<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/NCT03837938</url>
  </required_header>
  <id_info>
    <org_study_id>LDP0114</org_study_id>
    <nct_id>NCT03837938</nct_id>
  </id_info>
  <brief_title>Clinical Trial of Efficacy and Safety of Levopront® 30 mg/5 ml in Patients With Dry Cough</brief_title>
  <acronym>LDP0114</acronym>
  <official_title>Multicenter Open-label Randomized Clinical Trial of the Efficacy and Safety of Levopront® Syrup 30 mg/5 ml in Comparison With Libexin® 100 mg Tablets in Patients With Dry Non-productive Cough Caused by Acute Upper Respiratory Infection</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dompé Farmaceutici S.p.A</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Dompé Farmaceutici S.p.A</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Primary objective:&#xD;
&#xD;
      To assess the efficacy of Levopront® in comparison with Libexin® based on daytime cough&#xD;
      resolution rate by Day 8.&#xD;
&#xD;
      The daytime cough symptoms resolution corresponds to 0 or 1 points on the &quot;Six-point daytime&#xD;
      and nighttime cough assessment scale&quot;.&#xD;
&#xD;
      Secondary objectives:&#xD;
&#xD;
      Treatment effect assessment in terms of the following efficacy and safety parameters:&#xD;
&#xD;
        -  To assess the efficacy of Levopront® in comparison with Libexin® based on nighttime&#xD;
           cough resolution rate by Day 8.&#xD;
&#xD;
        -  Daytime and nighttime cough symptoms resolution according to &quot;Six-point daytime and&#xD;
           nighttime cough assessment scale&quot; by Day 4.&#xD;
&#xD;
        -  Change in severity and frequency of daytime and nighttime cough according to &quot;Six-point&#xD;
           daytime and nighttime cough assessment scale&quot; on Day 4 and Day 8 from baseline on Day 1.&#xD;
&#xD;
        -  Cough intensity change according to the visual-analogue scale on Day 4 and Day 8 from&#xD;
           baseline on Day 1.&#xD;
&#xD;
        -  Change of FEV1 on Day 8 from baseline values on Day 1.&#xD;
&#xD;
        -  Rate of Adverse events (AE) and Serious Adverse Events (SAE) of the various severity&#xD;
           according to subjective complaints, laboratory test results, physical examination, vital&#xD;
           signs and spirometry&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a multicenter, open-label, randomized, clinical trial to assess the efficacy and&#xD;
      safety of Levopront® syrup 30 mg/5 ml in comparison with Libexin® 100 mg tablets in patients&#xD;
      suffering from dry non-productive cough caused by acute upper respiratory infection&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 9, 2016</start_date>
  <completion_date type="Actual">July 31, 2018</completion_date>
  <primary_completion_date type="Actual">March 6, 2018</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>It is an open-label clinical trial</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Daytime cough resolution rate by Day 8 - Levopront® vs Libexin®</measure>
    <time_frame>Daytime by Day 8</time_frame>
    <description>The daytime cough symptoms resolution corresponds to 0 or 1 points on the &quot;Six-point daytime and nighttime cough assessment scale&quot;.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Nighttime cough resolution rate by Day 8 - Levopront® vs Libexin®</measure>
    <time_frame>Nighttime by Day 8</time_frame>
    <description>Efficacy comparative assessment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Daytime and nighttime cough symptoms resolution daytime and nighttime cough assessment scale</measure>
    <time_frame>Daytime by Day 4</time_frame>
    <description>Daytime cough (scoring during &gt;08:00 up to 22:00 h) evaluated on a 6-point scale: 5 = no cough during the day to 0 = distressing coughs most of the day.&#xD;
Night-time cough (scoring during &gt;22:00 up to 08:00 h) evaluated on a 6-point scale: 5 = no cough during the night to 0 = distressing coughs preventing any sleep.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in severity and frequency of daytime and nighttime cough according to &quot;Six-point daytime and nighttime cough assessment scale&quot;</measure>
    <time_frame>Day 4 and Day 8</time_frame>
    <description>Daytime cough (scoring during &gt;08:00 up to 22:00 h) evaluated on a 6-point scale: 5 = no cough during the day to 0 = distressing coughs most of the day.&#xD;
Night-time cough (scoring during &gt;22:00 up to 08:00 h) evaluated on a 6-point scale: 5 = no cough during the night to 0 = distressing coughs preventing any sleep.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cough intensity change according to the visual-analogue scale.</measure>
    <time_frame>Day 4 and Day 8</time_frame>
    <description>A 100 mm scale between 'no cough' (0) and 'the worst cough severity' (100)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of FEV1 on Day 8 from baseline values.</measure>
    <time_frame>Day 8</time_frame>
    <description>Forced expiratory volume in 1 second.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">184</enrollment>
  <condition>Cough</condition>
  <arm_group>
    <arm_group_label>Levopront® syrup 30 mg/5 ml</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Levopront® (levodropropizine) syrup 30 mg/5 ml 10 ml t.i.d. for 7 days The study drugs will be taken t.i.d. (with the interval of not less than 6 hours, between meals) during 7 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Libexin® 100 mg tablets</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Libexin® (prenoxdiazine) 100 mg tablets&#xD;
1 tablet t.i.d. for 7 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Levopront® syrup 30 mg/5 ml</intervention_name>
    <description>The first study drug administration will be performed at the clinical site on the day of randomization; the last study drug administration will be performed in the evening before Day 8 (±1).</description>
    <arm_group_label>Levopront® syrup 30 mg/5 ml</arm_group_label>
    <other_name>levodropropizine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Libexin®</intervention_name>
    <description>The first study drug administration will be performed at the clinical site on the day of randomization; the last study drug administration will be performed in the evening before Day 8 (±1).</description>
    <arm_group_label>Libexin® 100 mg tablets</arm_group_label>
    <other_name>prenoxdiazine</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Subjects should meet the following inclusion criteria to be included into this clinical&#xD;
        trial:&#xD;
&#xD;
          1. Signed Informed Consent Form&#xD;
&#xD;
          2. Male or female aged from 18 to 65 (inclusive)&#xD;
&#xD;
          3. Dry non-productive cough as a symptom of acute upper respiratory infection (IDC codes&#xD;
             J00-J06)&#xD;
&#xD;
          4. Daytime cough symptom score ≥ 3 points according to the &quot;Six-point daytime and&#xD;
             nighttime cough assessment scale&quot;&#xD;
&#xD;
          5. Pre-bronchodilator FEV1 ≥ 70% of the predicted values, post-bronchodilator FEV1&#xD;
             increase of ≤ 12% or ≤ 200 ml compared to the baseline, FEV1/FVC (Tiffeneau index) ≥&#xD;
             0.7&#xD;
&#xD;
          6. Patient's consent to follow the protocol procedures, including the completion of the&#xD;
             patient's diary&#xD;
&#xD;
          7. Patient's consent to use the adequate contraception methods throughout the study&#xD;
             period. The adequate birth control methods are as follows:&#xD;
&#xD;
               -  Oral or transdermal contraceptives&#xD;
&#xD;
               -  Condoms or diaphragms (barrier method) with spermicide&#xD;
&#xD;
               -  Intrauterine contraceptive devices&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Subjects with any of the following conditions will be excluded from the study:&#xD;
&#xD;
          1. Hypersensitivity or individual contraindications to Levodropropizine, Prenoxdiazine or&#xD;
             additives of the study drug&#xD;
&#xD;
          2. Hereditary fructose intolerance, glucose-lactose malabsorption, lactase deficiency,&#xD;
             sucrose-isomaltose deficiency&#xD;
&#xD;
          3. Tuberculosis, bronchial asthma, malignant tumors of lungs or bronchi, COPD, severe&#xD;
             respiratory failure (cyanosis, need for respiratory support) or other lung pathology&#xD;
             at screening or in history&#xD;
&#xD;
          4. Inhalation anesthesia within 3 months before screening&#xD;
&#xD;
          5. Smoking history of more than 10 pack-years&#xD;
&#xD;
          6. Previous use of cough medicines, ACE inhibitors or amiodarone within 30 days before&#xD;
             screening&#xD;
&#xD;
          7. Contraindications or inability to perform spirometry&#xD;
&#xD;
          8. Necessity (in the Investigator's opinion) of prescribing mucolytic agents,&#xD;
             expectorants, antibiotics or other medications prohibited by the protocol during the&#xD;
             study&#xD;
&#xD;
          9. Excessive mucous excretion which (in the Investigator's opinion) could be a&#xD;
             contraindication to prescribing anti-cough medicines; decreased mucociliary function&#xD;
             (Kartagener's syndrome, ciliary dyskinesia)&#xD;
&#xD;
         10. Malignant tumors in the past 5 years (except for the basal cell carcinoma)&#xD;
&#xD;
         11. Serious cardiovascular disease at the moment or within 12 months prior to screening,&#xD;
             including: Chronic heart failure class III or IV (according to the classification of&#xD;
             the New York Heart Association), severe arrhythmias requiring treatment with&#xD;
             antiarrhythmic drugs class Ia, Ib, Ic or III, unstable angina, myocardial infarction,&#xD;
             heart surgery and coronary arteries, serious valvular heart disease, transient&#xD;
             ischemic attack or stroke, uncontrolled hypertension with systolic blood pressure &gt;&#xD;
             180 mmHg and diastolic blood pressure &gt; 110 mmHg, pulmonary embolism or deep vein&#xD;
             thrombosis&#xD;
&#xD;
         12. Gastric or duodenal ulcers, gastroesophageal reflux disease within a period of 12&#xD;
             months before screening&#xD;
&#xD;
         13. Systemic autoimmune disorders and connective tissue diseases that require (currently&#xD;
             or previously) administration of systemic glucocorticosteroids, cytostatic medications&#xD;
             or penicillamine&#xD;
&#xD;
         14. Signs of intensive non-controlled concurrent disease, including disorders of the&#xD;
             nervous system, endocrine system, kidneys, liver or gastrointestinal tract, which (in&#xD;
             the Investigator's opinion) could prevent the patient's participation in the study&#xD;
&#xD;
         15. History of alcohol or drug abuse at screening or in the past, which results in the&#xD;
             inability of the patient to participate in the study at the Investigator's discretion&#xD;
&#xD;
         16. Taking part in another clinical trial or use of study drug within 30 days before&#xD;
             screening&#xD;
&#xD;
         17. Pregnant or breast-feeding women or women planning pregnancy during the clinical&#xD;
             trial; women of childbearing potential (including not sterilized operatively and in&#xD;
             postmenopausal period of less than 2 years), not using appropriate methods of&#xD;
             contraception&#xD;
&#xD;
         18. Inability to read or write; unwillingness to understand and follow the procedures of&#xD;
             the study protocol; violation of the drug administration regimen or procedure&#xD;
             execution that, at the discretion of the Investigator, can impact he results of the&#xD;
             study or safety of the patient and interfere his further participation in the study;&#xD;
             any other concomitant medical or serious mental conditions that make the patient&#xD;
             unsuitable for participation in the clinical study, limit the validity of receiving an&#xD;
             informed consent or may affect the patient's ability to participate in the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mauro P Ferrari, Pharm D</last_name>
    <role>Study Director</role>
    <affiliation>Dompé SpA Milan</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>State Public Healthcare Institution of Moscow &quot;City Clinical Hospital # 71 of Moscow Healthcare Department&quot;</name>
      <address>
        <city>Moscow</city>
        <zip>121374</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Laboratory of Pulmonology, State Budgetary Educational Institution of Higher Professional Education &quot;Moscow State Medical-Stomatological University n.a. A.I. Evdokimov&quot; under Ministry of Health of the Russian Federation (Clinical base of state budget</name>
      <address>
        <city>Moscow</city>
        <zip>127473</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>State Budgetary Educational Institution of Higher Professional Education &quot;Ryazan' State Medical University n.a. academician I.P. Pavlov&quot; under Ministry of Health of the Russian Federation</name>
      <address>
        <city>Ryazan</city>
        <zip>390026</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>&quot;Institute of Medical Research&quot; LLC</name>
      <address>
        <city>Saint-Petersburg</city>
        <zip>196084</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint-Petersburg State Healthcare Institution &quot;Nikolaevskaya Hospital&quot;</name>
      <address>
        <city>Saint-Petersburg</city>
        <zip>198510</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>State Healthcare Institution &quot;Regional Clinical Hospital&quot;</name>
      <address>
        <city>Saratov</city>
        <zip>410053</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>LLC Treatment-and-prophylactic institution on the &quot;Smolensk clinic&quot;</name>
      <address>
        <city>Smolensk</city>
        <zip>214016</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>State Autonomous Healthcare Institution of Yaroslavl Region &quot;Clinical Hospital of Emergency care n.a. N.V. Solovyev&quot;</name>
      <address>
        <city>Yaroslavl</city>
        <zip>150003</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Russian Federation</country>
  </location_countries>
  <verification_date>May 2018</verification_date>
  <study_first_submitted>January 28, 2019</study_first_submitted>
  <study_first_submitted_qc>February 11, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 12, 2019</study_first_posted>
  <last_update_submitted>February 11, 2019</last_update_submitted>
  <last_update_submitted_qc>February 11, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 12, 2019</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>Cough</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dipropizine</mesh_term>
  </intervention_browse>
  <pending_results>
    <submitted>October 10, 2022</submitted>
    <returned>August 25, 2023</returned>
  </pending_results>
  <!-- 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/NCT03837938
org study id: LDP0114
nct id: NCT03837938
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Primary objective:

      To assess the efficacy of Levopront® in comparison with Libexin® based on daytime cough
      resolution rate by Day 8.

      The daytime cough symptoms resolution corresponds to 0 or 1 points on the "Six-point daytime
      and nighttime cough assessment scale".

      Secondary objectives:

      Treatment effect assessment in terms of the following efficacy and safety parameters:

        -  To assess the efficacy of Levopront® in comparison with Libexin® based on nighttime
           cough resolution rate by Day 8.

        -  Daytime and nighttime cough symptoms resolution according to "Six-point daytime and
           nighttime cough assessment scale" by Day 4.

        -  Change in severity and frequency of daytime and nighttime cough according to "Six-point
           daytime and nighttime cough assessment scale" on Day 4 and Day 8 from baseline on Day 1.

        -  Cough intensity change according to the visual-analogue scale on Day 4 and Day 8 from
           baseline on Day 1.

        -  Change of FEV1 on Day 8 from baseline values on Day 1.

        -  Rate of Adverse events (AE) and Serious Adverse Events (SAE) of the various severity
           according to subjective complaints, laboratory test results, physical examination, vital
           signs and spirometry
This is a multicenter, open-label, randomized, clinical trial to assess the efficacy and
      safety of Levopront® syrup 30 mg/5 ml in comparison with Libexin® 100 mg tablets in patients
      suffering from dry non-productive cough caused by acute upper respiratory infection
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
masking description: It is an open-label clinical trial
measure: Daytime cough resolution rate by Day 8 - Levopront® vs Libexin®
time frame: Daytime by Day 8
description: The daytime cough symptoms resolution corresponds to 0 or 1 points on the "Six-point daytime and nighttime cough assessment scale".
measure: Nighttime cough resolution rate by Day 8 - Levopront® vs Libexin®
time frame: Nighttime by Day 8
description: Efficacy comparative assessment
measure: Daytime and nighttime cough symptoms resolution daytime and nighttime cough assessment scale
time frame: Daytime by Day 4
description: Daytime cough (scoring during >08:00 up to 22:00 h) evaluated on a 6-point scale: 5 = no cough during the day to 0 = distressing coughs most of the day.
Night-time cough (scoring during >22:00 up to 08:00 h) evaluated on a 6-point scale: 5 = no cough during the night to 0 = distressing coughs preventing any sleep.
measure: Change in severity and frequency of daytime and nighttime cough according to "Six-point daytime and nighttime cough assessment scale"
time frame: Day 4 and Day 8
description: Daytime cough (scoring during >08:00 up to 22:00 h) evaluated on a 6-point scale: 5 = no cough during the day to 0 = distressing coughs most of the day.
Night-time cough (scoring during >22:00 up to 08:00 h) evaluated on a 6-point scale: 5 = no cough during the night to 0 = distressing coughs preventing any sleep.
measure: Cough intensity change according to the visual-analogue scale.
time frame: Day 4 and Day 8
description: A 100 mm scale between 'no cough' (0) and 'the worst cough severity' (100)
measure: Change of FEV1 on Day 8 from baseline values.
time frame: Day 8
description: Forced expiratory volume in 1 second.
arm group label: Levopront® syrup 30 mg/5 ml
arm group type: Experimental
description: Levopront® (levodropropizine) syrup 30 mg/5 ml 10 ml t.i.d. for 7 days The study drugs will be taken t.i.d. (with the interval of not less than 6 hours, between meals) during 7 days.
arm group label: Libexin® 100 mg tablets
arm group type: Active Comparator
description: Libexin® (prenoxdiazine) 100 mg tablets
1 tablet t.i.d. for 7 days.
intervention type: Drug
intervention name: Levopront® syrup 30 mg/5 ml
description: The first study drug administration will be performed at the clinical site on the day of randomization; the last study drug administration will be performed in the evening before Day 8 (±1).
arm group label: Levopront® syrup 30 mg/5 ml
other name: levodropropizine
intervention type: Drug
intervention name: Libexin®
description: The first study drug administration will be performed at the clinical site on the day of randomization; the last study drug administration will be performed in the evening before Day 8 (±1).
arm group label: Libexin® 100 mg tablets
other name: prenoxdiazine
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Mauro P Ferrari, Pharm D
role: Study Director
affiliation: Dompé SpA Milan
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Russian Federation
responsible party type: Sponsor
mesh term: Cough
mesh term: Dipropizine
submitted: October 10, 2022
returned: August 25, 2023