<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/NCT01681576</url>
  </required_header>
  <id_info>
    <org_study_id>CLCZ696A2222</org_study_id>
    <nct_id>NCT01681576</nct_id>
  </id_info>
  <brief_title>Assessment of LCZ696 and Valsartan in Asian Patients With Salt-sensitive Hypertension</brief_title>
  <official_title>A Randomized, Double-blind, Crossover Study to Assess the Effects of LCZ696 and Valsartan in Asian Patients With Salt-sensitive Hypertension</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novartis</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will evaluate the effect of LCZ696 and valsartan on natriuresis, diuresis, and&#xD;
      blood pressure in salt-sensitive Asian hypertensive patients.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">October 2013</completion_date>
  <primary_completion_date type="Actual">October 2013</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>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cumulative Sodium Excretion (Natriuresis) at Day 1</measure>
    <time_frame>0-6 and 0-24 hours on Day 1</time_frame>
    <description>Urine will be collected in fractions of 6 to 24 hours post-dose. From each fraction, a sample will be drawn for analysis of sodium Day 1</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cumulative Sodium Excretion (Natriuresis) at Day 28</measure>
    <time_frame>0-6 and 0-24 hours on Day 28</time_frame>
    <description>Urine will be collected in fractions of 6 to 24 hours post-dose. From each fraction, a sample will be drawn for analysis of sodium Day 28</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Urine Volume (Diuresis) Over Time</measure>
    <time_frame>Day -1, Day 1 &amp; Day 28</time_frame>
    <description>Urine will be collected and volume measured in fractions of 0 to 6 hours and 0 to 24 hours Day-1, Day 1 and Day 28</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Seated Office Blood Pressure (BP) (Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)) Over Time</measure>
    <time_frame>Day-1, Day 14 and Day 28</time_frame>
    <description>Seated Office BP (systolic blood pressure (SBP) and diastolic blood pressure (DBP))measurements will be performed at trough(immediately prior to dosing at the clinic). Arterial BP readings will be made with an automated BP device.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Sitting Pulse Pressure (PP) Over Time</measure>
    <time_frame>Day-1, Day 14 and Day 28</time_frame>
    <description>Sitting mean pulse pressure rate was calculated between ambulatory SBP and DBP measurements</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">72</enrollment>
  <condition>Salt-sensitive Hypertension</condition>
  <arm_group>
    <arm_group_label>LCZ696 followed by Valsartan</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Period 1: LCZ696 400mg QD for 4 weeks then washout followed by Period 2: Valsartan 320mg QD for 4 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Valsartan followed by LCZ696</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Period 1: Valsartan 320mg QD for 4 weeks then washout followed by Period 2: LCZ696 400mg QD for 4 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Valsartan</intervention_name>
    <description>Valsartan 320mg tablet once daily</description>
    <arm_group_label>LCZ696 followed by Valsartan</arm_group_label>
    <arm_group_label>Valsartan followed by LCZ696</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>LCZ696</intervention_name>
    <description>LCZ696 400mg tablet once daily</description>
    <arm_group_label>LCZ696 followed by Valsartan</arm_group_label>
    <arm_group_label>Valsartan followed by LCZ696</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  Written informed consent must be obtained before any study assessment is performed.&#xD;
&#xD;
          -  Males and females of non-childbearing potential and of legal age (at least 18 years or&#xD;
             older as defined by local law).&#xD;
&#xD;
          -  Asian patients with mild to moderate essential hypertension, untreated or currently&#xD;
             taking antihypertensive therapy with up to two drugs.&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  Women of child-bearing potential.&#xD;
&#xD;
          -  History of angioedema, drug-related or otherwise&#xD;
&#xD;
          -  History of hypersensitivity to LCZ696, valsartan, or drugs of similar chemical&#xD;
             classes.&#xD;
&#xD;
          -  Severe hypertension (grade 3 of WHO classification; msDBP ≥100 mmHg and/or msSBP ≥ 180&#xD;
             mmHg) at screening or at the end of the washout period.&#xD;
&#xD;
          -  History or evidence of a secondary form of hypertension,&#xD;
&#xD;
          -  Transient ischemic cerebral attack (TIA) during the 12 months prior to screening or&#xD;
             any history of stroke.&#xD;
&#xD;
          -  History of myocardial infarction, coronary bypass surgery or percutaneous coronary&#xD;
             intervention (PCI) during 12 month prior to screening.&#xD;
&#xD;
          -  Current or history of hypertensive retinopathy.&#xD;
&#xD;
          -  Previous or current diagnosis of heart failure (NYHA Class II-IV).&#xD;
&#xD;
          -  Clinically significant valvular heart disease at screening.&#xD;
&#xD;
        Other protocol defined inclusion/exclusion criteria may apply&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Novartis Pharmaceuticals</last_name>
    <role>Study Director</role>
    <affiliation>Novartis Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Anaheim</city>
        <state>California</state>
        <zip>92801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Cypress</city>
        <state>California</state>
        <zip>90630</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Glendale</city>
        <state>California</state>
        <zip>91206</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Hong Kong</city>
        <state>Shatin, NT</state>
        <country>Hong Kong</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bucheon</city>
        <state>Gyeonggi-do</state>
        <zip>424-717</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Koyang-si</city>
        <state>Gyeonggi-do</state>
        <zip>410-773</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Seoul</city>
        <state>Korea</state>
        <zip>110 744</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Seoul</city>
        <zip>120-752</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Seoul</city>
        <zip>152-703</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Singapore</city>
        <zip>119228</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Singapore</city>
        <zip>169609</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Taipei</city>
        <state>Taiwan, ROC</state>
        <zip>112</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Taichung</city>
        <zip>40447</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Taipei</city>
        <zip>10002</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Taipei</city>
        <zip>114</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Hong Kong</country>
    <country>Korea, Republic of</country>
    <country>Singapore</country>
    <country>Taiwan</country>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2015</verification_date>
  <study_first_submitted>August 30, 2012</study_first_submitted>
  <study_first_submitted_qc>September 5, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 10, 2012</study_first_posted>
  <results_first_submitted>July 10, 2015</results_first_submitted>
  <results_first_submitted_qc>September 8, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">October 9, 2015</results_first_posted>
  <last_update_submitted>October 12, 2015</last_update_submitted>
  <last_update_submitted_qc>October 12, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 10, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>hypertension, salt sensitivity, valsartan, LCZ696</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypertension</mesh_term>
    <mesh_term>Hypersensitivity</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Valsartan</mesh_term>
    <mesh_term>Sacubitril and valsartan sodium hydrate drug combination</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Period 1: 4 weeks treatment with LCZ696 400mg QD or Valsartan 320mg, 1-2 weeks wash-out, followed by period 2, 4 weeks treatment with Valsartan 320mg QD or LCZ696 400mg QD</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>LCZ696 Followed by Valsartan</title>
          <description>Period 1: LCZ696 400mg QD for 4 weeks then washout followed by Period 2: Valsartan 320mg QD for 4 weeks</description>
        </group>
        <group group_id="P2">
          <title>Valsartan Followed by LCZ696</title>
          <description>Period 1: Valsartan 320mg QD for 4 weeks then washout followed by Period 2: LCZ696 400mg QD for 4 weeks</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Period 1</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="36"/>
                <participants group_id="P2" count="36"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="34"/>
                <participants group_id="P2" count="36"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Deviation</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Period 2</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="34">Period 2: Valsartan 320mg</participants>
                <participants group_id="P2" count="36">Period 2: LCZ696 400mg</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="30"/>
                <participants group_id="P2" count="35"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>subject/guardian decision</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Non-compliance with study treatment</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>LCZ696 Followed by Valsartan</title>
          <description>Period 1: LCZ696 400mg QD for 4 weeks then washout followed by Period 2: Valsartan 320mg QD for 4 weeks</description>
        </group>
        <group group_id="B2">
          <title>Valsartan 320mg</title>
          <description>Period 1: 4 weeks treatment with Valsartan 320mg QD, 1-2 weeks wash-out, followed by period 2, 4 weeks treatment with LCZ696 400mg QD</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="36"/>
            <count group_id="B2" value="36"/>
            <count group_id="B3" value="72"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="55.7" spread="12.5"/>
                    <measurement group_id="B2" value="58.9" spread="7.5"/>
                    <measurement group_id="B3" value="57.3" spread="10.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="26"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                    <measurement group_id="B2" value="23"/>
                    <measurement group_id="B3" value="46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Cumulative Sodium Excretion (Natriuresis) at Day 1</title>
        <description>Urine will be collected in fractions of 6 to 24 hours post-dose. From each fraction, a sample will be drawn for analysis of sodium Day 1</description>
        <time_frame>0-6 and 0-24 hours on Day 1</time_frame>
        <population>Pharmacodynamic PD analysis set: Patients with any available PD data, who received any study drug and experienced no protocol deviations with relevant impact on PD data.</population>
        <group_list>
          <group group_id="O1">
            <title>LCZ696 - ALL</title>
            <description>LCZ696 400mg QD</description>
          </group>
          <group group_id="O2">
            <title>Valsartan -ALL</title>
            <description>Valsartan 320mg QD</description>
          </group>
        </group_list>
        <measure>
          <title>Cumulative Sodium Excretion (Natriuresis) at Day 1</title>
          <description>Urine will be collected in fractions of 6 to 24 hours post-dose. From each fraction, a sample will be drawn for analysis of sodium Day 1</description>
          <population>Pharmacodynamic PD analysis set: Patients with any available PD data, who received any study drug and experienced no protocol deviations with relevant impact on PD data.</population>
          <units>mmol</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="70"/>
                <count group_id="O2" value="67"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>0-6h (n=69,66)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="61.26" spread="31.167"/>
                    <measurement group_id="O2" value="37.13" spread="20.761"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>0-24h (n=69,66)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="188.87" spread="74.458"/>
                    <measurement group_id="O2" value="138.92" spread="58.905"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cumulative Sodium Excretion (Natriuresis) at Day 28</title>
        <description>Urine will be collected in fractions of 6 to 24 hours post-dose. From each fraction, a sample will be drawn for analysis of sodium Day 28</description>
        <time_frame>0-6 and 0-24 hours on Day 28</time_frame>
        <population>Pharmacodynamic PD analysis set: Patients with any available PD data, who received any study drug and experienced no protocol deviations with relevant impact on PD data.</population>
        <group_list>
          <group group_id="O1">
            <title>LCZ696 - ALL</title>
            <description>LCZ696 400mg</description>
          </group>
          <group group_id="O2">
            <title>Valsartan - ALL</title>
            <description>Valsartan 320mg QD</description>
          </group>
        </group_list>
        <measure>
          <title>Cumulative Sodium Excretion (Natriuresis) at Day 28</title>
          <description>Urine will be collected in fractions of 6 to 24 hours post-dose. From each fraction, a sample will be drawn for analysis of sodium Day 28</description>
          <population>Pharmacodynamic PD analysis set: Patients with any available PD data, who received any study drug and experienced no protocol deviations with relevant impact on PD data.</population>
          <units>mmol</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="70"/>
                <count group_id="O2" value="67"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>0-6h (n=69,66)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="39.30" spread="18.841"/>
                    <measurement group_id="O2" value="44.57" spread="23.479"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>0-24h (n=69,66)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="144.71" spread="51.094"/>
                    <measurement group_id="O2" value="153.82" spread="62.449"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Urine Volume (Diuresis) Over Time</title>
        <description>Urine will be collected and volume measured in fractions of 0 to 6 hours and 0 to 24 hours Day-1, Day 1 and Day 28</description>
        <time_frame>Day -1, Day 1 &amp; Day 28</time_frame>
        <population>Pharmacodynamic PD analysis set: Patients with any available PD data, who received any study drug and experienced no protocol deviations with relevant impact on PD data.</population>
        <group_list>
          <group group_id="O1">
            <title>LCZ696 - ALL</title>
            <description>LCZ696 400mg</description>
          </group>
          <group group_id="O2">
            <title>Valsartan - ALL</title>
            <description>Valsartan 320mg QD</description>
          </group>
        </group_list>
        <measure>
          <title>Urine Volume (Diuresis) Over Time</title>
          <description>Urine will be collected and volume measured in fractions of 0 to 6 hours and 0 to 24 hours Day-1, Day 1 and Day 28</description>
          <population>Pharmacodynamic PD analysis set: Patients with any available PD data, who received any study drug and experienced no protocol deviations with relevant impact on PD data.</population>
          <units>mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="70"/>
                <count group_id="O2" value="67"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day -1 0-6h (n=70,67)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="855.1" spread="450.28"/>
                    <measurement group_id="O2" value="806.2" spread="462.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day -1 0-24h (n=70,67)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2752.8" spread="722.53"/>
                    <measurement group_id="O2" value="2756.2" spread="1010.86"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 1 0-6h (n=70,67)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1215.9" spread="475.57"/>
                    <measurement group_id="O2" value="923.0" spread="443.65"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 1 0-24h (n=70,67)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3172.3" spread="957.70"/>
                    <measurement group_id="O2" value="2813.8" spread="930.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 28 0-6h (n=69,66)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="948.8" spread="415.14"/>
                    <measurement group_id="O2" value="1042.7" spread="530.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 28 0-24h (n=69,66)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2820.0" spread="847.81"/>
                    <measurement group_id="O2" value="3000.2" spread="1139.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Seated Office Blood Pressure (BP) (Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)) Over Time</title>
        <description>Seated Office BP (systolic blood pressure (SBP) and diastolic blood pressure (DBP))measurements will be performed at trough(immediately prior to dosing at the clinic). Arterial BP readings will be made with an automated BP device.</description>
        <time_frame>Day-1, Day 14 and Day 28</time_frame>
        <population>Pharmacodynamic PD analysis set: Patients with any available PD data, who received any study drug and experienced no protocol deviations with relevant impact on PD data.</population>
        <group_list>
          <group group_id="O1">
            <title>LCZ696 - ALL</title>
            <description>LCZ696 400mg</description>
          </group>
          <group group_id="O2">
            <title>Valsartan - ALL</title>
            <description>Valsartan 320mg QD</description>
          </group>
        </group_list>
        <measure>
          <title>Seated Office Blood Pressure (BP) (Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)) Over Time</title>
          <description>Seated Office BP (systolic blood pressure (SBP) and diastolic blood pressure (DBP))measurements will be performed at trough(immediately prior to dosing at the clinic). Arterial BP readings will be made with an automated BP device.</description>
          <population>Pharmacodynamic PD analysis set: Patients with any available PD data, who received any study drug and experienced no protocol deviations with relevant impact on PD data.</population>
          <units>mmHg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="70"/>
                <count group_id="O2" value="67"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day -1 Sitting SBP (n=70,67)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="140.20" spread="13.691"/>
                    <measurement group_id="O2" value="137.85" spread="12.703"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 28 Sitting SBP (n=69,66)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="127.01" spread="12.723"/>
                    <measurement group_id="O2" value="132.07" spread="15.195"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14 Sitting DBP (n=69,66)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="80.43" spread="7.808"/>
                    <measurement group_id="O2" value="80.57" spread="9.246"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 28 Sitting DBP (n=69,66)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="80.44" spread="7.840"/>
                    <measurement group_id="O2" value="81.40" spread="9.276"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14 Sitting SBP (n=69,66)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="126.88" spread="12.451"/>
                    <measurement group_id="O2" value="129.23" spread="12.784"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day -1 Sitting DBP (n=70,67)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="86.63" spread="8.955"/>
                    <measurement group_id="O2" value="85.59" spread="9.299"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Sitting Pulse Pressure (PP) Over Time</title>
        <description>Sitting mean pulse pressure rate was calculated between ambulatory SBP and DBP measurements</description>
        <time_frame>Day-1, Day 14 and Day 28</time_frame>
        <population>Pharmacodynamic PD analysis set: Patients with any available PD data, who received any study drug and experienced no protocol deviations with relevant impact on PD data.</population>
        <group_list>
          <group group_id="O1">
            <title>LCZ696 - ALL</title>
            <description>LCZ696 400mg</description>
          </group>
          <group group_id="O2">
            <title>Valsartan - ALL</title>
            <description>Valsartan 320mg QD</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Sitting Pulse Pressure (PP) Over Time</title>
          <description>Sitting mean pulse pressure rate was calculated between ambulatory SBP and DBP measurements</description>
          <population>Pharmacodynamic PD analysis set: Patients with any available PD data, who received any study drug and experienced no protocol deviations with relevant impact on PD data.</population>
          <units>mmHg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="70"/>
                <count group_id="O2" value="67"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day -1 Sitting mean PP (n=70,67)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="63.91" spread="8.392"/>
                    <measurement group_id="O2" value="64.92" spread="10.086"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14 Sitting mean PP (n=69,66)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="71.91" spread="10.370"/>
                    <measurement group_id="O2" value="69.61" spread="8.888"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 28 Sitting mean PP (n=69,66)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="65.21" spread="8.999"/>
                    <measurement group_id="O2" value="63.63" spread="8.843"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <desc>Overall, 72 patients with salt-sensitive hypertension were randomized to one of the two crossover treatment arms. For the Safety Set: overall, 71 patients were exposed to at least one dose of LCZ696 400 mg and a total of 67 patients were exposed to at least one dose of valsartan 320 mg.</desc>
      <group_list>
        <group group_id="E1">
          <title>LCZ696 400 mg QD</title>
          <description>LCZ696 400 mg QD</description>
        </group>
        <group group_id="E2">
          <title>Valsartan 320 mg QD</title>
          <description>Valsartan 320 mg QD</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="67"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>2</frequency_threshold>
        <default_vocab>MedDRA</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="67"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>DRY MOUTH</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="67"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>NASOPHARYNGITIS</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="67"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>BACK PAIN</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="67"/>
              </event>
              <event>
                <sub_title>FLANK PAIN</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="67"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>DIZZINESS</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="67"/>
              </event>
              <event>
                <sub_title>HEADACHE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="67"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>HAEMATURIA</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="67"/>
              </event>
              <event>
                <sub_title>PYURIA</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="67"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>COUGH</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="67"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Study Director</name_or_title>
      <organization>Novartis</organization>
      <phone>862-778-8300</phone>
    </point_of_contact>
  </clinical_results>
</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/NCT01681576
org study id: CLCZ696A2222
nct id: NCT01681576
lead sponsor: 
has dmc: No
This study will evaluate the effect of LCZ696 and valsartan on natriuresis, diuresis, and
      blood pressure in salt-sensitive Asian hypertensive patients.
allocation: Randomized
intervention model: Crossover Assignment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Cumulative Sodium Excretion (Natriuresis) at Day 1
time frame: 0-6 and 0-24 hours on Day 1
description: Urine will be collected in fractions of 6 to 24 hours post-dose. From each fraction, a sample will be drawn for analysis of sodium Day 1
measure: Cumulative Sodium Excretion (Natriuresis) at Day 28
time frame: 0-6 and 0-24 hours on Day 28
description: Urine will be collected in fractions of 6 to 24 hours post-dose. From each fraction, a sample will be drawn for analysis of sodium Day 28
measure: Urine Volume (Diuresis) Over Time
time frame: Day -1, Day 1 & Day 28
description: Urine will be collected and volume measured in fractions of 0 to 6 hours and 0 to 24 hours Day-1, Day 1 and Day 28
measure: Seated Office Blood Pressure (BP) (Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)) Over Time
time frame: Day-1, Day 14 and Day 28
description: Seated Office BP (systolic blood pressure (SBP) and diastolic blood pressure (DBP))measurements will be performed at trough(immediately prior to dosing at the clinic). Arterial BP readings will be made with an automated BP device.
measure: Mean Sitting Pulse Pressure (PP) Over Time
time frame: Day-1, Day 14 and Day 28
description: Sitting mean pulse pressure rate was calculated between ambulatory SBP and DBP measurements
arm group label: LCZ696 followed by Valsartan
arm group type: Experimental
description: Period 1: LCZ696 400mg QD for 4 weeks then washout followed by Period 2: Valsartan 320mg QD for 4 weeks
arm group label: Valsartan followed by LCZ696
arm group type: Experimental
description: Period 1: Valsartan 320mg QD for 4 weeks then washout followed by Period 2: LCZ696 400mg QD for 4 weeks
intervention type: Drug
intervention name: Valsartan
description: Valsartan 320mg tablet once daily
arm group label: LCZ696 followed by Valsartan
arm group label: Valsartan followed by LCZ696
intervention type: Drug
intervention name: LCZ696
description: LCZ696 400mg tablet once daily
arm group label: LCZ696 followed by Valsartan
arm group label: Valsartan followed by LCZ696
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Novartis Pharmaceuticals
role: Study Director
affiliation: Novartis Pharmaceuticals
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
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facility: 
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facility: 
country: Hong Kong
country: Korea, Republic of
country: Singapore
country: Taiwan
country: United States
responsible party type: Sponsor
mesh term: Hypertension
mesh term: Hypersensitivity
mesh term: Valsartan
mesh term: Sacubitril and valsartan sodium hydrate drug combination
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 