<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/NCT01706536</url>
  </required_header>
  <id_info>
    <org_study_id>EP-101-04 (SUN101)</org_study_id>
    <nct_id>NCT01706536</nct_id>
  </id_info>
  <brief_title>A Study of the Efficacy and Safety of EP-101 ( (SUN101) in Subjects With Moderate to Severe Chronic Obstructive Pulmonary Disease</brief_title>
  <acronym>GOLDEN-2</acronym>
  <official_title>A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study of the Efficacy and Safety of EP-101 (SUN101) in Subjects With Moderate to Severe Chronic Obstructive Pulmonary Disease: GOLDEN-2 (Glycopyrrolate for Obstructive Lung Disease Via Electronic Nebulizer)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sunovion Respiratory Development Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sunovion Respiratory Development Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a randomized, double-blind, placebo-controlled, parallel arm study. The study&#xD;
      population will consist of subjects, 35 to 75 years of age, with a diagnosis of moderate to&#xD;
      severe COPD per Global Initiative for Chronic Obstructive Lung Disease guidelines.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized, double-blind, placebo-controlled, parallel arm study. The study&#xD;
      population will consist of subjects, 35 to 75 years of age, with a diagnosis of moderate to&#xD;
      severe COPD per Global Initiative for Chronic Obstructive Lung Disease guidelines (GOLD,&#xD;
      2011). The primary analysis will compare each of the EP-101 (SUN101) dose groups to placebo&#xD;
      with respect to the change from baseline in morning trough FEV1 on Day 29. Trough FEV1 is&#xD;
      defined as the mean of the two FEV1 values obtained at 23 hours 30 minutes and 24 hours after&#xD;
      Day 28 AM dose (ie, approximately 12 hours after the previous PM dose).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">April 2013</completion_date>
  <primary_completion_date type="Actual">April 2013</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in Morning Trough Forced Expiratory Volume in 1 Second (FEV1)</measure>
    <time_frame>Baseline and Day 29</time_frame>
    <description>Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines. Trough FEV1 was defined as the mean of the spirometry values collected at 23 hours 30 minutes and 24 hours after the in-clinic morning dose (i.e. approximately 12 hrs after the previous evening dose).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The Standardized Change From Baseline FEV1 AUC(0-12)</measure>
    <time_frame>Day 28</time_frame>
    <description>Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Standardized Change From Baseline FEV1 AUC(12-24)</measure>
    <time_frame>Day 28</time_frame>
    <description>Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Peak FEV1 Change From Baseline</measure>
    <time_frame>Day 28</time_frame>
    <description>Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines. Peak FEV1 is defined as the highest postdose FEV1 value within 4 hrs after the morning dose.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Number of Subjects With Treatment-emergent Adverse Events</measure>
    <time_frame>Baseline up to Day 28</time_frame>
    <description>Treatment-emergent adverse events were those which first occurred or increased in severity or relationship to study drug after the first dose of double-blind study drug.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Number of Subjects With Treatment-emergent Serious Adverse Events</measure>
    <time_frame>Baseline up to Day 28</time_frame>
    <description>Treatment-emergent serious adverse events were those which first occurred or increased in severity or relationship to study drug after the first dose of double-blind study drug.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Number of Subjects With Treatment-emergent Adverse Events Leading to Study Medication Discontinuation</measure>
    <time_frame>Baseline up to Day 28</time_frame>
    <description>Treatment-emergent adverse events were those which first occurred or increased in severity or relationship to study drug after the first dose of double-blind study drug.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Percentage of Subjects With Treatment-emergent Adverse Events</measure>
    <time_frame>Baseline up to Day 28</time_frame>
    <description>Treatment-emergent adverse events were those which first occurred or increased in severity or relationship to study drug after the first dose of double-blind study drug.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Percentage of Subjects With Treatment-emergent Serious Adverse Events</measure>
    <time_frame>Baseline up to Day 28</time_frame>
    <description>Treatment-emergent serious adverse events were those which first occurred or increased in severity or relationship to study drug after the first dose of double-blind study drug.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Percentage of Subjects With Treatment-emergent Adverse Events Leading to Study Medication Discontinuation</measure>
    <time_frame>Baseline up to Day 28</time_frame>
    <description>Treatment-emergent adverse events were those which first occurred or increased in severity or relationship to study drug after the first dose of double-blind study drug.</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">275</enrollment>
  <condition>COPD</condition>
  <arm_group>
    <arm_group_label>EP-101 Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>EP-101 Placebo AM + EP-101 Placebo PM</description>
  </arm_group>
  <arm_group>
    <arm_group_label>EP 101 12.5 mcg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>EP-101 12.5 mcg AM + EP-101 12.5 mcg PM</description>
  </arm_group>
  <arm_group>
    <arm_group_label>EP-101 25 mcg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>EP-101 25 mcg AM + EP-101 25 mcg PM</description>
  </arm_group>
  <arm_group>
    <arm_group_label>EP-101 50 mcg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>EP-101 50 mcg AM + EP-101 50 mcg PM</description>
  </arm_group>
  <arm_group>
    <arm_group_label>EP-101 100 mcg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>EP-101 100 mcg AM + EP-101 100 mcg PM</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>EP-101 Placebo AM + EP-101 Placebo PM</description>
    <arm_group_label>EP-101 Placebo</arm_group_label>
    <other_name>SUN101</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>EP-101 12.5 mcg</intervention_name>
    <description>EP-101 12.5 mcg AM + EP-101 12.5 mcg PM</description>
    <arm_group_label>EP 101 12.5 mcg</arm_group_label>
    <other_name>SUN101</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>EP-101 25 mcg</intervention_name>
    <description>EP-101 25 mcg AM + EP-101 25 mcg PM</description>
    <arm_group_label>EP-101 25 mcg</arm_group_label>
    <other_name>SUN101</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>EP-101 50 mcg</intervention_name>
    <description>EP-101 50 mcg AM + EP-101 50 mcg PM</description>
    <arm_group_label>EP-101 50 mcg</arm_group_label>
    <other_name>SUN101</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>EP-101 100 mcg</intervention_name>
    <description>EP-101 100 mcg AM + EP-101 100 mcg PM</description>
    <arm_group_label>EP-101 100 mcg</arm_group_label>
    <other_name>SUN101</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male and female subjects age 35 through 75 years, inclusive.&#xD;
&#xD;
          -  A clinical diagnosis of moderate to severe COPD according to GOLD guidelines (2011).&#xD;
&#xD;
          -  Current smokers or ex-smokers with at least 10 pack-year smoking history (eg, at least&#xD;
             1 pack/day for 10 years, or equivalent).&#xD;
&#xD;
          -  Post-bronchodilator (following inhalation of ipratropium bromide MDI) FEV1 ≥ 30% and ≤&#xD;
             70% of predicted normal value during the Screening Period.&#xD;
&#xD;
          -  Post-bronchodilator (following inhalation of ipratropium bromide MDI) FEV1/FVC ratio &lt;&#xD;
             0.70 during the Screening Period.&#xD;
&#xD;
          -  Post-bronchodilator (following inhalation of ipratropium bromide MDI) improvement in&#xD;
             FEV1 ≥ 12% and ≥ 100 mL during the Screening Period.&#xD;
&#xD;
          -  Ability to perform reproducible spirometry according to the American Thoracic Society&#xD;
             (ATS) and European Respiratory Society (ERS) guidelines (2005).&#xD;
&#xD;
          -  Subject, if female ≤ 65 years of age and of child bearing potential, must have a&#xD;
             negative serum pregnancy test at screening. Females of childbearing potential must be&#xD;
             instructed to and agree to avoid pregnancy during the study and must use an acceptable&#xD;
             method of birth control:&#xD;
&#xD;
               -  a. An oral contraceptive, an intrauterine device (IUD), implantable&#xD;
                  contraceptive, transdermal or injectable contraceptive for at least 1 month prior&#xD;
                  to entering the study with continued use throughout the study and for thirty days&#xD;
                  following study participation.&#xD;
&#xD;
               -  b. Barrier method of contraception, eg, condom and/or diaphragm with spermicide&#xD;
                  while participating in the study.&#xD;
&#xD;
               -  c. Abstinence.&#xD;
&#xD;
          -  Willing and able to provide written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Current evidence or recent history of any clinically significant and unstable disease&#xD;
             (other than COPD) or abnormality in the opinion of the Investigator that would put the&#xD;
             subject at risk or which would compromise the quality of the study data; including but&#xD;
             not limited to cardiovascular disease, myocardial infarction, cardiac failure,&#xD;
             uncontrolled hypertension, life-threatening arrhythmias, uncontrolled diabetes,&#xD;
             neurologic or neuromuscular disease, liver disease, gastrointestinal disease or&#xD;
             electrolyte abnormalities.&#xD;
&#xD;
          -  Current evidence or history of clinically significant abnormal cardiac rhythm and/or&#xD;
             conduction findings, including Holter monitoring results during the Screening Period.&#xD;
&#xD;
          -  Concomitant pulmonary disease or primary diagnosis of asthma.&#xD;
&#xD;
          -  History of malignancy of any organ system, treated or untreated within the past 5&#xD;
             years, with the exception of localized basal cell carcinoma of the skin&#xD;
&#xD;
          -  Recent history of COPD exacerbation requiring hospitalization or need for increased&#xD;
             treatments for COPD within 6 weeks prior to the Screening Period.&#xD;
&#xD;
          -  Use of daily oxygen therapy &gt; 10 hours per day.&#xD;
&#xD;
          -  Use of systemic steroids within 3 months prior to the Screening Period.&#xD;
&#xD;
          -  Respiratory tract infection within 6 weeks prior to or during the Screening Period.&#xD;
&#xD;
          -  History of tuberculosis, bronchiectasis or other non-specific pulmonary disease.&#xD;
&#xD;
          -  History of urinary retention or bladder neck obstruction type symptoms.&#xD;
&#xD;
          -  History of narrow-angle glaucoma.&#xD;
&#xD;
          -  Prolonged QTc interval (&gt; 450msec for males and &gt; 470msec for females) during the&#xD;
             Screening Period, or history of long QT syndrome.&#xD;
&#xD;
          -  Recent history (previous 12 months) of excessive use or abuse of narcotic/illegal&#xD;
             drugs.&#xD;
&#xD;
          -  History of hypersensitivity or intolerance to β2-agonists or anticholinergics.&#xD;
&#xD;
          -  Participation in another investigational drug study where drug was received within 30&#xD;
             days prior to the Screening Period.&#xD;
&#xD;
          -  Female subject who is pregnant or lactating&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>35 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Respiratory Medical Director, MD</last_name>
    <role>Study Director</role>
    <affiliation>Sunovion Respiratory Development</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Jasper Summit Research, LLC</name>
      <address>
        <city>Jasper</city>
        <state>Alabama</state>
        <zip>35501</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pulmonary Associates, PA</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85006</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>California Research Medical Group, Inc.</name>
      <address>
        <city>Fullerton</city>
        <state>California</state>
        <zip>92835</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UCLA David Geffen School of Medicine</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Integrated Research Group</name>
      <address>
        <city>Riverside</city>
        <state>California</state>
        <zip>92506</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Capital Allergy &amp; Respiratory Disease Center</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95819</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institute of HealthCare Assessment, Inc.</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92120</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Research of West Florida</name>
      <address>
        <city>Clearwater</city>
        <state>Florida</state>
        <zip>33765</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Research of West Florida</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33603</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Georgia Clinical Research</name>
      <address>
        <city>Austell</city>
        <state>Georgia</state>
        <zip>30106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gwinnett Biomedical Research</name>
      <address>
        <city>Lawrenceville</city>
        <state>Georgia</state>
        <zip>30046</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Veritas Clinical Specialities, LTD</name>
      <address>
        <city>Topeka</city>
        <state>Kansas</state>
        <zip>66606</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Minnesota Lung Center</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55407</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>American Health Research</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28207</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>North Carolina Clinical Research</name>
      <address>
        <city>Raleigh</city>
        <state>North Carolina</state>
        <zip>27607</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New Horizons Clinical Research</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Research Institute of Southern Oregon, PC</name>
      <address>
        <city>Medford</city>
        <state>Oregon</state>
        <zip>97504</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sunstone Medical Research LLC</name>
      <address>
        <city>Medford</city>
        <state>Oregon</state>
        <zip>97504</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Allergy Associates Research Center</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Greenville Pharmaceutical Research, Inc</name>
      <address>
        <city>Greenville</city>
        <state>South Carolina</state>
        <zip>29615</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Upstate Pharmaceutical Research</name>
      <address>
        <city>Greenville</city>
        <state>South Carolina</state>
        <zip>29615</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>South Carolina Pharmaceutical Research</name>
      <address>
        <city>Spartanburg</city>
        <state>South Carolina</state>
        <zip>29303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CU Pharmacuetical Research</name>
      <address>
        <city>Union</city>
        <state>South Carolina</state>
        <zip>29379</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor College of Medicine</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Central Texas Health Research</name>
      <address>
        <city>New Braunfels</city>
        <state>Texas</state>
        <zip>78130</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pulmonary Associates of Richmond, Inc.</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23225</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Donohue JF, Goodin T, Tosiello R, Wheeler A. Dose selection for glycopyrrolate/eFlow(R) phase III clinical studies: results from GOLDEN (Glycopyrrolate for Obstructive Lung Disease via Electronic Nebulizer) phase II dose-finding studies. Respir Res. 2017 Dec 4;18(1):202. doi: 10.1186/s12931-017-0681-z.</citation>
    <PMID>29202767</PMID>
  </results_reference>
  <verification_date>February 2018</verification_date>
  <study_first_submitted>October 10, 2012</study_first_submitted>
  <study_first_submitted_qc>October 10, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 15, 2012</study_first_posted>
  <results_first_submitted>January 2, 2018</results_first_submitted>
  <results_first_submitted_qc>February 6, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">March 8, 2018</results_first_posted>
  <disposition_first_submitted>May 14, 2014</disposition_first_submitted>
  <disposition_first_submitted_qc>May 14, 2014</disposition_first_submitted_qc>
  <disposition_first_posted type="Estimate">May 28, 2014</disposition_first_posted>
  <last_update_submitted>February 6, 2018</last_update_submitted>
  <last_update_submitted_qc>February 6, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">March 8, 2018</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>Lung Diseases, Obstructive</mesh_term>
    <mesh_term>Pulmonary Disease, Chronic Obstructive</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Out of 302 subjects, 294 completed the run-in period. 12 out of 294 subjects completed the run-in period, but did not enter the double-blind period. Total of 282 subjects entered the double-blind period.&#xD;
Specific details are outlined in the table below.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Placebo</title>
          <description>Placebo AM + Placebo PM&#xD;
Placebo:AM +Placebo PM</description>
        </group>
        <group group_id="P2">
          <title>EP 101 12.5 mcg</title>
          <description>EP-101 12.5 mcg AM + EP-101 12.5 mcg PM&#xD;
EP-101 12.5 mcg: EP-101 12.5 mcg AM + EP-101 12.5 mcg PM</description>
        </group>
        <group group_id="P3">
          <title>EP-101 25 mcg</title>
          <description>EP-101 25 mcg AM + EP-101 25 mcg PM&#xD;
EP-101 25 mcg: EP-101 25 mcg AM + EP-101 25 mcg PM</description>
        </group>
        <group group_id="P4">
          <title>EP-101 50 mcg</title>
          <description>EP-101 50 mcg AM + EP-101 50 mcg PM&#xD;
EP-101 50 mcg: EP-101 50 mcg AM + EP-101 50 mcg PM</description>
        </group>
        <group group_id="P5">
          <title>EP-101 100 mcg</title>
          <description>EP-101 100 mcg AM + EP-101 100 mcg PM&#xD;
EP-101 100 mcg: EP-101 100 mcg AM + EP-101 100 mcg PM</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="57"/>
                <participants group_id="P2" count="55"/>
                <participants group_id="P3" count="54"/>
                <participants group_id="P4" count="57"/>
                <participants group_id="P5" count="59"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="53"/>
                <participants group_id="P2" count="51"/>
                <participants group_id="P3" count="49"/>
                <participants group_id="P4" count="53"/>
                <participants group_id="P5" count="57"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="4"/>
                <participants group_id="P5" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="4"/>
                <participants group_id="P4" count="3"/>
                <participants group_id="P5" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>non compliance</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>ITT population</population>
      <group_list>
        <group group_id="B1">
          <title>Placebo</title>
          <description>Placebo AM + Placebo PM&#xD;
Placebo:AM +Placebo PM</description>
        </group>
        <group group_id="B2">
          <title>EP 101 12.5 mcg</title>
          <description>EP-101 12.5 mcg AM + EP-101 12.5 mcg PM&#xD;
EP-101 12.5 mcg: EP-101 12.5 mcg AM + EP-101 12.5 mcg PM</description>
        </group>
        <group group_id="B3">
          <title>EP-101 25 mcg</title>
          <description>EP-101 25 mcg AM + EP-101 25 mcg PM&#xD;
EP-101 25 mcg: EP-101 25 mcg AM + EP-101 25 mcg PM</description>
        </group>
        <group group_id="B4">
          <title>EP-101 50 mcg</title>
          <description>EP-101 50 mcg AM + EP-101 50 mcg PM&#xD;
EP-101 50 mcg: EP-101 50 mcg AM + EP-101 50 mcg PM</description>
        </group>
        <group group_id="B5">
          <title>EP-101 100 mcg</title>
          <description>EP-101 100 mcg AM + EP-101 100 mcg PM&#xD;
EP-101 100 mcg: EP-101 100 mcg AM + EP-101 100 mcg PM</description>
        </group>
        <group group_id="B6">
          <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="57"/>
            <count group_id="B2" value="55"/>
            <count group_id="B3" value="54"/>
            <count group_id="B4" value="57"/>
            <count group_id="B5" value="59"/>
            <count group_id="B6" value="282"/>
          </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 group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="30"/>
                    <measurement group_id="B2" value="36"/>
                    <measurement group_id="B3" value="40"/>
                    <measurement group_id="B4" value="36"/>
                    <measurement group_id="B5" value="42"/>
                    <measurement group_id="B6" value="184"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="27"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="14"/>
                    <measurement group_id="B4" value="21"/>
                    <measurement group_id="B5" value="17"/>
                    <measurement group_id="B6" value="98"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <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="63.0" spread="7.29"/>
                    <measurement group_id="B2" value="60.9" spread="7.79"/>
                    <measurement group_id="B3" value="59.6" spread="8.98"/>
                    <measurement group_id="B4" value="59.4" spread="8.70"/>
                    <measurement group_id="B5" value="59.4" spread="7.65"/>
                    <measurement group_id="B6" value="60.5" spread="8.16"/>
                  </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 group_id="B2" value="28"/>
                    <measurement group_id="B3" value="30"/>
                    <measurement group_id="B4" value="24"/>
                    <measurement group_id="B5" value="34"/>
                    <measurement group_id="B6" value="147"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                    <measurement group_id="B2" value="27"/>
                    <measurement group_id="B3" value="24"/>
                    <measurement group_id="B4" value="33"/>
                    <measurement group_id="B5" value="25"/>
                    <measurement group_id="B6" value="135"/>
                  </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="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="56"/>
                    <measurement group_id="B2" value="55"/>
                    <measurement group_id="B3" value="52"/>
                    <measurement group_id="B4" value="56"/>
                    <measurement group_id="B5" value="59"/>
                    <measurement group_id="B6" value="278"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" 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 group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="10"/>
                    <measurement group_id="B6" value="27"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="49"/>
                    <measurement group_id="B2" value="51"/>
                    <measurement group_id="B3" value="50"/>
                    <measurement group_id="B4" value="53"/>
                    <measurement group_id="B5" value="49"/>
                    <measurement group_id="B6" value="252"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="57"/>
                    <measurement group_id="B2" value="55"/>
                    <measurement group_id="B3" value="54"/>
                    <measurement group_id="B4" value="57"/>
                    <measurement group_id="B5" value="59"/>
                    <measurement group_id="B6" value="282"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Morning Trough Forced Expiratory Volume in 1 Second (FEV1)</title>
        <description>Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines. Trough FEV1 was defined as the mean of the spirometry values collected at 23 hours 30 minutes and 24 hours after the in-clinic morning dose (i.e. approximately 12 hrs after the previous evening dose).</description>
        <time_frame>Baseline and Day 29</time_frame>
        <population>The ITT population consisted of all subjects who were randomized to treatment and received at least 1 dose of double-blind study medication.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Placebo AM + Placebo PM&#xD;
Placebo:AM +Placebo PM</description>
          </group>
          <group group_id="O2">
            <title>EP 101 12.5 mcg</title>
            <description>EP-101 12.5 mcg AM + EP-101 12.5 mcg PM&#xD;
EP-101 12.5 mcg: EP-101 12.5 mcg AM + EP-101 12.5 mcg PM</description>
          </group>
          <group group_id="O3">
            <title>EP-101 25 mcg</title>
            <description>EP-101 25 mcg AM + EP-101 25 mcg PM&#xD;
EP-101 25 mcg: EP-101 25 mcg AM + EP-101 25 mcg PM</description>
          </group>
          <group group_id="O4">
            <title>EP-101 50 mcg</title>
            <description>EP-101 50 mcg AM + EP-101 50 mcg PM&#xD;
EP-101 50 mcg: EP-101 50 mcg AM + EP-101 50 mcg PM</description>
          </group>
          <group group_id="O5">
            <title>EP-101 100 mcg</title>
            <description>EP-101 100 mcg AM + EP-101 100 mcg PM&#xD;
EP-101 100 mcg: EP-101 100 mcg AM + EP-101 100 mcg PM</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Morning Trough Forced Expiratory Volume in 1 Second (FEV1)</title>
          <description>Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines. Trough FEV1 was defined as the mean of the spirometry values collected at 23 hours 30 minutes and 24 hours after the in-clinic morning dose (i.e. approximately 12 hrs after the previous evening dose).</description>
          <population>The ITT population consisted of all subjects who were randomized to treatment and received at least 1 dose of double-blind study medication.</population>
          <units>liters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="57"/>
                <count group_id="O2" value="55"/>
                <count group_id="O3" value="54"/>
                <count group_id="O4" value="57"/>
                <count group_id="O5" value="59"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0009" spread="0.16664"/>
                    <measurement group_id="O2" value="0.1055" spread="0.18013"/>
                    <measurement group_id="O3" value="0.1333" spread="0.26526"/>
                    <measurement group_id="O4" value="0.1336" spread="0.23813"/>
                    <measurement group_id="O5" value="0.1794" spread="0.21678"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>A sample size of 45 subjects per treatment arm provides approximately 80% power to detect a 0.12 L treatment difference in mean change in trough FEV1 between an active arm and the placebo arm at a significance level of 0.05 using a 2-group t-test and assumes a standard deviation for change in trough FEV1 of 200. Assuming a 20% discontinuation rate, approximately 55 subjects were enrolled into each treatment arm.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0043</p_value>
            <method>Least squares mean (SE)</method>
            <method_desc>In order to control for Type I error rate, a gate keeping methodology was used.</method_desc>
            <param_type>Least Squares Mean (SE)</param_type>
            <param_value>0.1168</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.04055</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.0369</ci_lower_limit>
            <ci_upper_limit>0.1966</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>A sample size of 45 subjects per treatment arm provides approximately 80% power to detect a 0.12 L treatment difference in mean change in trough FEV1 between an active arm and the placebo arm at a significance level of 0.05 using a 2-group t-test and assumes a standard deviation for change in trough FEV1 of 200. Assuming a 20% discontinuation rate, approximately 55 subjects were enrolled into each treatment arm.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0019</p_value>
            <p_value_desc>In order to control for Type I error rate, a gate keeping methodology was used</p_value_desc>
            <method>Least squares mean (SE)</method>
            <param_type>Least Squares Mean (SE)</param_type>
            <param_value>0.1284</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.04089</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.0479</ci_lower_limit>
            <ci_upper_limit>0.2089</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>A sample size of 45 subjects per treatment arm provides approximately 80% power to detect a 0.12 L treatment difference in mean change in trough FEV1 between an active arm and the placebo arm at a significance level of 0.05 using a 2-group t-test and assumes a standard deviation for change in trough FEV1 of 200. Assuming a 20% discontinuation rate, approximately 55 subjects were enrolled into each treatment arm.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0004</p_value>
            <p_value_desc>in order to control for Type 1 error rate, a gate keeping methodology was used</p_value_desc>
            <method>Least squares mean (SE)</method>
            <param_type>Least Squares Mean (SE)</param_type>
            <param_value>0.1462</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.04037</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.0667</ci_lower_limit>
            <ci_upper_limit>0.2257</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O5</group_id>
            </group_id_list>
            <groups_desc>A sample size of 45 subjects per treatment arm provides approximately 80% power to detect a 0.12 L treatment difference in mean change in trough FEV1 between an active arm and the placebo arm at a significance level of 0.05 using a 2-group t-test and assumes a standard deviation for change in trough FEV1 of 200. Assuming a 20% discontinuation rate, approximately 55 subjects were enrolled into each treatment arm.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>in order to control for type I error rate, a gate keeping methodology was used</p_value_desc>
            <method>Least squares mean (SE)</method>
            <param_type>Least Squares Mean (SE)</param_type>
            <param_value>0.1770</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.03953</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.0992</ci_lower_limit>
            <ci_upper_limit>0.2548</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Standardized Change From Baseline FEV1 AUC(0-12)</title>
        <description>Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines.</description>
        <time_frame>Day 28</time_frame>
        <population>The ITT population consisted of all subjects who were randomized to treatment and received at least 1 dose of double-blind study medication.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Placebo AM + Placebo PM&#xD;
Placebo AM + Placebo PM</description>
          </group>
          <group group_id="O2">
            <title>EP 101 12.5 mcg</title>
            <description>EP-101 12.5 mcg AM + EP-101 12.5 mcg PM&#xD;
EP-101 12.5 mcg: EP-101 12.5 mcg AM + EP-101 12.5 mcg PM</description>
          </group>
          <group group_id="O3">
            <title>EP-101 25 mcg</title>
            <description>EP-101 25 mcg AM + EP-101 25 mcg PM&#xD;
EP-101 25 mcg: EP-101 25 mcg AM + EP-101 25 mcg PM</description>
          </group>
          <group group_id="O4">
            <title>EP-101 50 mcg</title>
            <description>EP-101 50 mcg AM + EP-101 50 mcg PM&#xD;
EP-101 50 mcg: EP-101 50 mcg AM + EP-101 50 mcg PM</description>
          </group>
          <group group_id="O5">
            <title>EP-101 100 mcg</title>
            <description>EP-101 100 mcg AM + EP-101 100 mcg PM&#xD;
EP-101 100 mcg: EP-101 100 mcg AM + EP-101 100 mcg PM</description>
          </group>
        </group_list>
        <measure>
          <title>The Standardized Change From Baseline FEV1 AUC(0-12)</title>
          <description>Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines.</description>
          <population>The ITT population consisted of all subjects who were randomized to treatment and received at least 1 dose of double-blind study medication.</population>
          <units>liters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="57"/>
                <count group_id="O2" value="55"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="57"/>
                <count group_id="O5" value="59"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0055" spread="0.15426"/>
                    <measurement group_id="O2" value="0.1370" spread="0.17082"/>
                    <measurement group_id="O3" value="0.1720" spread="0.24720"/>
                    <measurement group_id="O4" value="0.1066" spread="0.20512"/>
                    <measurement group_id="O5" value="0.1815" spread="0.18544"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Standardized Change From Baseline FEV1 AUC(12-24)</title>
        <description>Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines.</description>
        <time_frame>Day 28</time_frame>
        <population>A substudy of subjects in the ITT population consisted of subjects who were randomized to treatment and received at least 1 dose of double-blind study medication and who had extended spirometry measurements.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Placebo AM + Placebo PM&#xD;
Placebo:AM +Placebo PM</description>
          </group>
          <group group_id="O2">
            <title>EP 101 12.5 mcg</title>
            <description>EP-101 12.5 mcg AM + EP-101 12.5 mcg PM&#xD;
EP-101 12.5 mcg: EP-101 12.5 mcg AM + EP-101 12.5 mcg PM</description>
          </group>
          <group group_id="O3">
            <title>EP-101 25 mcg</title>
            <description>EP-101 25 mcg AM + EP-101 25 mcg PM&#xD;
EP-101 25 mcg: EP-101 25 mcg AM + EP-101 25 mcg PM</description>
          </group>
          <group group_id="O4">
            <title>EP-101 50 mcg</title>
            <description>EP-101 50 mcg AM + EP-101 50 mcg PM&#xD;
EP-101 50 mcg: EP-101 50 mcg AM + EP-101 50 mcg PM</description>
          </group>
          <group group_id="O5">
            <title>EP-101 100 mcg</title>
            <description>EP-101 100 mcg AM + EP-101 100 mcg PM&#xD;
EP-101 100 mcg: EP-101 100 mcg AM + EP-101 100 mcg PM</description>
          </group>
        </group_list>
        <measure>
          <title>The Standardized Change From Baseline FEV1 AUC(12-24)</title>
          <description>Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines.</description>
          <population>A substudy of subjects in the ITT population consisted of subjects who were randomized to treatment and received at least 1 dose of double-blind study medication and who had extended spirometry measurements.</population>
          <units>liters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
                <count group_id="O2" value="26"/>
                <count group_id="O3" value="24"/>
                <count group_id="O4" value="25"/>
                <count group_id="O5" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.0725" spread="0.16509"/>
                    <measurement group_id="O2" value="0.0578" spread="0.14054"/>
                    <measurement group_id="O3" value="0.0563" spread="0.27985"/>
                    <measurement group_id="O4" value="0.0692" spread="0.19252"/>
                    <measurement group_id="O5" value="0.1284" spread="0.21688"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Peak FEV1 Change From Baseline</title>
        <description>Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines. Peak FEV1 is defined as the highest postdose FEV1 value within 4 hrs after the morning dose.</description>
        <time_frame>Day 28</time_frame>
        <population>The ITT population consisted of all subjects who were randomized to treatment and received at least 1 dose of double-blind study medication.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Placebo AM + Placebo PM&#xD;
Placebo:AM +Placebo PM</description>
          </group>
          <group group_id="O2">
            <title>EP 101 12.5 mcg</title>
            <description>EP-101 12.5 mcg AM + EP-101 12.5 mcg PM&#xD;
EP-101 12.5 mcg: EP-101 12.5 mcg AM + EP-101 12.5 mcg PM</description>
          </group>
          <group group_id="O3">
            <title>EP-101 25 mcg</title>
            <description>EP-101 25 mcg AM + EP-101 25 mcg PM&#xD;
EP-101 25 mcg: EP-101 25 mcg AM + EP-101 25 mcg PM</description>
          </group>
          <group group_id="O4">
            <title>EP-101 50 mcg</title>
            <description>EP-101 50 mcg AM + EP-101 50 mcg PM&#xD;
EP-101 50 mcg: EP-101 50 mcg AM + EP-101 50 mcg PM</description>
          </group>
          <group group_id="O5">
            <title>EP-101 100 mcg</title>
            <description>EP-101 100 mcg AM + EP-101 100 mcg PM&#xD;
EP-101 100 mcg: EP-101 100 mcg AM + EP-101 100 mcg PM</description>
          </group>
        </group_list>
        <measure>
          <title>The Peak FEV1 Change From Baseline</title>
          <description>Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines. Peak FEV1 is defined as the highest postdose FEV1 value within 4 hrs after the morning dose.</description>
          <population>The ITT population consisted of all subjects who were randomized to treatment and received at least 1 dose of double-blind study medication.</population>
          <units>liters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="55"/>
                <count group_id="O2" value="54"/>
                <count group_id="O3" value="54"/>
                <count group_id="O4" value="57"/>
                <count group_id="O5" value="59"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0931" spread="0.17808"/>
                    <measurement group_id="O2" value="0.2613" spread="0.18782"/>
                    <measurement group_id="O3" value="002960" spread=".0026303"/>
                    <measurement group_id="O4" value="0.2552" spread="0.22395"/>
                    <measurement group_id="O5" value="0.3165" spread="0.21409"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Number of Subjects With Treatment-emergent Adverse Events</title>
        <description>Treatment-emergent adverse events were those which first occurred or increased in severity or relationship to study drug after the first dose of double-blind study drug.</description>
        <time_frame>Baseline up to Day 28</time_frame>
        <population>The safety population consisted of all subjects who were randomized to treatment and received at least 1 dose of double-blind study medication. Safety analyses were performed using the actual drug a subject received.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Placebo AM + Placebo PM&#xD;
Placebo:AM +Placebo PM</description>
          </group>
          <group group_id="O2">
            <title>EP 101 12.5 mcg</title>
            <description>EP-101 12.5 mcg AM + EP-101 12.5 mcg PM&#xD;
EP-101 12.5 mcg: EP-101 12.5 mcg AM + EP-101 12.5 mcg PM</description>
          </group>
          <group group_id="O3">
            <title>EP-101 25 mcg</title>
            <description>EP-101 25 mcg AM + EP-101 25 mcg PM&#xD;
EP-101 25 mcg: EP-101 25 mcg AM + EP-101 25 mcg PM</description>
          </group>
          <group group_id="O4">
            <title>EP-101 50 mcg</title>
            <description>EP-101 50 mcg AM + EP-101 50 mcg PM&#xD;
EP-101 50 mcg: EP-101 50 mcg AM + EP-101 50 mcg PM</description>
          </group>
          <group group_id="O5">
            <title>EP-101 100 mcg</title>
            <description>EP-101 100 mcg AM + EP-101 100 mcg PM&#xD;
EP-101 100 mcg: EP-101 100 mcg AM + EP-101 100 mcg PM</description>
          </group>
        </group_list>
        <measure>
          <title>The Number of Subjects With Treatment-emergent Adverse Events</title>
          <description>Treatment-emergent adverse events were those which first occurred or increased in severity or relationship to study drug after the first dose of double-blind study drug.</description>
          <population>The safety population consisted of all subjects who were randomized to treatment and received at least 1 dose of double-blind study medication. Safety analyses were performed using the actual drug a subject received.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="57"/>
                <count group_id="O2" value="55"/>
                <count group_id="O3" value="54"/>
                <count group_id="O4" value="57"/>
                <count group_id="O5" value="59"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                    <measurement group_id="O2" value="19"/>
                    <measurement group_id="O3" value="18"/>
                    <measurement group_id="O4" value="18"/>
                    <measurement group_id="O5" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Number of Subjects With Treatment-emergent Serious Adverse Events</title>
        <description>Treatment-emergent serious adverse events were those which first occurred or increased in severity or relationship to study drug after the first dose of double-blind study drug.</description>
        <time_frame>Baseline up to Day 28</time_frame>
        <population>The safety population consisted of all subjects who were randomized to treatment and received at least 1 dose of double-blind study medication. Safety analyses were performed using the actual drug a subject received.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Placebo AM + Placebo PM&#xD;
Placebo:AM +Placebo PM</description>
          </group>
          <group group_id="O2">
            <title>EP 101 12.5 mcg</title>
            <description>EP-101 12.5 mcg AM + EP-101 12.5 mcg PM&#xD;
EP-101 12.5 mcg: EP-101 12.5 mcg AM + EP-101 12.5 mcg PM</description>
          </group>
          <group group_id="O3">
            <title>EP-101 25 mcg</title>
            <description>EP-101 25 mcg AM + EP-101 25 mcg PM&#xD;
EP-101 25 mcg: EP-101 25 mcg AM + EP-101 25 mcg PM</description>
          </group>
          <group group_id="O4">
            <title>EP-101 50 mcg</title>
            <description>EP-101 50 mcg AM + EP-101 50 mcg PM&#xD;
EP-101 50 mcg: EP-101 50 mcg AM + EP-101 50 mcg PM</description>
          </group>
          <group group_id="O5">
            <title>EP-101 100 mcg</title>
            <description>EP-101 100 mcg AM + EP-101 100 mcg PM&#xD;
EP-101 100 mcg: EP-101 100 mcg AM + EP-101 100 mcg PM</description>
          </group>
        </group_list>
        <measure>
          <title>The Number of Subjects With Treatment-emergent Serious Adverse Events</title>
          <description>Treatment-emergent serious adverse events were those which first occurred or increased in severity or relationship to study drug after the first dose of double-blind study drug.</description>
          <population>The safety population consisted of all subjects who were randomized to treatment and received at least 1 dose of double-blind study medication. Safety analyses were performed using the actual drug a subject received.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="57"/>
                <count group_id="O2" value="55"/>
                <count group_id="O3" value="54"/>
                <count group_id="O4" value="57"/>
                <count group_id="O5" value="59"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="1"/>
                    <measurement group_id="O5" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Number of Subjects With Treatment-emergent Adverse Events Leading to Study Medication Discontinuation</title>
        <description>Treatment-emergent adverse events were those which first occurred or increased in severity or relationship to study drug after the first dose of double-blind study drug.</description>
        <time_frame>Baseline up to Day 28</time_frame>
        <population>The safety population consisted of all subjects who were randomized to treatment and received at least 1 dose of double-blind study medication. Safety analyses were performed using the actual drug a subject received.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Placebo AM + Placebo PM&#xD;
Placebo:AM +Placebo PM</description>
          </group>
          <group group_id="O2">
            <title>EP 101 12.5 mcg</title>
            <description>EP-101 12.5 mcg AM + EP-101 12.5 mcg PM&#xD;
EP-101 12.5 mcg: EP-101 12.5 mcg AM + EP-101 12.5 mcg PM</description>
          </group>
          <group group_id="O3">
            <title>EP-101 25 mcg</title>
            <description>EP-101 25 mcg AM + EP-101 25 mcg PM&#xD;
EP-101 25 mcg: EP-101 25 mcg AM + EP-101 25 mcg PM</description>
          </group>
          <group group_id="O4">
            <title>EP-101 50 mcg</title>
            <description>EP-101 50 mcg AM + EP-101 50 mcg PM&#xD;
EP-101 50 mcg: EP-101 50 mcg AM + EP-101 50 mcg PM</description>
          </group>
          <group group_id="O5">
            <title>EP-101 100 mcg</title>
            <description>EP-101 100 mcg AM + EP-101 100 mcg PM&#xD;
EP-101 100 mcg: EP-101 100 mcg AM + EP-101 100 mcg PM</description>
          </group>
        </group_list>
        <measure>
          <title>The Number of Subjects With Treatment-emergent Adverse Events Leading to Study Medication Discontinuation</title>
          <description>Treatment-emergent adverse events were those which first occurred or increased in severity or relationship to study drug after the first dose of double-blind study drug.</description>
          <population>The safety population consisted of all subjects who were randomized to treatment and received at least 1 dose of double-blind study medication. Safety analyses were performed using the actual drug a subject received.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="57"/>
                <count group_id="O2" value="55"/>
                <count group_id="O3" value="54"/>
                <count group_id="O4" value="57"/>
                <count group_id="O5" value="59"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="4"/>
                    <measurement group_id="O4" value="3"/>
                    <measurement group_id="O5" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Percentage of Subjects With Treatment-emergent Adverse Events</title>
        <description>Treatment-emergent adverse events were those which first occurred or increased in severity or relationship to study drug after the first dose of double-blind study drug.</description>
        <time_frame>Baseline up to Day 28</time_frame>
        <population>The safety population consisted of all subjects who were randomized to treatment and received at least 1 dose of double-blind study medication. Safety analyses were performed using the actual drug a subject received.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Placebo AM + Placebo PM&#xD;
Placebo:AM +Placebo PM</description>
          </group>
          <group group_id="O2">
            <title>EP 101 12.5 mcg</title>
            <description>EP-101 12.5 mcg AM + EP-101 12.5 mcg PM&#xD;
EP-101 12.5 mcg: EP-101 12.5 mcg AM + EP-101 12.5 mcg PM</description>
          </group>
          <group group_id="O3">
            <title>EP-101 25 mcg</title>
            <description>EP-101 25 mcg AM + EP-101 25 mcg PM&#xD;
EP-101 25 mcg: EP-101 25 mcg AM + EP-101 25 mcg PM</description>
          </group>
          <group group_id="O4">
            <title>EP-101 50 mcg</title>
            <description>EP-101 50 mcg AM + EP-101 50 mcg PM&#xD;
EP-101 50 mcg: EP-101 50 mcg AM + EP-101 50 mcg PM</description>
          </group>
          <group group_id="O5">
            <title>EP-101 100 mcg</title>
            <description>EP-101 100 mcg AM + EP-101 100 mcg PM&#xD;
EP-101 100 mcg: EP-101 100 mcg AM + EP-101 100 mcg PM</description>
          </group>
        </group_list>
        <measure>
          <title>The Percentage of Subjects With Treatment-emergent Adverse Events</title>
          <description>Treatment-emergent adverse events were those which first occurred or increased in severity or relationship to study drug after the first dose of double-blind study drug.</description>
          <population>The safety population consisted of all subjects who were randomized to treatment and received at least 1 dose of double-blind study medication. Safety analyses were performed using the actual drug a subject received.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="57"/>
                <count group_id="O2" value="55"/>
                <count group_id="O3" value="54"/>
                <count group_id="O4" value="57"/>
                <count group_id="O5" value="59"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26.3"/>
                    <measurement group_id="O2" value="34.5"/>
                    <measurement group_id="O3" value="33.3"/>
                    <measurement group_id="O4" value="31.6"/>
                    <measurement group_id="O5" value="28.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Percentage of Subjects With Treatment-emergent Serious Adverse Events</title>
        <description>Treatment-emergent serious adverse events were those which first occurred or increased in severity or relationship to study drug after the first dose of double-blind study drug.</description>
        <time_frame>Baseline up to Day 28</time_frame>
        <population>The safety population consisted of all subjects who were randomized to treatment and received at least 1 dose of double-blind study medication. Safety analyses were performed using the actual drug a subject received.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Placebo AM + Placebo PM&#xD;
Placebo:AM +Placebo PM</description>
          </group>
          <group group_id="O2">
            <title>EP 101 12.5 mcg</title>
            <description>EP-101 12.5 mcg AM + EP-101 12.5 mcg PM&#xD;
EP-101 12.5 mcg: EP-101 12.5 mcg AM + EP-101 12.5 mcg PM</description>
          </group>
          <group group_id="O3">
            <title>EP-101 25 mcg</title>
            <description>EP-101 25 mcg AM + EP-101 25 mcg PM&#xD;
EP-101 25 mcg: EP-101 25 mcg AM + EP-101 25 mcg PM</description>
          </group>
          <group group_id="O4">
            <title>EP-101 50 mcg</title>
            <description>EP-101 50 mcg AM + EP-101 50 mcg PM&#xD;
EP-101 50 mcg: EP-101 50 mcg AM + EP-101 50 mcg PM</description>
          </group>
          <group group_id="O5">
            <title>EP-101 100 mcg</title>
            <description>EP-101 100 mcg AM + EP-101 100 mcg PM&#xD;
EP-101 100 mcg: EP-101 100 mcg AM + EP-101 100 mcg PM</description>
          </group>
        </group_list>
        <measure>
          <title>The Percentage of Subjects With Treatment-emergent Serious Adverse Events</title>
          <description>Treatment-emergent serious adverse events were those which first occurred or increased in severity or relationship to study drug after the first dose of double-blind study drug.</description>
          <population>The safety population consisted of all subjects who were randomized to treatment and received at least 1 dose of double-blind study medication. Safety analyses were performed using the actual drug a subject received.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="57"/>
                <count group_id="O2" value="55"/>
                <count group_id="O3" value="54"/>
                <count group_id="O4" value="57"/>
                <count group_id="O5" value="59"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.5"/>
                    <measurement group_id="O2" value="3.6"/>
                    <measurement group_id="O3" value="3.7"/>
                    <measurement group_id="O4" value="1.8"/>
                    <measurement group_id="O5" value="5.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Percentage of Subjects With Treatment-emergent Adverse Events Leading to Study Medication Discontinuation</title>
        <description>Treatment-emergent adverse events were those which first occurred or increased in severity or relationship to study drug after the first dose of double-blind study drug.</description>
        <time_frame>Baseline up to Day 28</time_frame>
        <population>The safety population consisted of all subjects who were randomized to treatment and received at least 1 dose of double-blind study medication. Safety analyses were performed using the actual drug a subject received.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Placebo AM + Placebo PM&#xD;
Placebo:AM +Placebo PM</description>
          </group>
          <group group_id="O2">
            <title>EP 101 12.5 mcg</title>
            <description>EP-101 12.5 mcg AM + EP-101 12.5 mcg PM&#xD;
EP-101 12.5 mcg: EP-101 12.5 mcg AM + EP-101 12.5 mcg PM</description>
          </group>
          <group group_id="O3">
            <title>EP-101 25 mcg</title>
            <description>EP-101 25 mcg AM + EP-101 25 mcg PM&#xD;
EP-101 25 mcg: EP-101 25 mcg AM + EP-101 25 mcg PM</description>
          </group>
          <group group_id="O4">
            <title>EP-101 50 mcg</title>
            <description>EP-101 50 mcg AM + EP-101 50 mcg PM&#xD;
EP-101 50 mcg: EP-101 50 mcg AM + EP-101 50 mcg PM</description>
          </group>
          <group group_id="O5">
            <title>EP-101 100 mcg</title>
            <description>EP-101 100 mcg AM + EP-101 100 mcg PM&#xD;
EP-101 100 mcg: EP-101 100 mcg AM + EP-101 100 mcg PM</description>
          </group>
        </group_list>
        <measure>
          <title>The Percentage of Subjects With Treatment-emergent Adverse Events Leading to Study Medication Discontinuation</title>
          <description>Treatment-emergent adverse events were those which first occurred or increased in severity or relationship to study drug after the first dose of double-blind study drug.</description>
          <population>The safety population consisted of all subjects who were randomized to treatment and received at least 1 dose of double-blind study medication. Safety analyses were performed using the actual drug a subject received.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="57"/>
                <count group_id="O2" value="55"/>
                <count group_id="O3" value="54"/>
                <count group_id="O4" value="57"/>
                <count group_id="O5" value="59"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.5"/>
                    <measurement group_id="O2" value="5.5"/>
                    <measurement group_id="O3" value="7.4"/>
                    <measurement group_id="O4" value="5.3"/>
                    <measurement group_id="O5" value="1.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Baseline up to Day 28</time_frame>
      <desc>SAEs are defined as existing conditions which worsen or events which occur during the course of the clinical trial after treatment</desc>
      <group_list>
        <group group_id="E1">
          <title>Placebo</title>
          <description>Placebo AM + Placebo PM&#xD;
Placebo AM + Placebo PM</description>
        </group>
        <group group_id="E2">
          <title>EP 101 12.5 mcg</title>
          <description>EP-101 12.5 mcg AM + EP-101 12.5 mcg PM&#xD;
EP-101 12.5 mcg: EP-101 12.5 mcg AM + EP-101 12.5 mcg PM</description>
        </group>
        <group group_id="E3">
          <title>EP-101 25 mcg</title>
          <description>EP-101 25 mcg AM + EP-101 25 mcg PM&#xD;
EP-101 25 mcg: EP-101 25 mcg AM + EP-101 25 mcg PM</description>
        </group>
        <group group_id="E4">
          <title>EP-101 50 mcg</title>
          <description>EP-101 50 mcg AM + EP-101 50 mcg PM&#xD;
EP-101 50 mcg: EP-101 50 mcg AM + EP-101 50 mcg PM</description>
        </group>
        <group group_id="E5">
          <title>EP-101 100 mcg</title>
          <description>EP-101 100 mcg AM + EP-101 100 mcg PM&#xD;
EP-101 100 mcg: EP-101 100 mcg AM + EP-101 100 mcg PM</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (15.1)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="55"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="54"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="59"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>pancreatitis acute</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="55"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="59"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>non-cardiac chest pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="55"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="59"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>bronchitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="55"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="59"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>accidental overdose</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="55"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="59"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>blood pressure increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="55"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="59"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>lung neoplasm malignant</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="55"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E5" events="0" 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 (15.1)</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="3" subjects_at_risk="57"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="55"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="54"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="57"/>
                <counts group_id="E5" subjects_affected="6" subjects_at_risk="59"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="57"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="55"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E5" events="3" subjects_affected="3" subjects_at_risk="59"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>headache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="55"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="54"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="57"/>
                <counts group_id="E5" events="3" subjects_affected="3" subjects_at_risk="59"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Chronic Obstructive Pulmonary Disease</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="57"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="55"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="54"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="57"/>
                <counts group_id="E5" events="0" subjects_affected="0" 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>In the event the study is part of a multi-center study, the first publication of the results of the Study shall be made in conjunction with the results of other participating study sites as a multi-center publication; provided however, if a multi-center publication is not forthcoming within twenty-four (24) months following the completion of the study at all sites, Institution and Investigator shall be free to publish.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Respiratory Medical Director</name_or_title>
      <organization>Sunovion Pharmaceuticals Inc.</organization>
      <phone>1-866-503-6351</phone>
      <email>clinicaltrialsdisclosure@sunovion.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/NCT01706536
org study id: EP-101-04 (SUN101)
nct id: NCT01706536
lead sponsor: 
has dmc: No
This is a randomized, double-blind, placebo-controlled, parallel arm study. The study
      population will consist of subjects, 35 to 75 years of age, with a diagnosis of moderate to
      severe COPD per Global Initiative for Chronic Obstructive Lung Disease guidelines.
This is a randomized, double-blind, placebo-controlled, parallel arm study. The study
      population will consist of subjects, 35 to 75 years of age, with a diagnosis of moderate to
      severe COPD per Global Initiative for Chronic Obstructive Lung Disease guidelines (GOLD,
      2011). The primary analysis will compare each of the EP-101 (SUN101) dose groups to placebo
      with respect to the change from baseline in morning trough FEV1 on Day 29. Trough FEV1 is
      defined as the mean of the two FEV1 values obtained at 23 hours 30 minutes and 24 hours after
      Day 28 AM dose (ie, approximately 12 hours after the previous PM dose).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change From Baseline in Morning Trough Forced Expiratory Volume in 1 Second (FEV1)
time frame: Baseline and Day 29
description: Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines. Trough FEV1 was defined as the mean of the spirometry values collected at 23 hours 30 minutes and 24 hours after the in-clinic morning dose (i.e. approximately 12 hrs after the previous evening dose).
measure: The Standardized Change From Baseline FEV1 AUC(0-12)
time frame: Day 28
description: Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines.
measure: The Standardized Change From Baseline FEV1 AUC(12-24)
time frame: Day 28
description: Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines.
measure: The Peak FEV1 Change From Baseline
time frame: Day 28
description: Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines. Peak FEV1 is defined as the highest postdose FEV1 value within 4 hrs after the morning dose.
measure: The Number of Subjects With Treatment-emergent Adverse Events
time frame: Baseline up to Day 28
description: Treatment-emergent adverse events were those which first occurred or increased in severity or relationship to study drug after the first dose of double-blind study drug.
measure: The Number of Subjects With Treatment-emergent Serious Adverse Events
time frame: Baseline up to Day 28
description: Treatment-emergent serious adverse events were those which first occurred or increased in severity or relationship to study drug after the first dose of double-blind study drug.
measure: The Number of Subjects With Treatment-emergent Adverse Events Leading to Study Medication Discontinuation
time frame: Baseline up to Day 28
description: Treatment-emergent adverse events were those which first occurred or increased in severity or relationship to study drug after the first dose of double-blind study drug.
measure: The Percentage of Subjects With Treatment-emergent Adverse Events
time frame: Baseline up to Day 28
description: Treatment-emergent adverse events were those which first occurred or increased in severity or relationship to study drug after the first dose of double-blind study drug.
measure: The Percentage of Subjects With Treatment-emergent Serious Adverse Events
time frame: Baseline up to Day 28
description: Treatment-emergent serious adverse events were those which first occurred or increased in severity or relationship to study drug after the first dose of double-blind study drug.
measure: The Percentage of Subjects With Treatment-emergent Adverse Events Leading to Study Medication Discontinuation
time frame: Baseline up to Day 28
description: Treatment-emergent adverse events were those which first occurred or increased in severity or relationship to study drug after the first dose of double-blind study drug.
arm group label: EP-101 Placebo
arm group type: Placebo Comparator
description: EP-101 Placebo AM + EP-101 Placebo PM
arm group label: EP 101 12.5 mcg
arm group type: Experimental
description: EP-101 12.5 mcg AM + EP-101 12.5 mcg PM
arm group label: EP-101 25 mcg
arm group type: Experimental
description: EP-101 25 mcg AM + EP-101 25 mcg PM
arm group label: EP-101 50 mcg
arm group type: Experimental
description: EP-101 50 mcg AM + EP-101 50 mcg PM
arm group label: EP-101 100 mcg
arm group type: Experimental
description: EP-101 100 mcg AM + EP-101 100 mcg PM
intervention type: Drug
intervention name: Placebo
description: EP-101 Placebo AM + EP-101 Placebo PM
arm group label: EP-101 Placebo
other name: SUN101
intervention type: Drug
intervention name: EP-101 12.5 mcg
description: EP-101 12.5 mcg AM + EP-101 12.5 mcg PM
arm group label: EP 101 12.5 mcg
other name: SUN101
intervention type: Drug
intervention name: EP-101 25 mcg
description: EP-101 25 mcg AM + EP-101 25 mcg PM
arm group label: EP-101 25 mcg
other name: SUN101
intervention type: Drug
intervention name: EP-101 50 mcg
description: EP-101 50 mcg AM + EP-101 50 mcg PM
arm group label: EP-101 50 mcg
other name: SUN101
intervention type: Drug
intervention name: EP-101 100 mcg
description: EP-101 100 mcg AM + EP-101 100 mcg PM
arm group label: EP-101 100 mcg
other name: SUN101
criteria: 
gender: All
minimum age: 35 Years
maximum age: 75 Years
healthy volunteers: No
last name: Respiratory Medical Director, MD
role: Study Director
affiliation: Sunovion Respiratory Development
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country: United States
citation: Donohue JF, Goodin T, Tosiello R, Wheeler A. Dose selection for glycopyrrolate/eFlow(R) phase III clinical studies: results from GOLDEN (Glycopyrrolate for Obstructive Lung Disease via Electronic Nebulizer) phase II dose-finding studies. Respir Res. 2017 Dec 4;18(1):202. doi: 10.1186/s12931-017-0681-z.
PMID: 29202767
responsible party type: Sponsor
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 