<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/NCT04445688</url>
  </required_header>
  <id_info>
    <org_study_id>APN-006</org_study_id>
    <nct_id>NCT04445688</nct_id>
  </id_info>
  <brief_title>Crossover Trial of AD036 in Obstructive Sleep Apnea</brief_title>
  <official_title>Phase 2, Randomized, 3-Period, Placebo-Controlled Crossover Study to Evaluate the Efficacy and Safety in Obstructive Sleep Apnea of AD036 Versus Placebo or Atomoxetine</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Apnimed</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Apnimed</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a randomized, 3-Period, Placebo-Controlled, Crossover, phase 2 clinical study to&#xD;
      examine the efficacy and safety of AD036 versus placebo or atomoxetine in patients with&#xD;
      obstructive sleep apnea.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study is designed to examine the efficacy and safety of AD036 to treat obstructive sleep&#xD;
      apnea. The study is a three-period single-dose randomized crossover design in which patients&#xD;
      will undergo overnight Home Sleep Apnea Testing (HSAT) with dosing of one of the following 3&#xD;
      treatments: AD036, Atomoxetine, or Placebo. Participants will return 1 week after their final&#xD;
      crossover HSAT for an end of study (EOS) Visit.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 15, 2020</start_date>
  <completion_date type="Actual">December 1, 2020</completion_date>
  <primary_completion_date type="Actual">December 1, 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Apnea-Hypopnea Index</measure>
    <time_frame>1 day</time_frame>
    <description>Apnea-Hypopnea Index(Disease severity is often defined based on the number of apneas and hypopneas per hour during sleep), AD036 vs. placebo</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Hypoxic Burden</measure>
    <time_frame>1 day</time_frame>
    <description>Hypoxic burden (a way to measure oxygen desaturation) determined by measuring the respiratory event-associated area under the desaturation curve from pre-event baseline, AD036 vs. placebo. Hypoxic Burden was measured during polysomnography (type of sleep study), while the patient was asleep</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ODI</measure>
    <time_frame>1 day</time_frame>
    <description>Oxygen Desaturation Index, measured by pulse-oximetry, AD036 vs. placebo</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">62</enrollment>
  <condition>Obstructive Sleep Apnea</condition>
  <arm_group>
    <arm_group_label>AD036</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>AD036 oral capsule administered before sleep</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Atomoxetine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Atomoxetine oral capsule administered before sleep</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo oral capsule administered before sleep</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AD036</intervention_name>
    <description>Oral administration before bed</description>
    <arm_group_label>AD036</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Atomoxetine</intervention_name>
    <description>Oral administration before bed</description>
    <arm_group_label>Atomoxetine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Oral administration before bed</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or Female, between 25 to 65 years of age, inclusive, at the Screening Visit.&#xD;
&#xD;
          -  AHI 10 to &lt;20, or AHI ≥20 if meets PSG criteria&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of narcolepsy.&#xD;
&#xD;
          -  Clinically significant craniofacial malformation.&#xD;
&#xD;
          -  Clinically significant cardiac disease (e.g., rhythm disturbances, coronary artery&#xD;
             disease or cardiac failure) or hypertension requiring more than 2 medications for&#xD;
             control. A medication for these purposes is defined by dosage form, such that a&#xD;
             combination antihypertensive medication is considered 1 medication&#xD;
&#xD;
          -  CPAP should not be used for at least 2 weeks prior to first study PSG&#xD;
&#xD;
          -  History of using oral or nasal devices for the treatment of OSA may enroll as long as&#xD;
             the devices are not used during participation in the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>25 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Preferred Research Partners, Inc.</name>
      <address>
        <city>Little Rock</city>
        <state>Arkansas</state>
        <zip>72211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SDS Clinical Trials, Inc.</name>
      <address>
        <city>Santa Ana</city>
        <state>California</state>
        <zip>92705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Center for Sleep and Wake Disorders</name>
      <address>
        <city>Chevy Chase</city>
        <state>Maryland</state>
        <zip>20815</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sleep Medicine &amp; Research Center, St. Luke's Hospital</name>
      <address>
        <city>Chesterfield</city>
        <state>Missouri</state>
        <zip>63017</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CTI Clinical Research Center</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Schweitzer PK, Maynard JP, Wylie PE, Emsellem HA, Sands SA. Efficacy of atomoxetine plus oxybutynin in the treatment of obstructive sleep apnea with moderate pharyngeal collapsibility. Sleep Breath. 2023 May;27(2):495-503. doi: 10.1007/s11325-022-02634-x. Epub 2022 May 13.</citation>
    <PMID>35551600</PMID>
  </results_reference>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>June 19, 2020</study_first_submitted>
  <study_first_submitted_qc>June 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 24, 2020</study_first_posted>
  <results_first_submitted>July 19, 2023</results_first_submitted>
  <results_first_submitted_qc>August 15, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">August 21, 2023</results_first_posted>
  <disposition_first_submitted>May 26, 2021</disposition_first_submitted>
  <disposition_first_submitted_qc>August 15, 2023</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">August 21, 2023</disposition_first_posted>
  <last_update_submitted>September 8, 2023</last_update_submitted>
  <last_update_submitted_qc>September 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 14, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Apnea</mesh_term>
    <mesh_term>Sleep Apnea Syndromes</mesh_term>
    <mesh_term>Sleep Apnea, Obstructive</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atomoxetine Hydrochloride</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>September 15, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/88/NCT04445688/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 18, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/88/NCT04445688/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>5 clinical sites screened 101 participants 62 were randomized. This was an unblinded three period placebo controlled study. Participants who withdrew were not replaced.</recruitment_details>
      <pre_assignment_details>All participants were centrally randomized to one of 6 sequences (A - B - C, B - C - A, C - B - A, A - C - B, B - A - C, C - A - B). A 1-week minimum washout period occurred between each of the 3 arm assignments.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>All Participants</title>
          <description>oral capsules administered before bedtime. Treatment A: AD036, Treatment B: atomoxetine + placebo, Treatment C: placebo + placebo</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>First Intervention</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="62"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Treatment A</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Treatment B</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Treatment C</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="62"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Washout (One Week)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="62"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="59"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Second Intervention</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="59"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Treatment A</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Treatment B</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Treatment C</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="59"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Washout (One Week)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="59"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="59"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Third Intervention</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="59"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Treatment A</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Treatment B</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Treatment C</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="59"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>All Participants</title>
          <description>oral capsules administered before bedtime. Treatment A: AD036, Treatment B: atomoxetine + placebo, Treatment C: placebo + placebo</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="62"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="59"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="53" lower_limit="28" upper_limit="66"/>
                  </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="31"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="58"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="41"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BMI (kg/m^2)</title>
          <units>kg/m^2</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="32.30" lower_limit="22.6" upper_limit="39.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Apnea-Hypopnea Index</title>
        <description>Apnea-Hypopnea Index(Disease severity is often defined based on the number of apneas and hypopneas per hour during sleep), AD036 vs. placebo</description>
        <time_frame>1 day</time_frame>
        <population>The efficacy was analyzed using the mITT Population comprised of all participants who took at least 1 dose of any of the study treatments and had at least 1 measurement on the primary endpoint. Sixty (96.8%) patients were included in the mITT Population. Patients were analyzed for efficacy according to the treatment sequence into which they were randomized. Due to insufficient data quality of the home sleep test, AHI could not be determined in some treatment conditions.</population>
        <group_list>
          <group group_id="O1">
            <title>AD036</title>
            <description>AD036 oral capsule administered before sleep&#xD;
AD036: Oral administration before bed</description>
          </group>
          <group group_id="O2">
            <title>Atomoxetine</title>
            <description>Atomoxetine oral capsule administered before sleep&#xD;
Atomoxetine: Oral administration before bed</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Placebo oral capsule administered before sleep&#xD;
Placebo: Oral administration before bed</description>
          </group>
        </group_list>
        <measure>
          <title>Apnea-Hypopnea Index</title>
          <description>Apnea-Hypopnea Index(Disease severity is often defined based on the number of apneas and hypopneas per hour during sleep), AD036 vs. placebo</description>
          <population>The efficacy was analyzed using the mITT Population comprised of all participants who took at least 1 dose of any of the study treatments and had at least 1 measurement on the primary endpoint. Sixty (96.8%) patients were included in the mITT Population. Patients were analyzed for efficacy according to the treatment sequence into which they were randomized. Due to insufficient data quality of the home sleep test, AHI could not be determined in some treatment conditions.</population>
          <units>events/hour</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="54"/>
                <count group_id="O2" value="56"/>
                <count group_id="O3" value="57"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.5" lower_limit="7.2" upper_limit="15.8"/>
                    <measurement group_id="O2" value="11.5" lower_limit="7.2" upper_limit="15.8"/>
                    <measurement group_id="O3" value="18.8" lower_limit="14.5" upper_limit="23.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>ANOVA</method>
            <param_type>difference in Least Squares Mean</param_type>
            <param_value>-7.3</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-10.2</ci_lower_limit>
            <ci_upper_limit>-4.4</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Hypoxic Burden</title>
        <description>Hypoxic burden (a way to measure oxygen desaturation) determined by measuring the respiratory event-associated area under the desaturation curve from pre-event baseline, AD036 vs. placebo. Hypoxic Burden was measured during polysomnography (type of sleep study), while the patient was asleep</description>
        <time_frame>1 day</time_frame>
        <population>The efficacy was analyzed using the mITT Population comprised of all participants who took at least 1 dose of any of the study treatments and had at least 1 measurement on the primary endpoint. Sixty (96.8%) patients were included in the mITT Population. Patients were analyzed for efficacy according to the treatment sequence into which they were randomized. Due to insufficient data quality of the home sleep test, hypoxic burden could not be determined in some treatment conditions.</population>
        <group_list>
          <group group_id="O1">
            <title>AD036</title>
            <description>AD036 oral capsule administered before sleep&#xD;
AD036: Oral administration before bed</description>
          </group>
          <group group_id="O2">
            <title>Atomoxetine</title>
            <description>Atomoxetine oral capsule administered before sleep&#xD;
Atomoxetine: Oral administration before bed</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Placebo oral capsule administered before sleep&#xD;
Placebo: Oral administration before bed</description>
          </group>
        </group_list>
        <measure>
          <title>Hypoxic Burden</title>
          <description>Hypoxic burden (a way to measure oxygen desaturation) determined by measuring the respiratory event-associated area under the desaturation curve from pre-event baseline, AD036 vs. placebo. Hypoxic Burden was measured during polysomnography (type of sleep study), while the patient was asleep</description>
          <population>The efficacy was analyzed using the mITT Population comprised of all participants who took at least 1 dose of any of the study treatments and had at least 1 measurement on the primary endpoint. Sixty (96.8%) patients were included in the mITT Population. Patients were analyzed for efficacy according to the treatment sequence into which they were randomized. Due to insufficient data quality of the home sleep test, hypoxic burden could not be determined in some treatment conditions.</population>
          <units>%min/hour</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="54"/>
                <count group_id="O2" value="56"/>
                <count group_id="O3" value="57"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24.3" lower_limit="13.5" upper_limit="35.1"/>
                    <measurement group_id="O2" value="26.8" lower_limit="16.1" upper_limit="37.6"/>
                    <measurement group_id="O3" value="46.1" lower_limit="35.4" upper_limit="56.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>ANOVA</method>
            <param_type>difference in Least Squares Mean</param_type>
            <param_value>-21.8</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-29.5</ci_lower_limit>
            <ci_upper_limit>-14.1</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>ODI</title>
        <description>Oxygen Desaturation Index, measured by pulse-oximetry, AD036 vs. placebo</description>
        <time_frame>1 day</time_frame>
        <population>The efficacy was analyzed using the mITT Population comprised of all participants who took at least 1 dose of any of the study treatments and had at least 1 measurement on the primary endpoint. Sixty (96.8%) patients were included in the mITT Population. Patients were analyzed for efficacy according to the treatment sequence into which they were randomized. Mean (SD) of ODI (4%). Due to insufficient data quality of the home sleep test, ODI could not be determined in some treatment conditions.</population>
        <group_list>
          <group group_id="O1">
            <title>AD036</title>
            <description>AD036 oral capsule administered before sleep&#xD;
AD036: Oral administration before bed</description>
          </group>
          <group group_id="O2">
            <title>Atomoxetine</title>
            <description>Atomoxetine oral capsule administered before sleep&#xD;
Atomoxetine: Oral administration before bed</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Placebo oral capsule administered before sleep&#xD;
Placebo: Oral administration before bed</description>
          </group>
        </group_list>
        <measure>
          <title>ODI</title>
          <description>Oxygen Desaturation Index, measured by pulse-oximetry, AD036 vs. placebo</description>
          <population>The efficacy was analyzed using the mITT Population comprised of all participants who took at least 1 dose of any of the study treatments and had at least 1 measurement on the primary endpoint. Sixty (96.8%) patients were included in the mITT Population. Patients were analyzed for efficacy according to the treatment sequence into which they were randomized. Mean (SD) of ODI (4%). Due to insufficient data quality of the home sleep test, ODI could not be determined in some treatment conditions.</population>
          <units>events/hour</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="54"/>
                <count group_id="O2" value="56"/>
                <count group_id="O3" value="57"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.8" lower_limit="8.4" upper_limit="17.1"/>
                    <measurement group_id="O2" value="13.3" lower_limit="9.0" upper_limit="17.7"/>
                    <measurement group_id="O3" value="20.1" lower_limit="15.8" upper_limit="24.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>ANOVA</method>
            <param_type>difference in Least Squares Mean</param_type>
            <param_value>-7.3</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-10.5</ci_lower_limit>
            <ci_upper_limit>-4.2</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>10 weeks</time_frame>
      <desc>Planned time points for all adverse events assessments at each study visit</desc>
      <group_list>
        <group group_id="E1">
          <title>AD036</title>
          <description>AD036 oral capsule administered before sleep&#xD;
AD036: Oral administration before bed</description>
        </group>
        <group group_id="E2">
          <title>Atomoxetine</title>
          <description>Atomoxetine oral capsule administered before sleep&#xD;
Atomoxetine: Oral administration before bed</description>
        </group>
        <group group_id="E3">
          <title>Placebo</title>
          <description>Placebo oral capsule administered before sleep&#xD;
Placebo: Oral administration before bed</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="59"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="59"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (23.0)</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="8" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="62"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="59"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="59"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="62"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="59"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="59"/>
                <counts group_id="E2" events="7" subjects_affected="7" subjects_at_risk="62"/>
                <counts group_id="E3" events="4" subjects_affected="4" subjects_at_risk="59"/>
              </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>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Clinical Trials</name_or_title>
      <organization>Apnimed, Inc</organization>
      <phone>617-500-8880</phone>
      <email>clinicaltrials@apnimed.com</email>
    </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/NCT04445688
org study id: APN-006
nct id: NCT04445688
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a randomized, 3-Period, Placebo-Controlled, Crossover, phase 2 clinical study to
      examine the efficacy and safety of AD036 versus placebo or atomoxetine in patients with
      obstructive sleep apnea.
The study is designed to examine the efficacy and safety of AD036 to treat obstructive sleep
      apnea. The study is a three-period single-dose randomized crossover design in which patients
      will undergo overnight Home Sleep Apnea Testing (HSAT) with dosing of one of the following 3
      treatments: AD036, Atomoxetine, or Placebo. Participants will return 1 week after their final
      crossover HSAT for an end of study (EOS) Visit.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Apnea-Hypopnea Index
time frame: 1 day
description: Apnea-Hypopnea Index(Disease severity is often defined based on the number of apneas and hypopneas per hour during sleep), AD036 vs. placebo
measure: Hypoxic Burden
time frame: 1 day
description: Hypoxic burden (a way to measure oxygen desaturation) determined by measuring the respiratory event-associated area under the desaturation curve from pre-event baseline, AD036 vs. placebo. Hypoxic Burden was measured during polysomnography (type of sleep study), while the patient was asleep
measure: ODI
time frame: 1 day
description: Oxygen Desaturation Index, measured by pulse-oximetry, AD036 vs. placebo
arm group label: AD036
arm group type: Experimental
description: AD036 oral capsule administered before sleep
arm group label: Atomoxetine
arm group type: Active Comparator
description: Atomoxetine oral capsule administered before sleep
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo oral capsule administered before sleep
intervention type: Drug
intervention name: AD036
description: Oral administration before bed
arm group label: AD036
intervention type: Drug
intervention name: Atomoxetine
description: Oral administration before bed
arm group label: Atomoxetine
intervention type: Drug
intervention name: Placebo
description: Oral administration before bed
arm group label: Placebo
criteria: 
gender: All
minimum age: 25 Years
maximum age: 65 Years
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
citation: Schweitzer PK, Maynard JP, Wylie PE, Emsellem HA, Sands SA. Efficacy of atomoxetine plus oxybutynin in the treatment of obstructive sleep apnea with moderate pharyngeal collapsibility. Sleep Breath. 2023 May;27(2):495-503. doi: 10.1007/s11325-022-02634-x. Epub 2022 May 13.
PMID: 35551600
responsible party type: Sponsor
mesh term: Apnea
mesh term: Sleep Apnea Syndromes
mesh term: Sleep Apnea, Obstructive
mesh term: Atomoxetine Hydrochloride
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 