<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/NCT04483115</url>
  </required_header>
  <id_info>
    <org_study_id>TPN171H-P201</org_study_id>
    <nct_id>NCT04483115</nct_id>
  </id_info>
  <brief_title>Acute Haemodynamic Study of TPN171H in Patients With Pulmonary Arterial Hypertension</brief_title>
  <official_title>Multi-center, Randomized，Placebo and Positive Controlled Clinical Study of TPN171H Tablets on Acute Haemodynamics in Patients With Pulmonary Arterial Hypertension</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vigonvita Life Sciences</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Shanghai Institute of Materia Medica, Chinese Academy of Sciences</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Vigonvita Life Sciences</source>
  <oversight_info>
    <has_dmc>No</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>
      This study is a phase IIa proof-of-concept study to evaluate the effect of single-dose&#xD;
      TPN171H tablets on acute haemodynamic parameters in patients with pulmonary arterial&#xD;
      hypertension.The trial is expected to include 60 patients, divided into 6 groups, according&#xD;
      to 1:1:1:1:1:1 into the placebo group and the test drugs 2.5mg, 5mg, 10mg group, tadalafil&#xD;
      tablets 20mg, 40mg group, each group 10 cases.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is a multi-center, randomized, placebo and positive controlled phase IIa&#xD;
      proof-of-concept study to evaluate the effect of single-dose TPN171H tablets on acute&#xD;
      hemodynamic parameters in patients with pulmonary arterial hypertension.The trial is expected&#xD;
      to include 60 patients, divided into 6 groups, according to 1:1:1:1:1:1 into the placebo&#xD;
      group and the test drugs 2.5mg, 5mg, 10mg group, tadalafil tablets 20mg, 40mg group, each&#xD;
      group 10 cases. During the screening period, the tube placement period, and the observation&#xD;
      period, the patients will conduct various inspections and evaluation observations as&#xD;
      required.&#xD;
&#xD;
      The Swan-Ganz floating catheter and echocardiography were used to evaluate the efficacy of&#xD;
      TPN171H; PK parameters: including Tmax, Cmax, AUC0-t , t1/2,CL/F, Vz/F, λz; Safety evaluation&#xD;
      indicators include: vital signs, physical examination, laboratory examination (blood routine,&#xD;
      blood biochemistry, blood gas analysis), 12-lead ECG, adverse events.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 16, 2020</start_date>
  <completion_date type="Actual">June 29, 2022</completion_date>
  <primary_completion_date type="Actual">June 29, 2022</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>Percentage of the maximum change in pulmonary vascular resistance(PVR) to the second baseline</measure>
    <time_frame>Within 24 hours after drug administration</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time of maximum change in PVR</measure>
    <time_frame>Within 24 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The area under the curve for reduction in PVR</measure>
    <time_frame>Within 24 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in arterial oxygenation</measure>
    <time_frame>Within 24 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in right ventricular function</measure>
    <time_frame>Within 24 hours after drug administration</time_frame>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Pulmonary Arterial Hypertension</condition>
  <arm_group>
    <arm_group_label>TPN171H 2.5mg group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TPN171H 2.5mg tablet + Placebo 10mg tablet</description>
  </arm_group>
  <arm_group>
    <arm_group_label>TPN171H 5mg group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TPN171H 5mg tablet + Placebo 10mg tablet</description>
  </arm_group>
  <arm_group>
    <arm_group_label>TPN171H 10mg group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TPN171H 10mg tablet + Placebo 5mg tablet</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo 5mg tablet+ Placebo 10mg tablet</description>
  </arm_group>
  <arm_group>
    <arm_group_label>tadalafil 20mg group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>tadalafil tablet 20mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>tadalafil 40mg group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>tadalafil tablets 20mg *2</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TPN171H</intervention_name>
    <description>Tablets; Oral; Single dose</description>
    <arm_group_label>TPN171H 10mg group</arm_group_label>
    <arm_group_label>TPN171H 2.5mg group</arm_group_label>
    <arm_group_label>TPN171H 5mg group</arm_group_label>
    <other_name>Simmerafil</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Tablets; Oral; Single dose</description>
    <arm_group_label>Placebo group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tadalafil</intervention_name>
    <description>Tablets; Oral; Single dose</description>
    <arm_group_label>tadalafil 20mg group</arm_group_label>
    <arm_group_label>tadalafil 40mg group</arm_group_label>
    <other_name>ADCIRCA</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients aged 18 to 75;&#xD;
&#xD;
          -  Patients who have voluntarily decided to participate in this study, and signed the&#xD;
             informed consent form;&#xD;
&#xD;
          -  Patients who are able to understand and follow study plans and instructions;&#xD;
&#xD;
          -  Patients with symtomatic PAH (Group1), a pulmonary vascular resistance (PVR) &gt; 3 Wood,&#xD;
             a mean pulmonary artery pressure (mPVP) ≥25 mmHg and a pulmonary artery wedge pressure&#xD;
             (PAWP) ≤ 15 mmHg either due to:&#xD;
&#xD;
               1. Idiopathic PAH (IPAH)&#xD;
&#xD;
               2. Familial PAH&#xD;
&#xD;
               3. Associated PAH due to drugs or toxins&#xD;
&#xD;
               4. Associated PAH due to connective tissue disease&#xD;
&#xD;
               5. Associated PAH due to congenital heart disease, if patients underwent surgical&#xD;
                  correction more than 1 year prior to screening&#xD;
&#xD;
          -  Have a current diagnosis of being in WHO functional class II or III;&#xD;
&#xD;
          -  Patients who are willing to take proper contraceptive during the study and within 3&#xD;
             months after the study completed.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  All types of PH except subtypes of Group1 specified in the inclusion criteria;&#xD;
&#xD;
          -  Moderate to severe COPD (FEV1 &lt; 60% predicted);&#xD;
&#xD;
          -  Moderate to severe restrictive lung disease (FVC &lt; 70% predicted);&#xD;
&#xD;
          -  Pre-treatment with PAH therapy within the last 1 months before the screening visit&#xD;
             (including endothelin receptor antagonists, PDE5 inhibitors, guanylate cyclase agonist&#xD;
             and prostacycline analogues);&#xD;
&#xD;
          -  A &quot;positive&quot; response to acute vasodilator testing;&#xD;
&#xD;
          -  Coagulation dysfunction (defined as activated partial thromboplastin time and&#xD;
             international normalized ratio are both &gt;1.5 times upper limit normal) or patients&#xD;
             with potential bleeding risk;&#xD;
&#xD;
          -  Hepatic dysfunction indicated by: serum bilirubin&gt;3 times upper limit normal, ALT and&#xD;
             AST&gt;2.5 times upper limit normal;&#xD;
&#xD;
          -  Renal insufficiency (creatinine clearance&lt;30 mL/min)；&#xD;
&#xD;
          -  Systolic blood pressure&lt;90 mmHg at screening;&#xD;
&#xD;
          -  QT prolongation at screening, whose values (QTcF) exceeding 450 msec in males and 470&#xD;
             msec in females;&#xD;
&#xD;
          -  Have enrolled in/or have a plan of an exercise training program for pulmonary&#xD;
             rehabilitation before the screening visit/or during the study;&#xD;
&#xD;
          -  Patients who have a recent (within 3 months) history of abusing alcohol or illicit&#xD;
             drugs;&#xD;
&#xD;
          -  Body weight&lt;40 kg；&#xD;
&#xD;
          -  Patients who have participated in a clinical study involving another investigational&#xD;
             drug within 1 month before the screening visit;&#xD;
&#xD;
          -  For any other reasons that affect compliance with the study protocol, especially the&#xD;
             long-term monitoring of floating catheters, according to the decision of&#xD;
             investigators;&#xD;
&#xD;
          -  HBV, HCV, HIV or Tp infection;&#xD;
&#xD;
          -  Patients with gastrointestinal, urinary, reproductive, immunologic, endocrine, or&#xD;
             central nervous system disease that, in the opinion of the investigator, will affect&#xD;
             the study;&#xD;
&#xD;
          -  Have a history of malignancies within 2 years, except for a cured basal cell or skin&#xD;
             squamous cell carcinoma;&#xD;
&#xD;
          -  Pregnant women, or breast feeding women;&#xD;
&#xD;
          -  Patients with hypersensitivity to iloprost or any of the excipients.&#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_official>
    <last_name>Yong Huo</last_name>
    <role>Principal Investigator</role>
    <affiliation>Peking University First Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Peking Union Medical College Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100032</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Peking University First Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100034</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fuwai Hospital CAMS&amp;PUMC</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100037</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The First Affiliated Hospital of Chongqing Medical University</name>
      <address>
        <city>Chongqing</city>
        <state>Chongqing</state>
        <zip>400016</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gansu Provincial Hospital</name>
      <address>
        <city>Lanzhou</city>
        <state>Gansu</state>
        <zip>730000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science &amp; Technology</name>
      <address>
        <city>Wuhan</city>
        <state>Hubei</state>
        <zip>430030</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Second Xiangya Hospital of Central South University</name>
      <address>
        <city>Changsha</city>
        <state>Hunan</state>
        <zip>410011</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>First Affiliated Hospital Of Gannan Medical University</name>
      <address>
        <city>Ganzhou</city>
        <state>Jiangxi</state>
        <zip>341000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shanghai Pulmonary Hospital</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200433</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>December 2021</verification_date>
  <study_first_submitted>July 15, 2020</study_first_submitted>
  <study_first_submitted_qc>July 20, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 23, 2020</study_first_posted>
  <last_update_submitted>June 30, 2022</last_update_submitted>
  <last_update_submitted_qc>June 30, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 1, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>pulmonary arterial hypertension</keyword>
  <keyword>Acute Haemodynamic Study</keyword>
  <keyword>PK/PD study</keyword>
  <keyword>TPN171H</keyword>
  <keyword>Simmerafil</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pulmonary Arterial Hypertension</mesh_term>
    <mesh_term>Familial Primary Pulmonary Hypertension</mesh_term>
    <mesh_term>Hypertension</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tadalafil</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT04483115
org study id: TPN171H-P201
nct id: NCT04483115
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study is a phase IIa proof-of-concept study to evaluate the effect of single-dose
      TPN171H tablets on acute haemodynamic parameters in patients with pulmonary arterial
      hypertension.The trial is expected to include 60 patients, divided into 6 groups, according
      to 1:1:1:1:1:1 into the placebo group and the test drugs 2.5mg, 5mg, 10mg group, tadalafil
      tablets 20mg, 40mg group, each group 10 cases.
This study is a multi-center, randomized, placebo and positive controlled phase IIa
      proof-of-concept study to evaluate the effect of single-dose TPN171H tablets on acute
      hemodynamic parameters in patients with pulmonary arterial hypertension.The trial is expected
      to include 60 patients, divided into 6 groups, according to 1:1:1:1:1:1 into the placebo
      group and the test drugs 2.5mg, 5mg, 10mg group, tadalafil tablets 20mg, 40mg group, each
      group 10 cases. During the screening period, the tube placement period, and the observation
      period, the patients will conduct various inspections and evaluation observations as
      required.

      The Swan-Ganz floating catheter and echocardiography were used to evaluate the efficacy of
      TPN171H; PK parameters: including Tmax, Cmax, AUC0-t , t1/2,CL/F, Vz/F, λz; Safety evaluation
      indicators include: vital signs, physical examination, laboratory examination (blood routine,
      blood biochemistry, blood gas analysis), 12-lead ECG, adverse events.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Percentage of the maximum change in pulmonary vascular resistance(PVR) to the second baseline
time frame: Within 24 hours after drug administration
measure: Time of maximum change in PVR
time frame: Within 24 hours after drug administration
measure: The area under the curve for reduction in PVR
time frame: Within 24 hours after drug administration
measure: Change in arterial oxygenation
time frame: Within 24 hours after drug administration
measure: Change in right ventricular function
time frame: Within 24 hours after drug administration
arm group label: TPN171H 2.5mg group
arm group type: Experimental
description: TPN171H 2.5mg tablet + Placebo 10mg tablet
arm group label: TPN171H 5mg group
arm group type: Experimental
description: TPN171H 5mg tablet + Placebo 10mg tablet
arm group label: TPN171H 10mg group
arm group type: Experimental
description: TPN171H 10mg tablet + Placebo 5mg tablet
arm group label: Placebo group
arm group type: Placebo Comparator
description: Placebo 5mg tablet+ Placebo 10mg tablet
arm group label: tadalafil 20mg group
arm group type: Active Comparator
description: tadalafil tablet 20mg
arm group label: tadalafil 40mg group
arm group type: Active Comparator
description: tadalafil tablets 20mg *2
intervention type: Drug
intervention name: TPN171H
description: Tablets; Oral; Single dose
arm group label: TPN171H 10mg group
arm group label: TPN171H 2.5mg group
arm group label: TPN171H 5mg group
other name: Simmerafil
intervention type: Drug
intervention name: Placebo
description: Tablets; Oral; Single dose
arm group label: Placebo group
intervention type: Drug
intervention name: Tadalafil
description: Tablets; Oral; Single dose
arm group label: tadalafil 20mg group
arm group label: tadalafil 40mg group
other name: ADCIRCA
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Yong Huo
role: Principal Investigator
affiliation: Peking University First Hospital
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: China
responsible party type: Sponsor
mesh term: Pulmonary Arterial Hypertension
mesh term: Familial Primary Pulmonary Hypertension
mesh term: Hypertension
mesh term: Tadalafil
sharing ipd: No