<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/NCT02988869</url>
  </required_header>
  <id_info>
    <org_study_id>NEU-22.12</org_study_id>
    <nct_id>NCT02988869</nct_id>
  </id_info>
  <brief_title>Tiotropium/Formoterol Via Discair® vs Tiotropium Monotherapy or Tiotropium + Formoterol Free Combination Treatment</brief_title>
  <official_title>Comparison of Bronchodilator Efficacy of Tiotropium/Formoterol Combination Treatment Administered (qd) Via Discair® With Tiotropium (qd) Monotherapy or Tiotropium (qd) + Formoterol (Bid) Free Combination Treatment in Patients With Chronic Obstructive Pulmonary Disease (COPD)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Neutec Ar-Ge San ve Tic A.Ş</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Neutec Ar-Ge San ve Tic A.Ş</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The overall objective is to asses the bronchodilator effect of once daily&#xD;
      Tiotropium/Formoterol combination delivered via Discair® by comparing Tiotropium (q.d.)&#xD;
      monotherapy delivered via Handihaler and tiotropium (q.d.) delivered via Handihaler +&#xD;
      formoterol (b.i.d) delivered via Aerolizer free combination treatment in patients with stable&#xD;
      moderate to severe COPD.&#xD;
&#xD;
      Spirometric measurements (FEV1, FVC) will be performed for a period of 24 h at 12 different&#xD;
      times: pre-treatment (15 min prior to the first dose) and post-treatment (30. min, 60 min [1&#xD;
      hr], 120 min [2 hr], 180 min [3 hr], 240 min [4 hr], 360 min [6 hr], 480 min [8 hr], 600 min&#xD;
      [10 hr], 720 min [12 hr], 840 min [14 hr],1440 min [24 hr].&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The overall objective is to asses the bronchodilator effect of once daily&#xD;
      Tiotropium/Formoterol combination delivered via Discair® by comparing Tiotropium (q.d.)&#xD;
      monotherapy delivered via Handihaler and tiotropium (q.d.) delivered via Handihaler +&#xD;
      formoterol (b.i.d) delivered via Aerolizer free combination treatment in patients with stable&#xD;
      moderate to severe COPD.&#xD;
&#xD;
      Patients will be randomly assigned to receive Tiotropium/Formoterol combination as dry powder&#xD;
      for inhalation by Discair® (test inhaler, n = 29) or Tiotropium as dry powder capsule for&#xD;
      inhalation by HandiHaler or tiotropium dry powder capsule for inhalation by HandiHaler +&#xD;
      formoterol as dry powder capsule for inhalation by Aerolizer. Patients will be evaluated at 4&#xD;
      consecutive visits: baseline (enrollment), screening, treatment, and 24h after treatment.&#xD;
&#xD;
      For newly diagnosed and formerly diagnosed patients who are not on COPD medication, the&#xD;
      screening visit will be performed on the day of enrollment. For formerly diagnosed patients&#xD;
      receiving COPD treatment, the day of the screening visit will be based on the completion of a&#xD;
      run-in period, with the length determined by the specific medication. During the run-in&#xD;
      period, salbutamol (100 µg inhaler) will be prescribed as a rescue medication.&#xD;
&#xD;
      Spirometric measurements (FEV1, FVC) will be performed for a period of 24 h at 12 different&#xD;
      times: pre-treatment (15 min prior to the first dose) and post-treatment (30. min, 60 min [1&#xD;
      hr], 120 min [2 hr], 180 min [3 hr], 240 min [4 hr], 360 min [6 hr], 480 min [8 hr], 600 min&#xD;
      [10 hr], 720 min [12 hr], 840 min [14 hr],1440 min [24 hr].&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 2016</start_date>
  <completion_date type="Actual">August 2017</completion_date>
  <primary_completion_date type="Actual">August 2017</primary_completion_date>
  <phase>Phase 4</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mean max change (ml) from baseline in FEV1 over a period of 24 h.</measure>
    <time_frame>Pre-treatment (10 minutes prior to the first dose of randomized study medication) and post-treatment (Day 1)</time_frame>
    <description>Spirometric measurements will be made at 10 minutes prior to the first dose of randomized study medication and and post-treatment at 30. min, 60 min, 120 min, 180 min, 240 min, 360 min, 480 min, 600 min, 720 min, 840 min, 1440 min.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Mean % change from baseline in FEV1 over a period of 24 h.</measure>
    <time_frame>Pre-treatment (10 minutes prior to the first dose of randomized study medication) and post-treatment (Day 1)</time_frame>
    <description>Spirometric measurements will be made at 10 minutes prior to the first dose of randomized study medication and and post-treatment at 30. min, 60 min, 120 min, 180 min, 240 min, 360 min, 480 min, 600 min, 720 min, 840 min, 1440 min.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Mean max change (ml) from baseline in FVC over a period of 24 h.</measure>
    <time_frame>Pre-treatment (10 minutes prior to the first dose of randomized study medication) and post-treatment (Day 1)</time_frame>
    <description>Spirometric measurements will be made at 10 minutes prior to the first dose of randomized study medication and and post-treatment at 30. min, 60 min, 120 min, 180 min, 240 min, 360 min, 480 min, 600 min, 720 min, 840 min, 1440 min.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Mean % change from baseline in FVC over a period of 24 h.</measure>
    <time_frame>Pre-treatment (10 minutes prior to the first dose of randomized study medication) and post-treatment (Day 1)</time_frame>
    <description>Spirometric measurements will be made at 10 minutes prior to the first dose of randomized study medication and and post-treatment at 30. min, 60 min, 120 min, 180 min, 240 min, 360 min, 480 min, 600 min, 720 min, 840 min, 1440 min.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>FEV1 (AUC0-12) response</measure>
    <time_frame>From pre-treatment (10 minutes prior to the first dose of randomized study medication) to 12 hours post-treatment (Day 1)</time_frame>
    <description>Spirometric measurements will be made at 10 minutes prior to the first dose of randomized study medication and and post-treatment at 30. min, 60 min, 120 min, 180 min, 240 min, 360 min, 480 min, 600 min, 720 min, 840 min, 1440 min.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>FVC (AUC0-12) response</measure>
    <time_frame>From pre-treatment (10 minutes prior to the first dose of randomized study medication) to 12 hours post-treatment (Day 1)</time_frame>
    <description>Spirometric measurements will be made at 10 minutes prior to the first dose of randomized study medication and and post-treatment at 30. min, 60 min, 120 min, 180 min, 240 min, 360 min, 480 min, 600 min, 720 min, 840 min, 1440 min.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>FEV1 (AUC0-24) response</measure>
    <time_frame>From pre-treatment (10 minutes prior to the first dose of randomized study medication) to 24 hours post-treatment (Day 1)</time_frame>
    <description>Spirometric measurements will be made at 10 minutes prior to the first dose of randomized study medication and and post-treatment at 30. min, 60 min, 120 min, 180 min, 240 min, 360 min, 480 min, 600 min, 720 min, 840 min, 1440 min.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>FVC (AUC0-24) response</measure>
    <time_frame>From pre-treatment (10 minutes prior to the first dose of randomized study medication) to 24 hours post-treatment (Day 1)</time_frame>
    <description>Spirometric measurements will be made at 10 minutes prior to the first dose of randomized study medication and and post-treatment at 30. min, 60 min, 120 min, 180 min, 240 min, 360 min, 480 min, 600 min, 720 min, 840 min, 1440 min.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>FEV1 (AUC12-24) response</measure>
    <time_frame>From pre-treatment (10 minutes prior to the first dose of randomized study medication) to 24 hours post-treatment (Day 1)</time_frame>
    <description>Spirometric measurements will be made at 10 minutes prior to the first dose of randomized study medication and and post-treatment at 30. min, 60 min, 120 min, 180 min, 240 min, 360 min, 480 min, 600 min, 720 min, 840 min, 1440 min.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>FVC (AUC12-24) response</measure>
    <time_frame>From pre-treatment (10 minutes prior to the first dose of randomized study medication) to 24 hours post-treatment (Day 1)</time_frame>
    <description>Spirometric measurements will be made at 10 minutes prior to the first dose of randomized study medication and and post-treatment at 30. min, 60 min, 120 min, 180 min, 240 min, 360 min, 480 min, 600 min, 720 min, 840 min, 1440 min.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The time to onset of bronchodilator effect</measure>
    <time_frame>Pre-treatment (10 minutes prior to the first dose of randomized study medication) and post-treatment (Day 1)</time_frame>
    <description>Spirometric measurements will be made at 10 minutes prior to the first dose of randomized study medication and and post-treatment at 30. min, 60 min, 120 min, 180 min, 240 min, 360 min, 480 min, 600 min, 720 min, 840 min, 1440 min.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The time to onset of maximum effect</measure>
    <time_frame>Pre-treatment (10 minutes prior to the first dose of randomized study medication) and post-treatment (Day 1)</time_frame>
    <description>Spirometric measurements will be made at 10 minutes prior to the first dose of randomized study medication and and post-treatment at 30. min, 60 min, 120 min, 180 min, 240 min, 360 min, 480 min, 600 min, 720 min, 840 min, 1440 min.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of safety (Physical examination, numbers of adverse reactions and abnormal laboratory values related to treatment)</measure>
    <time_frame>Predose and up to 24 hours postdose</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">84</enrollment>
  <condition>COPD</condition>
  <arm_group>
    <arm_group_label>Tiotropium/Formoterol</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tiotropium/Formoterol 18/12 mcg Inhalation Powder (1 puff) once daily via Discair®</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Tiotropium</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Tiotropium 18 mcg Inhalation Powder (1 puff) once daily via Handihaler</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Tiotropium + Formoterol</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Tiotropium 18 mcg Inhalation Powder (1 puff) once daily via Handihaler + Formoterol 12 mcg Inhalation Powder (1 puff) twice daily via Aerolizer</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tiotropium/Formoterol</intervention_name>
    <description>Tiotropium/Formoterol 18/12 mcg Inhalation Powder (1 puff) once daily via Discair®</description>
    <arm_group_label>Tiotropium/Formoterol</arm_group_label>
    <other_name>TRITON 18/12 mcg Discair Inhalation Powder</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tiotropium</intervention_name>
    <description>Tiotropium 18 mcg Inhalation Powder (1 puff) once daily via Handihaler</description>
    <arm_group_label>Tiotropium</arm_group_label>
    <other_name>SPIRIVA 18 mcg Inhalation Powder</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Formoterol</intervention_name>
    <description>Formoterol 12 mcg Inhalation Powder (1 puff) twice daily via Aerolizer</description>
    <arm_group_label>Tiotropium + Formoterol</arm_group_label>
    <other_name>FORADIL 12 mcg Inhalation Powder</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tiotropium</intervention_name>
    <description>Tiotropium 18 mcg Inhalation Powder (1 puff) once daily via Handihaler</description>
    <arm_group_label>Tiotropium + Formoterol</arm_group_label>
    <other_name>SPIRIVA Inhalation Powder</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients aged ≥40 years with COPD diagnosis according to the current GOLD (The Global&#xD;
             Initiative for Chronic Obstructive Lung Disease) strategy.&#xD;
&#xD;
          -  Patients who have symptomatic stable moderate to severe COPD diagnosis with&#xD;
             post-bronchodilator FEV1/FVC ratio &lt;0.70, and FEV1 &lt;80% of predicted normal at&#xD;
             screening visit.&#xD;
&#xD;
          -  Current smokers or ex-smokers with a smoking history of at least 10 pack-years&#xD;
&#xD;
          -  Patients who have no exacerbation within last 4 weeks&#xD;
&#xD;
          -  Female patients with childbearing potential using effective birth control method&#xD;
&#xD;
          -  Patients who signed written informed consent prior to participation&#xD;
&#xD;
          -  Patients who accept to comply with the requirements of the protocol&#xD;
&#xD;
          -  Patients who have a capability of communicate with investigator&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of hypersensitivity to drugs contains anticholinergics, beta-adrenergic,&#xD;
             lactose&#xD;
&#xD;
          -  Diagnosis of asthma&#xD;
&#xD;
          -  Patients vaccinated with live attenuated vaccines within 2 weeks prior to screening&#xD;
             visit or during run-in period.&#xD;
&#xD;
          -  Patients who had COPD exacerbation or lower respiratory track infections that required&#xD;
             antibiotic, oral or parenteral corticosteroid treatment within 4 weeks prior to&#xD;
             screening visit or during run-in period.&#xD;
&#xD;
          -  Patients who have a history of myocardial infarction, hearth failure, acute ischemic&#xD;
             coroner disease or severe cardiac arrhythmia requiring treatment within least 6 weeks&#xD;
&#xD;
          -  Patients who have lung cancer&#xD;
&#xD;
          -  Patients with active tuberculosis&#xD;
&#xD;
          -  Patients who use oxygen therapy&#xD;
&#xD;
          -  Patients who have common interstitial lung diseases like cystic fibrosis,&#xD;
             bronchiolitis obliterans&#xD;
&#xD;
          -  Patients with serious liver or renal disease that leads to organ failure&#xD;
&#xD;
          -  Women who are pregnant or nursing&#xD;
&#xD;
          -  History of allergic rhinitis and atopy&#xD;
&#xD;
          -  Known symptomatic prostatic hypertrophy requiring drug therapy or operation&#xD;
&#xD;
          -  Patients with narrow-angle glaucoma requiring drug therapy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Pinar Yildiz, Professor Doctor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital-Turkey</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital</name>
      <address>
        <city>Istanbul</city>
        <zip>34020</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Turkey</country>
  </location_countries>
  <results_reference>
    <citation>Yildiz BP, Bayraktaroglu M, Gunen H. Bronchodilator efficacy of tiotropium/formoterol (18/12 microg once daily via a Discair inhaler), tiotropium alone (18 microg by Handihaler) or combined with formoterol (12 microg twice daily by Aerolizer) in adults with moderate-to-severe stable COPD. Curr Med Res Opin. 2019 Dec;35(12):2187-2196. doi: 10.1080/03007995.2019.1654722. Epub 2019 Sep 16.</citation>
    <PMID>31397184</PMID>
  </results_reference>
  <results_reference>
    <citation>Yildiz BP, Bayraktaroglu M, Gunen H. Reply: Re: Yildiz BP, Bayraktaroglu M, Gunen H. Bronchodilator efficacy of tiotropium/formoterol (18/12 mug once daily via a discair inhaler), tiotropium alone (18 mug by handihaler) or combined with formoterol (12 mug twice daily by aerolizer) in adults with moderate-to-severe stable COPD. Curr Med Res Opin. 2019;35(12):2187-2196. Curr Med Res Opin. 2020 Jun;36(6):1061-1062. doi: 10.1080/03007995.2020.1754187. Epub 2020 Apr 29. No abstract available.</citation>
    <PMID>32270722</PMID>
  </results_reference>
  <verification_date>December 2017</verification_date>
  <study_first_submitted>October 6, 2016</study_first_submitted>
  <study_first_submitted_qc>December 8, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 9, 2016</study_first_posted>
  <last_update_submitted>June 12, 2020</last_update_submitted>
  <last_update_submitted_qc>June 12, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 16, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>COPD</keyword>
  <keyword>Tiotropium</keyword>
  <keyword>Formoterol</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Formoterol Fumarate</mesh_term>
    <mesh_term>Tiotropium Bromide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02988869
org study id: NEU-22.12
nct id: NCT02988869
lead sponsor: 
has dmc: No
The overall objective is to asses the bronchodilator effect of once daily
      Tiotropium/Formoterol combination delivered via Discair® by comparing Tiotropium (q.d.)
      monotherapy delivered via Handihaler and tiotropium (q.d.) delivered via Handihaler +
      formoterol (b.i.d) delivered via Aerolizer free combination treatment in patients with stable
      moderate to severe COPD.

      Spirometric measurements (FEV1, FVC) will be performed for a period of 24 h at 12 different
      times: pre-treatment (15 min prior to the first dose) and post-treatment (30. min, 60 min [1
      hr], 120 min [2 hr], 180 min [3 hr], 240 min [4 hr], 360 min [6 hr], 480 min [8 hr], 600 min
      [10 hr], 720 min [12 hr], 840 min [14 hr],1440 min [24 hr].
The overall objective is to asses the bronchodilator effect of once daily
      Tiotropium/Formoterol combination delivered via Discair® by comparing Tiotropium (q.d.)
      monotherapy delivered via Handihaler and tiotropium (q.d.) delivered via Handihaler +
      formoterol (b.i.d) delivered via Aerolizer free combination treatment in patients with stable
      moderate to severe COPD.

      Patients will be randomly assigned to receive Tiotropium/Formoterol combination as dry powder
      for inhalation by Discair® (test inhaler, n = 29) or Tiotropium as dry powder capsule for
      inhalation by HandiHaler or tiotropium dry powder capsule for inhalation by HandiHaler +
      formoterol as dry powder capsule for inhalation by Aerolizer. Patients will be evaluated at 4
      consecutive visits: baseline (enrollment), screening, treatment, and 24h after treatment.

      For newly diagnosed and formerly diagnosed patients who are not on COPD medication, the
      screening visit will be performed on the day of enrollment. For formerly diagnosed patients
      receiving COPD treatment, the day of the screening visit will be based on the completion of a
      run-in period, with the length determined by the specific medication. During the run-in
      period, salbutamol (100 µg inhaler) will be prescribed as a rescue medication.

      Spirometric measurements (FEV1, FVC) will be performed for a period of 24 h at 12 different
      times: pre-treatment (15 min prior to the first dose) and post-treatment (30. min, 60 min [1
      hr], 120 min [2 hr], 180 min [3 hr], 240 min [4 hr], 360 min [6 hr], 480 min [8 hr], 600 min
      [10 hr], 720 min [12 hr], 840 min [14 hr],1440 min [24 hr].
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Mean max change (ml) from baseline in FEV1 over a period of 24 h.
time frame: Pre-treatment (10 minutes prior to the first dose of randomized study medication) and post-treatment (Day 1)
description: Spirometric measurements will be made at 10 minutes prior to the first dose of randomized study medication and and post-treatment at 30. min, 60 min, 120 min, 180 min, 240 min, 360 min, 480 min, 600 min, 720 min, 840 min, 1440 min.
measure: Mean % change from baseline in FEV1 over a period of 24 h.
time frame: Pre-treatment (10 minutes prior to the first dose of randomized study medication) and post-treatment (Day 1)
description: Spirometric measurements will be made at 10 minutes prior to the first dose of randomized study medication and and post-treatment at 30. min, 60 min, 120 min, 180 min, 240 min, 360 min, 480 min, 600 min, 720 min, 840 min, 1440 min.
measure: Mean max change (ml) from baseline in FVC over a period of 24 h.
time frame: Pre-treatment (10 minutes prior to the first dose of randomized study medication) and post-treatment (Day 1)
description: Spirometric measurements will be made at 10 minutes prior to the first dose of randomized study medication and and post-treatment at 30. min, 60 min, 120 min, 180 min, 240 min, 360 min, 480 min, 600 min, 720 min, 840 min, 1440 min.
measure: Mean % change from baseline in FVC over a period of 24 h.
time frame: Pre-treatment (10 minutes prior to the first dose of randomized study medication) and post-treatment (Day 1)
description: Spirometric measurements will be made at 10 minutes prior to the first dose of randomized study medication and and post-treatment at 30. min, 60 min, 120 min, 180 min, 240 min, 360 min, 480 min, 600 min, 720 min, 840 min, 1440 min.
measure: FEV1 (AUC0-12) response
time frame: From pre-treatment (10 minutes prior to the first dose of randomized study medication) to 12 hours post-treatment (Day 1)
description: Spirometric measurements will be made at 10 minutes prior to the first dose of randomized study medication and and post-treatment at 30. min, 60 min, 120 min, 180 min, 240 min, 360 min, 480 min, 600 min, 720 min, 840 min, 1440 min.
measure: FVC (AUC0-12) response
time frame: From pre-treatment (10 minutes prior to the first dose of randomized study medication) to 12 hours post-treatment (Day 1)
description: Spirometric measurements will be made at 10 minutes prior to the first dose of randomized study medication and and post-treatment at 30. min, 60 min, 120 min, 180 min, 240 min, 360 min, 480 min, 600 min, 720 min, 840 min, 1440 min.
measure: FEV1 (AUC0-24) response
time frame: From pre-treatment (10 minutes prior to the first dose of randomized study medication) to 24 hours post-treatment (Day 1)
description: Spirometric measurements will be made at 10 minutes prior to the first dose of randomized study medication and and post-treatment at 30. min, 60 min, 120 min, 180 min, 240 min, 360 min, 480 min, 600 min, 720 min, 840 min, 1440 min.
measure: FVC (AUC0-24) response
time frame: From pre-treatment (10 minutes prior to the first dose of randomized study medication) to 24 hours post-treatment (Day 1)
description: Spirometric measurements will be made at 10 minutes prior to the first dose of randomized study medication and and post-treatment at 30. min, 60 min, 120 min, 180 min, 240 min, 360 min, 480 min, 600 min, 720 min, 840 min, 1440 min.
measure: FEV1 (AUC12-24) response
time frame: From pre-treatment (10 minutes prior to the first dose of randomized study medication) to 24 hours post-treatment (Day 1)
description: Spirometric measurements will be made at 10 minutes prior to the first dose of randomized study medication and and post-treatment at 30. min, 60 min, 120 min, 180 min, 240 min, 360 min, 480 min, 600 min, 720 min, 840 min, 1440 min.
measure: FVC (AUC12-24) response
time frame: From pre-treatment (10 minutes prior to the first dose of randomized study medication) to 24 hours post-treatment (Day 1)
description: Spirometric measurements will be made at 10 minutes prior to the first dose of randomized study medication and and post-treatment at 30. min, 60 min, 120 min, 180 min, 240 min, 360 min, 480 min, 600 min, 720 min, 840 min, 1440 min.
measure: The time to onset of bronchodilator effect
time frame: Pre-treatment (10 minutes prior to the first dose of randomized study medication) and post-treatment (Day 1)
description: Spirometric measurements will be made at 10 minutes prior to the first dose of randomized study medication and and post-treatment at 30. min, 60 min, 120 min, 180 min, 240 min, 360 min, 480 min, 600 min, 720 min, 840 min, 1440 min.
measure: The time to onset of maximum effect
time frame: Pre-treatment (10 minutes prior to the first dose of randomized study medication) and post-treatment (Day 1)
description: Spirometric measurements will be made at 10 minutes prior to the first dose of randomized study medication and and post-treatment at 30. min, 60 min, 120 min, 180 min, 240 min, 360 min, 480 min, 600 min, 720 min, 840 min, 1440 min.
measure: Evaluation of safety (Physical examination, numbers of adverse reactions and abnormal laboratory values related to treatment)
time frame: Predose and up to 24 hours postdose
arm group label: Tiotropium/Formoterol
arm group type: Experimental
description: Tiotropium/Formoterol 18/12 mcg Inhalation Powder (1 puff) once daily via Discair®
arm group label: Tiotropium
arm group type: Active Comparator
description: Tiotropium 18 mcg Inhalation Powder (1 puff) once daily via Handihaler
arm group label: Tiotropium + Formoterol
arm group type: Active Comparator
description: Tiotropium 18 mcg Inhalation Powder (1 puff) once daily via Handihaler + Formoterol 12 mcg Inhalation Powder (1 puff) twice daily via Aerolizer
intervention type: Drug
intervention name: Tiotropium/Formoterol
description: Tiotropium/Formoterol 18/12 mcg Inhalation Powder (1 puff) once daily via Discair®
arm group label: Tiotropium/Formoterol
other name: TRITON 18/12 mcg Discair Inhalation Powder
intervention type: Drug
intervention name: Tiotropium
description: Tiotropium 18 mcg Inhalation Powder (1 puff) once daily via Handihaler
arm group label: Tiotropium
other name: SPIRIVA 18 mcg Inhalation Powder
intervention type: Drug
intervention name: Formoterol
description: Formoterol 12 mcg Inhalation Powder (1 puff) twice daily via Aerolizer
arm group label: Tiotropium + Formoterol
other name: FORADIL 12 mcg Inhalation Powder
intervention type: Drug
intervention name: Tiotropium
description: Tiotropium 18 mcg Inhalation Powder (1 puff) once daily via Handihaler
arm group label: Tiotropium + Formoterol
other name: SPIRIVA Inhalation Powder
criteria: 
gender: All
minimum age: 40 Years
maximum age: N/A
healthy volunteers: No
last name: Pinar Yildiz, Professor Doctor
role: Principal Investigator
affiliation: Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital-Turkey
facility: 
country: Turkey
citation: Yildiz BP, Bayraktaroglu M, Gunen H. Bronchodilator efficacy of tiotropium/formoterol (18/12 microg once daily via a Discair inhaler), tiotropium alone (18 microg by Handihaler) or combined with formoterol (12 microg twice daily by Aerolizer) in adults with moderate-to-severe stable COPD. Curr Med Res Opin. 2019 Dec;35(12):2187-2196. doi: 10.1080/03007995.2019.1654722. Epub 2019 Sep 16.
PMID: 31397184
citation: Yildiz BP, Bayraktaroglu M, Gunen H. Reply: Re: Yildiz BP, Bayraktaroglu M, Gunen H. Bronchodilator efficacy of tiotropium/formoterol (18/12 mug once daily via a discair inhaler), tiotropium alone (18 mug by handihaler) or combined with formoterol (12 mug twice daily by aerolizer) in adults with moderate-to-severe stable COPD. Curr Med Res Opin. 2019;35(12):2187-2196. Curr Med Res Opin. 2020 Jun;36(6):1061-1062. doi: 10.1080/03007995.2020.1754187. Epub 2020 Apr 29. No abstract available.
PMID: 32270722
responsible party type: Sponsor
mesh term: Formoterol Fumarate
mesh term: Tiotropium Bromide
sharing ipd: No