532 placebo
Drug: SHR placebo
once daily(QD) for 4weeks

Active Comparator: Hydrochlorothiazide
up to 3 cohorts of subjects will receive multiple dose of oral Hydrochlorothiazide 25mg
Drug: Hydrochlorothiazide 25 mg
once daily(QD) for 4weeks

Outcome Measures
Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. Change From Baseline in Clinic Systolic Blood Pressure (SBP) and Clinic Diastolic Blood Pressure (DBP) [ Time Frame: Baseline to end of the study (up to 32 days) ]
    Each subject has their office blood pressure every day of each treatment period (total of 28 days of treatment). The difference between baseline and D28 of each office BP value are calculated and recorded.

  2. Change from baseline in 24h Urine sodium [ Time Frame: from baseline to Day 8; from D28 to D32 (up to 32 days) ]
    Urine sodium (Na) levels were measured over 24-hours and different time period of 24 hours on Day -1 (baseline) and on Day 1to Day 7, Day28 to Day 32. The total amount of Na excreted in the Urine for Day-1 (baseline) and Day1 to Day 7, Day 28 to Day 32 were calculated and recorded and the difference between the 2 values are recorded.

  3. Change from baseline in 24h Urine Volume [ Time Frame: from baseline to Day 8; from D28 to D32 (up to 32 days) ]
    Urine Volume were measured over 24-hours and different time period of 24 hours on Day -1 (baseline) and on Day 1to Day 7, Day28 to Day 32.The total amount of Urine excreted for Day-1 (baseline) and Day1 to Day 7, Day 28 to Day 32 were calculated and recorded and the difference between the 2 values are recorded.


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)
  • History or active stroke, chronic seizures, or major neurological disorder
  • History of osteoporosis, nephrocalcinosis, nephrolithiasis or hypercalciuria
  • History or active malignant neoplastic disease. Exceptions: malignancies which have been successfully treated and non-recurrence >10 years prior to the screening visit
  • Patients having following diseases may affect drug absorption, distribution, metabolism and excretion:

Gastrointestinal diseases such as irritable bowel syndrome, inflammatory bowel diseases including ulcerative colitis, Crohn's disease, malabsorption syndrome, microbial dysbiosis, intestinal infection; History of gastrointestinal operations, such as gastric resection and bypass, small intestinal resection and colonic resection which may affect drug absorption

  • History of acute or chronic kidney diseases
  • Dehydration or volume-depletion
  • Clinically significant chronic or acute infectious diseases occur within 2 weeks before the start of the study (enrolment);
  • Major surgery within 3 months before dosing
  • Donation of blood/plasma within 1 month before dosing or blood/plasma (≥400 mL) within 3 months before dosing
  • Unstable or severe urinary, digestive, psychiatric, neural, hematological and other diseases, or lab abnormalities, the investigators determine that participants in the study will be at unacceptable risk

Taking or having the following medication history:

  • Participant need taking Cytochrome P450 3A4 (CYP3A4) inhibitors (such as ritonavir, indinavir, nelfinavir, erythromycin, telithromycin, clarithromycin, chloramphenicol, fluconazole, ketoconazole, itraconazole, verapamil or diltiazem) as well as strong/moderate CYP3A4 inducers (such as phenytoin, carbamazepine, oxcarbazepine, phenobarbital, efavirenz, nevirapine, rifampicin, modafinil, cyproterone or progestin) at least 2 weeks or 5 half-lives prior to administration of the initial dose of study drug until the post study visit
  • Use of non-steroidal anti-inflammatory drugs (NSAIDs) at least 2 weeks before 1st dose of study drug until the post study visit
  • use of systemic glucocorticoid therapy

Any laboratory examination result meet the following criteria at screening/baseline:

  • Serum potassium < 3.5mmol/L or > 5.5mmol/L
  • Serum creatinine more than ULN, Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) more than 2.0 x ULN or total bilirubin more than 1.5 x ULN at screening/baseline visit
  • Creatinine kinase (CK) more than 3.0 x ULN at screening/baseline visit;
  • Clinically significant abnormalities of coagulation and thyroid function
  • HbsAg and Hepatitis B Virus (HBV)-DNA> 1000 cps/ml, Hepatitis C Virus Antibody (HCVAb), syphilis and HIV antibodies were positive at screening visit
  • Serum pregnant test positive at screening/baseline visit
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Bo Zhu, Medical Director +86-21-6105-3271 zhubo@hrglobe.cn
Contact: Li jun Tang, Project Manager +86 1870616501 tanglijun@hrglobe.cn

Sponsors and Collaborators
Jiangsu HengRui Medicine Co., Ltd.
Tracking Information
First Submitted Date  ICMJE May 28, 2019
First Posted Date  ICMJE June 3, 2019
Last Update Posted Date June 3, 2019
Estimated Study Start Date  ICMJE June 2019
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 31, 2019)
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)
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: May 31, 2019)
  • Change From Baseline in Clinic Systolic Blood Pressure (SBP) and Clinic Diastolic Blood Pressure (DBP) [ Time Frame: Baseline to end of the study (up to 32 days) ]
    Each subject has their office blood pressure every day of each treatment period (total of 28 days of treatment). The difference between baseline and D28 of each office BP value are calculated and recorded.
  • Change from baseline in 24h Urine sodium [ Time Frame: from baseline to Day 8; from D28 to D32 (up to 32 days) ]
    Urine sodium (Na) levels were measured over 24-hours and different time period of 24 hours on Day -1 (baseline) and on Day 1to Day 7, Day28 to Day 32. The total amount of Na excreted in the Urine for Day-1 (baseline) and Day1 to Day 7, Day 28 to Day 32 were calculated and recorded and the difference between the 2 values are recorded.
  • Change from baseline in 24h Urine Volume [ Time Frame: from baseline to Day 8; from D28 to D32 (up to 32 days) ]
    Urine Volume were measured over 24-hours and different time period of 24 hours on Day -1 (baseline) and on Day 1to Day 7, Day28 to Day 32.The total amount of Urine excreted for Day-1 (baseline) and Day1 to Day 7, Day 28 to Day 32 were calculated and recorded and the difference between the 2 values are recorded.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Effect Study of SHR0532 (Drug Code) Tablets in Patients With Mild Hypertension
Official Title  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Hypertension
Intervention  ICMJE
  • Drug: SHR0532
    once daily(QD) for 4weeks
  • Drug: SHR placebo
    once daily(QD) for 4weeks
  • Drug: Hydrochlorothiazide 25 mg
    once daily(QD) for 4weeks
Study Arms  ICMJE
  • Experimental: SHR0532 tablet
    up to 3 cohorts of subjects will receive multiple dose of oral tablets
    Intervention: Drug: SHR0532
  • Placebo Comparator: SHR0532 placebo
    up to 3 cohorts of subjects will receive multiple dose of oral SHR0532 placebo
    Intervention: Drug: SHR placebo
  • Active Comparator: Hydrochlorothiazide
    up to 3 cohorts of subjects will receive multiple dose of oral Hydrochlorothiazide 25mg
    Intervention: Drug: Hydrochlorothiazide 25 mg
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: May 31, 2019)
36
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2019
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
  • History or active stroke, chronic seizures, or major neurological disorder
  • History of osteoporosis, nephrocalcinosis, nephrolithiasis or hypercalciuria
  • History or active malignant neoplastic disease. Exceptions: malignancies which have been successfully treated and non-recurrence >10 years prior to the screening visit
  • Patients having following diseases may affect drug absorption, distribution, metabolism and excretion:

Gastrointestinal diseases such as irritable bowel syndrome, inflammatory bowel diseases including ulcerative colitis, Crohn's disease, malabsorption syndrome, microbial dysbiosis, intestinal infection; History of gastrointestinal operations, such as gastric resection and bypass, small intestinal resection and colonic resection which may affect drug absorption

  • History of acute or chronic kidney diseases
  • Dehydration or volume-depletion
  • Clinically significant chronic or acute infectious diseases occur within 2 weeks before the start of the study (enrolment);
  • Major surgery within 3 months before dosing
  • Donation of blood/plasma within 1 month before dosing or blood/plasma (≥400 mL) within 3 months before dosing
  • Unstable or severe urinary, digestive, psychiatric, neural, hematological and other diseases, or lab abnormalities, the investigators determine that participants in the study will be at unacceptable risk

Taking or having the following medication history:

  • Participant need taking Cytochrome P450 3A4 (CYP3A4) inhibitors (such as ritonavir, indinavir, nelfinavir, erythromycin, telithromycin, clarithromycin, chloramphenicol, fluconazole, ketoconazole, itraconazole, verapamil or diltiazem) as well as strong/moderate CYP3A4 inducers (such as phenytoin, carbamazepine, oxcarbazepine, phenobarbital, efavirenz, nevirapine, rifampicin, modafinil, cyproterone or progestin) at least 2 weeks or 5 half-lives prior to administration of the initial dose of study drug until the post study visit
  • Use of non-steroidal anti-inflammatory drugs (NSAIDs) at least 2 weeks before 1st dose of study drug until the post study visit
  • use of systemic glucocorticoid therapy

Any laboratory examination result meet the following criteria at screening/baseline:

  • Serum potassium < 3.5mmol/L or > 5.5mmol/L
  • Serum creatinine more than ULN, Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) more than 2.0 x ULN or total bilirubin more than 1.5 x ULN at screening/baseline visit
  • Creatinine kinase (CK) more than 3.0 x ULN at screening/baseline visit;
  • Clinically significant abnormalities of coagulation and thyroid function
  • HbsAg and Hepatitis B Virus (HBV)-DNA> 1000 cps/ml, Hepatitis C Virus Antibody (HCVAb), syphilis and HIV antibodies were positive at screening visit
  • Serum pregnant test positive at screening/baseline visit
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03971929
Other Study ID Numbers  ICMJE SHR0532-102
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Jiangsu HengRui Medicine Co., Ltd.
Study Sponsor  ICMJE Jiangsu HengRui Medicine Co., Ltd.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Jiangsu HengRui Medicine Co., Ltd.
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP