<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/NCT01663233</url>
  </required_header>
  <id_info>
    <org_study_id>CLCZ696A2319</org_study_id>
    <nct_id>NCT01663233</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of LCZ696 200 mg + Amlodipine 5 mg in Comparison With Amlodipine 5 mg in Hypertensive Patients Not Responding to Amlodipine</brief_title>
  <official_title>A Randomized, 8-week, Double-blind, Parallel-group, Active-controlled, Multicenter Study to Evaluate the Efficacy and Safety of the Combination of LCZ696 200 mg + Amlodipine 5 mg in Comparison With Amlodipine 5 mg in Patients With Essential Hypertension Not Adequately Responsive to Amlodipine 5 mg Monotherapy Treatment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novartis</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will assess whether LCZ696 when used in combination with amlodipine will provide&#xD;
      greater BP lowering benefit compared to amlodipine alone in Asian hypertensive patients not&#xD;
      adequately responsive to amlodipine therapy.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">May 2013</completion_date>
  <primary_completion_date type="Actual">May 2013</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Mean 24-hour Ambulatory Blood Pressure Monitoring (ABPM) Systolic Blood Pressure (maSBP)</measure>
    <time_frame>8 weeks</time_frame>
    <description>The change in mean 24 hour ambulatory systolic blood pressure (maSBP) from baseline to end of the study (week 8) in the 2 groups was measured. A greater reduction from baseline in the LCZ696 group indicates a positive treatment effect.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Mean 24-hour ABPM Diastolic Blood Pressure (maDBP)</measure>
    <time_frame>8 weeks</time_frame>
    <description>The change in mean 24 hour maDBP from baseline to end of the study was measured. A reduction from baseline indicates a positive treatment effect.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Mean Sitting Systolic Blood Pressure (msSBP)</measure>
    <time_frame>8 weeks</time_frame>
    <description>The change in the patient's msSBP from baseline to end of the study was measured. A reduction from baseline indicates a positive treatment effect.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Mean Sitting Diastolic Blood Pressure (msDBP)</measure>
    <time_frame>8 weeks</time_frame>
    <description>The change in the patient's msDBP from baseline to end of the study was measured. A reduction from baseline indicates a positive treatment effect.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Sitting Pulse Pressure (PP)</measure>
    <time_frame>8 weeks</time_frame>
    <description>The change in the patient's mean sitting PP from baseline to end of the study was measured. Pulse pressure measures the difference in mean sitting systolic blood pressure and mean sitting diastolic blood pressure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Achieving Systolic and Diastolic Blood Pressure Control (&lt; 140/90 mmHg)</measure>
    <time_frame>8 weeks</time_frame>
    <description>The number of participants achieving a systolic and diastolic blood pressure &lt; 140/90 mmHg was measured. This outcome measure shows how well a given blood pressure treatment can achieve a given blood pressure target or goal. Participants who achieved the target blood pressure were determined based on the mean SBP and DBP measurements taken at the end of the study. If the participants' BP measurement was below the above target, they were considered to have successful blood pressure control.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Achieving Successful Response in msSBP (&lt; 140 mmHg or a Reduction ≥ 20 mmHg From Baseline)</measure>
    <time_frame>8 weeks</time_frame>
    <description>The number of participants who achieved successful treatment response in the msSBP of &lt; 140mmHg or a reduction ≥ 20 mmHg from baseline after completing study treatment was measured. Participants who achieved either of the above targets were deemed as a having a successful response.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Achieving Successful Response in msDBP (&lt; 90 mmHg or a Reduction ≥ 10 mmHg From Baseline)</measure>
    <time_frame>8 weeks of treatment</time_frame>
    <description>The number of participants who achieved successful treatment response in msDBP of &lt; 90mmHg or a reduction ≥ 10mmHg from baseline after completing study treatment was measured. Participants who achieved either of the above targets were deemed as having a successful response.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Adverse Event</measure>
    <time_frame>8 weeks</time_frame>
    <description>Participants were monitored for adverse events, serious adverse events and death.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">266</enrollment>
  <condition>Essential Hypertension</condition>
  <arm_group>
    <arm_group_label>LCZ696 and amlodipine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (had an office msSBP ≥145 mmHg and &lt;180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 200mg of LCZ696 in combination with 5 mg of amlodipine for 8 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Amlodipine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (had an office msSBP ≥145 mmHg and &lt;180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 5 mg of amlodipine and placebo to LCZ696 for 8 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>LCZ696</intervention_name>
    <description>LCZ696 will use tablets available at a strength of 200mg. Patients will be instructed to take the prescribed medication once a day.</description>
    <arm_group_label>LCZ696 and amlodipine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Amlodipine</intervention_name>
    <description>Amlodipine will use tablets available at a strength of 5 mg. Patients will be instructed to take the prescribed medication once a day.</description>
    <arm_group_label>Amlodipine</arm_group_label>
    <arm_group_label>LCZ696 and amlodipine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Matching placebo to LCZ696</description>
    <arm_group_label>Amlodipine</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Patients must give written informed consent and have a diagnosis of hypertension:&#xD;
&#xD;
        Untreated patients must have an msSBP ≥ 150 mmHg and &lt; 180 mmHg at both Visit 1 and Visit&#xD;
        101. Pre-treated patients must have an msSBP ≥ 145 mmHg and &lt; 180 mmHg after wash out at&#xD;
        Visit 101. All patients must have an office msSBP ≥ 145 mmHg and &lt; 180 mmHg at the&#xD;
        completion of the 4-week run-in epoch (at the randomization visit (Visit 201).&#xD;
&#xD;
        Patients must successfully complete ABPM and pass technical requirements at Visit 201.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Malignant or severe hypertension (grade 3 of WHO classification; msDBP ≥110 mmHg and/or&#xD;
        msSBP ≥ 180 mmHg).&#xD;
&#xD;
        History of angioedema, drug-related or otherwise. History or evidence of a secondary form&#xD;
        of hypertension. Transient ischemic cerebral attack (TIA) during the 12 months prior to&#xD;
        Visit 1 or any history of stroke.&#xD;
&#xD;
        History of myocardial infarction, coronary bypass surgery or PCI during the 12 months prior&#xD;
        to Visit 1&#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>Shijiazhuang</city>
        <state>Hebei</state>
        <zip>050000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Chongqing</city>
        <zip>400042</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Shanghai</city>
        <zip>200025</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Tianjin</city>
        <zip>300142</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Edogawa-ku</city>
        <state>Tokyo</state>
        <zip>133-0061</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Katsushika-ku</city>
        <state>Tokyo</state>
        <zip>124-0024</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Kiyose-city</city>
        <state>Tokyo</state>
        <zip>204-0021</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Kunitachi</city>
        <state>Tokyo</state>
        <zip>186-0001</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Shibuya-ku</city>
        <state>Tokyo</state>
        <zip>150-0002</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Shinagawa-ku</city>
        <state>Tokyo</state>
        <zip>142-0063</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Toshima-ku</city>
        <state>Tokyo</state>
        <zip>171-0021</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Wonju</city>
        <state>Gangwon-Do</state>
        <zip>220-701</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Koyang</city>
        <state>Kyunggi</state>
        <zip>410-719</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Busan</city>
        <zip>602-739</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Daegu</city>
        <zip>705-703</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Daegu</city>
        <zip>705-718</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Seoul</city>
        <zip>150-713</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Kuching</city>
        <state>Sarawak</state>
        <zip>94300</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Kuala Lumpur</city>
        <zip>56000</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Quezon City</city>
        <state>Manila</state>
        <zip>1100</zip>
        <country>Philippines</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Manila</city>
        <state>Metro Manila</state>
        <zip>1000</zip>
        <country>Philippines</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Quezon City</city>
        <zip>1100</zip>
        <country>Philippines</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Quezon City</city>
        <zip>1102</zip>
        <country>Philippines</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Valenzuela City</city>
        <zip>1441</zip>
        <country>Philippines</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>China</country>
    <country>Japan</country>
    <country>Korea, Republic of</country>
    <country>Malaysia</country>
    <country>Philippines</country>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>October 2015</verification_date>
  <study_first_submitted>August 8, 2012</study_first_submitted>
  <study_first_submitted_qc>August 10, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 13, 2012</study_first_posted>
  <results_first_submitted>July 21, 2015</results_first_submitted>
  <results_first_submitted_qc>July 21, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">August 18, 2015</results_first_posted>
  <last_update_submitted>October 1, 2015</last_update_submitted>
  <last_update_submitted_qc>October 1, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 23, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Essential hypertension</keyword>
  <keyword>High blood pressure</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypertension</mesh_term>
    <mesh_term>Essential Hypertension</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Amlodipine</mesh_term>
    <mesh_term>Sacubitril and valsartan sodium hydrate drug combination</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>LCZ696 and Amlodipine</title>
          <description>Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and &lt;180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 200mg of LCZ696 in combination with 5 mg of amlodipine for 8 weeks.</description>
        </group>
        <group group_id="P2">
          <title>Amlodipine</title>
          <description>Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and &lt;180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 5 mg of amlodipine and placebo to LCZ696 for 8 weeks.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="130"/>
                <participants group_id="P2" count="136"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="126"/>
                <participants group_id="P2" count="129"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="2"/>
              </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="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>LCZ696 and Amlodipine</title>
          <description>Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and &lt;180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 200mg of LCZ696 in combination with 5 mg of amlodipine for 8 weeks.</description>
        </group>
        <group group_id="B2">
          <title>Amlodipine</title>
          <description>Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and &lt;180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 5 mg of amlodipine and placebo to LCZ696 for 8 weeks.</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="130"/>
            <count group_id="B2" value="136"/>
            <count group_id="B3" value="266"/>
          </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="55.4" spread="9.31"/>
                    <measurement group_id="B2" value="55.5" spread="9.43"/>
                    <measurement group_id="B3" value="55.4" spread="9.35"/>
                  </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="49"/>
                    <measurement group_id="B2" value="61"/>
                    <measurement group_id="B3" value="110"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="81"/>
                    <measurement group_id="B2" value="75"/>
                    <measurement group_id="B3" value="156"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Mean 24-hour Ambulatory Blood Pressure Monitoring (ABPM) Systolic Blood Pressure (maSBP)</title>
        <description>The change in mean 24 hour ambulatory systolic blood pressure (maSBP) from baseline to end of the study (week 8) in the 2 groups was measured. A greater reduction from baseline in the LCZ696 group indicates a positive treatment effect.</description>
        <time_frame>8 weeks</time_frame>
        <population>FAS: This set included all randomized participants who received at least one dose of study medication. Among the 266 Full Analysis Set (FAS) participants, 251 participants (123 participants in the LCZ696 + amlodipine group and 128 participants in the amlodipine group) had eligible ABPM at both baseline and endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>LCZ696 and Amlodipine</title>
            <description>Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and &lt;180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 200mg of LCZ696 in combination with 5 mg of amlodipine for 8 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Amlodipine</title>
            <description>Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and &lt;180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 5 mg of amlodipine and placebo to LCZ696 for 8 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Mean 24-hour Ambulatory Blood Pressure Monitoring (ABPM) Systolic Blood Pressure (maSBP)</title>
          <description>The change in mean 24 hour ambulatory systolic blood pressure (maSBP) from baseline to end of the study (week 8) in the 2 groups was measured. A greater reduction from baseline in the LCZ696 group indicates a positive treatment effect.</description>
          <population>FAS: This set included all randomized participants who received at least one dose of study medication. Among the 266 Full Analysis Set (FAS) participants, 251 participants (123 participants in the LCZ696 + amlodipine group and 128 participants in the amlodipine group) had eligible ABPM at both baseline and endpoint.</population>
          <units>mmHg</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="123"/>
                <count group_id="O2" value="128"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-13.93" spread="0.56"/>
                    <measurement group_id="O2" value="-0.82" spread="0.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Mean 24-hour ABPM Diastolic Blood Pressure (maDBP)</title>
        <description>The change in mean 24 hour maDBP from baseline to end of the study was measured. A reduction from baseline indicates a positive treatment effect.</description>
        <time_frame>8 weeks</time_frame>
        <population>FAS: This set included all randomized participants who received at least one dose of study medication. Among the 266 Full Analysis Set (FAS) participants, 251 participants (123 participants in the LCZ696 + amlodipine group and 128 participants in the amlodipine group) had eligible ABPM at both baseline and endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>LCZ696 and Amlodipine</title>
            <description>Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and &lt;180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 200mg of LCZ696 in combination with 5 mg of amlodipine for 8 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Amlodipine</title>
            <description>Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and &lt;180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 5 mg of amlodipine and placebo to LCZ696 for 8 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Mean 24-hour ABPM Diastolic Blood Pressure (maDBP)</title>
          <description>The change in mean 24 hour maDBP from baseline to end of the study was measured. A reduction from baseline indicates a positive treatment effect.</description>
          <population>FAS: This set included all randomized participants who received at least one dose of study medication. Among the 266 Full Analysis Set (FAS) participants, 251 participants (123 participants in the LCZ696 + amlodipine group and 128 participants in the amlodipine group) had eligible ABPM at both baseline and endpoint.</population>
          <units>mmHg</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="123"/>
                <count group_id="O2" value="128"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.03" spread="0.38"/>
                    <measurement group_id="O2" value="-0.33" spread="0.37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Mean Sitting Systolic Blood Pressure (msSBP)</title>
        <description>The change in the patient's msSBP from baseline to end of the study was measured. A reduction from baseline indicates a positive treatment effect.</description>
        <time_frame>8 weeks</time_frame>
        <population>FAS</population>
        <group_list>
          <group group_id="O1">
            <title>LCZ696 and Amlodipine</title>
            <description>Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and &lt;180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 200mg of LCZ696 in combination with 5 mg of amlodipine for 8 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Amlodipine</title>
            <description>Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and &lt;180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 5 mg of amlodipine and placebo to LCZ696 for 8 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Mean Sitting Systolic Blood Pressure (msSBP)</title>
          <description>The change in the patient's msSBP from baseline to end of the study was measured. A reduction from baseline indicates a positive treatment effect.</description>
          <population>FAS</population>
          <units>mmHg</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="130"/>
                <count group_id="O2" value="136"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-19.60" spread="1.35"/>
                    <measurement group_id="O2" value="-9.34" spread="1.33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Mean Sitting Diastolic Blood Pressure (msDBP)</title>
        <description>The change in the patient's msDBP from baseline to end of the study was measured. A reduction from baseline indicates a positive treatment effect.</description>
        <time_frame>8 weeks</time_frame>
        <population>FAS</population>
        <group_list>
          <group group_id="O1">
            <title>LCZ696 and Amlodipine</title>
            <description>Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and &lt;180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 200mg of LCZ696 in combination with 5 mg of amlodipine for 8 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Amlodipine</title>
            <description>Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and &lt;180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 5 mg of amlodipine and placebo to LCZ696 for 8 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Mean Sitting Diastolic Blood Pressure (msDBP)</title>
          <description>The change in the patient's msDBP from baseline to end of the study was measured. A reduction from baseline indicates a positive treatment effect.</description>
          <population>FAS</population>
          <units>mmHg</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="130"/>
                <count group_id="O2" value="136"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-9.22" spread="0.83"/>
                    <measurement group_id="O2" value="-3.96" spread="0.82"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Sitting Pulse Pressure (PP)</title>
        <description>The change in the patient's mean sitting PP from baseline to end of the study was measured. Pulse pressure measures the difference in mean sitting systolic blood pressure and mean sitting diastolic blood pressure.</description>
        <time_frame>8 weeks</time_frame>
        <population>FAS</population>
        <group_list>
          <group group_id="O1">
            <title>LCZ696 and Amlodipine</title>
            <description>Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and &lt;180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 200mg of LCZ696 in combination with 5 mg of amlodipine for 8 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Amlodipine</title>
            <description>Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and &lt;180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 5 mg of amlodipine and placebo to LCZ696 for 8 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Sitting Pulse Pressure (PP)</title>
          <description>The change in the patient's mean sitting PP from baseline to end of the study was measured. Pulse pressure measures the difference in mean sitting systolic blood pressure and mean sitting diastolic blood pressure.</description>
          <population>FAS</population>
          <units>mmHg</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="130"/>
                <count group_id="O2" value="136"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-10.31" spread="0.90"/>
                    <measurement group_id="O2" value="-5.46" spread="0.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Achieving Systolic and Diastolic Blood Pressure Control (&lt; 140/90 mmHg)</title>
        <description>The number of participants achieving a systolic and diastolic blood pressure &lt; 140/90 mmHg was measured. This outcome measure shows how well a given blood pressure treatment can achieve a given blood pressure target or goal. Participants who achieved the target blood pressure were determined based on the mean SBP and DBP measurements taken at the end of the study. If the participants' BP measurement was below the above target, they were considered to have successful blood pressure control.</description>
        <time_frame>8 weeks</time_frame>
        <population>FAS</population>
        <group_list>
          <group group_id="O1">
            <title>LCZ696 and Amlodipine</title>
            <description>Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and &lt;180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 200mg of LCZ696 in combination with 5 mg of amlodipine for 8 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Amlodipine</title>
            <description>Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and &lt;180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 5 mg of amlodipine and placebo to LCZ696 for 8 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Achieving Systolic and Diastolic Blood Pressure Control (&lt; 140/90 mmHg)</title>
          <description>The number of participants achieving a systolic and diastolic blood pressure &lt; 140/90 mmHg was measured. This outcome measure shows how well a given blood pressure treatment can achieve a given blood pressure target or goal. Participants who achieved the target blood pressure were determined based on the mean SBP and DBP measurements taken at the end of the study. If the participants' BP measurement was below the above target, they were considered to have successful blood pressure control.</description>
          <population>FAS</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="130"/>
                <count group_id="O2" value="136"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="89"/>
                    <measurement group_id="O2" value="46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Achieving Successful Response in msSBP (&lt; 140 mmHg or a Reduction ≥ 20 mmHg From Baseline)</title>
        <description>The number of participants who achieved successful treatment response in the msSBP of &lt; 140mmHg or a reduction ≥ 20 mmHg from baseline after completing study treatment was measured. Participants who achieved either of the above targets were deemed as a having a successful response.</description>
        <time_frame>8 weeks</time_frame>
        <population>FAS</population>
        <group_list>
          <group group_id="O1">
            <title>LCZ696 and Amlodipine</title>
            <description>Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and &lt;180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 200mg of LCZ696 in combination with 5 mg of amlodipine for 8 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Amlodipine</title>
            <description>Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and &lt;180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 5 mg of amlodipine and placebo to LCZ696 for 8 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Achieving Successful Response in msSBP (&lt; 140 mmHg or a Reduction ≥ 20 mmHg From Baseline)</title>
          <description>The number of participants who achieved successful treatment response in the msSBP of &lt; 140mmHg or a reduction ≥ 20 mmHg from baseline after completing study treatment was measured. Participants who achieved either of the above targets were deemed as a having a successful response.</description>
          <population>FAS</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="130"/>
                <count group_id="O2" value="136"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="98"/>
                    <measurement group_id="O2" value="53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Achieving Successful Response in msDBP (&lt; 90 mmHg or a Reduction ≥ 10 mmHg From Baseline)</title>
        <description>The number of participants who achieved successful treatment response in msDBP of &lt; 90mmHg or a reduction ≥ 10mmHg from baseline after completing study treatment was measured. Participants who achieved either of the above targets were deemed as having a successful response.</description>
        <time_frame>8 weeks of treatment</time_frame>
        <population>FAS</population>
        <group_list>
          <group group_id="O1">
            <title>LCZ696 and Amlodipine</title>
            <description>Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and &lt;180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 200mg of LCZ696 in combination with 5 mg of amlodipine for 8 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Amlodipine</title>
            <description>Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and &lt;180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 5 mg of amlodipine and placebo to LCZ696 for 8 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Achieving Successful Response in msDBP (&lt; 90 mmHg or a Reduction ≥ 10 mmHg From Baseline)</title>
          <description>The number of participants who achieved successful treatment response in msDBP of &lt; 90mmHg or a reduction ≥ 10mmHg from baseline after completing study treatment was measured. Participants who achieved either of the above targets were deemed as having a successful response.</description>
          <population>FAS</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="130"/>
                <count group_id="O2" value="136"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="112"/>
                    <measurement group_id="O2" value="95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Adverse Event</title>
        <description>Participants were monitored for adverse events, serious adverse events and death.</description>
        <time_frame>8 weeks</time_frame>
        <population>Safety Set: The safety set included all randomized participants who received at least one dose of study medication.</population>
        <group_list>
          <group group_id="O1">
            <title>LCZ696 and Amlodipine</title>
            <description>Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and &lt;180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 200mg of LCZ696 in combination with 5 mg of amlodipine for 8 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Amlodipine</title>
            <description>Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and &lt;180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 5 mg of amlodipine and placebo to LCZ696 for 8 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Adverse Event</title>
          <description>Participants were monitored for adverse events, serious adverse events and death.</description>
          <population>Safety Set: The safety set included all randomized participants who received at least one dose of study medication.</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="130"/>
                <count group_id="O2" value="136"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Adverse Events (serious and non-serious)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26"/>
                    <measurement group_id="O2" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Deaths</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>LCZ696 and Amlodipine</title>
          <description>Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and &lt;180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 200mg of LCZ696 in combination with 5 mg of amlodipine for 8 weeks.</description>
        </group>
        <group group_id="E2">
          <title>Amlodipine</title>
          <description>Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (an office msSBP ≥145 mmHg and &lt;180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 5 mg of amlodipine and placebo to LCZ696 for 8 weeks.</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="130"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="136"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>2</frequency_threshold>
        <default_vocab>16.0</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="13" subjects_at_risk="130"/>
                <counts group_id="E2" subjects_affected="19" subjects_at_risk="136"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>NASOPHARYNGITIS</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="130"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="136"/>
              </event>
              <event>
                <sub_title>UPPER RESPIRATORY TRACT INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="130"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="136"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>DYSLIPIDAEMIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="130"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="136"/>
              </event>
              <event>
                <sub_title>HYPOKALAEMIA</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="130"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="136"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>DIZZINESS</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="130"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="136"/>
              </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 Pharmaceuticals</organization>
      <phone>+1 (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/NCT01663233
org study id: CLCZ696A2319
nct id: NCT01663233
lead sponsor: 
has dmc: Yes
This study will assess whether LCZ696 when used in combination with amlodipine will provide
      greater BP lowering benefit compared to amlodipine alone in Asian hypertensive patients not
      adequately responsive to amlodipine therapy.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Change in Mean 24-hour Ambulatory Blood Pressure Monitoring (ABPM) Systolic Blood Pressure (maSBP)
time frame: 8 weeks
description: The change in mean 24 hour ambulatory systolic blood pressure (maSBP) from baseline to end of the study (week 8) in the 2 groups was measured. A greater reduction from baseline in the LCZ696 group indicates a positive treatment effect.
measure: Change in Mean 24-hour ABPM Diastolic Blood Pressure (maDBP)
time frame: 8 weeks
description: The change in mean 24 hour maDBP from baseline to end of the study was measured. A reduction from baseline indicates a positive treatment effect.
measure: Change in Mean Sitting Systolic Blood Pressure (msSBP)
time frame: 8 weeks
description: The change in the patient's msSBP from baseline to end of the study was measured. A reduction from baseline indicates a positive treatment effect.
measure: Change in Mean Sitting Diastolic Blood Pressure (msDBP)
time frame: 8 weeks
description: The change in the patient's msDBP from baseline to end of the study was measured. A reduction from baseline indicates a positive treatment effect.
measure: Change in Sitting Pulse Pressure (PP)
time frame: 8 weeks
description: The change in the patient's mean sitting PP from baseline to end of the study was measured. Pulse pressure measures the difference in mean sitting systolic blood pressure and mean sitting diastolic blood pressure.
measure: Number of Participants Achieving Systolic and Diastolic Blood Pressure Control (< 140/90 mmHg)
time frame: 8 weeks
description: The number of participants achieving a systolic and diastolic blood pressure < 140/90 mmHg was measured. This outcome measure shows how well a given blood pressure treatment can achieve a given blood pressure target or goal. Participants who achieved the target blood pressure were determined based on the mean SBP and DBP measurements taken at the end of the study. If the participants' BP measurement was below the above target, they were considered to have successful blood pressure control.
measure: Number of Participants Achieving Successful Response in msSBP (< 140 mmHg or a Reduction ≥ 20 mmHg From Baseline)
time frame: 8 weeks
description: The number of participants who achieved successful treatment response in the msSBP of < 140mmHg or a reduction ≥ 20 mmHg from baseline after completing study treatment was measured. Participants who achieved either of the above targets were deemed as a having a successful response.
measure: Number of Participants Achieving Successful Response in msDBP (< 90 mmHg or a Reduction ≥ 10 mmHg From Baseline)
time frame: 8 weeks of treatment
description: The number of participants who achieved successful treatment response in msDBP of < 90mmHg or a reduction ≥ 10mmHg from baseline after completing study treatment was measured. Participants who achieved either of the above targets were deemed as having a successful response.
measure: Number of Participants With Adverse Event
time frame: 8 weeks
description: Participants were monitored for adverse events, serious adverse events and death.
arm group label: LCZ696 and amlodipine
arm group type: Experimental
description: Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (had an office msSBP ≥145 mmHg and <180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 200mg of LCZ696 in combination with 5 mg of amlodipine for 8 weeks.
arm group label: Amlodipine
arm group type: Active Comparator
description: Participants, first treated with 5 mg of amlodipine for 4 weeks to determine if they were not adequately responding to amlodipine (had an office msSBP ≥145 mmHg and <180 mmHg) and who met all inclusion and exclusion criteria), were randomized to receive 5 mg of amlodipine and placebo to LCZ696 for 8 weeks.
intervention type: Drug
intervention name: LCZ696
description: LCZ696 will use tablets available at a strength of 200mg. Patients will be instructed to take the prescribed medication once a day.
arm group label: LCZ696 and amlodipine
intervention type: Drug
intervention name: Amlodipine
description: Amlodipine will use tablets available at a strength of 5 mg. Patients will be instructed to take the prescribed medication once a day.
arm group label: Amlodipine
arm group label: LCZ696 and amlodipine
intervention type: Drug
intervention name: Placebo
description: Matching placebo to LCZ696
arm group label: Amlodipine
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Novartis Pharmaceuticals
role: Study Director
affiliation: Novartis Pharmaceuticals
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country: China
country: Japan
country: Korea, Republic of
country: Malaysia
country: Philippines
country: Taiwan
responsible party type: Sponsor
mesh term: Hypertension
mesh term: Essential Hypertension
mesh term: Amlodipine
mesh term: Sacubitril and valsartan sodium hydrate drug combination
participant flow: 
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outcome list: 
reported events: 
certain agreements: 
point of contact: 