<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03756103</url>
  </required_header>
  <id_info>
    <org_study_id>SPH3127-201</org_study_id>
    <nct_id>NCT03756103</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy of SPH3127 on Treating Mild-moderate Essential Hypertension Patients</brief_title>
  <official_title>To Evaluate the Safety and Efficacy of SPH3127 on Treating Mild-moderate Essential Hypertension Patients: A Randomized, Double-Blinded, Dose-Exploration and Placebo-Controlled Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shanghai Pharmaceuticals Holding Co., Ltd</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>R&amp;G Pharma Studies Co.,Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Shanghai Pharmaceuticals Holding Co., Ltd</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      SPH3127 tablet is a of renin inhibitor. It is expected to be a new drug for essential&#xD;
      hypertension. This is a phase IIa trial which designed to evaluate its efficacy and safety on&#xD;
      treating mild-moderate essential hypertension patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a dose finding trial. Totally 120 mild-moderate essential hypertension patients will&#xD;
      be enrolled. All the patients will be randomized (1:1:1:1) into four groups (SPH3127 50mg,&#xD;
      SPH3127 100mg, SPH3127 200mg and placebo).&#xD;
&#xD;
      The trial has three phases: the screening phase, the leading phase and the treating phase.&#xD;
&#xD;
      The primary endpoints are the changes of DBP and SBP compared to the baseline after 8 weeks&#xD;
      of treatment.&#xD;
&#xD;
      All the adverse events are required to be collected for safety analyzing.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 11, 2019</start_date>
  <completion_date type="Actual">June 30, 2020</completion_date>
  <primary_completion_date type="Actual">June 30, 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes From Baseline in Seated Systolic Blood Pressure (SBP) and Seated Diastolic Blood Pressure (DBP) After 8 Weeks of Treatment.</measure>
    <time_frame>Baseline to 54-58 days</time_frame>
    <description>To compare the changes of SBP and DBP after 8 weeks of treatment between each group.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes from Baseline in Seated SBP and DBP after 2, 4 and 6 Weeks of Treatment.</measure>
    <time_frame>Baseline to 14±2, 28±2 and 42±2 days</time_frame>
    <description>To compare the changes of seated SBP and DBP after 2, 4 and 6 weeks of treatment between each group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from Baseline in 24-hour Ambulatory Blood Pressure after 8 Weeks of Treatment.</measure>
    <time_frame>Baseline to 54-58 days</time_frame>
    <description>To compare the change from baseline in 24-hour ambulatory blood pressure in each group after 8 weeks of treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effectiveness Rate after 4 and 8 Weeks of Treatment.</measure>
    <time_frame>Baseline to 28±2 and 56±2 days</time_frame>
    <description>To compare the rates that SBP decreased more than 20 mmHg or DBP decreased more than 10 mmHg between each group after 4 and 8 weeks of treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hypertension Controlled Rates after 4 and 8 Weeks of Treatment.</measure>
    <time_frame>Baseline to 28±2 and 56±2 days</time_frame>
    <description>To compare the rates that seated SBP &lt; 140 mmHg and DBP &lt; 90 mmHg between each group after 4 and 8 weeks of treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from Baseline in Plasma Renin Activity (PRA) Following 2, 4, 6 and 8 Weeks of Treatment.</measure>
    <time_frame>Baseline to 14±2, 28±2,42±2 and 56±2 days</time_frame>
    <description>To compare the changes of plasma renin activity (PRA) in each group after 2, 4, 6 and 8 weeks of treatment.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">120</enrollment>
  <condition>Hypertension,Essential</condition>
  <arm_group>
    <arm_group_label>SPH3127 tablet Dose 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Low-dose group</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SPH3127 tablet Dose 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Mid-dose group</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SPH3127 tablet Dose 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>High-dose group</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SPH3127 tablet Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo Control group</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SPH3127 tablet Dose 1</intervention_name>
    <description>Oral SPH3127 tablet, a kind of renion inhibitor, 50 mg, once daily for 8 weeks.</description>
    <arm_group_label>SPH3127 tablet Dose 1</arm_group_label>
    <other_name>renion inhibitor</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SPH3127 tablet Dose 2</intervention_name>
    <description>Oral SPH3127 tablet, a kind of renion inhibitor, 100 mg, once daily for 8 weeks.</description>
    <arm_group_label>SPH3127 tablet Dose 2</arm_group_label>
    <other_name>renion inhibitor</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SPH3127 tablet Dose 3</intervention_name>
    <description>Oral SPH3127 tablet, a kind of renion inhibitor, 200 mg, once daily for 8 weeks.</description>
    <arm_group_label>SPH3127 tablet Dose 3</arm_group_label>
    <other_name>renion inhibitor</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SPH3127 tablet Placebo</intervention_name>
    <description>Oral SPH3127 tablet placebo, once daily for 8 weeks.</description>
    <arm_group_label>SPH3127 tablet Placebo</arm_group_label>
    <other_name>renion inhibitor placebo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female who is 18 - 65 years old.&#xD;
&#xD;
          2. Subject who is meeting the diagnostic criteria of mild-moderate essential&#xD;
             hypertension：mean seated Systolic Blood Pressure (SBP) (2~3 times average) ≥ 140 mmHg&#xD;
             and ≤ 179 mmHg and mean seated Diastolic Blood Pressure (DBP) (2~3 times average)≥ 90&#xD;
             and ≤ 109 mmHg.&#xD;
&#xD;
          3. Laboratory testing should:&#xD;
&#xD;
        （1） GFR* ≥ 60mL/min （2） AST or ALT is less than 2 times upper limit of normal （3）&#xD;
        Hemoglobin ≥ 90g/L （4） Serum potassium ≥ 3.5mmol/L and ≤ 5.5mmol/L *the conversion formulas&#xD;
        for GFR* Male：GFR=186×（Scr)^-1.154×(age)^-0.203；&#xD;
        Female：GFR=186×（Scr)^-1.154×(age)^-0.203×0.742； Serum creatinine(Scr) unit：µmol/L.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subject who is diagnosed as a secondary hypertension.&#xD;
&#xD;
          2. Subject who is suspected to be malignant hypertension, hypertensive emergency,&#xD;
             hypertensive urgencies patients.&#xD;
&#xD;
          3. Subject who is at risk when the current anti-hypertensive therapy discontinued.&#xD;
&#xD;
          4. Subject who is suffered by chronic congestive heart failure (NYHA III and IV) or&#xD;
             myocardial infarction within 6 months. Subject has had or is currently suffered by&#xD;
             serious heart disease, such as unstable angina, cardiogenic shock, arrhythmia to that&#xD;
             needs treatment, heart valve disease, hypertrophic cardiomyopathy, rheumatic heart&#xD;
             disease, etc.&#xD;
&#xD;
          5. Subject who is suffered by severe cerebrovascular disease or shock within 6 months,&#xD;
             such as hypertensive encephalopathy, cerebrovascular injury, cerebral hemorrhage,&#xD;
             transient ischemic attack etc.&#xD;
&#xD;
          6. Subject who is suffered by severe or malignant retinopathy. The severe lesions is&#xD;
             defined as retinal hemorrhage, micro aneurysm, cotton wool patches, hard exudate or a&#xD;
             combination of these symptoms. The malignant lesions defined as the combination of&#xD;
             severe retinopathy and optic disc edema.&#xD;
&#xD;
          7. Subject's medication compliance is not suitable for this trial (use of medication is&#xD;
             &lt;80% or &gt;120% in the leading phase).&#xD;
&#xD;
          8. Subject whose work is associated with such condition as work at height, motor driver&#xD;
             or operating dangerous machine etc.&#xD;
&#xD;
          9. Subject who is suffered by aorta-arteritis, large aneurysm or aortic dissection,&#xD;
             severe subclavian artery stenosis in the past.&#xD;
&#xD;
         10. Subject who had a gastrointestinal surgery history that may significantly alter drug&#xD;
             absorption, distribution, metabolism and excretion（For example: gastroectomy,&#xD;
             gastroenteroanastomosis or enterectomy, gastric bypass, gastrointestinal anastomosis,&#xD;
             gastrointestinal band surgery, etc.).&#xD;
&#xD;
         11. Subject who have drug allergy history and anaphylactic reaction.&#xD;
&#xD;
         12. Subject who is lactating, or is planning to pregnant within six months after the&#xD;
             trial.&#xD;
&#xD;
         13. Subject whose diabetes is out of controlled. Defined as fasting blood-glucose is &gt; 7.8&#xD;
             mmol/L or glycosylated hemoglobin is&gt;7.5%.&#xD;
&#xD;
         14. Subject who has a history of malignant tumor.&#xD;
&#xD;
         15. Subject who has a history of mental disorders.&#xD;
&#xD;
         16. Subject who has abnormal thyroid function examination or abnormal urine protein check&#xD;
             value in urine routine(Urine protein test result is a &quot;+&quot; is considered abnormal).&#xD;
&#xD;
         17. Subject who has participated clinical trials within past 3 months (as a subject).&#xD;
&#xD;
         18. Subject who is planning or in use of other non-antihypertensive drugs which may affect&#xD;
             blood pressure（for example: Monoamine oxidase inhibitors, anesthetics, tricyclic and&#xD;
             tetracyclic antidepressants, non-steroidal anti-inflammatory drugs, reproductive oral&#xD;
             contraceptive pills, thyroid hormones, adrenocortical hormones, etc.).&#xD;
&#xD;
         19. Subject who is planning or in use of other antihypertensive drugs during the trial.&#xD;
&#xD;
         20. Subject who is alcohol abuse （adult male/female consume more than 25g of alcohol per&#xD;
             day: 25g of alcohol is equivalent to 200 mL of yellow rice wine/wine (15 degrees),&#xD;
             780mL of beer (4 degrees), 62 mL of liquor (50 degrees)） or drug abuse.&#xD;
&#xD;
         21. Subject that investigators considered to be not suitable for this study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Chinese</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Changsheng Ma, Doctor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Beijing Anzhen Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Beijing Anzhen Hospital, Capital Medical University</name>
      <address>
        <city>Beijing</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beijing Hospital</name>
      <address>
        <city>Beijing</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Second Xiangya Hospital of Central South University</name>
      <address>
        <city>Changsha</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Xiangya Hospital Central South University</name>
      <address>
        <city>Changsha</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>West China Hospital of Sichuan University</name>
      <address>
        <city>Chengdu</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Second People's Hospital of Guangdong Province</name>
      <address>
        <city>Guangdong</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Inner Mongolia Medical University Affiliated Hospital</name>
      <address>
        <city>Hohhot</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ruijin Hospital, Shanghai Jiao Tong University School of Medicine</name>
      <address>
        <city>Shanghai</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Union Hospital of Tongji Medical College, Huazhong University of Science and Technology</name>
      <address>
        <city>Wuhan</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Xuzhou Central Hospital</name>
      <address>
        <city>Xuzhou</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>November 16, 2018</study_first_submitted>
  <study_first_submitted_qc>November 26, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 28, 2018</study_first_posted>
  <last_update_submitted>November 11, 2021</last_update_submitted>
  <last_update_submitted_qc>November 11, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 15, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>mild-moderate essential hypertension</keyword>
  <keyword>SPH3127 tablet</keyword>
  <keyword>renin inhibitor</keyword>
  <keyword>efficacy</keyword>
  <keyword>safety</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypertension</mesh_term>
    <mesh_term>Essential Hypertension</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03756103
org study id: SPH3127-201
nct id: NCT03756103
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
SPH3127 tablet is a of renin inhibitor. It is expected to be a new drug for essential
      hypertension. This is a phase IIa trial which designed to evaluate its efficacy and safety on
      treating mild-moderate essential hypertension patients.
This is a dose finding trial. Totally 120 mild-moderate essential hypertension patients will
      be enrolled. All the patients will be randomized (1:1:1:1) into four groups (SPH3127 50mg,
      SPH3127 100mg, SPH3127 200mg and placebo).

      The trial has three phases: the screening phase, the leading phase and the treating phase.

      The primary endpoints are the changes of DBP and SBP compared to the baseline after 8 weeks
      of treatment.

      All the adverse events are required to be collected for safety analyzing.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Changes From Baseline in Seated Systolic Blood Pressure (SBP) and Seated Diastolic Blood Pressure (DBP) After 8 Weeks of Treatment.
time frame: Baseline to 54-58 days
description: To compare the changes of SBP and DBP after 8 weeks of treatment between each group.
measure: Changes from Baseline in Seated SBP and DBP after 2, 4 and 6 Weeks of Treatment.
time frame: Baseline to 14±2, 28±2 and 42±2 days
description: To compare the changes of seated SBP and DBP after 2, 4 and 6 weeks of treatment between each group.
measure: Changes from Baseline in 24-hour Ambulatory Blood Pressure after 8 Weeks of Treatment.
time frame: Baseline to 54-58 days
description: To compare the change from baseline in 24-hour ambulatory blood pressure in each group after 8 weeks of treatment.
measure: Effectiveness Rate after 4 and 8 Weeks of Treatment.
time frame: Baseline to 28±2 and 56±2 days
description: To compare the rates that SBP decreased more than 20 mmHg or DBP decreased more than 10 mmHg between each group after 4 and 8 weeks of treatment.
measure: Hypertension Controlled Rates after 4 and 8 Weeks of Treatment.
time frame: Baseline to 28±2 and 56±2 days
description: To compare the rates that seated SBP < 140 mmHg and DBP < 90 mmHg between each group after 4 and 8 weeks of treatment.
measure: Changes from Baseline in Plasma Renin Activity (PRA) Following 2, 4, 6 and 8 Weeks of Treatment.
time frame: Baseline to 14±2, 28±2,42±2 and 56±2 days
description: To compare the changes of plasma renin activity (PRA) in each group after 2, 4, 6 and 8 weeks of treatment.
arm group label: SPH3127 tablet Dose 1
arm group type: Experimental
description: Low-dose group
arm group label: SPH3127 tablet Dose 2
arm group type: Experimental
description: Mid-dose group
arm group label: SPH3127 tablet Dose 3
arm group type: Experimental
description: High-dose group
arm group label: SPH3127 tablet Placebo
arm group type: Placebo Comparator
description: Placebo Control group
intervention type: Drug
intervention name: SPH3127 tablet Dose 1
description: Oral SPH3127 tablet, a kind of renion inhibitor, 50 mg, once daily for 8 weeks.
arm group label: SPH3127 tablet Dose 1
other name: renion inhibitor
intervention type: Drug
intervention name: SPH3127 tablet Dose 2
description: Oral SPH3127 tablet, a kind of renion inhibitor, 100 mg, once daily for 8 weeks.
arm group label: SPH3127 tablet Dose 2
other name: renion inhibitor
intervention type: Drug
intervention name: SPH3127 tablet Dose 3
description: Oral SPH3127 tablet, a kind of renion inhibitor, 200 mg, once daily for 8 weeks.
arm group label: SPH3127 tablet Dose 3
other name: renion inhibitor
intervention type: Drug
intervention name: SPH3127 tablet Placebo
description: Oral SPH3127 tablet placebo, once daily for 8 weeks.
arm group label: SPH3127 tablet Placebo
other name: renion inhibitor placebo
criteria: 
gender: All
gender based: Yes
gender description: Chinese
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Changsheng Ma, Doctor
role: Principal Investigator
affiliation: Beijing Anzhen Hospital
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: China
responsible party type: Sponsor
mesh term: Hypertension
mesh term: Essential Hypertension
sharing ipd: Undecided