<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/NCT01672008</url>
  </required_header>
  <id_info>
    <org_study_id>NOX-100-ORIENT201</org_study_id>
    <nct_id>NCT01672008</nct_id>
  </id_info>
  <brief_title>NOX-100 for Preventing Hypotension During Hemodialysis</brief_title>
  <official_title>A Phase IIa Study of Safety and Efficacy of NOX-100 for Preventing Hypotension in Patients During Hemodialysis Sessions</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medinox, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Orient Europharma Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Medinox, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is designed to evaluate the safety, tolerability and efficacy profile of NOX-100&#xD;
      to reduce intradialytic hypotension (IDH) in patients undergoing chronic hemodialysis (HD).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a 2-stage, prospective, randomized, double-blind, multi-dose, placebo-controlled,&#xD;
      cross-over, phase IIa study to evaluate the safety, tolerability and efficacy profiles of&#xD;
      NOX-100 to reduce the number of intradialytic hypotension episodes. At single-blind stage I,&#xD;
      the eligible subject will receive a 1-week run-in period followed by a 1-week NOX-100&#xD;
      treatment in a dose of 0.4mg/kg/hr. To evaluate the clearance of NOX-100, plasma levels of&#xD;
      NOX-100 at the end of the 1st dialysis and prior to the 2nd dialysis will be measured. An&#xD;
      interim analysis will be undertaken after the completion of first stage. The following&#xD;
      process should be conducted only if the plasma level of NOX-100 decreases by 90% or more in&#xD;
      these patients and all safety data have been reviewed by the medical monitor.&#xD;
&#xD;
      At double blind stage II, patients will be randomized to one of the following treatment&#xD;
      sequences in a 1:1 ratio.&#xD;
&#xD;
        -  Sequence A: NOX-100 treatment phase followed by Placebo treatment phase&#xD;
&#xD;
        -  Sequence B: Placebo treatment phase followed by NOX-100 treatment phase&#xD;
&#xD;
      After a 1-week placebo, the subjects will receive the two 4-week treatment (sequence A or&#xD;
      sequence B)which are separated by 1-week wash-out. In the NOX-100 treatment phase, subjects&#xD;
      will subsequently receive NOX-100 in doses of 1.2, 2.5, 5, and 10 mg/kg/hr at the first three&#xD;
      dialysis sessions over each week. In the placebo treatment phase, subjects will receive&#xD;
      comparative placebo for four weeks. For the first 20 subjects, the treatment dose could be&#xD;
      escalated only after the individual safety data have been reviewed by an unblinded medical&#xD;
      monitor.&#xD;
&#xD;
      To confirm if there is hepatic metabolism of NOX-100 between dialysis sessions, a&#xD;
      pre-dialysis plasma level will be tested at the 2nd dialysis of Week 2, 5, 7 and 10 in the&#xD;
      second stage.&#xD;
&#xD;
      In both stages, the blood pressure will be measured pre-HD, every 30 minutes during HD and&#xD;
      post-HD for monitoring the hypotension episode. For safety assessment, all AE(s), SAE(s) and&#xD;
      any signs/symptoms during HD will be recorded. The safety of study drug will be followed&#xD;
      until 4 weeks after last treatment.&#xD;
&#xD;
      A Data and Safety Monitoring Board (DSMB) will be established prior to start of the trial and&#xD;
      the DSMB meeting will be hold every 6~12 months during study period. Both medical monitor and&#xD;
      DSMB will be responsible for safeguarding the interests of trial participants.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">July 2015</completion_date>
  <primary_completion_date type="Actual">July 2015</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of hypotension episode requiring intervention</measure>
    <time_frame>10 weeks</time_frame>
    <description>Number reduction of symptomatic hypotension requiring intervention during HD with NOX-100 treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>systolic blood pressure (SBP)</measure>
    <time_frame>10 weeks</time_frame>
    <description>Change in systolic blood pressure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Onset of symptoms of hypotension during HD</measure>
    <time_frame>10 weeks</time_frame>
    <description>Time to onset of symptoms of hypotension during HD</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The need for treatment intervention to raise BP.</measure>
    <time_frame>10 weeks</time_frame>
    <description>Time to conduct a treatment intervention to raise BP</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">62</enrollment>
  <condition>Hypotension</condition>
  <arm_group>
    <arm_group_label>NOX-100/Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>After enrollment, subjects will be randomly assigned to one of the following treatment sequences in a 1:1 ratio.&#xD;
Sequence A: NOX-100 treatment phase followed by Placebo treatment phase Sequence B: Placebo treatment phase followed by NOX-100 treatment phase</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo/NOX-100</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>After enrollment, subjects will be randomly assigned to one of the following treatment sequences in a 1:1 ratio.&#xD;
Sequence A: NOX-100 treatment phase followed by Placebo treatment phase Sequence B: Placebo treatment phase followed by NOX-100 treatment phase</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NOX-100</intervention_name>
    <arm_group_label>NOX-100/Placebo</arm_group_label>
    <arm_group_label>Placebo/NOX-100</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Males or non-pregnant, non-lactating females 20-80 years of age&#xD;
&#xD;
          -  Patients who are hemodialysis dependent with a history of end-stage renal disease&#xD;
             (ESRD) for at least 3 months and need at least three HD sessions per week&#xD;
&#xD;
          -  History of intradialytic hypotension defined by at least 4 episodes with a fall in SBP&#xD;
             of &gt; 20 mmHg within 30 days prior to signing the ICF. At least two of the episodes&#xD;
             must have caused symptoms requiring an intervention&#xD;
&#xD;
          -  No change in anti-hypertensive regimen for at least one month prior to&#xD;
             enrollment/randomization&#xD;
&#xD;
          -  Be willing to sign the Informed Consent Form&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects with adequate laboratory results at screening&#xD;
&#xD;
          -  Subjects with major psychiatric illness&#xD;
&#xD;
          -  Subjects with history of arrhythmia or severe congestive heart failure (New York Heart&#xD;
             Association (NYHA) Class III and IV) within past 6 months, or those with hypoxic&#xD;
             myocardium confirmed by EKG&#xD;
&#xD;
          -  Subjects with history of cirrhosis&#xD;
&#xD;
          -  Subjects with active infection disease defined as current treatment with&#xD;
             anti-infection agent(s)&#xD;
&#xD;
          -  Subjects who need to receive nitrate and nitrite medication(s) (such as nitroglycerin,&#xD;
             isosorbide mononitrate, and isosorbide dinitrate) for regular treatment&#xD;
&#xD;
          -  Subjects who need to receive unstable dose of midodrine, etilefrine or amezinium&#xD;
             treatment within 7 days prior to receive the study treatment.&#xD;
&#xD;
          -  More than 14 drinks of alcohol per week&#xD;
&#xD;
          -  Use of any investigational drug or participation in any drug study within 30 days&#xD;
             prior to enrollment/randomization&#xD;
&#xD;
          -  Any clinical condition, including the presence of laboratory abnormalities, which&#xD;
             places the subject at unacceptable risk to participate in the study or confounds the&#xD;
             ability to interpret data from the study as judged by the investigator&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Monte Lai, Ph.D.</last_name>
    <role>Study Chair</role>
    <affiliation>Medinox, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Kaohsiung Chang Gung Memorial Hospital</name>
      <address>
        <city>Kaohsiung</city>
        <zip>83301</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Keelung Chang Gung Memorial Hospital</name>
      <address>
        <city>Keelung</city>
        <zip>20401</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Far Eastern Memorial Hospital</name>
      <address>
        <city>New Taipei City</city>
        <zip>22056</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Buddhist TzuChi General Hospital, Taipei Branch</name>
      <address>
        <city>New Taipei City</city>
        <zip>23142</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>China Medical University Hospital</name>
      <address>
        <city>Taichung</city>
        <zip>40447</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shin Kong Wu Ho-Su Memorial Hospital</name>
      <address>
        <city>Taipei</city>
        <zip>11168</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>December 2015</verification_date>
  <study_first_submitted>August 21, 2012</study_first_submitted>
  <study_first_submitted_qc>August 21, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 24, 2012</study_first_posted>
  <last_update_submitted>December 30, 2015</last_update_submitted>
  <last_update_submitted_qc>December 30, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 31, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>NOX-100</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypotension</mesh_term>
  </condition_browse>
  <pending_results>
    <submitted>November 17, 2016</submitted>
    <returned>January 13, 2017</returned>
  </pending_results>
  <!-- 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/NCT01672008
org study id: NOX-100-ORIENT201
nct id: NCT01672008
lead sponsor: 
collaborator: 
has dmc: Yes
This study is designed to evaluate the safety, tolerability and efficacy profile of NOX-100
      to reduce intradialytic hypotension (IDH) in patients undergoing chronic hemodialysis (HD).
This is a 2-stage, prospective, randomized, double-blind, multi-dose, placebo-controlled,
      cross-over, phase IIa study to evaluate the safety, tolerability and efficacy profiles of
      NOX-100 to reduce the number of intradialytic hypotension episodes. At single-blind stage I,
      the eligible subject will receive a 1-week run-in period followed by a 1-week NOX-100
      treatment in a dose of 0.4mg/kg/hr. To evaluate the clearance of NOX-100, plasma levels of
      NOX-100 at the end of the 1st dialysis and prior to the 2nd dialysis will be measured. An
      interim analysis will be undertaken after the completion of first stage. The following
      process should be conducted only if the plasma level of NOX-100 decreases by 90% or more in
      these patients and all safety data have been reviewed by the medical monitor.

      At double blind stage II, patients will be randomized to one of the following treatment
      sequences in a 1:1 ratio.

        -  Sequence A: NOX-100 treatment phase followed by Placebo treatment phase

        -  Sequence B: Placebo treatment phase followed by NOX-100 treatment phase

      After a 1-week placebo, the subjects will receive the two 4-week treatment (sequence A or
      sequence B)which are separated by 1-week wash-out. In the NOX-100 treatment phase, subjects
      will subsequently receive NOX-100 in doses of 1.2, 2.5, 5, and 10 mg/kg/hr at the first three
      dialysis sessions over each week. In the placebo treatment phase, subjects will receive
      comparative placebo for four weeks. For the first 20 subjects, the treatment dose could be
      escalated only after the individual safety data have been reviewed by an unblinded medical
      monitor.

      To confirm if there is hepatic metabolism of NOX-100 between dialysis sessions, a
      pre-dialysis plasma level will be tested at the 2nd dialysis of Week 2, 5, 7 and 10 in the
      second stage.

      In both stages, the blood pressure will be measured pre-HD, every 30 minutes during HD and
      post-HD for monitoring the hypotension episode. For safety assessment, all AE(s), SAE(s) and
      any signs/symptoms during HD will be recorded. The safety of study drug will be followed
      until 4 weeks after last treatment.

      A Data and Safety Monitoring Board (DSMB) will be established prior to start of the trial and
      the DSMB meeting will be hold every 6~12 months during study period. Both medical monitor and
      DSMB will be responsible for safeguarding the interests of trial participants.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Number of hypotension episode requiring intervention
time frame: 10 weeks
description: Number reduction of symptomatic hypotension requiring intervention during HD with NOX-100 treatment.
measure: systolic blood pressure (SBP)
time frame: 10 weeks
description: Change in systolic blood pressure
measure: Onset of symptoms of hypotension during HD
time frame: 10 weeks
description: Time to onset of symptoms of hypotension during HD
measure: The need for treatment intervention to raise BP.
time frame: 10 weeks
description: Time to conduct a treatment intervention to raise BP
arm group label: NOX-100/Placebo
arm group type: Experimental
description: After enrollment, subjects will be randomly assigned to one of the following treatment sequences in a 1:1 ratio.
Sequence A: NOX-100 treatment phase followed by Placebo treatment phase Sequence B: Placebo treatment phase followed by NOX-100 treatment phase
arm group label: Placebo/NOX-100
arm group type: Experimental
description: After enrollment, subjects will be randomly assigned to one of the following treatment sequences in a 1:1 ratio.
Sequence A: NOX-100 treatment phase followed by Placebo treatment phase Sequence B: Placebo treatment phase followed by NOX-100 treatment phase
intervention type: Drug
intervention name: NOX-100
arm group label: NOX-100/Placebo
arm group label: Placebo/NOX-100
criteria: 
gender: All
minimum age: 20 Years
maximum age: 80 Years
healthy volunteers: No
last name: Monte Lai, Ph.D.
role: Study Chair
affiliation: Medinox, Inc.
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Taiwan
responsible party type: Sponsor
mesh term: Hypotension
submitted: November 17, 2016
returned: January 13, 2017