xml: <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/NCT05983250</url>
    </required_header>
    <id_info>
      <org_study_id>TNX-103-06</org_study_id>
      <nct_id>NCT05983250</nct_id>
    </id_info>
    <brief_title>LEVosimendan to Improve Exercise Limitation in Patients With PH-HFpEF</brief_title>
    <acronym>LEVEL</acronym>
    <official_title>A Phase 3, Double-Blind, Randomized, Placebo-Controlled Study of Levosimendan in Pulmonary Hypertension Patients With Heart Failure With Preserved Left Ventricular Ejection Fraction (PH-HFpEF)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Tenax Therapeutics, Inc.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Medpace, Inc.</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>Tenax Therapeutics, Inc.</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        This study will evaluate the efficacy of TNX-103 (levosimendan) compared with placebo in&#xD;
        subjects with PH-HFpEF as measured by the change in 6-Minute Walk Distance (6 MWD; Day 1 to&#xD;
        Week 12).&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This is a Phase 3, double-blind, randomized, placebo-controlled study of levosimendan in&#xD;
        patients with PH-HFpEF. There will be a Screening Period of up to 30 days. Subjects will&#xD;
        provide written informed consent prior to completing any study procedures. Upon meeting all&#xD;
        eligibility criteria, patients will continue to the 12-week randomized, double-blind&#xD;
        treatment phase. Approximately 152 subjects will be randomized in a 1:1 ratio to receive an&#xD;
        oral dose of levosimendan or placebo 2 mg/day for Weeks 1 to 4 and 3 mg/day for Weeks 5 to&#xD;
        12. Subjects will return to the clinical site at Weeks 4, 8, and 12.&#xD;
  &#xD;
        All randomized subjects will have the option to enter the 92-week OLE following the&#xD;
        completion of all study events at Week 12.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">November 2023</start_date>
    <completion_date type="Anticipated">July 2027</completion_date>
    <primary_completion_date type="Anticipated">March 2027</primary_completion_date>
    <phase>Phase 3</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>
      <intervention_model_description>Double blind, randomized, placebo controlled</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
      <masking_description>The blind is maintained by the use of a matching placebo.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Six-minute walk distance from Baseline to Week 12</measure>
      <time_frame>12 weeks</time_frame>
    </primary_outcome>
    <secondary_outcome>
      <measure>KCCQ</measure>
      <time_frame>12 weeks</time_frame>
      <description>Change in KCCQ - Overall Summary Score</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Clinical Worsening Events</measure>
      <time_frame>12 weeks</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in NT-proBNP</measure>
      <time_frame>12 weeks</time_frame>
      <description>Decreases in NT-proBNP may indicate an improvement insymptoms</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change NYHA functional class</measure>
      <time_frame>12 weeks</time_frame>
      <description>On a scale of I-IV. Lower scores may indicate improvement in symptoms</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">152</enrollment>
    <condition>Pulmonary Hypertension</condition>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Placebo</description>
    </arm_group>
    <arm_group>
      <arm_group_label>TNX-103</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>levosimendan</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>TNX-103</intervention_name>
      <description>levosimendan 1 mg</description>
      <arm_group_label>TNX-103</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>Placebo</description>
      <arm_group_label>Placebo</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Men or women, greater than or equal to18 to 85 years of age.&#xD;
  &#xD;
            2. NYHA Class II or III or ambulatory NYHA class IV symptoms.&#xD;
  &#xD;
            3. A diagnosis of World Health Organization (WHO) Group 2 PH-HFpEF with qualifying&#xD;
               hemodynamics&#xD;
  &#xD;
            4. A qualifying Baseline RHC performed within 120 days. The RHC can be a historical RHC&#xD;
               done prior to study consent.&#xD;
  &#xD;
            5. A qualifying echocardiogram performed within 30 days showing an LVEF greater than or&#xD;
               equal to 40%&#xD;
  &#xD;
            6. A qualifying 6-MWD of at least 100 meters, but not more than 450 meters at Screening&#xD;
  &#xD;
            7. A 48-hour ambulatory cardiac rhythm monitor during the Screening Period to establish&#xD;
               the resting heart rate (HR) and rhythm.&#xD;
  &#xD;
            8. Chronic medications for heart failure with preserved ejection fraction (HFpEF) or&#xD;
               other serious underlying cardiac or pulmonary conditions should be administered at a&#xD;
               stable dose for greater than or equal to 30 days prior to the day of the Baseline&#xD;
               6-MWT.&#xD;
  &#xD;
            9. Female subjects of childbearing potential must have a negative urine pregnancy test&#xD;
               result at the Screening Visit and a negative urine pregnancy test and must not be&#xD;
               pregnant, lactating, or planning a pregnancy from the Screening Visit to 7 months&#xD;
               after the last dose of study drug.&#xD;
  &#xD;
           10. Female subjects of childbearing potential will be included if they are either sexually&#xD;
               inactive (abstinent) for 90 days prior to the first dose of study drug, or are using a&#xD;
               highly effective birth control method&#xD;
  &#xD;
           11. Female subjects of nonchildbearing potential will be included if they meet the&#xD;
               following definition of nonchildbearing potential: are either surgically sterile or&#xD;
               postmenopausal.&#xD;
  &#xD;
           12. Male patients with female partners of childbearing potential must use highly effective&#xD;
               methods of birth control during their participation in the study and for a period of 4&#xD;
               months after the last dose of study drug.&#xD;
  &#xD;
           13. Patients must agree to abstain from egg or sperm donation through 7 months for female&#xD;
               patients and 4 months for male patients after administration of the last dose of study&#xD;
               drug.&#xD;
  &#xD;
           14. Ability to adhere to study visit schedule and understand and comply with all protocol&#xD;
               requirements.&#xD;
  &#xD;
           15. Signed informed consent document indicating that they understand the purpose and&#xD;
               procedures required for the study and are willing to participate in the study.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. A diagnosis of PH WHO Groups 1, 3, 4, or 5.&#xD;
  &#xD;
            2. Walking activity that is limited by anything other than shortness of breath or fatigue&#xD;
               attributed to PH-HFpEF.&#xD;
  &#xD;
            3. Echocardiographic evidence for hypertrophic cardiomyopathy, restrictive&#xD;
               cardiomyopathy, constrictive pericarditis, cardiac amyloidosis, or infiltrative&#xD;
               cardiomyopathy&#xD;
  &#xD;
            4. Structural heart repair or replacement of the aortic valve or mitral valve (surgical&#xD;
               or percutaneous) within the past 12 months. OR, planned valve intervention in the next&#xD;
               6 months. OR, the presence of echocardiographic findings of significant valve disease&#xD;
               as assessed from the qualifying echocardiogram&#xD;
  &#xD;
            5. Any of the following clinical laboratory values within 30 days as specified:&#xD;
  &#xD;
                 1. Hemoglobin &lt;10 g/dL per local laboratory.&#xD;
  &#xD;
                 2. Serum alanine aminotransferase or aspartate aminotransferase levels &gt;3× upper&#xD;
                    limit of normal (ULN) or total bilirubin &gt;3× ULN.&#xD;
  &#xD;
                 3. Electrocardiogram (ECG) with a QTcF &gt;450 msec for males and &gt;470 msec for females&#xD;
                    at Screening and Baseline in the absence of right bundle branch block.&#xD;
  &#xD;
                 4. Platelet count &lt;75,000/mm3.&#xD;
  &#xD;
            6. A diagnosis of pre-existing lung disease&#xD;
  &#xD;
            7. Recent documentation of significant underlying lung disease&#xD;
  &#xD;
            8. Documentation of pulmonary thromboembolism in the last 12 months&#xD;
  &#xD;
            9. Cardiovascular co-morbidities&#xD;
  &#xD;
           10. Receipt of any approved pulmonary arterial hypertension-specific therapies&#xD;
  &#xD;
           11. Hospitalization for any indication within 30 days&#xD;
  &#xD;
           12. Receipt of any intravenous (IV) inotropes within 30 days&#xD;
  &#xD;
           13. Body mass index greater than or equal to 50 kg/m2.&#xD;
  &#xD;
           14. Estimated glomerular filtration rate (eGFR) &lt;30 mL/min/1.73m2&#xD;
  &#xD;
           15. Known history of chronic liver disease&#xD;
  &#xD;
           16. Prior exposure to levosimendan&#xD;
  &#xD;
           17. Current enrollment in or completion of any other investigational product study within&#xD;
               30 days of Screening.&#xD;
  &#xD;
           18. Initiation of an exercise program for cardiopulmonary rehabilitation within 45 days&#xD;
  &#xD;
           19. History of severe allergic or anaphylactic reaction or hypersensitivity to the&#xD;
               excipients in the investigational product.&#xD;
  &#xD;
           20. Major surgery within 60 days. Subjects must have completely recovered from any&#xD;
               previous surgery.&#xD;
  &#xD;
           21. Prior heart, lung, or heart-lung transplants or life expectancy of &lt;12 months&#xD;
  &#xD;
           22. Pregnancy or breastfeeding in females&#xD;
  &#xD;
           23. History of active malignancy, with the exception of fully treated basal cell&#xD;
               carcinoma, cervical carcinoma in situ, or squamous cell carcinomas of the skin.&#xD;
  &#xD;
           24. History of clinically significant other diseases that may limit or complicate&#xD;
               participation in the study.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>85 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Kevin Crawford</last_name>
      <phone>19198552145</phone>
      <email>k.crawford@tenaxthera.com</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 1, 2023</study_first_submitted>
    <study_first_submitted_qc>August 1, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 9, 2023</study_first_posted>
    <last_update_submitted>August 30, 2023</last_update_submitted>
    <last_update_submitted_qc>August 30, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 5, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>HFpEF</keyword>
    <keyword>Pulmonary hypertension group 2</keyword>
    <keyword>PH-HFpEF</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Hypertension, Pulmonary</mesh_term>
      <mesh_term>Hypertension</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05983250
  org study id: TNX-103-06
  nct id: NCT05983250
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  is us export: No
  This study will evaluate the efficacy of TNX-103 (levosimendan) compared with placebo in
        subjects with PH-HFpEF as measured by the change in 6-Minute Walk Distance (6 MWD; Day 1 to
        Week 12).
  This is a Phase 3, double-blind, randomized, placebo-controlled study of levosimendan in
        patients with PH-HFpEF. There will be a Screening Period of up to 30 days. Subjects will
        provide written informed consent prior to completing any study procedures. Upon meeting all
        eligibility criteria, patients will continue to the 12-week randomized, double-blind
        treatment phase. Approximately 152 subjects will be randomized in a 1:1 ratio to receive an
        oral dose of levosimendan or placebo 2 mg/day for Weeks 1 to 4 and 3 mg/day for Weeks 5 to
        12. Subjects will return to the clinical site at Weeks 4, 8, and 12.
  
        All randomized subjects will have the option to enter the 92-week OLE following the
        completion of all study events at Week 12.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: Double blind, randomized, placebo controlled
  primary purpose: Treatment
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  masking description: The blind is maintained by the use of a matching placebo.
  measure: Six-minute walk distance from Baseline to Week 12
  time frame: 12 weeks
  measure: KCCQ
  time frame: 12 weeks
  description: Change in KCCQ - Overall Summary Score
  measure: Clinical Worsening Events
  time frame: 12 weeks
  measure: Change in NT-proBNP
  time frame: 12 weeks
  description: Decreases in NT-proBNP may indicate an improvement insymptoms
  measure: Change NYHA functional class
  time frame: 12 weeks
  description: On a scale of I-IV. Lower scores may indicate improvement in symptoms
  arm group label: Placebo
  arm group type: Placebo Comparator
  description: Placebo
  arm group label: TNX-103
  arm group type: Active Comparator
  description: levosimendan
  intervention type: Drug
  intervention name: TNX-103
  description: levosimendan 1 mg
  arm group label: TNX-103
  intervention type: Drug
  intervention name: Placebo
  description: Placebo
  arm group label: Placebo
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 85 Years
  healthy volunteers: No
  last name: Kevin Crawford
  phone: 19198552145
  email: k.crawford@tenaxthera.com
  responsible party type: Sponsor
  mesh term: Hypertension, Pulmonary
  mesh term: Hypertension
  sharing ipd: No