<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/NCT03016832</url>
  </required_header>
  <id_info>
    <org_study_id>SZCT-2016-01</org_study_id>
    <nct_id>NCT03016832</nct_id>
  </id_info>
  <brief_title>Clinical Trial of HuangKui Capsule to Treat Diabetic Kidney Disease</brief_title>
  <official_title>A Randomized, Double-blind, Parallel-controlled, Multi-center Clinical Trial of HuangKui Capsule to Treat Diabetic Kidney Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jiangsu Famous Medical Technology Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Jiangsu Famous Medical Technology Co., Ltd.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      1. Name of Investigational Products Huangkui capsule.&#xD;
&#xD;
        2. Trial Topic A Randomized, Double-blinded, Parallel, controlled, Multicenter Clinical&#xD;
           Trial of Huangkui Capsule in Treating Type II Diabetic Nephropathy (DKD)&#xD;
&#xD;
        3. Trial Objectives Primary objective:To evaluate HuangKui capsule efficacy for treatment&#xD;
           of type II diabetes ACR.&#xD;
&#xD;
           Secondary objective: To evaluate the efficacy of HuangKui capsule on 24-hour urinary&#xD;
           protein changes、reduce PCR-increase eGFR, improve micro-inflammatory state, and&#xD;
           improving Traditional Chinese medicine clinical efficacy&#xD;
&#xD;
        4. Trial Design Designed as a block randomized, double-blinded, parallel controlled,&#xD;
           multi-center clinical trial.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      1. Name of Investigational Products Huangkui capsule&#xD;
&#xD;
        2. Trial Topic A Randomized, Double-blinded, Parallel, controlled, Multicenter Clinical&#xD;
           Trial ofHuangkui Capsule in Treating Type II Diabetic Nephropathy (DKD)&#xD;
&#xD;
        3. Trial Objectives Primary objective: To evaluate HuangKui capsule efficacy for treatment&#xD;
           of type II diabetes ACR.&#xD;
&#xD;
           Secondary objective: To evaluate the efficacy of HuangKui capsule on 24-hour urinary&#xD;
           protein changes、reduce PCR-increase eGFR, improve micro-inflammatory state, and&#xD;
           improving Traditional Chinese medicine clinical efficacy.&#xD;
&#xD;
        4. Trial Design Designed as a block randomized, double-blinded, parallel controlled,&#xD;
           multi-center clinical tria 4.1 Multi-center: The trial is proposed to be conducted in&#xD;
           the department of Nephrology or Endocrinology of nine hospitals simultaneously.&#xD;
&#xD;
           4.2 Randomization:Using stratified block randomized design. The randomization numbers&#xD;
           were generated with SAS statistical software.&#xD;
&#xD;
           4.3 Arms: The study subjects were divided into 3 arms: Huangkui arm, controlled arm and&#xD;
           combined treatment arm.&#xD;
&#xD;
           4.4 Estimation of subject numbers&#xD;
&#xD;
           This study was based on the main indicator ACR to calculate the sample size, according&#xD;
           to the clinical protocol:&#xD;
&#xD;
           ①The change of ACR of Irbesartan combined with Huangkui capsule is superior than&#xD;
           Irbesartan monotherapy.&#xD;
&#xD;
           ②The changes of ACR in the monotherapy group were significantly lower than those in the&#xD;
           irbesartan monotherapy group According to the experience of clinical treatment, it was&#xD;
           found that the change of ACR was about 12.85mg / g before treatment with Irbesartan&#xD;
           combined with Huangkui capsule group and 6.50mg / g before and after treatment with&#xD;
           Irbesartan group, and α = 0.05 (bilateral (1-β) = 80%, the standard deviation of the&#xD;
           change value before and after ACR treatment with irbesartan combined with Huangkui&#xD;
           capsule group was 17.18, Check the sample size calculation formula The number of samples&#xD;
           in each group was calculated as n western medicine group = n combined treatment group =&#xD;
           110 cases.&#xD;
&#xD;
           Another group based on the clinical treatment experience to take the standard deviation&#xD;
           of 17.18, take α = 0.025 (unilateral test), β = 0.2, that is, the degree of control&#xD;
           (1-β) = 80% of the case, the non-inferior boundary value of 6.50mg / g, according to the&#xD;
           non-inferior test sample size calculation formula, The number of samples in each group&#xD;
           was calculated as n western medicine group = n Chinese traditional treatment group = 110&#xD;
           cases.According to the program requirements, the three groups were designed to be 1: 1:&#xD;
           1, taking into account the blanding method and 20% rejection rate. ultimately a total of&#xD;
           414 cases included in the case, each group of 138 cases.&#xD;
&#xD;
           4.5 Blinding: double-blinding. Blinding will be conducted by statisticians as two levels&#xD;
           of blinding. Level 1 Blinding: blinding of the investigational products. The&#xD;
           investigational products and comparative products use unified packaging; level 2&#xD;
           blinding: the blinding of the packaging box of investigational products.&#xD;
&#xD;
        5. Diagnostic criteria The etiology of Diabetic nephropathy is kidney damage, referred to&#xD;
           DN in the past (diabetic nephropathy). But in 2007, the American Foundation for Kidney&#xD;
           Disease (NKF) developed guidelines for the life quality of kidney disease (NKF / KDOQI).&#xD;
           The guidelines recommend that DKD (diabetic kidney disease) instead of DN. In 2014, the&#xD;
           American Diabetes Association (ADA) and NKF reached a consensus that DKD referred to the&#xD;
           chronic kidney disease caused by diabetes, including glomerular filtration rate (GFR)&#xD;
           which is less than 60ml.min-1.1.73m-2 or urine white Protein / creatinine ratio (ACR) is&#xD;
           higher than 30 mg / g for more than 3 months,associated with diabetic retinopathy.&#xD;
&#xD;
           During having diagnosis, if one of the following circumstances happened, we should&#xD;
           consider its CKD is caused by (1) no diabetic retinopathy; (2) GFR lower or decreased&#xD;
           rapidly; (3) a sharp increase in proteinuria or nephrotic syndrome; (4) refractory&#xD;
           hypertension; (5) urinary sediment activity;(6) symptoms or signs of other systemic&#xD;
           diseases; (7) glomerular filtration rate decreased by more than 30% within 2-3 months&#xD;
           after initiation of treatment with angiotensin converting enzyme inhibitors (ACEI) or&#xD;
           angiotensin II receptor antagonists (ARB).&#xD;
&#xD;
           5.2 Table of TCM symptom/signs Diagnostic dosage It is refer to &quot;Clinical research&#xD;
           guidelines of new drug of Traditional Chinese Medicine &quot;(2002 version), which published&#xD;
           by China Medical Science andTechnology Press&#xD;
&#xD;
        6. Treatment options 6.1 Basic treatment 6.1.1 Anti-hypotensive We can choose&#xD;
           antihypertensive drugs Monotherapy or combined controling blood pressure expect ACEI and&#xD;
           ARB, control blood pressure in 160 / 90mmHg the following 6.1.2 Anti-hypoglycemic We can&#xD;
           use oral hypoglycemic agents or insulin for hypoglycemic, so that glycosylated&#xD;
           hemoglobin ≤ 8.5%.&#xD;
&#xD;
           6.1.3 Anti-hypolipidemic We can choose to use statins or fibrates lipid-lowering drugs.&#xD;
           6.1.4 Diet control Patients with edema should limit the salt and water, daily sodium&#xD;
           intake &lt;5g; high protein diet increased glomerular hyperperfusion, high filtration, and&#xD;
           therefore advocated the principle of high quality low-protein diet. Protein intake&#xD;
           should be a high biological value of animal protein-based, early protein intake should&#xD;
           be limited to 1g/（kg•d） 6.2 Investigational products Huangkui Capsule: produced by SZYY&#xD;
           Group Pharmaceutical Limited, Jiangsu, 0.5g×30 capsules/box Placebo that simulates&#xD;
           Huangkui capsule: produced by SZYY Group Pharmaceutical Limited, 0.5g×30 capsules/box&#xD;
           Irbesartan tablets: produced by Sanofi (Hangzhou) Pharmaceutical Co., Ltd., 150mg×7&#xD;
           capsules/box Placebo that simulates Irbesartan tablets: produced by SZYY Group&#xD;
           Pharmaceutical Limited, Jiangsu, 150mg×7 capsules/box 6.3 Trial process 6.3.1 Treatment&#xD;
           for observation period The subjects who meet the inclusion criteria will be randomized&#xD;
           into three groups at a 1:1:1 ratio.&#xD;
&#xD;
           Test group: Placebo drug that simulates Irbesartan tablets 150mg /qd, oral dose;&#xD;
           Huangkui Capsule 2.5g/tid, oral dose.&#xD;
&#xD;
           Control group: irbesartan tablets 150mg /qd, oral dose; Placebo drug that simulates&#xD;
           Huangkui capsule 2.5g/tid, oral dose.&#xD;
&#xD;
           Combined treatment group: irbesartan tablets 150mg /qd, oral dose; Huangkui Capsule&#xD;
           2.5g/tid, oral dose.&#xD;
&#xD;
           6.3.2 period of treatment Treatment observation period is 24 weeks, follow-up points:&#xD;
           Week 0, 4, 8, 12, 16, 20, 24.&#xD;
&#xD;
           6.4 Concomitant medications During the import period and throughout the treatment, do&#xD;
           not use the RAS blockers (ARB or ACEI) other than the investigational product irbesartan&#xD;
           and Potassium-sparing diuretics, Calcium dobesilate, Aldehyde-containing starch, or&#xD;
           other Chinese medicine which can reduce proteinuria.&#xD;
&#xD;
           If other medicines have been used before the trial, the subjects can continue to use&#xD;
           them. The use of these medicines should be recorded.&#xD;
&#xD;
           6.5 ACR Detection Specimens: one - time morning urine (after 5:00); Urinary creatinine&#xD;
           detection method: enzyme kinetics; urinary albumin detection method : immune&#xD;
           turbidimetric method. 6.6 PCR detection Specimens: 24h urine Urine creatinine detection&#xD;
           method: Enzyme kinetic method Urine protein detection method: dye binding method PCR =&#xD;
           urinary protein / creatinine&#xD;
&#xD;
        7. Efficacy endpoint 7.1 Efficacy endpoint 7.1.1 Primary endpoints ACR baseline changes and&#xD;
           changes in the rate 7.1.2 Secondary endpoints （1）24-hour urinary protein quantification&#xD;
           baseline changes and changes in the rate （2）PCR baseline changes and changing rate&#xD;
           （3）Glomerular filtration rate (eGFR)baseline changes （4）High sensitivity C - reactive&#xD;
           protein baseline values （5）TCM syndromes Efficacy endpoint Changes and the rate change&#xD;
           before and after treatment. [Time point: baseline,12-weeks treatment,24-weeks treatment]&#xD;
&#xD;
           7.2 Efficacy endpoint Evaluation endpoints 7.2.1 The ACR change rate ( refer to &quot;Guiding&#xD;
           principles of clinical research on the treatment of chronic nephritis with traditional&#xD;
           Chinese medicine&quot;, 2002 version; The State Administration of Traditional Chinese&#xD;
           Medicine in 1987 to develop the Efficacy endpoint of chronic glomerulonephritis standard&#xD;
           ) Complete remission: ACR is less than 30mg/g; Markedly effective: ACR decreased more&#xD;
           than 50% before treatment Effective: ACR decreased more than 30%-50% before treatment&#xD;
           Invalid: those who did not meet these targets. 7.2.2 Efficacy endpoint for TCM syndrome&#xD;
           Changes in value and rate before and after treatment before and after treatment [Time&#xD;
           point: baseline,12-weeks treatment,24-weeks treatment]&#xD;
&#xD;
        8. Safety Evaluation endpoints 8.1 Vital signs, such as such as body temperature, pulse,&#xD;
           breathing, blood pressure and so on.&#xD;
&#xD;
           8.2 Blood, urine routine test, liver function test(ALB、ALT、AST), renal function&#xD;
           test(Bun、SCr, UA、eGFR), electrocardiogram, blood potassium, blood sugar; Adverse&#xD;
           events/adverse reactions.&#xD;
&#xD;
        9. Statistical Methods All statistical calculations were carried out using SAS v9.3&#xD;
           statistical analysis software, hypothesis testing are used bilateral test, unless&#xD;
           otherwise specified, the overall comparison between the test level = 0.05.&#xD;
&#xD;
      Statistical analysis includes：Three groups of subjects enrolled No., drop out and excluded&#xD;
      cases, demographic and other baseline characteristics, compliance, efficacy analysis and&#xD;
      safety analysis.&#xD;
&#xD;
      For quantitative data, we conduct descriptive statistical analysis with cases, averages,&#xD;
      standard deviation, minimum, median, maximum, upper quartile (Q1), lower quartile (Q3) and&#xD;
      95% confidence interval (95% CI). Comparisons between treatment groups were performed using&#xD;
      either an analysis of variance or a Wilcoxon rank sum test. If the influence of covariates is&#xD;
      taken into account, a general linear model (GLM) is used.&#xD;
&#xD;
      Descriptive statistical analysis of qualitative data is given in terms of the number of cases&#xD;
      and their percentages. Count data were compared between each treatment group, using x2 test,&#xD;
      Fisher exact probability method; grade data in each treatment group or between groups before&#xD;
      and after treatment comparison analysis, Wilcoxon rank sum test. If the effects of the center&#xD;
      or other factors are taken into account, a CMH x2 test or Logistic regression is used.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>January 2017</start_date>
  <completion_date type="Anticipated">December 2018</completion_date>
  <primary_completion_date type="Anticipated">May 2018</primary_completion_date>
  <phase>Early Phase 1</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>ACR</measure>
    <time_frame>every 4 week，a total of 24 weeks</time_frame>
    <description>ACR baseline changes and changes in the rate</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>24-hour urinary protein</measure>
    <time_frame>every 4 week,，a total of 24 weeks</time_frame>
    <description>24-hour urinary protein quantification baseline changes and changes in the rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PCR</measure>
    <time_frame>every 12 week,，a total of 24 weeks</time_frame>
    <description>PCR baseline changes and changing rat</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Glomerular filtration rate</measure>
    <time_frame>every 12 week,，a total of 24 weeks</time_frame>
    <description>Glomerular filtration rate (eGFR) baseline changes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TCM syndromes Efficacy endpoint</measure>
    <time_frame>baseline,12-weeks treatment,24-weeks treatment</time_frame>
    <description>Changes and the rate change before and after treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>High sensitivity C</measure>
    <time_frame>baseline,12-weeks treatment,24-weeks treatment</time_frame>
    <description>High sensitivity C - reactive protein baseline values</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">414</enrollment>
  <condition>Diabetic Kidney Disease</condition>
  <arm_group>
    <arm_group_label>Huangkui</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Placebo drug that simulates Irbesartan tablets 150mg /qd, oral dosing; HuangKui Capsule 2.5g/tid, oral dosing</description>
  </arm_group>
  <arm_group>
    <arm_group_label>controlled</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Placebo drug that simulates Irbesartan tablets 150mg /qd, oral dosing; HuangKui Capsule 2.5g/tid, oral dosing irbesartan tablets 150mg /qd, oral dosing; Placebo drug that simulates HuangKui capsule 2.5g/tid, oral dosing</description>
  </arm_group>
  <arm_group>
    <arm_group_label>combined treatment</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>irbesartan tablets 150mg /qd, oral dosing HuangKui Capsule 2.5g/tid, oral dosing.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo drug that simulates Irbesartan tablets</intervention_name>
    <description>Placebo drug that simulates Irbesartan tablets 150mg /qd, oral dosing</description>
    <arm_group_label>Huangkui</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>irbesartan tablets</intervention_name>
    <description>irbesartan tablets 150mg /qd, oral dosing</description>
    <arm_group_label>combined treatment</arm_group_label>
    <arm_group_label>controlled</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo drug that simulates HuangKui capsule</intervention_name>
    <description>Placebo drug that simulates HuangKui capsule 2.5g/tid, oral dosing</description>
    <arm_group_label>controlled</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>HuangKui Capsule</intervention_name>
    <description>HuangKui Capsule 2.5g/tid, oral dosing.</description>
    <arm_group_label>Huangkui</arm_group_label>
    <arm_group_label>combined treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Aged 18 to 75 years old, male or female&#xD;
&#xD;
          2. Meet the diagnostic criteria of type 2 diabetes published by the World Health&#xD;
             Organization (WHO) in 1999: fasting plasma glucose&gt;126mg/dL (or&gt;7.0mmol/L), 2h&#xD;
             postprandial blood glucose&gt;200mg/dL (or&gt;11.1mmol/L), or 2h blood glucose in OGTT&#xD;
             test&gt;200mg/dL(11.1mmol/L), random blood glucose test≥200mg/dL(11.1mmol/L)&#xD;
&#xD;
          3. Meet Diabetic Kidney Disease (DKD) and the United States Diabetes Association (ADA)&#xD;
             and the American Kidney Foundation (NKF) diagnostic criteria in 2007 ; 300mg/g ≤ ACR&#xD;
             &lt;2000mg/g&#xD;
&#xD;
          4. e-GFR&gt;30 mL/min (CKD-Epi formula),&#xD;
&#xD;
          5. Glycated hemoglobin ≤8.5%&#xD;
&#xD;
          6. Agree to sign informed consent form.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Type 1 diabetes&#xD;
&#xD;
          2. Other secondary glomerulonephritis caused by Non-diabetes disease;&#xD;
&#xD;
          3. Taking Huangkui capsule, ACEI and / or ARB drugs within 2 months;&#xD;
&#xD;
          4. Taking glucocorticoid, immunosuppressive agents and Tripterygium wilfordii drug&#xD;
             history within one month;&#xD;
&#xD;
          5. Taking three or more antihypertensive drugs, but the blood pressure is&#xD;
             still&gt;160/90mmHg&#xD;
&#xD;
          6. With other diseases, syndromes, or comorbidities that may affect the diagnosis and&#xD;
             therapeutic effect of the target indications&#xD;
&#xD;
          7. The treatments received may affect the evaluation of efficacy and safety endpoints&#xD;
&#xD;
          8. With phychological or pathological conditions which may affect the evaluation of&#xD;
             efficacy endpoints and safety endpointssuch as the menstrual period, or heart, brain,&#xD;
             liver and hematopoietic system and other serious primary disease&#xD;
&#xD;
          9. With high risk, such as pregnant women or childbearing during the trial, be allergy to&#xD;
             the Abelmoschus Moschatus Capsule and irbesartan, in the dangerous condition with&#xD;
             unexpected accidents.&#xD;
&#xD;
         10. Alcohol or drug abuse&#xD;
&#xD;
         11. Noncompliance, such as unwilling to accept research procedures or suffering from&#xD;
             mental illness and other diseases&#xD;
&#xD;
         12. Other: Such as poor compliance, or can not attend the follow-up visit in time for some&#xD;
             reasons;&#xD;
&#xD;
         13. Is participating in another clinical study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Wei Sun, Doctor</last_name>
    <phone>13505199801</phone>
    <email>jssunwei@163.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Jiangsu Province Hospital of TCM</name>
      <address>
        <city>Nanjing</city>
        <state>Jiangsu</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Wei Sun</last_name>
      <phone>+86 13505199801</phone>
      <email>jssunwei@163.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>December 2016</verification_date>
  <study_first_submitted>January 4, 2017</study_first_submitted>
  <study_first_submitted_qc>January 8, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 11, 2017</study_first_posted>
  <last_update_submitted>July 3, 2017</last_update_submitted>
  <last_update_submitted_qc>July 3, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">July 5, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Diabetic Nephropathies</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Irbesartan</mesh_term>
  </intervention_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/NCT03016832
org study id: SZCT-2016-01
nct id: NCT03016832
lead sponsor: 
has dmc: No
1. Name of Investigational Products Huangkui capsule.

        2. Trial Topic A Randomized, Double-blinded, Parallel, controlled, Multicenter Clinical
           Trial of Huangkui Capsule in Treating Type II Diabetic Nephropathy (DKD)

        3. Trial Objectives Primary objective:To evaluate HuangKui capsule efficacy for treatment
           of type II diabetes ACR.

           Secondary objective: To evaluate the efficacy of HuangKui capsule on 24-hour urinary
           protein changes、reduce PCR-increase eGFR, improve micro-inflammatory state, and
           improving Traditional Chinese medicine clinical efficacy

        4. Trial Design Designed as a block randomized, double-blinded, parallel controlled,
           multi-center clinical trial.
1. Name of Investigational Products Huangkui capsule

        2. Trial Topic A Randomized, Double-blinded, Parallel, controlled, Multicenter Clinical
           Trial ofHuangkui Capsule in Treating Type II Diabetic Nephropathy (DKD)

        3. Trial Objectives Primary objective: To evaluate HuangKui capsule efficacy for treatment
           of type II diabetes ACR.

           Secondary objective: To evaluate the efficacy of HuangKui capsule on 24-hour urinary
           protein changes、reduce PCR-increase eGFR, improve micro-inflammatory state, and
           improving Traditional Chinese medicine clinical efficacy.

        4. Trial Design Designed as a block randomized, double-blinded, parallel controlled,
           multi-center clinical tria 4.1 Multi-center: The trial is proposed to be conducted in
           the department of Nephrology or Endocrinology of nine hospitals simultaneously.

           4.2 Randomization:Using stratified block randomized design. The randomization numbers
           were generated with SAS statistical software.

           4.3 Arms: The study subjects were divided into 3 arms: Huangkui arm, controlled arm and
           combined treatment arm.

           4.4 Estimation of subject numbers

           This study was based on the main indicator ACR to calculate the sample size, according
           to the clinical protocol:

           ①The change of ACR of Irbesartan combined with Huangkui capsule is superior than
           Irbesartan monotherapy.

           ②The changes of ACR in the monotherapy group were significantly lower than those in the
           irbesartan monotherapy group According to the experience of clinical treatment, it was
           found that the change of ACR was about 12.85mg / g before treatment with Irbesartan
           combined with Huangkui capsule group and 6.50mg / g before and after treatment with
           Irbesartan group, and α = 0.05 (bilateral (1-β) = 80%, the standard deviation of the
           change value before and after ACR treatment with irbesartan combined with Huangkui
           capsule group was 17.18, Check the sample size calculation formula The number of samples
           in each group was calculated as n western medicine group = n combined treatment group =
           110 cases.

           Another group based on the clinical treatment experience to take the standard deviation
           of 17.18, take α = 0.025 (unilateral test), β = 0.2, that is, the degree of control
           (1-β) = 80% of the case, the non-inferior boundary value of 6.50mg / g, according to the
           non-inferior test sample size calculation formula, The number of samples in each group
           was calculated as n western medicine group = n Chinese traditional treatment group = 110
           cases.According to the program requirements, the three groups were designed to be 1: 1:
           1, taking into account the blanding method and 20% rejection rate. ultimately a total of
           414 cases included in the case, each group of 138 cases.

           4.5 Blinding: double-blinding. Blinding will be conducted by statisticians as two levels
           of blinding. Level 1 Blinding: blinding of the investigational products. The
           investigational products and comparative products use unified packaging; level 2
           blinding: the blinding of the packaging box of investigational products.

        5. Diagnostic criteria The etiology of Diabetic nephropathy is kidney damage, referred to
           DN in the past (diabetic nephropathy). But in 2007, the American Foundation for Kidney
           Disease (NKF) developed guidelines for the life quality of kidney disease (NKF / KDOQI).
           The guidelines recommend that DKD (diabetic kidney disease) instead of DN. In 2014, the
           American Diabetes Association (ADA) and NKF reached a consensus that DKD referred to the
           chronic kidney disease caused by diabetes, including glomerular filtration rate (GFR)
           which is less than 60ml.min-1.1.73m-2 or urine white Protein / creatinine ratio (ACR) is
           higher than 30 mg / g for more than 3 months,associated with diabetic retinopathy.

           During having diagnosis, if one of the following circumstances happened, we should
           consider its CKD is caused by (1) no diabetic retinopathy; (2) GFR lower or decreased
           rapidly; (3) a sharp increase in proteinuria or nephrotic syndrome; (4) refractory
           hypertension; (5) urinary sediment activity;(6) symptoms or signs of other systemic
           diseases; (7) glomerular filtration rate decreased by more than 30% within 2-3 months
           after initiation of treatment with angiotensin converting enzyme inhibitors (ACEI) or
           angiotensin II receptor antagonists (ARB).

           5.2 Table of TCM symptom/signs Diagnostic dosage It is refer to "Clinical research
           guidelines of new drug of Traditional Chinese Medicine "(2002 version), which published
           by China Medical Science andTechnology Press

        6. Treatment options 6.1 Basic treatment 6.1.1 Anti-hypotensive We can choose
           antihypertensive drugs Monotherapy or combined controling blood pressure expect ACEI and
           ARB, control blood pressure in 160 / 90mmHg the following 6.1.2 Anti-hypoglycemic We can
           use oral hypoglycemic agents or insulin for hypoglycemic, so that glycosylated
           hemoglobin ≤ 8.5%.

           6.1.3 Anti-hypolipidemic We can choose to use statins or fibrates lipid-lowering drugs.
           6.1.4 Diet control Patients with edema should limit the salt and water, daily sodium
           intake <5g; high protein diet increased glomerular hyperperfusion, high filtration, and
           therefore advocated the principle of high quality low-protein diet. Protein intake
           should be a high biological value of animal protein-based, early protein intake should
           be limited to 1g/（kg•d） 6.2 Investigational products Huangkui Capsule: produced by SZYY
           Group Pharmaceutical Limited, Jiangsu, 0.5g×30 capsules/box Placebo that simulates
           Huangkui capsule: produced by SZYY Group Pharmaceutical Limited, 0.5g×30 capsules/box
           Irbesartan tablets: produced by Sanofi (Hangzhou) Pharmaceutical Co., Ltd., 150mg×7
           capsules/box Placebo that simulates Irbesartan tablets: produced by SZYY Group
           Pharmaceutical Limited, Jiangsu, 150mg×7 capsules/box 6.3 Trial process 6.3.1 Treatment
           for observation period The subjects who meet the inclusion criteria will be randomized
           into three groups at a 1:1:1 ratio.

           Test group: Placebo drug that simulates Irbesartan tablets 150mg /qd, oral dose;
           Huangkui Capsule 2.5g/tid, oral dose.

           Control group: irbesartan tablets 150mg /qd, oral dose; Placebo drug that simulates
           Huangkui capsule 2.5g/tid, oral dose.

           Combined treatment group: irbesartan tablets 150mg /qd, oral dose; Huangkui Capsule
           2.5g/tid, oral dose.

           6.3.2 period of treatment Treatment observation period is 24 weeks, follow-up points:
           Week 0, 4, 8, 12, 16, 20, 24.

           6.4 Concomitant medications During the import period and throughout the treatment, do
           not use the RAS blockers (ARB or ACEI) other than the investigational product irbesartan
           and Potassium-sparing diuretics, Calcium dobesilate, Aldehyde-containing starch, or
           other Chinese medicine which can reduce proteinuria.

           If other medicines have been used before the trial, the subjects can continue to use
           them. The use of these medicines should be recorded.

           6.5 ACR Detection Specimens: one - time morning urine (after 5:00); Urinary creatinine
           detection method: enzyme kinetics; urinary albumin detection method : immune
           turbidimetric method. 6.6 PCR detection Specimens: 24h urine Urine creatinine detection
           method: Enzyme kinetic method Urine protein detection method: dye binding method PCR =
           urinary protein / creatinine

        7. Efficacy endpoint 7.1 Efficacy endpoint 7.1.1 Primary endpoints ACR baseline changes and
           changes in the rate 7.1.2 Secondary endpoints （1）24-hour urinary protein quantification
           baseline changes and changes in the rate （2）PCR baseline changes and changing rate
           （3）Glomerular filtration rate (eGFR)baseline changes （4）High sensitivity C - reactive
           protein baseline values （5）TCM syndromes Efficacy endpoint Changes and the rate change
           before and after treatment. [Time point: baseline,12-weeks treatment,24-weeks treatment]

           7.2 Efficacy endpoint Evaluation endpoints 7.2.1 The ACR change rate ( refer to "Guiding
           principles of clinical research on the treatment of chronic nephritis with traditional
           Chinese medicine", 2002 version; The State Administration of Traditional Chinese
           Medicine in 1987 to develop the Efficacy endpoint of chronic glomerulonephritis standard
           ) Complete remission: ACR is less than 30mg/g; Markedly effective: ACR decreased more
           than 50% before treatment Effective: ACR decreased more than 30%-50% before treatment
           Invalid: those who did not meet these targets. 7.2.2 Efficacy endpoint for TCM syndrome
           Changes in value and rate before and after treatment before and after treatment [Time
           point: baseline,12-weeks treatment,24-weeks treatment]

        8. Safety Evaluation endpoints 8.1 Vital signs, such as such as body temperature, pulse,
           breathing, blood pressure and so on.

           8.2 Blood, urine routine test, liver function test(ALB、ALT、AST), renal function
           test(Bun、SCr, UA、eGFR), electrocardiogram, blood potassium, blood sugar; Adverse
           events/adverse reactions.

        9. Statistical Methods All statistical calculations were carried out using SAS v9.3
           statistical analysis software, hypothesis testing are used bilateral test, unless
           otherwise specified, the overall comparison between the test level = 0.05.

      Statistical analysis includes：Three groups of subjects enrolled No., drop out and excluded
      cases, demographic and other baseline characteristics, compliance, efficacy analysis and
      safety analysis.

      For quantitative data, we conduct descriptive statistical analysis with cases, averages,
      standard deviation, minimum, median, maximum, upper quartile (Q1), lower quartile (Q3) and
      95% confidence interval (95% CI). Comparisons between treatment groups were performed using
      either an analysis of variance or a Wilcoxon rank sum test. If the influence of covariates is
      taken into account, a general linear model (GLM) is used.

      Descriptive statistical analysis of qualitative data is given in terms of the number of cases
      and their percentages. Count data were compared between each treatment group, using x2 test,
      Fisher exact probability method; grade data in each treatment group or between groups before
      and after treatment comparison analysis, Wilcoxon rank sum test. If the effects of the center
      or other factors are taken into account, a CMH x2 test or Logistic regression is used.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: ACR
time frame: every 4 week，a total of 24 weeks
description: ACR baseline changes and changes in the rate
measure: 24-hour urinary protein
time frame: every 4 week,，a total of 24 weeks
description: 24-hour urinary protein quantification baseline changes and changes in the rate
measure: PCR
time frame: every 12 week,，a total of 24 weeks
description: PCR baseline changes and changing rat
measure: Glomerular filtration rate
time frame: every 12 week,，a total of 24 weeks
description: Glomerular filtration rate (eGFR) baseline changes
measure: TCM syndromes Efficacy endpoint
time frame: baseline,12-weeks treatment,24-weeks treatment
description: Changes and the rate change before and after treatment.
measure: High sensitivity C
time frame: baseline,12-weeks treatment,24-weeks treatment
description: High sensitivity C - reactive protein baseline values
arm group label: Huangkui
arm group type: Experimental
description: Placebo drug that simulates Irbesartan tablets 150mg /qd, oral dosing; HuangKui Capsule 2.5g/tid, oral dosing
arm group label: controlled
arm group type: Active Comparator
description: Placebo drug that simulates Irbesartan tablets 150mg /qd, oral dosing; HuangKui Capsule 2.5g/tid, oral dosing irbesartan tablets 150mg /qd, oral dosing; Placebo drug that simulates HuangKui capsule 2.5g/tid, oral dosing
arm group label: combined treatment
arm group type: Other
description: irbesartan tablets 150mg /qd, oral dosing HuangKui Capsule 2.5g/tid, oral dosing.
intervention type: Drug
intervention name: Placebo drug that simulates Irbesartan tablets
description: Placebo drug that simulates Irbesartan tablets 150mg /qd, oral dosing
arm group label: Huangkui
intervention type: Drug
intervention name: irbesartan tablets
description: irbesartan tablets 150mg /qd, oral dosing
arm group label: combined treatment
arm group label: controlled
intervention type: Drug
intervention name: Placebo drug that simulates HuangKui capsule
description: Placebo drug that simulates HuangKui capsule 2.5g/tid, oral dosing
arm group label: controlled
intervention type: Drug
intervention name: HuangKui Capsule
description: HuangKui Capsule 2.5g/tid, oral dosing.
arm group label: Huangkui
arm group label: combined treatment
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Wei Sun, Doctor
phone: 13505199801
email: jssunwei@163.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Kidney Diseases
mesh term: Diabetic Nephropathies
mesh term: Irbesartan
sharing ipd: Undecided