<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/NCT04467697</url>
  </required_header>
  <id_info>
    <org_study_id>MRS-TU-2019EXT</org_study_id>
    <nct_id>NCT04467697</nct_id>
  </id_info>
  <brief_title>Ambulatory Blood Pressure Monitoring (ABPM) Extension Study of Oral Testosterone Undecanoate in Hypogonadal Men</brief_title>
  <official_title>A 6 Month, Open Label, Ambulatory Blood Pressure Monitoring (ABPM) Extension Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Marius Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Syneos Health</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Marius Pharmaceuticals</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this six-month treatment extension study is&#xD;
&#xD;
        -  to assess feasibility of a lower starting dose of SOV2012-F1 (daily dose of 400 mg [200&#xD;
           mg with breakfast meal and 200mg with dinner meal]) to titrate individual doses in order&#xD;
           to further enhance drug administration.&#xD;
&#xD;
        -  To examine the blood pressure (BP) effects of Marius's oral testosterone undecanoate&#xD;
           formulation, SOV2012-F1, using 24-hour ambulatory blood pressure monitoring (ABPM).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is the six-month treatment extension of Study MRS-TU-2019, which like Study MRS-TU-2019&#xD;
      (NCT03198728), is an open-label study. The MRS-TU-2019 ABPM Extension Study (MRS-TU-2019EXT;&#xD;
      NCT04467697), will extend the participation for up to 170 MRS-TU-2019 subjects who chose to&#xD;
      enroll into the MRS-TU-2019EXT, for a target of 135 evaluable subjects reaching the 4-month&#xD;
      ABPM assessment&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 18, 2018</start_date>
  <completion_date type="Actual">May 1, 2020</completion_date>
  <primary_completion_date type="Actual">May 1, 2020</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from baseline in 24-hour average ambulatory systolic blood pressure (sBP) after approximately 120 days treatment</measure>
    <time_frame>120 days</time_frame>
    <description>Measured by Ambulatory Blood Pressure Monitoring (ABPM)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>To determine response to a lower starting dose of oral SOV2012-F1 with up and down titration</measure>
    <time_frame>90 days</time_frame>
    <description>Percentage of SOV2012-F1-treated subjects with a plasma T Cavg within the normal range after 90 days of treatment. Measured by Plasma T concentration.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in 24-hour average ambulatory systolic blood pressure, using ABPM, after approximately 180 days (+/-3) of treatment.</measure>
    <time_frame>180 days</time_frame>
    <description>Measured by Ambulatory Blood Pressure Monitoring (ABPM)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measuring ambulatory blood pressure by ABPM after 120 days (+/-3) and 180 days (+/-3) of SOV treatment</measure>
    <time_frame>120 and 180 days</time_frame>
    <description>Measured by Ambulatory Blood Pressure Monitoring (ABPM) at:&#xD;
Change from baseline in 7 AM to 10:30 PM -hour average ambulatory systolic blood pressure (daytime)&#xD;
Change from baseline in 11 PM to 6:30 AM -hour average ambulatory systolic blood pressure (nighttime)&#xD;
Maximum 24-hour systolic ambulatory blood pressure&#xD;
Change from baseline in 7 AM to 10:30 PM -hour average ambulatory diastolic blood pressure (daytime)&#xD;
Change from baseline in 11 PM to 6:30 AM -hour average ambulatory diastolic blood pressure (nighttime)&#xD;
Change from baseline in 24-hour mean diastolic blood pressure (dBP)&#xD;
Maximum 24-hour diastolic blood pressure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measuring ambulatory heart rate by ABPM after 120 days (±3) of SOV treatment, and after 180 days (±3) of SOV treatment.</measure>
    <time_frame>120 and 180 days</time_frame>
    <description>Measured by Ambulatory Blood Pressure Monitoring (ABPM) at:&#xD;
Change from baseline in 24-hour average ambulatory heartrate&#xD;
Change from baseline in 7 AM to 10:30 PM -hour average ambulatory heartrate (daytime)&#xD;
Change from baseline in 11 PM to 6:30 AM -hour average ambulatory heartrate (nighttime)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Observed and change from baseline in half hourly systolic blood pressure and diastolic blood pressure, as measured by ABPM after after 120 days (±3) of SOV treatment, and after 180 days (±3) of SOV treatment.</measure>
    <time_frame>120 and 180 days</time_frame>
    <description>Measured by Ambulatory Blood Pressure Monitoring (ABPM) in mm HG</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Observed and change from baseline in half hourly heart rate measurement, as measured by ABPM after after 120 days (±3) of SOV treatment, and after 180 days (±3) of SOV treatment.</measure>
    <time_frame>120 and 180 days</time_frame>
    <description>Measured by Ambulatory Blood Pressure Monitoring (ABPM) in beats per minute</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of SOV2012-F1-treated subjects with maximum plasma testosterone concentration (T Cmax) values after 90 days of treatment: &lt; 1500 ng/dL; &gt; 1800 to ≤ 2500 ng/dL; &gt; 2500 ng/dL.</measure>
    <time_frame>90 days</time_frame>
    <description>Measured by plasma T levels</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Incidence of AEs, SAEs and AEs leading to MRS-TU-2019EXT study withdrawal of SOV2012-F1 treated subjects.</measure>
    <time_frame>90, 120 and 180 days</time_frame>
    <description>Number of subjects of adverse events (AEs), serious adverse events (SAEs), and AEs leading to study withdrawal in SOV2012-F1-treated subjects</description>
  </other_outcome>
  <other_outcome>
    <measure>Observed and change from baseline in blood pressure (BP) obtained using in-clinic BP measurement during the treatment period.</measure>
    <time_frame>90, 120 and 180 days</time_frame>
    <description>Measured by in-clinic BP measurement, mm HG</description>
  </other_outcome>
  <other_outcome>
    <measure>Observed and change from baseline in heartrate (HR) obtained using in-clinic HR measurement during the treatment period.</measure>
    <time_frame>90, 120 and 180 days</time_frame>
    <description>Measured by in-clinic HR measurement, beats per minute</description>
  </other_outcome>
  <other_outcome>
    <measure>Assess observed and change from baseline in hematology parameters in Liver function tests</measure>
    <time_frame>90 and 180 days</time_frame>
    <description>Alanine aminotransferase [ALT], aspartate aminotransferase [AST], and alkaline phosphatase in SOV2012-F1 treated subjects during the treatment period measured by laboratory assessment, measured in Units per Liter (U/L)</description>
  </other_outcome>
  <other_outcome>
    <measure>Assess observed and change from baseline in hematology parameters in Liver function tests</measure>
    <time_frame>90 and 180 days</time_frame>
    <description>Total bilirubin in SOV2012-F1 treated subjects during the treatment period measured by laboratory assessment, measured in mg/dL</description>
  </other_outcome>
  <other_outcome>
    <measure>Assess observed and change from baseline in hematology parameters (hemoglobin) in SOV2012-F1 treated subjects during the treatment period.</measure>
    <time_frame>90 and 180 days</time_frame>
    <description>Measured by laboratory assessment.</description>
  </other_outcome>
  <other_outcome>
    <measure>Assess observed and change from baseline in hormone levels.</measure>
    <time_frame>90 and 180 days</time_frame>
    <description>Luteinizing hormone [LH], follicle-stimulating hormone [FSH], dihydrotestosterone [DHT], sex hormone-binding globulin [SHBG], thyroid stimulating hormone [TSH] in SOV2012-F1 treated subjects during the treatment period measured by laboratory assessment.</description>
  </other_outcome>
  <other_outcome>
    <measure>Assess observed and change from baseline in lipid profiles (high and low-density lipoproteins, total cholesterol, triglycerides) in SOV2012-F1 treated subjects during the treatment period.</measure>
    <time_frame>90 and 180 days</time_frame>
    <description>Measured by laboratory assessment</description>
  </other_outcome>
  <other_outcome>
    <measure>Assess observed and change from baseline in Serum prostate-specific antigen (PSA) in SOV2012-F1 treated subjects during the treatment period.</measure>
    <time_frame>90 and 180 days</time_frame>
    <description>Measured by laboratory assessment</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">173</enrollment>
  <condition>Hypogonadism, Male</condition>
  <arm_group>
    <arm_group_label>SOV2012-F1-treated</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients treated with SOV2012-F1, starting daily dose in MRS-TU-2019EXT is 400 mg - (200 mg with morning meal and 200 mg with evening meal). Dosing is titrated up to a maximum of 600 mg SOV2012-F1 per day (300 mg in the morning and 300 mg in the evening) based on plasma T after 14 and 42 days of treatment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SOV2012-F1</intervention_name>
    <description>oral preparation of testosterone undecanoate (TU)</description>
    <arm_group_label>SOV2012-F1-treated</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        For all subjects participating in MRS-TU-2019EXT, whether rolling on from MRS-TU-2019 or&#xD;
        newly enrolling, the following MRS-TU-2019EXT Inclusion/Exclusion Criteria apply:&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
        1. Completion of MRS-TU-2019 Day 365/ End of Treatment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Upper arm circumference &gt; 45 cm.&#xD;
&#xD;
          2. Long distance driving or planned driving trip (&gt; 60 mins duration where the subject is&#xD;
             doing the driving) during period of wearing ABPM cuff.&#xD;
&#xD;
          3. Expected / known forthcoming change to antihypertensive medication(s) during the&#xD;
             MRS-TU-2019 EXT extension study.&#xD;
&#xD;
          4. Cardiac arrhythmias that, in the opinion of the investigator, interfere with the&#xD;
             ability of the ABPM recorder to obtain reliable measurements.&#xD;
&#xD;
          5. Use of T implantable pellets since completion of Day 365/EOT visit in MRS-TU- 2019.&#xD;
&#xD;
        For newly enrolling subjects into MRS-TU-2019EXT (naïve to MRS-TU-2019), the applicable&#xD;
        Inclusion/Exclusion criteria from the MRS-TU-2019 study, also must be met :&#xD;
&#xD;
        MRS-TU-2019 Key Inclusion Criteria:&#xD;
&#xD;
          1. Male aged 18 to 65 years, inclusive, at the time of providing informed consent to&#xD;
             participate in the study.&#xD;
&#xD;
          2. Hypogonadism defined as having 2 consecutive serum total T levels ≤ 281 ng/dL based on&#xD;
             a blood sample, drawn at least 3 days apart, between 7 a.m. and 10 a.m.&#xD;
&#xD;
          3. At least 1 clinical feature consistent with male hypogonadism. If a subject is&#xD;
             receiving commercial TRT prior to Screening Visit 1, he must have a history of at&#xD;
             least 1 clinical feature consistent with male hypogonadism.&#xD;
&#xD;
          4. Must be naïve to androgen replacement therapy or washed out adequately of prior&#xD;
             androgen replacement therapies; willing to cease current T treatment; or currently not&#xD;
             taking any T treatment. Subjects must remain off all forms of T, except for dispensed&#xD;
             study drug, throughout the entire study.&#xD;
&#xD;
          5. No unstable ongoing concomitant medical conditions. Treated and well-controlled&#xD;
             conditions such as type 2 diabetes, hypertension, or dyslipidemia are acceptable with&#xD;
             stable medication in place for at least 3 months prior to study entry:&#xD;
&#xD;
               1. Hemoglobin A1c &lt; 8.0%&#xD;
&#xD;
               2. BP &lt; 150/90 mm Hg&#xD;
&#xD;
                  • *for MRS-TU-2019EXT ABPM Extension Study, the in-clinic, average BP must be &lt;&#xD;
                  140/90 for inclusion into the MRS-TU-2019EXT study.&#xD;
&#xD;
               3. Low-density lipoprotein cholesterol &lt; 190 mg/dL.&#xD;
&#xD;
          6. Subjects with an endocrine disorder requiring treatment other than hypogonadism must&#xD;
             be on a stable dose of replacement medication for at least 3 months prior to study&#xD;
             entry.&#xD;
&#xD;
          7. Adequate venous access to allow collection of a number of blood samples via a venous&#xD;
             cannula.&#xD;
&#xD;
          8. Written informed consent to participate in the study and ability to comply with all&#xD;
             study requirements.&#xD;
&#xD;
        MRS-TU-2019 Key Exclusion Criteria:&#xD;
&#xD;
          1. Serum PSA &gt; 2.5 ng/ml and/or abnormal prostate gland on palpation, e.g., palpable&#xD;
             nodes, at Screening Visit 2.&#xD;
&#xD;
          2. Received oral, topical, intranasal, or buccal T therapy within the previous 2 weeks,&#xD;
             intramuscular T injection of short-acting duration within the previous 4 weeks,&#xD;
             intramuscular T injection of long-acting duration within the previous 20 weeks, or T&#xD;
             implantable pellets within the previous 6 months.&#xD;
&#xD;
             *For ABPM Extension Study Only: Newly Enrolled Subjects to MRS-TU-2019EXT ABPM&#xD;
             Extension Study, patients must not have received prior testosterone replacement&#xD;
             therapy within 8 weeks of the start of the study, with the exception of T implantable&#xD;
             pellets which are excluded for 6 months.&#xD;
&#xD;
          3. Use of any drug that could interfere with measurement or assessment of serum androgen&#xD;
             levels, including 5 alpha-reductase inhibitors, anabolic steroids, and drugs with&#xD;
             antiandrogenic properties (e.g., spironolactone, cimetidine, flutamide, bicalutamide,&#xD;
             and ketoconazole). These drugs must be stopped for at least 1 month prior to study&#xD;
             entry (6 months in the case of dutasteride). Patients taking potent, long- acting&#xD;
             opiate therapy on a daily basis are not eligible for the study. Conversely, ad hoc use&#xD;
             of potent, short-acting opiates for a period of less than 7 days may be permitted&#xD;
             after discussion with the Marius Pharmaceuticals medical monitor.&#xD;
&#xD;
          4. Use of over-the-counter products, including natural health products (e.g., food&#xD;
             supplements and herbal supplements such as saw palmetto or phytoestrogens) that may&#xD;
             affect total T levels, within 7 days prior to study entry.&#xD;
&#xD;
          5. History of drug or alcohol abuse within the past 2 years that in the opinion of the&#xD;
             investigator could interfere with study participation and/or influence study efficacy&#xD;
             and safety endpoints assessments.&#xD;
&#xD;
          6. Unstable or chronic disease that could interfere with participation in the study or&#xD;
             patient safety, including psychiatric disorders.&#xD;
&#xD;
          7. Myocardial infarction, coronary artery surgery, heart failure, stroke, unstable&#xD;
             angina, or other unstable cardiovascular disease within the past 6 months.&#xD;
&#xD;
          8. Abnormal ECG considered clinically significant by investigator at Screening.&#xD;
&#xD;
          9. Diagnosis of any cancer within the previous 5 years other than basal or squamous cell&#xD;
             skin cancer with clear margins.&#xD;
&#xD;
         10. Any surgical or medical condition that might alter administration of the study drug or&#xD;
             comparator, including history of gastric surgery, cholecystectomy, vagotomy, small&#xD;
             bowel resection, or any surgical procedure or medications (e.g., GLP-1 agonists and&#xD;
             motility agents such as domperidone, metoclopramide, etc.) that might interfere with&#xD;
             gastrointestinal motility, pH, or absorption of TU.&#xD;
&#xD;
         11. Duodenal or gastric ulcers, or gastrointestinal/rectal bleeding during the 3 months&#xD;
             prior to screening.&#xD;
&#xD;
         12. Chronic skin conditions on the chest or upper arms that would prevent administration&#xD;
             of AndroGel in a manner designed to ensure reliable and consistent absorption thereof&#xD;
&#xD;
         13. Human immunodeficiency virus (HIV) infection.&#xD;
&#xD;
         14. Chronic hepatitis B virus and/or hepatitis C virus (HCV) infection (as determined by&#xD;
             positive testing for hepatitis B virus surface antigen or HCV antibody with&#xD;
             confirmatory testing, i.e., detectable serum HCV ribonucleic acid [RNA])&#xD;
&#xD;
         15. Clinically significant abnormal laboratory values at screening including but not&#xD;
             limited to:&#xD;
&#xD;
               1. Elevated liver enzymes (aspartate aminotransferase [AST], alanine&#xD;
                  aminotransferase [ALT] &gt; 2X upper limit of normal)&#xD;
&#xD;
               2. Estimated glomerular filtration rate &lt; 60 ml/min/1.73 m2 as calculated by the&#xD;
                  Modification of Diet in Renal Disease formula&#xD;
&#xD;
               3. Hemoglobin &lt; 11.0 g/dL or &gt; 16.0 g/dL. For a subject previously on testosterone&#xD;
                  replacement therapy with less than 30 days washout prior to screening Visit 2,&#xD;
                  hemoglobin &lt; 11.0 g/dL or &gt; 17.0 g/dL.&#xD;
&#xD;
         16. Severe or untreated obstructive sleep apnea syndrome.&#xD;
&#xD;
         17. Severe lower urinary tract symptoms (American Urological Association/ IPSS ≥ 19).&#xD;
&#xD;
         18. History of any clinically significant illness, infection, or surgical procedure within&#xD;
             1 month prior to study entry.&#xD;
&#xD;
         19. Past, current, or suspected prostate or breast cancer.&#xD;
&#xD;
         20. History of long QT syndrome or unexplained sudden death in a first-degree relative&#xD;
             (parent, sibling, or child).&#xD;
&#xD;
         21. Concurrent treatment with medications that may impact the absorption, distribution,&#xD;
             metabolism, or excretion of TU or place the subject at risk for treatment with T.&#xD;
&#xD;
         22. Subject has a partner who is currently pregnant or planning pregnancy during the&#xD;
             course of the study.&#xD;
&#xD;
         23. Treatment with any other investigational drug within 30 days of study entry or &gt; 5&#xD;
             half- lives (whichever is longer) and at any time during the study.&#xD;
&#xD;
         24. History of noncompliance to medical regimens or potential unreliability in the opinion&#xD;
             of the investigator.&#xD;
&#xD;
         25. Unwilling or unable to comply to the dietary requirements for this study.&#xD;
&#xD;
         26. History of polycythemia, either idiopathic or associated with TRT.&#xD;
&#xD;
         27. Donated blood (≥ 500 mL) within the 12-week period prior to study entry.&#xD;
&#xD;
         28. History of an abnormal bleeding tendency or thrombophlebitis within the previous 2&#xD;
             years that is not linked to venipuncture or intravenous cannulation.&#xD;
&#xD;
         29. Onset of gynecomastia within the previous 6 months.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <gender_based>Yes</gender_based>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alistair Smith, MB, ChB</last_name>
    <role>Study Director</role>
    <affiliation>Syneos Health</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Om Dhingra, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Marius Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Alabama Clinical Therapeutics, LLC</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35235</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Coastal Clinic Research Inc</name>
      <address>
        <city>Mobile</city>
        <state>Alabama</state>
        <zip>36608</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>South Florida Medical Research</name>
      <address>
        <city>Aventura</city>
        <state>Florida</state>
        <zip>33180</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>PAB Clinical Research</name>
      <address>
        <city>Brandon</city>
        <state>Florida</state>
        <zip>33511</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jacksonville Impotence Treatment Center</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32223</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>My Community Research Center</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33155</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oviedo Medical Research, LLC</name>
      <address>
        <city>Oviedo</city>
        <state>Florida</state>
        <zip>32765</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Meridien Research</name>
      <address>
        <city>Saint Petersburg</city>
        <state>Florida</state>
        <zip>33709</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwest Clinical Trials</name>
      <address>
        <city>Boise</city>
        <state>Idaho</state>
        <zip>83704</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centex Studies, Inc.</name>
      <address>
        <city>Lake Charles</city>
        <state>Louisiana</state>
        <zip>70601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Quality Clinical Research, Inc.</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Palm Research Center, Inc.</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89148</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Accumed Research Associates</name>
      <address>
        <city>Garden City</city>
        <state>New York</state>
        <zip>11530</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Manhattan Medical Research Practice, PLLC</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rapha Institute for Clinical Research</name>
      <address>
        <city>Fayetteville</city>
        <state>North Carolina</state>
        <zip>28314</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Urologic Consultant of SE Pennyslvania</name>
      <address>
        <city>Bala-Cynwyd</city>
        <state>Pennsylvania</state>
        <zip>19004</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Coastal Carolina Research Center</name>
      <address>
        <city>Mount Pleasant</city>
        <state>South Carolina</state>
        <zip>29464</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Diabetes Endocrine Consultants</name>
      <address>
        <city>Chattanooga</city>
        <state>Tennessee</state>
        <zip>37411</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centex Studies, Inc.</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77058</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://clinicaltrials.gov/ct2/show/NCT03198728</url>
    <description>MRS-TU-2019 protocol, ClinicalTrials.gov ID: NCT03198728</description>
  </link>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>July 1, 2020</study_first_submitted>
  <study_first_submitted_qc>July 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 13, 2020</study_first_posted>
  <disposition_first_submitted>January 13, 2021</disposition_first_submitted>
  <disposition_first_submitted_qc>January 13, 2021</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">January 15, 2021</disposition_first_posted>
  <last_update_submitted>January 15, 2021</last_update_submitted>
  <last_update_submitted_qc>January 15, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 20, 2021</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>Hypogonadism</mesh_term>
    <mesh_term>Eunuchism</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted, but a results disposition has been submitted           -->
</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/NCT04467697
org study id: MRS-TU-2019EXT
nct id: NCT04467697
lead sponsor: 
collaborator: 
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this six-month treatment extension study is

        -  to assess feasibility of a lower starting dose of SOV2012-F1 (daily dose of 400 mg [200
           mg with breakfast meal and 200mg with dinner meal]) to titrate individual doses in order
           to further enhance drug administration.

        -  To examine the blood pressure (BP) effects of Marius's oral testosterone undecanoate
           formulation, SOV2012-F1, using 24-hour ambulatory blood pressure monitoring (ABPM).
This is the six-month treatment extension of Study MRS-TU-2019, which like Study MRS-TU-2019
      (NCT03198728), is an open-label study. The MRS-TU-2019 ABPM Extension Study (MRS-TU-2019EXT;
      NCT04467697), will extend the participation for up to 170 MRS-TU-2019 subjects who chose to
      enroll into the MRS-TU-2019EXT, for a target of 135 evaluable subjects reaching the 4-month
      ABPM assessment
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change from baseline in 24-hour average ambulatory systolic blood pressure (sBP) after approximately 120 days treatment
time frame: 120 days
description: Measured by Ambulatory Blood Pressure Monitoring (ABPM)
measure: To determine response to a lower starting dose of oral SOV2012-F1 with up and down titration
time frame: 90 days
description: Percentage of SOV2012-F1-treated subjects with a plasma T Cavg within the normal range after 90 days of treatment. Measured by Plasma T concentration.
measure: Change from baseline in 24-hour average ambulatory systolic blood pressure, using ABPM, after approximately 180 days (+/-3) of treatment.
time frame: 180 days
description: Measured by Ambulatory Blood Pressure Monitoring (ABPM)
measure: Measuring ambulatory blood pressure by ABPM after 120 days (+/-3) and 180 days (+/-3) of SOV treatment
time frame: 120 and 180 days
description: Measured by Ambulatory Blood Pressure Monitoring (ABPM) at:
Change from baseline in 7 AM to 10:30 PM -hour average ambulatory systolic blood pressure (daytime)
Change from baseline in 11 PM to 6:30 AM -hour average ambulatory systolic blood pressure (nighttime)
Maximum 24-hour systolic ambulatory blood pressure
Change from baseline in 7 AM to 10:30 PM -hour average ambulatory diastolic blood pressure (daytime)
Change from baseline in 11 PM to 6:30 AM -hour average ambulatory diastolic blood pressure (nighttime)
Change from baseline in 24-hour mean diastolic blood pressure (dBP)
Maximum 24-hour diastolic blood pressure
measure: Measuring ambulatory heart rate by ABPM after 120 days (±3) of SOV treatment, and after 180 days (±3) of SOV treatment.
time frame: 120 and 180 days
description: Measured by Ambulatory Blood Pressure Monitoring (ABPM) at:
Change from baseline in 24-hour average ambulatory heartrate
Change from baseline in 7 AM to 10:30 PM -hour average ambulatory heartrate (daytime)
Change from baseline in 11 PM to 6:30 AM -hour average ambulatory heartrate (nighttime)
measure: Observed and change from baseline in half hourly systolic blood pressure and diastolic blood pressure, as measured by ABPM after after 120 days (±3) of SOV treatment, and after 180 days (±3) of SOV treatment.
time frame: 120 and 180 days
description: Measured by Ambulatory Blood Pressure Monitoring (ABPM) in mm HG
measure: Observed and change from baseline in half hourly heart rate measurement, as measured by ABPM after after 120 days (±3) of SOV treatment, and after 180 days (±3) of SOV treatment.
time frame: 120 and 180 days
description: Measured by Ambulatory Blood Pressure Monitoring (ABPM) in beats per minute
measure: Percentage of SOV2012-F1-treated subjects with maximum plasma testosterone concentration (T Cmax) values after 90 days of treatment: < 1500 ng/dL; > 1800 to ≤ 2500 ng/dL; > 2500 ng/dL.
time frame: 90 days
description: Measured by plasma T levels
measure: Incidence of AEs, SAEs and AEs leading to MRS-TU-2019EXT study withdrawal of SOV2012-F1 treated subjects.
time frame: 90, 120 and 180 days
description: Number of subjects of adverse events (AEs), serious adverse events (SAEs), and AEs leading to study withdrawal in SOV2012-F1-treated subjects
measure: Observed and change from baseline in blood pressure (BP) obtained using in-clinic BP measurement during the treatment period.
time frame: 90, 120 and 180 days
description: Measured by in-clinic BP measurement, mm HG
measure: Observed and change from baseline in heartrate (HR) obtained using in-clinic HR measurement during the treatment period.
time frame: 90, 120 and 180 days
description: Measured by in-clinic HR measurement, beats per minute
measure: Assess observed and change from baseline in hematology parameters in Liver function tests
time frame: 90 and 180 days
description: Alanine aminotransferase [ALT], aspartate aminotransferase [AST], and alkaline phosphatase in SOV2012-F1 treated subjects during the treatment period measured by laboratory assessment, measured in Units per Liter (U/L)
measure: Assess observed and change from baseline in hematology parameters in Liver function tests
time frame: 90 and 180 days
description: Total bilirubin in SOV2012-F1 treated subjects during the treatment period measured by laboratory assessment, measured in mg/dL
measure: Assess observed and change from baseline in hematology parameters (hemoglobin) in SOV2012-F1 treated subjects during the treatment period.
time frame: 90 and 180 days
description: Measured by laboratory assessment.
measure: Assess observed and change from baseline in hormone levels.
time frame: 90 and 180 days
description: Luteinizing hormone [LH], follicle-stimulating hormone [FSH], dihydrotestosterone [DHT], sex hormone-binding globulin [SHBG], thyroid stimulating hormone [TSH] in SOV2012-F1 treated subjects during the treatment period measured by laboratory assessment.
measure: Assess observed and change from baseline in lipid profiles (high and low-density lipoproteins, total cholesterol, triglycerides) in SOV2012-F1 treated subjects during the treatment period.
time frame: 90 and 180 days
description: Measured by laboratory assessment
measure: Assess observed and change from baseline in Serum prostate-specific antigen (PSA) in SOV2012-F1 treated subjects during the treatment period.
time frame: 90 and 180 days
description: Measured by laboratory assessment
arm group label: SOV2012-F1-treated
arm group type: Experimental
description: Patients treated with SOV2012-F1, starting daily dose in MRS-TU-2019EXT is 400 mg - (200 mg with morning meal and 200 mg with evening meal). Dosing is titrated up to a maximum of 600 mg SOV2012-F1 per day (300 mg in the morning and 300 mg in the evening) based on plasma T after 14 and 42 days of treatment.
intervention type: Drug
intervention name: SOV2012-F1
description: oral preparation of testosterone undecanoate (TU)
arm group label: SOV2012-F1-treated
criteria: 
gender: Male
gender based: Yes
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Alistair Smith, MB, ChB
role: Study Director
affiliation: Syneos Health
last name: Om Dhingra, PhD
role: Study Chair
affiliation: Marius Pharmaceuticals
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
url: https://clinicaltrials.gov/ct2/show/NCT03198728
description: MRS-TU-2019 protocol, ClinicalTrials.gov ID: NCT03198728
responsible party type: Sponsor
mesh term: Hypogonadism
mesh term: Eunuchism
sharing ipd: Undecided