xml: <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/NCT06037408</url>
    </required_header>
    <id_info>
      <org_study_id>Pro00072822</org_study_id>
      <nct_id>NCT06037408</nct_id>
    </id_info>
    <brief_title>The Effect of N115 on Coughing in IDF Patients</brief_title>
    <official_title>The Effect of Sodium Pyruvate Nasal Spray on Coughing in Patients With Idiopathic Pulmonary Fibrosis</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Cellular Sciences, inc.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Family First Medical Research Center</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Cellular Sciences, inc.</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The purpose of this clinical trial is to administer a sodium pyruvate nasal spray that&#xD;
        eliminates nasal oxidative stresses, caused by oxygen radicals, and demonstrate the efficacy&#xD;
        of sodium pyruvate to reduce coughing and increase lung functions in patients with idiopathic&#xD;
        pulmonary fibrosis. This will be a 21-day double-blinded randomized placebo-controlled trial&#xD;
        designed to determine if patients with idiopathic pulmonary fibrosis treated with 20mM sodium&#xD;
        pyruvate in 0.9% sodium chloride nasal spray solution will have reduced chronic coughing, as&#xD;
        well as increased lung function (FEV1, FVC endpoints of 12% or more within the first week)&#xD;
        and improved FEV1/FVC ratios.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Idiopathic pulmonary fibrosis (IPF) belongs to a group of conditions called interstitial lung&#xD;
        diseases (also known as ILD), which describes lung diseases that involve inflammation or&#xD;
        scarring in the lung. IPF is a chronic progressive lung disorder associated with excessive&#xD;
        tissue remodeling, scarring, and fibrosis, which makes the lungs unable to effectively&#xD;
        transport oxygen into the bloodstream resulting in decreased lung function and increased&#xD;
        nasal inflammation with increased mucus and coughing and poor quality of life. IPF usually&#xD;
        affects people between the ages of 30 and 70. The most common signs and symptoms of IPF are&#xD;
        shortness of breath and persistent dry, hacking cough. Many affected individuals also&#xD;
        experience a loss of appetite and gradual weight loss. Most affected individuals survive 3 to&#xD;
        5 years after their diagnosis. However, the course of the disease is highly variable; some&#xD;
        affected people become seriously ill within a few months, while others may live with the&#xD;
        disease for a decade or longer. In most cases, IPF is sporadic and results from environmental&#xD;
        damage to the lungs and not genetic factors. However, a small percentage of people have&#xD;
        genetic risk factors resulting in familial pulmonary fibrosis.&#xD;
  &#xD;
        Sodium pyruvate is a natural antioxidant of the human body and as an antioxidant it has been&#xD;
        shown to significantly reduce inflammatory agents throughout the human body, including the&#xD;
        lungs and nasal passages, allowing nasal nitric oxide to reach the lungs to increase&#xD;
        bronchodilation (11-27). In addition to 8 human clinical studies conducted on the effect of&#xD;
        inhaled sodium pyruvate on the lungs, 7 human nasal inhalation clinical studies were&#xD;
        conducted using a sodium pyruvate nasal spray which showed decreased nasal inflammation, a&#xD;
        reduction in inflammatory cytokines, and when measured, demonstrated an increase in lung&#xD;
        functions, a decrease in coughing, including in patients with pulmonary fibrosis and IPF.&#xD;
        Cellular Sciences received Orphan Drug designations for Cystic Fibrosis and Interstitial lung&#xD;
        Disease.&#xD;
  &#xD;
        A previous open label phase 2, 21-day, sub-chronic clinical trial was conducted that included&#xD;
        15 patients with pulmonary fibrosis (9 with pulmonary fibrosis and chronic obstructive&#xD;
        pulmonary disease (COPD) and 6 with idiopathic pulmonary fibrosis without COPD) that remained&#xD;
        on their normal medications but were also administered a 20 mM (2.2 mg/mL) sodium pyruvate&#xD;
        nasal spray 3 times per day for 22 days. The data from this study showed that coughing&#xD;
        episodes per 24 hours, and especially at night, were significantly reduced in all 15 patients&#xD;
        on day 8 by 30% (p = 0.007) and continued to decrease on day 14 by 55% (p = 0.0001) and on&#xD;
        the 22 day of the trial, coughing decreased by 59% (p = 0.0001). This correlated with a&#xD;
        significant (p = 0.010) improvement in nasal irritation/erythema with most patients being&#xD;
        free of irritation by day 22 (p &lt; 0.001); and a significant (p = 0.010) increase in the group&#xD;
        average expelled NO by day 8 (23). A significant (p = 0.010) improvement in lung function&#xD;
        (breathing) was observed in all patients with IPF without COPD (n6) by day 1, increasing to p&#xD;
        = 0.0005 by day 22 compared to their baseline therapies, determined by changes in FVC, FEV1,&#xD;
        PEF, and FEV1/FVC ratios. The improved FEV1/FVC ratio from 52% to 86% was clinically&#xD;
        significant and indicated that current therapies in use are inadequate to treat patient with&#xD;
        IPF.&#xD;
  &#xD;
        The current study will expand on these findings by conducting a phase 3, double-blind&#xD;
        placebo-controlled clinical trial to determine the effectiveness of 20mM sodium pyruvate&#xD;
        nasal spray to decrease coughing in idiopathic pulmonary fibrosis patients. Individuals with&#xD;
        a clinical diagnosis of idiopathic pulmonary fibrosis (as defined by the WHO and the Thoracic&#xD;
        Society) will be solicited for participation in this phase 3 trial. Patients will have their&#xD;
        degree of nasal inflammation and erythema, nasal cellular morphology, SaO2, and FEV1, FVC&#xD;
        levels and blood workup recorded (baseline). Women of child-bearing age will provide a urine&#xD;
        sample. The subjects will fill out a quality-of-life questionnaire (chronic respiratory&#xD;
        disease questionnaire (CRDQ), and they will be given a data logbook in which they will record&#xD;
        the number of coughs they experience each 24 hour period, for 7 days. The coughing data will&#xD;
        be entered into the patients' logbooks and will be separated into &quot;total coughs per 24&#xD;
        hours,&quot; and &quot;night-time coughs.&quot; These data will be used to establish a baseline for&#xD;
        coughing. After 7 days, patients will return to the clinic to begin the 21 day study where&#xD;
        they will be given drug or placebo in a double-blinded fashion and will record their coughs&#xD;
        daily in a logbook. Patients will return to the clinic on days 8, 15 and 22 for further&#xD;
        evaluation.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">August 15, 2023</start_date>
    <completion_date type="Anticipated">August 31, 2024</completion_date>
    <primary_completion_date type="Anticipated">August 15, 2024</primary_completion_date>
    <phase>Phase 3</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Triple (Participant, Care Provider, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Coughing</measure>
      <time_frame>21 days</time_frame>
      <description>Reduce coughing episodes in IPF patients by 25%. (An episode is defined as 5 or more coughs per hour.)</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>FEV1/FVC ratios</measure>
      <time_frame>21 days</time_frame>
      <description>Increase lung function (FEV1, FVC endpoints of 12% or more) and improve FEV1/FVC ratios.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">50</enrollment>
    <condition>Idiopathic Pulmonary Fibrosis</condition>
    <arm_group>
      <arm_group_label>20mM sodium pyruvate nasal spray treatment</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>Saline placebo control</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>20mM sodium pyruvate nasal spray</intervention_name>
      <description>The product is a 20 mM (0.2%, 2.2 mg/mL) sodium pyruvate nasal spray in 0.9% sodium chloride with 0.02% benzalkonium chloride preservative, pH 7.2 (N115). Subjects will self-administer 3 squirts per nostril of the nasal spray, 3 times daily; upon wakening, noon/midday, and before bedtime.</description>
      <arm_group_label>20mM sodium pyruvate nasal spray treatment</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Saline Placebo control nasal spray</intervention_name>
      <description>The placebo is 0.9% sodium chloride with 0.02% benzalkonium chloride preservative, pH 7.2. Subjects will self-administer 3 squirts per nostril of the nasal spray, 3 times daily; upon wakening, noon/midday, and before bedtime.</description>
      <arm_group_label>Saline placebo control</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Individuals with a clinical diagnosis of idiopathic pulmonary fibrosis in accordance&#xD;
               with the most recent collaborative guidelines from the American Thoracic Society, the&#xD;
               European Respiratory Society, the Japanese Respiratory Society, and the Latin American&#xD;
               Thoracic Association including HRCT scan and/or lung biopsy consistent with unusual&#xD;
               interstitial pneumonia (UIP), especially honeycombing, without identifiable cause&#xD;
               related to other ILD such as drug toxicity, occupational or environmental exposure or&#xD;
               connective tissue disease.&#xD;
  &#xD;
            -  condition-related cough.&#xD;
  &#xD;
            -  Mild to moderate FEV1 and FVC at 50% or greater of standard&#xD;
  &#xD;
            -  Individuals who agree to abstain from sexual intercourse, or agree to use condoms or&#xD;
               vaginal diaphragms or other devices designed to prevent contraception, during the&#xD;
               entire course of the study.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Pulmonary disease other than idiopathic pulmonary fibrosis.&#xD;
  &#xD;
            -  Respiratory infections in the last 2 weeks.&#xD;
  &#xD;
            -  Clinically significant cardiac disease including uncontrolled congestive heart failure&#xD;
               and unstable angina.&#xD;
  &#xD;
            -  Pregnancy (urine pregnancy test will be performed prior to enrollment).&#xD;
  &#xD;
            -  Females of childbearing potential age not on adequate contraception or lactating&#xD;
               females.&#xD;
  &#xD;
            -  Subjects less than 18 years of age.&#xD;
  &#xD;
            -  Hospitalization within last 6 months due to acute exacerbation of airway disease.&#xD;
  &#xD;
            -  Subjects with a clinically significant abnormal chest X-ray within past 12 months.&#xD;
  &#xD;
            -  Medication changes within 1 month of study entry except for antiviral, antibiotic, or&#xD;
               antimicrobial medications as well as corticosteroids, antihistamines, or&#xD;
               anti-inflammatory medications.&#xD;
  &#xD;
            -  Subjects who have participated in another drug treatment study within the last month.&#xD;
  &#xD;
            -  Subjects with a current history of alcohol or recreational drug abuse.&#xD;
  &#xD;
            -  Subjects who have taken dietary supplements containing pyruvate within 24 hours prior&#xD;
               to the screening visit.&#xD;
  &#xD;
            -  Subjects with metabolic diseases (diabetes, hypoglycemia, etc.).&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>40 Years</minimum_age>
      <maximum_age>80 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Manuel M Lam, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Family First Medical Research Center</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Alain Martin, PhD</last_name>
      <phone>(908) 237-5161</phone>
      <email>al.martin.hq@emphycorp.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Family First Medical Research Center</name>
        <address>
          <city>Hialeah Gardens</city>
          <state>Florida</state>
          <zip>33016</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Manuel Lam, MD</last_name>
        <phone>786-665-9374</phone>
        <email>mmlam.pi.ff@gmail.com</email>
      </contact>
      <investigator>
        <last_name>Manuel Lam, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <reference>
      <citation>Wells AU. The revised ATS/ERS/JRS/ALAT diagnostic criteria for idiopathic pulmonary fibrosis (IPF)--practical implications. Respir Res. 2013;14 Suppl 1(Suppl 1):S2. doi: 10.1186/1465-9921-14-S1-S2. Epub 2013 Apr 16.</citation>
      <PMID>23734820</PMID>
    </reference>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>September 7, 2023</study_first_submitted>
    <study_first_submitted_qc>September 7, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 14, 2023</study_first_posted>
    <last_update_submitted>September 7, 2023</last_update_submitted>
    <last_update_submitted_qc>September 7, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 14, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Pulmonary Fibrosis</mesh_term>
      <mesh_term>Idiopathic Pulmonary Fibrosis</mesh_term>
      <mesh_term>Fibrosis</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06037408
  org study id: Pro00072822
  nct id: NCT06037408
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  The purpose of this clinical trial is to administer a sodium pyruvate nasal spray that
        eliminates nasal oxidative stresses, caused by oxygen radicals, and demonstrate the efficacy
        of sodium pyruvate to reduce coughing and increase lung functions in patients with idiopathic
        pulmonary fibrosis. This will be a 21-day double-blinded randomized placebo-controlled trial
        designed to determine if patients with idiopathic pulmonary fibrosis treated with 20mM sodium
        pyruvate in 0.9% sodium chloride nasal spray solution will have reduced chronic coughing, as
        well as increased lung function (FEV1, FVC endpoints of 12% or more within the first week)
        and improved FEV1/FVC ratios.
  Idiopathic pulmonary fibrosis (IPF) belongs to a group of conditions called interstitial lung
        diseases (also known as ILD), which describes lung diseases that involve inflammation or
        scarring in the lung. IPF is a chronic progressive lung disorder associated with excessive
        tissue remodeling, scarring, and fibrosis, which makes the lungs unable to effectively
        transport oxygen into the bloodstream resulting in decreased lung function and increased
        nasal inflammation with increased mucus and coughing and poor quality of life. IPF usually
        affects people between the ages of 30 and 70. The most common signs and symptoms of IPF are
        shortness of breath and persistent dry, hacking cough. Many affected individuals also
        experience a loss of appetite and gradual weight loss. Most affected individuals survive 3 to
        5 years after their diagnosis. However, the course of the disease is highly variable; some
        affected people become seriously ill within a few months, while others may live with the
        disease for a decade or longer. In most cases, IPF is sporadic and results from environmental
        damage to the lungs and not genetic factors. However, a small percentage of people have
        genetic risk factors resulting in familial pulmonary fibrosis.
  
        Sodium pyruvate is a natural antioxidant of the human body and as an antioxidant it has been
        shown to significantly reduce inflammatory agents throughout the human body, including the
        lungs and nasal passages, allowing nasal nitric oxide to reach the lungs to increase
        bronchodilation (11-27). In addition to 8 human clinical studies conducted on the effect of
        inhaled sodium pyruvate on the lungs, 7 human nasal inhalation clinical studies were
        conducted using a sodium pyruvate nasal spray which showed decreased nasal inflammation, a
        reduction in inflammatory cytokines, and when measured, demonstrated an increase in lung
        functions, a decrease in coughing, including in patients with pulmonary fibrosis and IPF.
        Cellular Sciences received Orphan Drug designations for Cystic Fibrosis and Interstitial lung
        Disease.
  
        A previous open label phase 2, 21-day, sub-chronic clinical trial was conducted that included
        15 patients with pulmonary fibrosis (9 with pulmonary fibrosis and chronic obstructive
        pulmonary disease (COPD) and 6 with idiopathic pulmonary fibrosis without COPD) that remained
        on their normal medications but were also administered a 20 mM (2.2 mg/mL) sodium pyruvate
        nasal spray 3 times per day for 22 days. The data from this study showed that coughing
        episodes per 24 hours, and especially at night, were significantly reduced in all 15 patients
        on day 8 by 30% (p = 0.007) and continued to decrease on day 14 by 55% (p = 0.0001) and on
        the 22 day of the trial, coughing decreased by 59% (p = 0.0001). This correlated with a
        significant (p = 0.010) improvement in nasal irritation/erythema with most patients being
        free of irritation by day 22 (p < 0.001); and a significant (p = 0.010) increase in the group
        average expelled NO by day 8 (23). A significant (p = 0.010) improvement in lung function
        (breathing) was observed in all patients with IPF without COPD (n6) by day 1, increasing to p
        = 0.0005 by day 22 compared to their baseline therapies, determined by changes in FVC, FEV1,
        PEF, and FEV1/FVC ratios. The improved FEV1/FVC ratio from 52% to 86% was clinically
        significant and indicated that current therapies in use are inadequate to treat patient with
        IPF.
  
        The current study will expand on these findings by conducting a phase 3, double-blind
        placebo-controlled clinical trial to determine the effectiveness of 20mM sodium pyruvate
        nasal spray to decrease coughing in idiopathic pulmonary fibrosis patients. Individuals with
        a clinical diagnosis of idiopathic pulmonary fibrosis (as defined by the WHO and the Thoracic
        Society) will be solicited for participation in this phase 3 trial. Patients will have their
        degree of nasal inflammation and erythema, nasal cellular morphology, SaO2, and FEV1, FVC
        levels and blood workup recorded (baseline). Women of child-bearing age will provide a urine
        sample. The subjects will fill out a quality-of-life questionnaire (chronic respiratory
        disease questionnaire (CRDQ), and they will be given a data logbook in which they will record
        the number of coughs they experience each 24 hour period, for 7 days. The coughing data will
        be entered into the patients' logbooks and will be separated into "total coughs per 24
        hours," and "night-time coughs." These data will be used to establish a baseline for
        coughing. After 7 days, patients will return to the clinic to begin the 21 day study where
        they will be given drug or placebo in a double-blinded fashion and will record their coughs
        daily in a logbook. Patients will return to the clinic on days 8, 15 and 22 for further
        evaluation.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Triple (Participant, Care Provider, Outcomes Assessor)
  measure: Coughing
  time frame: 21 days
  description: Reduce coughing episodes in IPF patients by 25%. (An episode is defined as 5 or more coughs per hour.)
  measure: FEV1/FVC ratios
  time frame: 21 days
  description: Increase lung function (FEV1, FVC endpoints of 12% or more) and improve FEV1/FVC ratios.
  arm group label: 20mM sodium pyruvate nasal spray treatment
  arm group type: Experimental
  arm group label: Saline placebo control
  arm group type: Placebo Comparator
  intervention type: Drug
  intervention name: 20mM sodium pyruvate nasal spray
  description: The product is a 20 mM (0.2%, 2.2 mg/mL) sodium pyruvate nasal spray in 0.9% sodium chloride with 0.02% benzalkonium chloride preservative, pH 7.2 (N115). Subjects will self-administer 3 squirts per nostril of the nasal spray, 3 times daily; upon wakening, noon/midday, and before bedtime.
  arm group label: 20mM sodium pyruvate nasal spray treatment
  intervention type: Other
  intervention name: Saline Placebo control nasal spray
  description: The placebo is 0.9% sodium chloride with 0.02% benzalkonium chloride preservative, pH 7.2. Subjects will self-administer 3 squirts per nostril of the nasal spray, 3 times daily; upon wakening, noon/midday, and before bedtime.
  arm group label: Saline placebo control
  criteria: 
  gender: All
  minimum age: 40 Years
  maximum age: 80 Years
  healthy volunteers: No
  last name: Manuel M Lam, MD
  role: Principal Investigator
  affiliation: Family First Medical Research Center
  last name: Alain Martin, PhD
  phone: (908) 237-5161
  email: al.martin.hq@emphycorp.com
  facility: 
  status: Recruiting
  contact: 
  investigator: 
  country: United States
  citation: Wells AU. The revised ATS/ERS/JRS/ALAT diagnostic criteria for idiopathic pulmonary fibrosis (IPF)--practical implications. Respir Res. 2013;14 Suppl 1(Suppl 1):S2. doi: 10.1186/1465-9921-14-S1-S2. Epub 2013 Apr 16.
  PMID: 23734820
  responsible party type: Sponsor
  mesh term: Pulmonary Fibrosis
  mesh term: Idiopathic Pulmonary Fibrosis
  mesh term: Fibrosis
  sharing ipd: No