<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/NCT02235909</url>
  </required_header>
  <id_info>
    <org_study_id>AR14.001</org_study_id>
    <nct_id>NCT02235909</nct_id>
  </id_info>
  <brief_title>An Efficacy and Safety Study in Children 6 to Less Than 18 Years of Age With Hypertension</brief_title>
  <official_title>A Randomized, Double-Blind, Efficacy and Safety Study of AR 14 (AZILSARTAN MEDOXOMIL) Treatment and Withdrawal, Followed by an Open-Label Extension, in Children 6 to Less Than 18 Years of Age With Hypertension</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Arbor Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Arbor Pharmaceuticals, 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>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the study is to evaluate the efficacy and safety of the study drug relative to&#xD;
      an active comparator losartan which is in the same class of drug and is approved for use in&#xD;
      the pediatric population aged 6 years and older. Approximately 260 subjects will participate&#xD;
      in a 6-week, double-blind, randomized, treatment phase, followed by a 2-week, double-blind,&#xD;
      randomized, placebo-controlled withdrawal phase. A 44-week, open-label extension in which all&#xD;
      subjects will receive azilsartan and other antihypertensive medications (if needed). Blood&#xD;
      pressure will be assessed throughout the study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The purpose of the study is to evaluate the efficacy and safety of the study drug relative to&#xD;
      an active comparator losartan which the same class of drug and is approved for use in the&#xD;
      pediatric population aged 6 years and older. Approximately 260 subjects will participate in a&#xD;
      6-week, double-blind, randomized, treatment phase, followed by a 2-week, double-blind,&#xD;
      randomized, placebo-controlled withdrawal phase. This study also includes a 44-week,&#xD;
      open-label extension Phase in which all subjects will receive azilsartan and other&#xD;
      antihypertensive medications (if needed) in order to reach an optimal blood pressure. Blood&#xD;
      pressure will be assessed in the clinic throughout the study, and subjects may also&#xD;
      participate in a 24-hour ambulatory blood pressure monitoring procedure at baseline, at the&#xD;
      end of the double-blind Phase and at the end of the open-label Phase.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 19, 2014</start_date>
  <completion_date type="Actual">September 27, 2020</completion_date>
  <primary_completion_date type="Actual">November 27, 2019</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>There are 3 phases in this study. Double-blind, withdrawal phase, and open-label phase.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
    <masking_description>Double-blind masking in the Double Blind Phase and Withdrawal Phase.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Blood Pressure</measure>
    <time_frame>Double-Blind and Withdrawal Phase</time_frame>
    <description>Change from Week 6/Final Visit of the double-blindPhase to Week 8/Final Visit of the WD Phase in trough clinic seated diastolic blood pressure between azilsartan medoxomil and placebo</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in blood Pressure relative to the comparator</measure>
    <time_frame>Double Blind and Withdrawal Phase</time_frame>
    <description>Change from Week 6/Final Visit of the double-blind Phase to Week 8/Final Visit of the withdrawal phase in trough clinic seated systolic blood pressure and mean arterial pressure (MAP) between azilsartan medoxomil and placebo.</description>
  </secondary_outcome>
  <number_of_arms>14</number_of_arms>
  <enrollment type="Actual">215</enrollment>
  <condition>Hypertension</condition>
  <arm_group>
    <arm_group_label>Double-blind: Azilsartan Medoxomil - Low dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>6-week, double-blind (DB), randomized, treatment phase (DB Phase): Azilsartan medoxomil Low-dose (AZM-L), 10 mg once daily.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Double blind phase: Losartan</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>6-week, double-blind (DB), randomized, treatment phase (DB Phase): Starting at Losartan 25/50 and force titrated to 50/100 mg daily at Week 2.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>WITHDRAWAL Phase: Azilsartan medoxomil LOW-dose</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Experimental Arm in the Withdrawal Phase, subjects will be randomized (1:1) to continue taking their previously assigned active treatment ( Azilsartan medoxomil low dose) that was taken in Double blind OR to be switched to placebo.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>WITHDRAWAL Phase: PLACEBO to match azilsartan medoxomil LOW DOSE</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>PLACEBO Arm in the Withdrawal Phase for subjects who were on Azilsartan medoxomil LOW dose) in Double blind then randomized (1:1) to placebo for withdrawal phase</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Open Label Phase: Azilsartan Medoxomil</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Azilsartan Medoxomil 10 mg which can be titrated to higher dose(s) (up to 40 mg for subjects &lt;50 kg or up to 80 mg for subjects ≥50 kg)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Open Label Phase: &quot;Other&quot;</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>If add-on therapy is needed, a calcium channel blocker, such as amlodipine; a diuretic, such as hydrochlorothiazide; or a beta-blocker such as metoprolol will be determined per the investigator's clinical judgment.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Withdrawal Phase: Losartan 50 mg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Withdrawal Phase, subjects will be randomized (1:1) to continue taking their previously assigned active treatment or to be switched to placebo.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Withdrawal Phase: PLACEBO to Losartan</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo Arm In the Withdrawal Phase, subjects will be randomized (1:1) to continue taking their previously assigned active treatment or to be switched to placebo.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Double-blind: Azilsartan Medoxomil - Medium dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>6-week, double-blind (DB), randomized, treatment phase (DB Phase), Azilsartan medoxomil Medium-dose (AZM-M), 20 mg once daily at Week 2.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Double-blind: Azilsartan Medoxomil - High dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>6-week, double-blind (DB), randomized, treatment phase (DB Phase): Azilsartan medoxomil High-dose (AZM-H), 40 mg AZM-M</description>
  </arm_group>
  <arm_group>
    <arm_group_label>WITHDRAWAL Azilsartan Medoxomil - Medium dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Experimental Arm in the Withdrawal Phase, subjects will be randomized (1:1) to continue taking their previously assigned active treatment ( Azilsartan medoxomil MEDIUM dose) that was taken in Double blind OR to be switched to placebo.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>WITHDRAWAL Azilsartan Medoxomil - High dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Experimental Arm in the Withdrawal Phase, subjects will be randomized (1:1) to continue taking their previously assigned active treatment ( Azilsartan medoxomil HIGH dose) that was taken in Double blind OR to be switched to placebo.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>WITHDRAWAL Phase: PLACEBO to match azilsartan medoxomil MEDIUM DOSE</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>PLACEBO Arm in the Withdrawal Phase for subjects who were on Azilsartan medoxomil MEDIUM dose) in Double blind then randomized (1:1) to matching placebofor withdrawal phase</description>
  </arm_group>
  <arm_group>
    <arm_group_label>WITHDRAWAL Phase: PLACEBO to match azilsartan medoxomil HIGH DOSE</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>PLACEBO Arm in the Withdrawal Phase for subjects who were on Azilsartan medoxomil HIGH dose) in Double blind then randomized (1:1) to matching placebofor withdrawal phase</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Azilsartan Medoxomil Low-dose</intervention_name>
    <arm_group_label>Double-blind: Azilsartan Medoxomil - High dose</arm_group_label>
    <arm_group_label>Double-blind: Azilsartan Medoxomil - Low dose</arm_group_label>
    <arm_group_label>Double-blind: Azilsartan Medoxomil - Medium dose</arm_group_label>
    <arm_group_label>Open Label Phase: &quot;Other&quot;</arm_group_label>
    <arm_group_label>Open Label Phase: Azilsartan Medoxomil</arm_group_label>
    <arm_group_label>WITHDRAWAL Phase: Azilsartan medoxomil LOW-dose</arm_group_label>
    <other_name>AZM</other_name>
    <other_name>AR14</other_name>
    <other_name>AZM-L</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Losartan</intervention_name>
    <arm_group_label>Double blind phase: Losartan</arm_group_label>
    <arm_group_label>WITHDRAWAL Phase: PLACEBO to match azilsartan medoxomil LOW DOSE</arm_group_label>
    <arm_group_label>Withdrawal Phase: Losartan 50 mg</arm_group_label>
    <other_name>Cozaar</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo for Azilsartan Medoxomil</intervention_name>
    <arm_group_label>WITHDRAWAL Phase: PLACEBO to match azilsartan medoxomil HIGH DOSE</arm_group_label>
    <arm_group_label>WITHDRAWAL Phase: PLACEBO to match azilsartan medoxomil MEDIUM DOSE</arm_group_label>
    <other_name>sugar pill</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo for Losartan</intervention_name>
    <arm_group_label>Withdrawal Phase: PLACEBO to Losartan</arm_group_label>
    <other_name>sugar pill</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>antihypertension medication - Add-on Therapy</intervention_name>
    <description>add-on therapy (e.g., a calcium channel blocker, such as amlodipine, a diuretic, such as hydrochlorothiazide, or a beta-blocker such as metoprolol) per PI's clinical judgment.</description>
    <arm_group_label>Open Label Phase: &quot;Other&quot;</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Azilsartan Medoxomil Medium-dose</intervention_name>
    <arm_group_label>Double-blind: Azilsartan Medoxomil - Medium dose</arm_group_label>
    <arm_group_label>WITHDRAWAL Azilsartan Medoxomil - Medium dose</arm_group_label>
    <other_name>AZM</other_name>
    <other_name>AR14</other_name>
    <other_name>AZM-M</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Azilsartan Medoxomil High-dose</intervention_name>
    <arm_group_label>Double-blind: Azilsartan Medoxomil - High dose</arm_group_label>
    <arm_group_label>WITHDRAWAL Azilsartan Medoxomil - High dose</arm_group_label>
    <other_name>AZM</other_name>
    <other_name>AR14</other_name>
    <other_name>AZM-H</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  The subject has hypertension (primary or secondary) defined as clinic Seated Diastolic&#xD;
             BP ≥95th percentile (by age, gender, and height) or ≥90th percentile (by age, gender,&#xD;
             height) if chronic renal disease, diabetes, heart failure or hypertensive target organ&#xD;
             damage is present&#xD;
&#xD;
               1. If currently treated: The subject has a documented historical diagnosis of&#xD;
                  hypertension AND a post-washout clinic Seated Diastolic BP meeting the above&#xD;
                  criteria on Day -1 (or Day 1 for subjects not participating in Ambulatory Blood&#xD;
                  Pressure Monitoring)&#xD;
&#xD;
               2. If currently untreated: The subject has elevated Seated Diastolic BP meeting the&#xD;
                  above criteria on 3 separate occasions before Randomization, including on Day -1&#xD;
                  (or Day 1 for subjects not participating in Ambulatory Blood Pressure Monitoring)&#xD;
&#xD;
          -  The subject is male or female and aged 6 to &lt;18 years at Baseline and weighs at least&#xD;
             25 kg&#xD;
&#xD;
          -  The subject agrees to continue their previously implemented nonpharmacological life&#xD;
             style modifications if begun prior to Screening. Note: For subjects participating in a&#xD;
             weight loss program, the weight maintenance&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  The subject has a clinic Seated Diastolic BP greater than 15 mm Hg and/or Seated&#xD;
             Diastolic BP greater than 10 mm Hg above the 99th percentile for age, gender, and&#xD;
             height as confirmed by the average (arithmetic mean) of 3 serial clinic seated BP&#xD;
             measurements at Screening/Visit 1&#xD;
&#xD;
          -  The subject has a diagnosis of malignant or accelerated hypertension&#xD;
&#xD;
          -  The subject is currently treated with more than 2 antihypertensive agents&#xD;
&#xD;
          -  The subject or parent/legal guardian is not willing for the subject's previous&#xD;
             antihypertensive medications to be stopped&#xD;
&#xD;
          -  The subject has participated in the intensive, active weight-loss phase of a&#xD;
             weight-loss program within 30 days prior to Screening/Visit 1&#xD;
&#xD;
          -  The subject has any of the following: severe renal impairment (eGFR &lt;30 mL/min/1.73 m2&#xD;
             by the Schwartz formula); is currently undergoing dialysis treatment; renovascular&#xD;
             disease affecting both kidneys or a solitary kidney; severe nephrotic syndrome not in&#xD;
             remission; or serum albumin &lt;2.5 g/dL&#xD;
&#xD;
          -  The subject has a history or clinical manifestations of severe cardiovascular,&#xD;
             hepato-biliary, gastrointestinal, endocrine-metabolic (e.g., hyperthyroidism,&#xD;
             Cushing's syndrome), hematologic, immunologic, genito-urinary, or psychiatric disease,&#xD;
             cancer, and/or any conditions that would interfere with the health status of the&#xD;
             subject through study participation, or would jeopardize study integrity in the&#xD;
             opinion of the investigator&#xD;
&#xD;
          -  The subject is suffering from uncorrected coarctation of the aorta, or hemodynamically&#xD;
             significant left ventricular outflow tract obstruction due to eg, aortic valvular&#xD;
             disease, or is likely to undergo a procedure known to affect blood pressure (eg,&#xD;
             repair of arterial anomalies) during the course of the study&#xD;
&#xD;
          -  The subject is poorly controlled diabetic defined as having a glycosylated hemoglobin&#xD;
             value &gt;8.5% at Screening/Visit 1&#xD;
&#xD;
          -  The subject has hyperkalemia as defined by the central laboratory's normal reference&#xD;
             range or any pertinent electrolyte disorders at Screening/Visit&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Years</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>steve Caras, MD</last_name>
    <role>Study Director</role>
    <affiliation>Arbor Pharmaceuticals, LLC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Advanced Research Center, INC</name>
      <address>
        <city>Anaheim</city>
        <state>California</state>
        <zip>92805</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Direct Helpers Research Center</name>
      <address>
        <city>Hialeah</city>
        <state>Florida</state>
        <zip>33012</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>JDH Medical Group LLC</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33125</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Miami/Jackson Memorial Hospital</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical Research Center of Miami II, Inc.</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33144</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pioneer Clinical Research</name>
      <address>
        <city>North Miami</city>
        <state>Florida</state>
        <zip>33162</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Georgia Clinical Research</name>
      <address>
        <city>Snellville</city>
        <state>Georgia</state>
        <zip>30078</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Zoe Center for Pediatrics</name>
      <address>
        <city>Thomaston</city>
        <state>Georgia</state>
        <zip>30286</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Louisville</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>David M. Headley, MD PA</name>
      <address>
        <city>Port Gibson</city>
        <state>Mississippi</state>
        <zip>39150</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mount Sinai PRIME</name>
      <address>
        <city>Lake Success</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical University of South Carolina (MUSC)</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memphis and Shelby County Pediatric Group</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38116</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southeast Texas Clinical Research Center</name>
      <address>
        <city>Beaumont</city>
        <state>Texas</state>
        <zip>77701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Children's Heart Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ericksen Research &amp; Development, LLC</name>
      <address>
        <city>Clinton</city>
        <state>Utah</state>
        <zip>84015</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mid-Columbia Research</name>
      <address>
        <city>Richland</city>
        <state>Washington</state>
        <zip>99352</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Italiano</name>
      <address>
        <city>Ciudad Autonoma</city>
        <state>Buenos Aires</state>
        <zip>1181</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de Niños</name>
      <address>
        <city>Ciudad Autonoma</city>
        <state>Buenos Aires</state>
        <zip>C1425EFD</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinica de Nefrologia, Urologia y Enf. Cardiovasculares S A</name>
      <address>
        <city>Santa Fe</city>
        <zip>S3000EPV</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clínica Nefrokids Ltda</name>
      <address>
        <city>Curitiba</city>
        <zip>80240-060</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital São Lucas da PUCRS</name>
      <address>
        <city>Porto Alegre</city>
        <zip>90610-000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto de Cardiologia do Rio Grande do Sul</name>
      <address>
        <city>Porto Alegre</city>
        <zip>90620-001</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fundação José Luiz Egydio Setúbal</name>
      <address>
        <city>São Paulo</city>
        <zip>01227-200</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Samaritano</name>
      <address>
        <city>São Paulo</city>
        <zip>01232-010</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Eurolatino Pesquisas Médicas Ltda.</name>
      <address>
        <city>Uberlândia</city>
        <zip>38411-186</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SHATPPD-Ruse EOOD</name>
      <address>
        <city>Ruse</city>
        <zip>7002</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fundacion Oftalmologica de Santander - FOSCAL</name>
      <address>
        <city>Bucaramanga</city>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fundacion Valle del Lili</name>
      <address>
        <city>Cali</city>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fundacion Hospitalaria San Vicente de Paul</name>
      <address>
        <city>Medellin</city>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Pablo Tobón Uribe</name>
      <address>
        <city>Medellin</city>
        <country>Colombia</country>
      </address>
    </facility>
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  <location>
    <facility>
      <name>Institucion Prestadora de Servicios de Salud de la Universidad de Antioquia &quot;IPS UNIVERSITARIA&quot;</name>
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        <city>Medellin</city>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Principal SMO Kft.</name>
      <address>
        <city>Baja</city>
        <zip>6500</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Svabhegy Plusz Gyermekegeszsegugyi Kozpont</name>
      <address>
        <city>Budapest</city>
        <zip>1037</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Szent Lukacs Korhaz Dombovar</name>
      <address>
        <city>Dombovar</city>
        <zip>7200</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Prehospital Med Kft.</name>
      <address>
        <city>Miskolc</city>
        <zip>3526</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Szegedi Tud.Egyetem Szent-Gyorgyi Albert Klin. Kozp.</name>
      <address>
        <city>Szeged</city>
        <zip>6720</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale Pediatrico Giovanni XXIII</name>
      <address>
        <city>Bari</city>
        <zip>70125</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico</name>
      <address>
        <city>Milano</city>
        <zip>20122</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>A.R.N.A.S. Ospedale Civico e Benfratelli, G. Cristina e M.Ascoli</name>
      <address>
        <city>Palermo</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto de Investigaciones Aplicadas a la Neurociencia A.C.</name>
      <address>
        <city>Durango</city>
        <zip>34000</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General de Mexico</name>
      <address>
        <city>Mexico City</city>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Accelerium S. de R.L. de C.V.</name>
      <address>
        <city>Monterrey</city>
        <zip>6400</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
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    <facility>
      <name>Centro de Investigacion Clinica Chapultepec S.A. de C.V.</name>
      <address>
        <city>Morelia</city>
        <zip>58260</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
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    <facility>
      <name>SPZOZ Uniwersytecki Dzieciecy Szpital Kliniczny im. L. Zamenhofa</name>
      <address>
        <city>Bialystok</city>
        <zip>15-274</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Uniwersytecki Szpital Dziecięcy w Krakowie</name>
      <address>
        <city>Krakow</city>
        <zip>30-663</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NZOZ TRI-medica</name>
      <address>
        <city>Lodz</city>
        <zip>93-338</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Praktyka Lekarzy Rodzinnych R.Jadach, M.Domanski NZOZ</name>
      <address>
        <city>Wroclaw</city>
        <zip>50-072</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>LCS Clinical Research Unit</name>
      <address>
        <city>Johannesburg</city>
        <state>Gauteng</state>
        <zip>2021</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Soweto Clinical Trial Centre</name>
      <address>
        <city>Soweto</city>
        <state>Gauteng</state>
        <zip>1818</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Netcare St. Anne's Hospital</name>
      <address>
        <city>Pietermaritzburg</city>
        <state>KwaZulu-Natal</state>
        <zip>3201</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Groote Schuur Hospital E13 Renal Unit</name>
      <address>
        <city>Cape Town</city>
        <state>Western Cape</state>
        <zip>7925</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Projects Research SA (PTY) LTD</name>
      <address>
        <city>Worcester</city>
        <state>Western Cape</state>
        <zip>6850</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CRISMO Bertha Gxowa Research Centre</name>
      <address>
        <city>Germiston</city>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cukurova University Medical Faculty</name>
      <address>
        <city>Adana</city>
        <zip>01330</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gazi University Medical Faculty</name>
      <address>
        <city>Ankara</city>
        <zip>06500</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istanbul University Istanbul Medical Faculty</name>
      <address>
        <city>Istanbul</city>
        <zip>34093</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dokuz Eylul University Medicine Faculty</name>
      <address>
        <city>Izmir</city>
        <zip>35100</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Erciyes University Medical Faculty</name>
      <address>
        <city>Kayseri</city>
        <zip>38039</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Celal Bayar University Medical Faculty</name>
      <address>
        <city>Manisa</city>
        <zip>45040</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CMI Chernivtsi City Children Clinical Hospital</name>
      <address>
        <city>Chernivtsi</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Regional Children CH Cardiology Department Kharkiv NMU</name>
      <address>
        <city>Kharkiv</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SI National Research Center of Radiation Medicine of NAMSU</name>
      <address>
        <city>Kyiv</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>USPC of ES EO&amp;T Transplantation of MHU</name>
      <address>
        <city>Kyiv</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>HSEI of Ukraine UMSA</name>
      <address>
        <city>Poltava</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SSU Division MU Ch of pediatrics</name>
      <address>
        <city>Sumy</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vynnitsa Regional Children CH pediatric department № 1 M.I. Pyrogov NMU</name>
      <address>
        <city>Vinnytsia</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CI Zaporizhzhia City Multibranch Children Hospital #5</name>
      <address>
        <city>Zaporizhzhia</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CI Zaporizhzhia Regional Clinical Children Hospital of ZRC</name>
      <address>
        <city>Zaporizhzhia</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Argentina</country>
    <country>Brazil</country>
    <country>Bulgaria</country>
    <country>Colombia</country>
    <country>Hungary</country>
    <country>Italy</country>
    <country>Mexico</country>
    <country>Poland</country>
    <country>South Africa</country>
    <country>Turkey</country>
    <country>Ukraine</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Puerto Rico</country>
  </removed_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>September 8, 2014</study_first_submitted>
  <study_first_submitted_qc>September 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 10, 2014</study_first_posted>
  <last_update_submitted>February 13, 2023</last_update_submitted>
  <last_update_submitted_qc>February 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 16, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Pediatric Hypertension</keyword>
  <keyword>High Blood Pressure</keyword>
  <keyword>Hypertension</keyword>
  <keyword>Pediatric</keyword>
  <keyword>Primary Hypertension</keyword>
  <keyword>Secondary Hypertension</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypertension</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Losartan</mesh_term>
    <mesh_term>Azilsartan medoxomil</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>December 12, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/09/NCT02235909/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 13, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/09/NCT02235909/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT02235909
org study id: AR14.001
nct id: NCT02235909
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of the study is to evaluate the efficacy and safety of the study drug relative to
      an active comparator losartan which is in the same class of drug and is approved for use in
      the pediatric population aged 6 years and older. Approximately 260 subjects will participate
      in a 6-week, double-blind, randomized, treatment phase, followed by a 2-week, double-blind,
      randomized, placebo-controlled withdrawal phase. A 44-week, open-label extension in which all
      subjects will receive azilsartan and other antihypertensive medications (if needed). Blood
      pressure will be assessed throughout the study.
The purpose of the study is to evaluate the efficacy and safety of the study drug relative to
      an active comparator losartan which the same class of drug and is approved for use in the
      pediatric population aged 6 years and older. Approximately 260 subjects will participate in a
      6-week, double-blind, randomized, treatment phase, followed by a 2-week, double-blind,
      randomized, placebo-controlled withdrawal phase. This study also includes a 44-week,
      open-label extension Phase in which all subjects will receive azilsartan and other
      antihypertensive medications (if needed) in order to reach an optimal blood pressure. Blood
      pressure will be assessed in the clinic throughout the study, and subjects may also
      participate in a 24-hour ambulatory blood pressure monitoring procedure at baseline, at the
      end of the double-blind Phase and at the end of the open-label Phase.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: There are 3 phases in this study. Double-blind, withdrawal phase, and open-label phase.
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
masking description: Double-blind masking in the Double Blind Phase and Withdrawal Phase.
measure: Change in Blood Pressure
time frame: Double-Blind and Withdrawal Phase
description: Change from Week 6/Final Visit of the double-blindPhase to Week 8/Final Visit of the WD Phase in trough clinic seated diastolic blood pressure between azilsartan medoxomil and placebo
measure: Change in blood Pressure relative to the comparator
time frame: Double Blind and Withdrawal Phase
description: Change from Week 6/Final Visit of the double-blind Phase to Week 8/Final Visit of the withdrawal phase in trough clinic seated systolic blood pressure and mean arterial pressure (MAP) between azilsartan medoxomil and placebo.
arm group label: Double-blind: Azilsartan Medoxomil - Low dose
arm group type: Experimental
description: 6-week, double-blind (DB), randomized, treatment phase (DB Phase): Azilsartan medoxomil Low-dose (AZM-L), 10 mg once daily.
arm group label: Double blind phase: Losartan
arm group type: Active Comparator
description: 6-week, double-blind (DB), randomized, treatment phase (DB Phase): Starting at Losartan 25/50 and force titrated to 50/100 mg daily at Week 2.
arm group label: WITHDRAWAL Phase: Azilsartan medoxomil LOW-dose
arm group type: Active Comparator
description: Experimental Arm in the Withdrawal Phase, subjects will be randomized (1:1) to continue taking their previously assigned active treatment ( Azilsartan medoxomil low dose) that was taken in Double blind OR to be switched to placebo.
arm group label: WITHDRAWAL Phase: PLACEBO to match azilsartan medoxomil LOW DOSE
arm group type: Placebo Comparator
description: PLACEBO Arm in the Withdrawal Phase for subjects who were on Azilsartan medoxomil LOW dose) in Double blind then randomized (1:1) to placebo for withdrawal phase
arm group label: Open Label Phase: Azilsartan Medoxomil
arm group type: Experimental
description: Azilsartan Medoxomil 10 mg which can be titrated to higher dose(s) (up to 40 mg for subjects <50 kg or up to 80 mg for subjects ≥50 kg)
arm group label: Open Label Phase: "Other"
arm group type: Other
description: If add-on therapy is needed, a calcium channel blocker, such as amlodipine; a diuretic, such as hydrochlorothiazide; or a beta-blocker such as metoprolol will be determined per the investigator's clinical judgment.
arm group label: Withdrawal Phase: Losartan 50 mg
arm group type: Active Comparator
description: Withdrawal Phase, subjects will be randomized (1:1) to continue taking their previously assigned active treatment or to be switched to placebo.
arm group label: Withdrawal Phase: PLACEBO to Losartan
arm group type: Placebo Comparator
description: Placebo Arm In the Withdrawal Phase, subjects will be randomized (1:1) to continue taking their previously assigned active treatment or to be switched to placebo.
arm group label: Double-blind: Azilsartan Medoxomil - Medium dose
arm group type: Experimental
description: 6-week, double-blind (DB), randomized, treatment phase (DB Phase), Azilsartan medoxomil Medium-dose (AZM-M), 20 mg once daily at Week 2.
arm group label: Double-blind: Azilsartan Medoxomil - High dose
arm group type: Experimental
description: 6-week, double-blind (DB), randomized, treatment phase (DB Phase): Azilsartan medoxomil High-dose (AZM-H), 40 mg AZM-M
arm group label: WITHDRAWAL Azilsartan Medoxomil - Medium dose
arm group type: Experimental
description: Experimental Arm in the Withdrawal Phase, subjects will be randomized (1:1) to continue taking their previously assigned active treatment ( Azilsartan medoxomil MEDIUM dose) that was taken in Double blind OR to be switched to placebo.
arm group label: WITHDRAWAL Azilsartan Medoxomil - High dose
arm group type: Experimental
description: Experimental Arm in the Withdrawal Phase, subjects will be randomized (1:1) to continue taking their previously assigned active treatment ( Azilsartan medoxomil HIGH dose) that was taken in Double blind OR to be switched to placebo.
arm group label: WITHDRAWAL Phase: PLACEBO to match azilsartan medoxomil MEDIUM DOSE
arm group type: Experimental
description: PLACEBO Arm in the Withdrawal Phase for subjects who were on Azilsartan medoxomil MEDIUM dose) in Double blind then randomized (1:1) to matching placebofor withdrawal phase
arm group label: WITHDRAWAL Phase: PLACEBO to match azilsartan medoxomil HIGH DOSE
arm group type: Experimental
description: PLACEBO Arm in the Withdrawal Phase for subjects who were on Azilsartan medoxomil HIGH dose) in Double blind then randomized (1:1) to matching placebofor withdrawal phase
intervention type: Drug
intervention name: Azilsartan Medoxomil Low-dose
arm group label: Double-blind: Azilsartan Medoxomil - High dose
arm group label: Double-blind: Azilsartan Medoxomil - Low dose
arm group label: Double-blind: Azilsartan Medoxomil - Medium dose
arm group label: Open Label Phase: "Other"
arm group label: Open Label Phase: Azilsartan Medoxomil
arm group label: WITHDRAWAL Phase: Azilsartan medoxomil LOW-dose
other name: AZM
other name: AR14
other name: AZM-L
intervention type: Drug
intervention name: Losartan
arm group label: Double blind phase: Losartan
arm group label: WITHDRAWAL Phase: PLACEBO to match azilsartan medoxomil LOW DOSE
arm group label: Withdrawal Phase: Losartan 50 mg
other name: Cozaar
intervention type: Drug
intervention name: Placebo for Azilsartan Medoxomil
arm group label: WITHDRAWAL Phase: PLACEBO to match azilsartan medoxomil HIGH DOSE
arm group label: WITHDRAWAL Phase: PLACEBO to match azilsartan medoxomil MEDIUM DOSE
other name: sugar pill
intervention type: Drug
intervention name: Placebo for Losartan
arm group label: Withdrawal Phase: PLACEBO to Losartan
other name: sugar pill
intervention type: Drug
intervention name: antihypertension medication - Add-on Therapy
description: add-on therapy (e.g., a calcium channel blocker, such as amlodipine, a diuretic, such as hydrochlorothiazide, or a beta-blocker such as metoprolol) per PI's clinical judgment.
arm group label: Open Label Phase: "Other"
intervention type: Drug
intervention name: Azilsartan Medoxomil Medium-dose
arm group label: Double-blind: Azilsartan Medoxomil - Medium dose
arm group label: WITHDRAWAL Azilsartan Medoxomil - Medium dose
other name: AZM
other name: AR14
other name: AZM-M
intervention type: Drug
intervention name: Azilsartan Medoxomil High-dose
arm group label: Double-blind: Azilsartan Medoxomil - High dose
arm group label: WITHDRAWAL Azilsartan Medoxomil - High dose
other name: AZM
other name: AR14
other name: AZM-H
criteria: 
gender: All
minimum age: 6 Years
maximum age: 18 Years
healthy volunteers: No
last name: steve Caras, MD
role: Study Director
affiliation: Arbor Pharmaceuticals, LLC
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country: Argentina
country: Brazil
country: Bulgaria
country: Colombia
country: Hungary
country: Italy
country: Mexico
country: Poland
country: South Africa
country: Turkey
country: Ukraine
country: United States
country: Puerto Rico
responsible party type: Sponsor
mesh term: Hypertension
mesh term: Losartan
mesh term: Azilsartan medoxomil
sharing ipd: No
provided document: 
provided document: 