<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/NCT03296072</url>
  </required_header>
  <id_info>
    <org_study_id>208166</org_study_id>
    <nct_id>NCT03296072</nct_id>
  </id_info>
  <brief_title>In Situ Erosion Study to Investigate the Effectiveness of an Experimental Toothpaste</brief_title>
  <official_title>A Randomized, Examiner Blind, Crossover, in Situ Erosion Study to Investigate the Efficacy of an Experimental Dentifrice in Remineralization of Previously Softened Enamel Compared to a Placebo Dentifrice</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>GlaxoSmithKline</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>GlaxoSmithKline</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This will be a randomized, controlled, single center, single- blind, 3 period, 3 treatment,&#xD;
      cross-over, in situ design which consists of placing pre-eroded bovine enamel specimens intra&#xD;
      orally using a palatal appliance and testing the remineralizing performance of the&#xD;
      experimental (dentifrice containing 0.254 Percent weight by weight [%, w/w] sodium fluoride&#xD;
      (1150 parts per million [ppm] fluoride) and 5% KNO3 [potassium nitrate]), comparator&#xD;
      (dentifrice containing 0.454% w/w stannous fluoride (1100 ppm fluoride) and placebo (Fluoride&#xD;
      free placebo containing 5% KNO3 [0 ppm fluoride] ) dentifrices 2 and 4 hours (hrs) post&#xD;
      treatment application, based on surface micro hardness measurements. This study will be&#xD;
      carried out in healthy adults with a maxillary dental arch suitable for the retention of the&#xD;
      palatal appliance.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The aim of this study is to investigate the performance of an experimental dentifrice&#xD;
      formulation in promoting enamel remineralization and inhibiting post-treatment enamel&#xD;
      demineralization in an in situ erosion model, in comparison with a fluoride-free placebo and&#xD;
      with a marketed competitor dentifrice product. The study will have 4 visits, 1 screening&#xD;
      visit to assess participants eligibility and 3 treatment visits to assess product efficacy,&#xD;
      where the treatment product will be dispensed and used under the supervision of a suitably&#xD;
      trained study site personnel. Prior to each treatment visit, there will be a washout period&#xD;
      of a minimum of 3 days. During this period participants will use their own dentifrice for at&#xD;
      least one day, and a fluoride free dentifrice (provided) for two days prior to the next&#xD;
      scheduled visit (including in the morning of the scheduled visit) to minimize any carry-over&#xD;
      effects of the fluoride toothpaste.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 13, 2017</start_date>
  <completion_date type="Actual">January 16, 2018</completion_date>
  <primary_completion_date type="Actual">January 16, 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>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Investigator, Outcomes Assessor)</masking>
    <masking_description>Laboratory sample analyst will be blinded to treatment received. All study products will be overwrapped to conceal any labelling.&#xD;
The dispensing staff will not be involved in any clinical assessments or laboratory analysis during the study. Dental examiner will also be blinded to the treatment received.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>% Surface Micro Hardness Recovery (SMHR; Comparison of 1150 Ppm Fluoride and 5% KNO3 Dentifrice Relative to a Fluoride Free Placebo Dentifrice to Enhance Remineralization of Enamel)</measure>
    <time_frame>After 4 hrs following single exposure of treatment</time_frame>
    <description>The %SMHR was calculated to assess the changes in mineralization status of enamel specimens. The mean indent length (micrometer) from five Knoop microindentations within each specimen was measured at baseline (B), after the first erosive challenge (E1), and after 2 and 4 hours intraoral phase (R). An increase in the indentation length compared to the baseline indicates softening of the enamel surface while decrease in the indentation length represents re-hardening of enamel surface. The %SMHR was calculated as : %SMHR = [(E1-R)/(E1-B)]*100. Greater values of %SMHR indicate that greater remineralization has occurred, thus higher values are more favorable.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>% Relative Erosion Resistance (RER; Comparison of 1150 Ppm Fluoride and 5% KNO3 Dentifrice Relative to a Fluoride Free Placebo Dentifrice to Inhibit Demineralization of Enamel)</measure>
    <time_frame>After 4 hrs following single exposure of treatment</time_frame>
    <description>The %RER was calculated to assess the ability of treated enamel specimens to provide a combined benefit in terms of enhanced remineralization and acid resistance of the enamel. The mean indent length (micrometer) from five Knoop microindentations within each specimen was measured at baseline (B), after the first erosive challenge (E1), and after the second erosive challenge (E2) (E2 is measured for after both 2 and 4 hours of remineralization). An increase in the indentation length compared to the baseline indicates softening of the enamel surface while decrease in the indentation length represents re-hardening of enamel surface. The %RER was calculated as : %RER = [(E1-E2)/ (E1-B)]*100. Higher values of %RER indicate greater resistance to erosion, thus higher values are more favorable.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Enamel Fluoride Uptake (EFU; Comparison of 1150 Ppm Fluoride and 5% KNO3 Dentifrice Relative to a Fluoride Free Placebo Dentifrice to Promote Fluoride Uptake in Enamel)</measure>
    <time_frame>After 4 hrs following single exposure of treatment</time_frame>
    <description>The EFU was measured to determine the amount of fluoride incorporation into the model erosive lesions. Each enamel specimen drilled to a depth of approximately 100 μm using a microdrill, through the entire lesion (four cores per specimen). The enamel powder pooled from four drilling samples was then, dissolved in a known volume of perchloric acid and immediately analyzed for fluoride content using a calibrated fluoride specific electrode. The amount of fluoride-uptake by enamel was calculated based on the amount of fluoride divided by the area of the enamel cores and expressed as microgram fluoride per square centimeter (μgF/cm^2). Higher values of EFU indicate greater incorporation of fluoride into the enamel and are thus more favorable.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>% SMHR (Comparison of 1150 Ppm Fluoride and 5% KNO3 Dentifrice Relative to Comparator Containing 1100 Ppm Fluoride)</measure>
    <time_frame>After 4 hrs following single exposure of treatment</time_frame>
    <description>The %SMHR was calculated to assess the changes in mineralization status of enamel specimens. The mean indent length (micrometer) from five Knoop microindentations within each specimen was measured at baseline (B), after the first erosive challenge (E1), and after 2 and 4 hours intraoral phase (R). An increase in the indentation length compared to the baseline indicates softening of the enamel surface while decrease in the indentation length represents re-hardening of enamel surface. The %SMHR was calculated as: %SMHR = [(E1-R)/(E1-B)]*100. Greater values of %SMHR indicate that greater remineralization has occurred, thus higher values are more favorable.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>% RER (Comparison of 1150 Ppm Fluoride and 5% KNO3 Dentifrice Relative to Comparator Containing 1100 Ppm Fluoride)</measure>
    <time_frame>After 4 hrs following single exposure of treatment</time_frame>
    <description>The %RER was calculated to assess the ability of treated enamel specimens to provide a combined benefit in terms of enhanced remineralization and acid resistance of the enamel. The mean indent length (micrometer) from five Knoop microindentations within each specimen was measured at baseline (B), after the first erosive challenge (E1), and after the second erosive challenge (E2) (E2 is measured for after both 2 and 4 hours of remineralization). An increase in the indentation length compared to the baseline indicates softening of the enamel surface while decrease in the indentation length represents re-hardening of enamel surface. The %RER was calculated as : %RER = [(E1-E2)/ (E1-B)]*100. Higher values of %RER indicate greater resistance to erosion, thus higher values are more favorable.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>EFU (Comparison of 1150 Ppm Fluoride and 5% KNO3 Dentifrice Relative to Comparator Containing 1100 Ppm Fluoride)</measure>
    <time_frame>After 4 hrs following single exposure of treatment</time_frame>
    <description>The EFU was measured to determine the amount of fluoride incorporation into the model erosive lesions. Each enamel specimen drilled to a depth of approximately 100 μm using a microdrill, through the entire lesion (four cores per specimen). The enamel powder pooled from four drilling samples was then, dissolved in a known volume of perchloric acid and immediately analyzed for fluoride content using a calibrated fluoride specific electrode. The amount of fluoride-uptake by enamel was calculated based on the amount of fluoride divided by the area of the enamel cores and expressed as microgram fluoride per square centimeter (μgF/cm^2). Higher values of EFU indicate greater incorporation of fluoride into the enamel and are thus more favorable.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">62</enrollment>
  <condition>Tooth Erosion</condition>
  <arm_group>
    <arm_group_label>Test product</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will apply a full ribbon of the test product (1.5 grams [g]) containing 0.254% w/w sodium fluoride and 5% KNO3.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Comparator Product</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will apply a full ribbon of the comparator product (1.5 g orally) containing 0.454% w/w stannous fluoride.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Product</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will apply a full ribbon of the placebo (1.5 g orally) containing 5% KNO3.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>0.254% w/w sodium fluoride and 5% KNO3</intervention_name>
    <description>Dentifrice containing 0.254% w/w sodium fluoride (1150 ppm fluoride) and 5% KNO3; plus 0.25% PVM/MA copolymer and 2.5% sodium lactate. Participants will brush it on the buccal surfaces of their natural teeth for 25 timed seconds and then swish the resulting toothpaste slurry around the mouth, without further brushing, for a timed period of 95 seconds. After expectorating the slurry, the participants will gently rinse their mouths with 15 millilitres [mL] of tap water for 10 seconds before expectorating again.</description>
    <arm_group_label>Test product</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>0.454% w/w stannous fluoride</intervention_name>
    <description>Dentifrice containing 0.454% w/w stannous fluoride (1100 ppm fluoride). Participants will brush it on the buccal surfaces of their natural teeth for 25 timed seconds and then swish the resulting toothpaste slurry around the mouth, without further brushing, for a timed period of 95 seconds. After expectorating the slurry, the participants will gently rinse their mouths with 15 mL of tap water for 10 seconds before expectorating again.</description>
    <arm_group_label>Comparator Product</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>5% KNO3</intervention_name>
    <description>Fluoride free placebo dentifrice containing 5% KNO3 (0 ppm fluoride), 0.25% PVM/MA copolymer and 2.5% lactate. Participants will brush it on the buccal surfaces of their natural teeth for 25 timed seconds and then swish the resulting toothpaste slurry around the mouth, without further brushing, for a timed period of 95 seconds. After expectorating the slurry, the participants will gently rinse their mouths with 15 mL of tap water for 10 seconds before expectorating again.</description>
    <arm_group_label>Placebo Product</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Evidence of a personally signed and dated informed consent.&#xD;
&#xD;
          -  Male and female participants who, at the time of screening, are between the ages of 18&#xD;
             and 65 years, inclusive.&#xD;
&#xD;
          -  Participant who is willing and able to comply with scheduled visits, treatment plan,&#xD;
             and other study procedures.&#xD;
&#xD;
          -  Good general and mental health with, in the opinion of the investigator or medically&#xD;
             qualified designee. No clinically significant and relevant abnormalities in medical&#xD;
             history or oral examination.&#xD;
&#xD;
          -  Male participant able to father children and female participant of childbearing&#xD;
             potential and at risk for pregnancy must agree to use a highly effective method of&#xD;
             contraception throughout the study and for 5 days after the last dose of assigned&#xD;
             treatment.&#xD;
&#xD;
          -  Good oral health without lesions of the oral cavity that could interfere with the&#xD;
             study evaluations.&#xD;
&#xD;
          -  Maxillary dental arch suitable for the retention of the palatal appliance&#xD;
&#xD;
          -  Unstimulated salivary flow rate of at least 0.2 mL/minute and a stimulated salivary&#xD;
             flow rate of at least 0.8 mL/minute.&#xD;
&#xD;
          -  Understands and is willing, able and likely to comply with all study procedures and&#xD;
             restrictions.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participants who are investigational site staff members directly involved in the&#xD;
             conduct of the study and their family members, site staff members otherwise supervised&#xD;
             by the investigator, or participants who are GSK employees directly involved in the&#xD;
             conduct of the study.&#xD;
&#xD;
          -  Participation in other studies involving investigational drug(s) within 30 days prior&#xD;
             to screening visit.&#xD;
&#xD;
          -  Participation in other studies involving investigational oral care or cosmetic&#xD;
             products within 30 days prior to screening visit.&#xD;
&#xD;
          -  Acute or chronic medical or psychiatric condition that may increase the risk&#xD;
             associated with study participation or investigational product administration or may&#xD;
             interfere with the interpretation of study results and, in the judgment of the&#xD;
             investigator, would make the participant inappropriate for entry into this study.&#xD;
&#xD;
          -  Pregnant female participant (self - reported).&#xD;
&#xD;
          -  Breastfeeding female participant.&#xD;
&#xD;
          -  Known or suspected intolerance or hypersensitivity to the study materials (or closely&#xD;
             related compounds) or any of their stated ingredients. Unwilling or unable to comply&#xD;
             with the lifestyle guidelines described in this protocol.&#xD;
&#xD;
          -  Medication that may interfere significantly with the saliva flow in the judgment of&#xD;
             the investigator. Should new medications that may interfere with the saliva flow be&#xD;
             added, a second salivary flow test will be performed.&#xD;
&#xD;
          -  Participant with any condition that would impact on their safety or wellbeing or&#xD;
             affect their ability to understand and follow study procedures and requirements.&#xD;
&#xD;
          -  Any sign of grossly carious lesions (active), moderate or severe periodontal&#xD;
             conditions, or severe tooth wear. Participant presenting at screening with minor&#xD;
             caries may continue in the study if their carious lesions are repaired prior to the&#xD;
             first treatment visit of the study.&#xD;
&#xD;
          -  Wears oral appliance or orthodontia (besides participants wearing permanent lower&#xD;
             retainers, which are eligible).&#xD;
&#xD;
          -  Recent history (within the last year) of alcohol or other substance abuse. Participant&#xD;
             who has previously been enrolled in this study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>GSK Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>GlaxoSmithKline</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217381&amp;amp;parentIdentifier=208166&amp;amp;attachmentIdentifier=2023405a-a4d3-4a83-81a3-646cce348c22&amp;amp;fileName=gsk-208166-protocol-redact.pdf&amp;amp;versionIdentifier=</url>
    <description>Related Info</description>
  </link>
  <link>
    <url>https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217381&amp;amp;parentIdentifier=208166&amp;amp;attachmentIdentifier=6d21b0dc-6a7f-469f-9dd7-40aeb2f0005d&amp;amp;fileName=gsk-208166-reporting-and-analysis-plan-redact.pdf&amp;amp;versionIdentifier=</url>
    <description>Related Info</description>
  </link>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>September 25, 2017</study_first_submitted>
  <study_first_submitted_qc>September 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 28, 2017</study_first_posted>
  <results_first_submitted>January 3, 2019</results_first_submitted>
  <results_first_submitted_qc>February 19, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">February 20, 2019</results_first_posted>
  <last_update_submitted>August 27, 2020</last_update_submitted>
  <last_update_submitted_qc>August 27, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 16, 2020</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>Tooth Erosion</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Listerine</mesh_term>
    <mesh_term>Fluorides</mesh_term>
    <mesh_term>Sodium Fluoride</mesh_term>
    <mesh_term>Tin Fluorides</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>IPD for this study will be made available via the Clinical Study Data Request site.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>IPD is available via the Clinical Study Data Request site (click on the link provided below)</ipd_time_frame>
    <ipd_access_criteria>Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.</ipd_access_criteria>
    <ipd_url>https://clinicalstudydatarequest.com/Posting.aspx?ID=20365</ipd_url>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>November 7, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/72/NCT03296072/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>February 27, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/72/NCT03296072/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were recruited from one center in United States of America.</recruitment_details>
      <pre_assignment_details>A total of 68 participates were screened, out of which 62 participants were randomized in the study and 6 participants were not randomized as all the 6 participants did not meet study criteria.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Test Product/Comparator Product/Placebo Product</title>
          <description>Participants in this arm received test product (0.254% weight by weight [w/w] sodium fluoride [NaF; 1150 parts per million {ppm} fluoride] and 5% potassium nitrate [KNO3]) followed by comparator (0.454% w/w stannous fluoride [SnF2; 1100 ppm fluoride]) and placebo product (5% KNO3 [0 ppm fluoride]) in Period 1, 2 and 3 respectively. Each treatment period was separated by a wash out period of minimum 3 days (including 2 day washout period using a non-fluoride toothpaste). Participants applied a full ribbon (1.5 grams [g]) of the allocated product and brushed the buccal surfaces of their natural teeth for 25 timed seconds and then swished the resulting toothpaste slurry around the mouth, without further brushing,for a timed period of 95 seconds. After expectorating the slurry, participants gently rinsed their mouths with 15 milliliters [mL] of tap water for 10 seconds before expectorating again.</description>
        </group>
        <group group_id="P2">
          <title>Test Product/Placebo Product/Comparator Product</title>
          <description>Participants in this arm received test product (0.254% w/w NaF [1150 ppm fluoride] and 5% KNO3) followed by placebo (5% KNO3 [0 ppm fluoride])and comparator product (0.454% w/w SnF2[1100 ppm fluoride]) in Period 1, 2 and 3 respectively. Each treatment period was separated by a wash out period of minimum 3 days (including 2 day washout period using a non-fluoride toothpaste). Participants applied a full ribbon (1.5 g) of the allocated product and brushed the buccal surfaces of their natural teeth for 25 timed seconds and then swished the resulting toothpaste slurry around the mouth, without further brushing, for a timed period of 95 seconds. After expectorating the slurry, the participants gently rinsed their mouths with 15 mL of tap water for 10 seconds before expectorating again.</description>
        </group>
        <group group_id="P3">
          <title>Comparator Product/Test Product/Placebo Product</title>
          <description>Participants in this arm received comparator product (0.454% w/w SnF2[1100 ppm fluoride]) followed by test (0.254% w/w NaF [1150 ppm fluoride] and 5% KNO3) and placebo product(5% KNO3 [0 ppm fluoride]) in Period 1, 2 and 3 respectively. Each treatment period was separated by a wash out period of minimum 3 days (including 2 day washout period using a non-fluoride toothpaste). Participants applied a full ribbon (1.5 g) of the allocated product and brushed the buccal surfaces of their natural teeth for 25 timed seconds and then swished the resulting toothpaste slurry around the mouth, without further brushing, for a timed period of 95 seconds. After expectorating the slurry, the participants gently rinsed their mouths with 15 mL of tap water for 10 seconds before expectorating again.</description>
        </group>
        <group group_id="P4">
          <title>Comparator Product/Placebo Product/ Test Product</title>
          <description>Participants in this arm received comparator product (0.454% w/w SnF2[1100 ppm fluoride]) followed by placebo (5% KNO3 [0 ppm fluoride])and test product (0.254% w/w NaF [1150 ppm fluoride] and 5% KNO3) in Period 1, 2 and 3 respectively. Each treatment period was separated by a wash out period of minimum 3 days (including 2 day washout period using a non-fluoride toothpaste). Participants applied a full ribbon (1.5 g) of the allocated product and brushed the buccal surfaces of their natural teeth for 25 timed seconds and then swished the resulting toothpaste slurry around the mouth, without further brushing, for a timed period of 95 seconds. After expectorating the slurry, the participants gently rinsed their mouths with 15 mL of tap water for 10 seconds before expectorating again.</description>
        </group>
        <group group_id="P5">
          <title>Placebo Product/Test Product/Comparator Product</title>
          <description>Participants in this arm received placebo product (5% KNO3 [0 ppm fluoride]) followed by test (0.254% w/w NaF [1150 ppm fluoride] and 5% KNO3) and comparator product (0.454% w/w SnF2 [1100 ppm fluoride]) in Period 1, 2 and 3 respectively. Each treatment period was separated by a wash out period of minimum 3 days (including 2 day washout period using a non-fluoride toothpaste). Participants applied a full ribbon (1.5 g) of the allocated product and brushed the buccal surfaces of their natural teeth for 25 timed seconds and then swished the resulting toothpaste slurry around the mouth, without further brushing, for a timed period of 95 seconds. After expectorating the slurry, the participants gently rinsed their mouths with 15 mL of tap water for 10 seconds before expectorating again.</description>
        </group>
        <group group_id="P6">
          <title>Placebo Product/Comparator Product/Test Product</title>
          <description>Participants in this arm received placebo product (5% KNO3 [0 ppm fluoride]) followed by comparator (0.454% w/w SnF2[1100 ppm fluoride]) and test product (0.254% w/w NaF [1150 ppm fluoride] and 5% KNO3) in Period 1, 2 and 3 respectively. Each treatment period was separated by a wash out period of minimum 3 days (including 2 day washout period using a non-fluoride toothpaste). Participants applied a full ribbon (1.5 g) of the allocated product and brushed the buccal surfaces of their natural teeth for 25 timed seconds and then swished the resulting toothpaste slurry around the mouth, without further brushing, for a timed period of 95 seconds. After expectorating the slurry, the participants gently rinsed their mouths with 15 mL of tap water for 10 seconds before expectorating again.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Treatment Period 1</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="11"/>
                <participants group_id="P3" count="10"/>
                <participants group_id="P4" count="10"/>
                <participants group_id="P5" count="10"/>
                <participants group_id="P6" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="11"/>
                <participants group_id="P3" count="10"/>
                <participants group_id="P4" count="10"/>
                <participants group_id="P5" count="10"/>
                <participants group_id="P6" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Treament Period 1: Wash Out Period</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="11"/>
                <participants group_id="P3" count="10"/>
                <participants group_id="P4" count="10"/>
                <participants group_id="P5" count="10"/>
                <participants group_id="P6" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="11"/>
                <participants group_id="P3" count="10"/>
                <participants group_id="P4" count="10"/>
                <participants group_id="P5" count="10"/>
                <participants group_id="P6" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Treament Period 2</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="11"/>
                <participants group_id="P3" count="10"/>
                <participants group_id="P4" count="10"/>
                <participants group_id="P5" count="10"/>
                <participants group_id="P6" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="11"/>
                <participants group_id="P3" count="10"/>
                <participants group_id="P4" count="10"/>
                <participants group_id="P5" count="10"/>
                <participants group_id="P6" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Treament Period 2: Wash Out Period</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="11"/>
                <participants group_id="P3" count="10"/>
                <participants group_id="P4" count="10"/>
                <participants group_id="P5" count="10"/>
                <participants group_id="P6" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="11"/>
                <participants group_id="P3" count="10"/>
                <participants group_id="P4" count="10"/>
                <participants group_id="P5" count="10"/>
                <participants group_id="P6" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Treament Period 3</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="11"/>
                <participants group_id="P3" count="10"/>
                <participants group_id="P4" count="10"/>
                <participants group_id="P5" count="10"/>
                <participants group_id="P6" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="11"/>
                <participants group_id="P3" count="10"/>
                <participants group_id="P4" count="10"/>
                <participants group_id="P5" count="10"/>
                <participants group_id="P6" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Safety Population included all randomized participants who received at least 1 dose of study treatment. This population was based on the treatment the participant actually received.</population>
      <group_list>
        <group group_id="B1">
          <title>Overall Participants</title>
          <description>All randomized participants were included for baseline evaluation. Participants applied a full ribbon of the test (0.254% w/w NaF [1150 ppm fluoride] and 5% KNO3), comparator (0.454% w/w SnF2[1100 ppm fluoride]) and placebo product (5% KNO3 [0 ppm fluoride]) and brushed the buccal surfaces of their natural teeth for 25 timed seconds and then swished the resulting toothpaste slurry around the mouth, without further brushing, for a timed period of 95 seconds. After expectorating the slurry, participants gently rinsed with 15 mL of tap water for 10 seconds before expectorating again.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="62"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="43.4" spread="13.38"/>
                  </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="45"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="58"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="42"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>% Surface Micro Hardness Recovery (SMHR; Comparison of 1150 Ppm Fluoride and 5% KNO3 Dentifrice Relative to a Fluoride Free Placebo Dentifrice to Enhance Remineralization of Enamel)</title>
        <description>The %SMHR was calculated to assess the changes in mineralization status of enamel specimens. The mean indent length (micrometer) from five Knoop microindentations within each specimen was measured at baseline (B), after the first erosive challenge (E1), and after 2 and 4 hours intraoral phase (R). An increase in the indentation length compared to the baseline indicates softening of the enamel surface while decrease in the indentation length represents re-hardening of enamel surface. The %SMHR was calculated as : %SMHR = [(E1-R)/(E1-B)]*100. Greater values of %SMHR indicate that greater remineralization has occurred, thus higher values are more favorable.</description>
        <time_frame>After 4 hrs following single exposure of treatment</time_frame>
        <population>The Intent-to-Treat (ITT) population was comprised of all randomized participants who received at least 1 dose of study treatment and had at least 1 post-baseline (post-treatment) primary efficacy evaluation. This population was based on the treatment to which the participant was randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Test Product</title>
            <description>Participants applied a full ribbon of the test product (1.5 g) containing 0.254% w/w NaF (1150 ppm fluoride) and 5% KNO3 and brushed the buccal surfaces of their natural teeth for 25 timed seconds and then swished the resulting toothpaste slurry around the mouth for 95 timed seconds. After expectorating the slurry, participants gently rinsed their mouth with 15 mL of tap water for 10 seconds before expectorating again.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Product</title>
            <description>Participants applied a full ribbon of the placebo (1.5 g) containing 5% KNO3 (0 ppm fluoride) and brushed the buccal surfaces of their natural teeth for 25 timed seconds and then swished the resulting toothpaste slurry around the mouth for 95 timed seconds. After expectorating the slurry, participants gently rinsed their mouth with 15 mL of tap water for 10 seconds before expectorating again.</description>
          </group>
        </group_list>
        <measure>
          <title>% Surface Micro Hardness Recovery (SMHR; Comparison of 1150 Ppm Fluoride and 5% KNO3 Dentifrice Relative to a Fluoride Free Placebo Dentifrice to Enhance Remineralization of Enamel)</title>
          <description>The %SMHR was calculated to assess the changes in mineralization status of enamel specimens. The mean indent length (micrometer) from five Knoop microindentations within each specimen was measured at baseline (B), after the first erosive challenge (E1), and after 2 and 4 hours intraoral phase (R). An increase in the indentation length compared to the baseline indicates softening of the enamel surface while decrease in the indentation length represents re-hardening of enamel surface. The %SMHR was calculated as : %SMHR = [(E1-R)/(E1-B)]*100. Greater values of %SMHR indicate that greater remineralization has occurred, thus higher values are more favorable.</description>
          <population>The Intent-to-Treat (ITT) population was comprised of all randomized participants who received at least 1 dose of study treatment and had at least 1 post-baseline (post-treatment) primary efficacy evaluation. This population was based on the treatment to which the participant was randomized.</population>
          <units>Percentage SMHR</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="62"/>
                <count group_id="O2" value="62"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29.67" spread="1.12"/>
                    <measurement group_id="O2" value="21.98" spread="1.12"/>
                  </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>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;.0001</p_value>
            <method>ANOVA</method>
            <method_desc>From ANOVA with fixed factors for study period and treatment, and a random effect for participant.</method_desc>
            <param_type>Difference of Least Square mean</param_type>
            <param_value>7.69</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>5.18</ci_lower_limit>
            <ci_upper_limit>10.19</ci_upper_limit>
            <estimate_desc>Difference is first-named treatment minus second-named treatment such that a positive difference favors the first named treatment.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>% Relative Erosion Resistance (RER; Comparison of 1150 Ppm Fluoride and 5% KNO3 Dentifrice Relative to a Fluoride Free Placebo Dentifrice to Inhibit Demineralization of Enamel)</title>
        <description>The %RER was calculated to assess the ability of treated enamel specimens to provide a combined benefit in terms of enhanced remineralization and acid resistance of the enamel. The mean indent length (micrometer) from five Knoop microindentations within each specimen was measured at baseline (B), after the first erosive challenge (E1), and after the second erosive challenge (E2) (E2 is measured for after both 2 and 4 hours of remineralization). An increase in the indentation length compared to the baseline indicates softening of the enamel surface while decrease in the indentation length represents re-hardening of enamel surface. The %RER was calculated as : %RER = [(E1-E2)/ (E1-B)]*100. Higher values of %RER indicate greater resistance to erosion, thus higher values are more favorable.</description>
        <time_frame>After 4 hrs following single exposure of treatment</time_frame>
        <population>The ITT population was comprised of all randomized participants who received at least 1 dose of study treatment and had at least 1 post-baseline (post-treatment) primary efficacy evaluation. This population was based on the treatment to which the participant was randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Test Product</title>
            <description>Participants applied a full ribbon of the test product (1.5 g) containing 0.254% w/w NaF (1150 ppm fluoride) and 5% KNO3 and brushed the buccal surfaces of their natural teeth for 25 timed seconds and then swished the resulting toothpaste slurry around the mouth for 95 timed seconds. After expectorating the slurry, participants gently rinsed their mouth with 15 mL of tap water for 10 seconds before expectorating again.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Product</title>
            <description>Participants applied a full ribbon of the placebo (1.5 g) containing 5% KNO3 (0 ppm fluoride) and brushed the buccal surfaces of their natural teeth for 25 timed seconds and then swished the resulting toothpaste slurry around the mouth for 95 timed seconds. After expectorating the slurry, participants gently rinsed their mouth with 15 mL of tap water for 10 seconds before expectorating again.</description>
          </group>
        </group_list>
        <measure>
          <title>% Relative Erosion Resistance (RER; Comparison of 1150 Ppm Fluoride and 5% KNO3 Dentifrice Relative to a Fluoride Free Placebo Dentifrice to Inhibit Demineralization of Enamel)</title>
          <description>The %RER was calculated to assess the ability of treated enamel specimens to provide a combined benefit in terms of enhanced remineralization and acid resistance of the enamel. The mean indent length (micrometer) from five Knoop microindentations within each specimen was measured at baseline (B), after the first erosive challenge (E1), and after the second erosive challenge (E2) (E2 is measured for after both 2 and 4 hours of remineralization). An increase in the indentation length compared to the baseline indicates softening of the enamel surface while decrease in the indentation length represents re-hardening of enamel surface. The %RER was calculated as : %RER = [(E1-E2)/ (E1-B)]*100. Higher values of %RER indicate greater resistance to erosion, thus higher values are more favorable.</description>
          <population>The ITT population was comprised of all randomized participants who received at least 1 dose of study treatment and had at least 1 post-baseline (post-treatment) primary efficacy evaluation. This population was based on the treatment to which the participant was randomized.</population>
          <units>Percentage RER</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="62"/>
                <count group_id="O2" value="62"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-23.65" spread="1.96"/>
                    <measurement group_id="O2" value="-56.94" spread="1.96"/>
                  </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>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;.0001</p_value>
            <method>ANOVA</method>
            <method_desc>From ANOVA with fixed factors for study period and treatment, and a random effect for participant.</method_desc>
            <param_type>Difference of Least Square mean</param_type>
            <param_value>33.29</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>28.89</ci_lower_limit>
            <ci_upper_limit>37.68</ci_upper_limit>
            <estimate_desc>Difference is first-named treatment minus second-named treatment such that a positive difference favors the first named treatment.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Enamel Fluoride Uptake (EFU; Comparison of 1150 Ppm Fluoride and 5% KNO3 Dentifrice Relative to a Fluoride Free Placebo Dentifrice to Promote Fluoride Uptake in Enamel)</title>
        <description>The EFU was measured to determine the amount of fluoride incorporation into the model erosive lesions. Each enamel specimen drilled to a depth of approximately 100 μm using a microdrill, through the entire lesion (four cores per specimen). The enamel powder pooled from four drilling samples was then, dissolved in a known volume of perchloric acid and immediately analyzed for fluoride content using a calibrated fluoride specific electrode. The amount of fluoride-uptake by enamel was calculated based on the amount of fluoride divided by the area of the enamel cores and expressed as microgram fluoride per square centimeter (μgF/cm^2). Higher values of EFU indicate greater incorporation of fluoride into the enamel and are thus more favorable.</description>
        <time_frame>After 4 hrs following single exposure of treatment</time_frame>
        <population>The ITT population was comprised of all randomized participants who received at least 1 dose of study treatment and had at least 1 post-baseline (post-treatment) primary efficacy evaluation. This population was based on the treatment to which the participant was randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Test Product</title>
            <description>Participants applied a full ribbon of the test product (1.5 g) containing 0.254% w/w NaF (1150 ppm fluoride) and 5% KNO3 and brushed the buccal surfaces of their natural teeth for 25 timed seconds and then swished the resulting toothpaste slurry around the mouth for 95 timed seconds. After expectorating the slurry, participants gently rinsed their mouth with 15 mL of tap water for 10 seconds before expectorating again.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Product</title>
            <description>Participants applied a full ribbon of the placebo (1.5 g) containing 5% KNO3 (0 ppm fluoride) and brushed the buccal surfaces of their natural teeth for 25 timed seconds and then swished the resulting toothpaste slurry around the mouth for 95 timed seconds. After expectorating the slurry, participants gently rinsed their mouth with 15 mL of tap water for 10 seconds before expectorating again.</description>
          </group>
        </group_list>
        <measure>
          <title>Enamel Fluoride Uptake (EFU; Comparison of 1150 Ppm Fluoride and 5% KNO3 Dentifrice Relative to a Fluoride Free Placebo Dentifrice to Promote Fluoride Uptake in Enamel)</title>
          <description>The EFU was measured to determine the amount of fluoride incorporation into the model erosive lesions. Each enamel specimen drilled to a depth of approximately 100 μm using a microdrill, through the entire lesion (four cores per specimen). The enamel powder pooled from four drilling samples was then, dissolved in a known volume of perchloric acid and immediately analyzed for fluoride content using a calibrated fluoride specific electrode. The amount of fluoride-uptake by enamel was calculated based on the amount of fluoride divided by the area of the enamel cores and expressed as microgram fluoride per square centimeter (μgF/cm^2). Higher values of EFU indicate greater incorporation of fluoride into the enamel and are thus more favorable.</description>
          <population>The ITT population was comprised of all randomized participants who received at least 1 dose of study treatment and had at least 1 post-baseline (post-treatment) primary efficacy evaluation. This population was based on the treatment to which the participant was randomized.</population>
          <units>Microgram fluoride per square centimeter</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="62"/>
                <count group_id="O2" value="62"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.98" spread="0.09"/>
                    <measurement group_id="O2" value="1.17" spread="0.09"/>
                  </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>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;.0001</p_value>
            <method>ANOVA</method>
            <method_desc>From ANOVA with fixed factors for study period and treatment, and a random effect for participant.</method_desc>
            <param_type>Difference of Least Square mean</param_type>
            <param_value>1.81</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.59</ci_lower_limit>
            <ci_upper_limit>2.04</ci_upper_limit>
            <estimate_desc>Difference is first-named treatment minus second-named treatment such that a positive difference favors the first named treatment.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>% SMHR (Comparison of 1150 Ppm Fluoride and 5% KNO3 Dentifrice Relative to Comparator Containing 1100 Ppm Fluoride)</title>
        <description>The %SMHR was calculated to assess the changes in mineralization status of enamel specimens. The mean indent length (micrometer) from five Knoop microindentations within each specimen was measured at baseline (B), after the first erosive challenge (E1), and after 2 and 4 hours intraoral phase (R). An increase in the indentation length compared to the baseline indicates softening of the enamel surface while decrease in the indentation length represents re-hardening of enamel surface. The %SMHR was calculated as: %SMHR = [(E1-R)/(E1-B)]*100. Greater values of %SMHR indicate that greater remineralization has occurred, thus higher values are more favorable.</description>
        <time_frame>After 4 hrs following single exposure of treatment</time_frame>
        <population>The ITT population was comprised of all randomized participants who received at least 1 dose of study treatment and had at least 1 post-baseline (post-treatment) primary efficacy evaluation. This population was based on the treatment to which the participant was randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Test Product</title>
            <description>Participants applied a full ribbon of the test product (1.5 g) containing 0.254% w/w NaF (1150 ppm fluoride) and 5% KNO3 and brushed the buccal surfaces of their natural teeth for 25 timed seconds and then swished the resulting toothpaste slurry around the mouth for 95 timed seconds. After expectorating the slurry, participants gently rinsed their mouth with 15 mL of tap water for 10 seconds before expectorating again.</description>
          </group>
          <group group_id="O2">
            <title>Comparator Product</title>
            <description>Participants applied a full ribbon of the placebo (1.5 g) containing 0.454% w/w SnF2 (1100 ppm fluoride) and brushed the buccal surfaces of their natural teeth for 25 timed seconds and then swished the resulting toothpaste slurry around the mouth for 95 timed seconds. After expectorating the slurry, participants gently rinsed their mouth with 15 mL of tap water for 10 seconds before expectorating again.</description>
          </group>
        </group_list>
        <measure>
          <title>% SMHR (Comparison of 1150 Ppm Fluoride and 5% KNO3 Dentifrice Relative to Comparator Containing 1100 Ppm Fluoride)</title>
          <description>The %SMHR was calculated to assess the changes in mineralization status of enamel specimens. The mean indent length (micrometer) from five Knoop microindentations within each specimen was measured at baseline (B), after the first erosive challenge (E1), and after 2 and 4 hours intraoral phase (R). An increase in the indentation length compared to the baseline indicates softening of the enamel surface while decrease in the indentation length represents re-hardening of enamel surface. The %SMHR was calculated as: %SMHR = [(E1-R)/(E1-B)]*100. Greater values of %SMHR indicate that greater remineralization has occurred, thus higher values are more favorable.</description>
          <population>The ITT population was comprised of all randomized participants who received at least 1 dose of study treatment and had at least 1 post-baseline (post-treatment) primary efficacy evaluation. This population was based on the treatment to which the participant was randomized.</population>
          <units>Percentage SMHR</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="62"/>
                <count group_id="O2" value="62"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29.67" spread="1.12"/>
                    <measurement group_id="O2" value="22.10" spread="1.12"/>
                  </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>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;.0001</p_value>
            <method>ANOVA</method>
            <method_desc>From ANOVA with fixed factors for study period and treatment, and a random effect for participant.</method_desc>
            <param_type>Difference of Least Square mean</param_type>
            <param_value>7.57</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>5.07</ci_lower_limit>
            <ci_upper_limit>11.07</ci_upper_limit>
            <estimate_desc>Difference is first-named treatment minus second-named treatment such that a positive difference favors the first named treatment.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>% RER (Comparison of 1150 Ppm Fluoride and 5% KNO3 Dentifrice Relative to Comparator Containing 1100 Ppm Fluoride)</title>
        <description>The %RER was calculated to assess the ability of treated enamel specimens to provide a combined benefit in terms of enhanced remineralization and acid resistance of the enamel. The mean indent length (micrometer) from five Knoop microindentations within each specimen was measured at baseline (B), after the first erosive challenge (E1), and after the second erosive challenge (E2) (E2 is measured for after both 2 and 4 hours of remineralization). An increase in the indentation length compared to the baseline indicates softening of the enamel surface while decrease in the indentation length represents re-hardening of enamel surface. The %RER was calculated as : %RER = [(E1-E2)/ (E1-B)]*100. Higher values of %RER indicate greater resistance to erosion, thus higher values are more favorable.</description>
        <time_frame>After 4 hrs following single exposure of treatment</time_frame>
        <population>The ITT population was comprised of all randomized participants who received at least 1 dose of study treatment and had at least 1 post-baseline (post-treatment) primary efficacy evaluation. This population was based on the treatment to which the participant was randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Test Product</title>
            <description>Participants applied a full ribbon of the test product (1.5 g) containing 0.254% w/w NaF (1150 ppm fluoride) and 5% KNO3 and brushed the buccal surfaces of their natural teeth for 25 timed seconds and then swished the resulting toothpaste slurry around the mouth for 95 timed seconds. After expectorating the slurry, participants gently rinsed their mouth with 15 mL of tap water for 10 seconds before expectorating again.</description>
          </group>
          <group group_id="O2">
            <title>Comparator Product</title>
            <description>Participants applied a full ribbon of the placebo (1.5 g) containing 0.454% w/w SnF2 (1100 ppm fluoride) and brushed the buccal surfaces of their natural teeth for 25 timed seconds and then swished the resulting toothpaste slurry around the mouth for 95 timed seconds. After expectorating the slurry, participants gently rinsed their mouth with 15 mL of tap water for 10 seconds before expectorating again.</description>
          </group>
        </group_list>
        <measure>
          <title>% RER (Comparison of 1150 Ppm Fluoride and 5% KNO3 Dentifrice Relative to Comparator Containing 1100 Ppm Fluoride)</title>
          <description>The %RER was calculated to assess the ability of treated enamel specimens to provide a combined benefit in terms of enhanced remineralization and acid resistance of the enamel. The mean indent length (micrometer) from five Knoop microindentations within each specimen was measured at baseline (B), after the first erosive challenge (E1), and after the second erosive challenge (E2) (E2 is measured for after both 2 and 4 hours of remineralization). An increase in the indentation length compared to the baseline indicates softening of the enamel surface while decrease in the indentation length represents re-hardening of enamel surface. The %RER was calculated as : %RER = [(E1-E2)/ (E1-B)]*100. Higher values of %RER indicate greater resistance to erosion, thus higher values are more favorable.</description>
          <population>The ITT population was comprised of all randomized participants who received at least 1 dose of study treatment and had at least 1 post-baseline (post-treatment) primary efficacy evaluation. This population was based on the treatment to which the participant was randomized.</population>
          <units>Percentage RER</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="62"/>
                <count group_id="O2" value="62"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-23.65" spread="1.96"/>
                    <measurement group_id="O2" value="-34.63" spread="1.96"/>
                  </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>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;.0001</p_value>
            <method>ANOVA</method>
            <method_desc>From ANOVA with fixed factors for study period and treatment, and a random effect for participant.</method_desc>
            <param_type>Difference of Least Square mean</param_type>
            <param_value>10.98</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>6.58</ci_lower_limit>
            <ci_upper_limit>15.37</ci_upper_limit>
            <estimate_desc>Difference is first-named treatment minus second-named treatment such that a positive difference favors the first named treatment.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>EFU (Comparison of 1150 Ppm Fluoride and 5% KNO3 Dentifrice Relative to Comparator Containing 1100 Ppm Fluoride)</title>
        <description>The EFU was measured to determine the amount of fluoride incorporation into the model erosive lesions. Each enamel specimen drilled to a depth of approximately 100 μm using a microdrill, through the entire lesion (four cores per specimen). The enamel powder pooled from four drilling samples was then, dissolved in a known volume of perchloric acid and immediately analyzed for fluoride content using a calibrated fluoride specific electrode. The amount of fluoride-uptake by enamel was calculated based on the amount of fluoride divided by the area of the enamel cores and expressed as microgram fluoride per square centimeter (μgF/cm^2). Higher values of EFU indicate greater incorporation of fluoride into the enamel and are thus more favorable.</description>
        <time_frame>After 4 hrs following single exposure of treatment</time_frame>
        <population>The ITT population was comprised of all randomized participants who received at least 1 dose of study treatment and had at least 1 post-baseline (post-treatment) primary efficacy evaluation. This population was based on the treatment to which the participant was randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Test Product</title>
            <description>Participants applied a full ribbon of the test product (1.5 g) containing 0.254% w/w NaF (1150 ppm fluoride) and 5% KNO3 and brushed the buccal surfaces of their natural teeth for 25 timed seconds and then swished the resulting toothpaste slurry around the mouth for 95 timed seconds. After expectorating the slurry, participants gently rinsed their mouth with 15 mL of tap water for 10 seconds before expectorating again.</description>
          </group>
          <group group_id="O2">
            <title>Comparator Product</title>
            <description>Participants applied a full ribbon of the placebo (1.5 g) containing 0.454% w/w SnF2 (1100 ppm fluoride) and brushed the buccal surfaces of their natural teeth for 25 timed seconds and then swished the resulting toothpaste slurry around the mouth for 95 timed seconds. After expectorating the slurry, participants gently rinsed their mouth with 15 mL of tap water for 10 seconds before expectorating again.</description>
          </group>
        </group_list>
        <measure>
          <title>EFU (Comparison of 1150 Ppm Fluoride and 5% KNO3 Dentifrice Relative to Comparator Containing 1100 Ppm Fluoride)</title>
          <description>The EFU was measured to determine the amount of fluoride incorporation into the model erosive lesions. Each enamel specimen drilled to a depth of approximately 100 μm using a microdrill, through the entire lesion (four cores per specimen). The enamel powder pooled from four drilling samples was then, dissolved in a known volume of perchloric acid and immediately analyzed for fluoride content using a calibrated fluoride specific electrode. The amount of fluoride-uptake by enamel was calculated based on the amount of fluoride divided by the area of the enamel cores and expressed as microgram fluoride per square centimeter (μgF/cm^2). Higher values of EFU indicate greater incorporation of fluoride into the enamel and are thus more favorable.</description>
          <population>The ITT population was comprised of all randomized participants who received at least 1 dose of study treatment and had at least 1 post-baseline (post-treatment) primary efficacy evaluation. This population was based on the treatment to which the participant was randomized.</population>
          <units>Microgram fluoride per square centimeter</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="62"/>
                <count group_id="O2" value="62"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.98" spread="0.09"/>
                    <measurement group_id="O2" value="2.01" spread="0.09"/>
                  </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>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;.0001</p_value>
            <method>ANOVA</method>
            <method_desc>From ANOVA with fixed factors for study period and treatment, and a random effect for participant.</method_desc>
            <param_type>Difference of Least Square mean</param_type>
            <param_value>0.97</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.75</ci_lower_limit>
            <ci_upper_limit>1.20</ci_upper_limit>
            <estimate_desc>Difference is first-named treatment minus second-named treatment such that a positive difference favors the first named treatment.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>4 hours</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Test Product</title>
          <description>Participants applied a full ribbon of the test product (1.5 g) containing 0.254% w/w NaF (1150 ppm fluoride) and 5% KNO3 and brushed the buccal surfaces of their natural teeth for 25 timed seconds and then swished the resulting toothpaste slurry around the mouth for 95 timed seconds. After expectorating the slurry, participants gently rinsed their mouth with 15 mL of tap water for 10 seconds before expectorating again.</description>
        </group>
        <group group_id="E2">
          <title>Comparator Product</title>
          <description>Participants applied a full ribbon of the placebo (1.5 g) containing 0.454% w/w SnF2 (1100 ppm fluoride) and brushed the buccal surfaces of their natural teeth for 25 timed seconds and then swished the resulting toothpaste slurry around the mouth for 95 timed seconds. After expectorating the slurry, participants gently rinsed their mouth with 15 mL of tap water for 10 seconds before expectorating again.</description>
        </group>
        <group group_id="E3">
          <title>Placebo Product</title>
          <description>Participants applied a full ribbon of the placebo (1.5 g) containing 5% KNO3 (0 ppm fluoride) and brushed the buccal surfaces of their natural teeth for 25 timed seconds and then swished the resulting toothpaste slurry around the mouth for 95 timed seconds. After expectorating the slurry, participants gently rinsed their mouth with 15 mL of tap water for 10 seconds before expectorating again.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="62"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="62"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="62"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="62"/>
                <counts group_id="E3" subjects_affected="10" subjects_at_risk="62"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dental caries</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="62"/>
              </event>
              <event>
                <sub_title>Lip haematoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="62"/>
              </event>
              <event>
                <sub_title>Mouth ulceration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="62"/>
              </event>
              <event>
                <sub_title>Oral Discomfort</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="62"/>
              </event>
              <event>
                <sub_title>Oral Mucosal Erthyema</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="62"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="62"/>
              </event>
              <event>
                <sub_title>Oral Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="62"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="62"/>
              </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="62"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="62"/>
              </event>
              <event>
                <sub_title>Gastrointestinal Bactetial Overgrowth</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="62"/>
              </event>
              <event>
                <sub_title>Herpes Zoster</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="62"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="62"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="62"/>
              </event>
              <event>
                <sub_title>Sinusistis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="62"/>
              </event>
              <event>
                <sub_title>Urinary Tract Infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="62"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Arthopod Bite</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="62"/>
              </event>
              <event>
                <sub_title>Burn Oral Cavity</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="62"/>
              </event>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="62"/>
              </event>
              <event>
                <sub_title>Joint Dislocation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="62"/>
              </event>
              <event>
                <sub_title>Palate Injury</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="62"/>
              </event>
              <event>
                <sub_title>Tooth Fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="62"/>
              </event>
              <event>
                <sub_title>Traumatic Ulcer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="62"/>
              </event>
              <event>
                <sub_title>Mouth Injury</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="62"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Periodic limb movement disorder</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="62"/>
              </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>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>GSK Response Center</name_or_title>
      <organization>GlaxoSmithKline</organization>
      <phone>866-435-7343 Ext:</phone>
      <email>GSKClinicalSupportHD@gsk.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/NCT03296072
org study id: 208166
nct id: NCT03296072
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
This will be a randomized, controlled, single center, single- blind, 3 period, 3 treatment,
      cross-over, in situ design which consists of placing pre-eroded bovine enamel specimens intra
      orally using a palatal appliance and testing the remineralizing performance of the
      experimental (dentifrice containing 0.254 Percent weight by weight [%, w/w] sodium fluoride
      (1150 parts per million [ppm] fluoride) and 5% KNO3 [potassium nitrate]), comparator
      (dentifrice containing 0.454% w/w stannous fluoride (1100 ppm fluoride) and placebo (Fluoride
      free placebo containing 5% KNO3 [0 ppm fluoride] ) dentifrices 2 and 4 hours (hrs) post
      treatment application, based on surface micro hardness measurements. This study will be
      carried out in healthy adults with a maxillary dental arch suitable for the retention of the
      palatal appliance.
The aim of this study is to investigate the performance of an experimental dentifrice
      formulation in promoting enamel remineralization and inhibiting post-treatment enamel
      demineralization in an in situ erosion model, in comparison with a fluoride-free placebo and
      with a marketed competitor dentifrice product. The study will have 4 visits, 1 screening
      visit to assess participants eligibility and 3 treatment visits to assess product efficacy,
      where the treatment product will be dispensed and used under the supervision of a suitably
      trained study site personnel. Prior to each treatment visit, there will be a washout period
      of a minimum of 3 days. During this period participants will use their own dentifrice for at
      least one day, and a fluoride free dentifrice (provided) for two days prior to the next
      scheduled visit (including in the morning of the scheduled visit) to minimize any carry-over
      effects of the fluoride toothpaste.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Double (Investigator, Outcomes Assessor)
masking description: Laboratory sample analyst will be blinded to treatment received. All study products will be overwrapped to conceal any labelling.
The dispensing staff will not be involved in any clinical assessments or laboratory analysis during the study. Dental examiner will also be blinded to the treatment received.
measure: % Surface Micro Hardness Recovery (SMHR; Comparison of 1150 Ppm Fluoride and 5% KNO3 Dentifrice Relative to a Fluoride Free Placebo Dentifrice to Enhance Remineralization of Enamel)
time frame: After 4 hrs following single exposure of treatment
description: The %SMHR was calculated to assess the changes in mineralization status of enamel specimens. The mean indent length (micrometer) from five Knoop microindentations within each specimen was measured at baseline (B), after the first erosive challenge (E1), and after 2 and 4 hours intraoral phase (R). An increase in the indentation length compared to the baseline indicates softening of the enamel surface while decrease in the indentation length represents re-hardening of enamel surface. The %SMHR was calculated as : %SMHR = [(E1-R)/(E1-B)]*100. Greater values of %SMHR indicate that greater remineralization has occurred, thus higher values are more favorable.
measure: % Relative Erosion Resistance (RER; Comparison of 1150 Ppm Fluoride and 5% KNO3 Dentifrice Relative to a Fluoride Free Placebo Dentifrice to Inhibit Demineralization of Enamel)
time frame: After 4 hrs following single exposure of treatment
description: The %RER was calculated to assess the ability of treated enamel specimens to provide a combined benefit in terms of enhanced remineralization and acid resistance of the enamel. The mean indent length (micrometer) from five Knoop microindentations within each specimen was measured at baseline (B), after the first erosive challenge (E1), and after the second erosive challenge (E2) (E2 is measured for after both 2 and 4 hours of remineralization). An increase in the indentation length compared to the baseline indicates softening of the enamel surface while decrease in the indentation length represents re-hardening of enamel surface. The %RER was calculated as : %RER = [(E1-E2)/ (E1-B)]*100. Higher values of %RER indicate greater resistance to erosion, thus higher values are more favorable.
measure: Enamel Fluoride Uptake (EFU; Comparison of 1150 Ppm Fluoride and 5% KNO3 Dentifrice Relative to a Fluoride Free Placebo Dentifrice to Promote Fluoride Uptake in Enamel)
time frame: After 4 hrs following single exposure of treatment
description: The EFU was measured to determine the amount of fluoride incorporation into the model erosive lesions. Each enamel specimen drilled to a depth of approximately 100 μm using a microdrill, through the entire lesion (four cores per specimen). The enamel powder pooled from four drilling samples was then, dissolved in a known volume of perchloric acid and immediately analyzed for fluoride content using a calibrated fluoride specific electrode. The amount of fluoride-uptake by enamel was calculated based on the amount of fluoride divided by the area of the enamel cores and expressed as microgram fluoride per square centimeter (μgF/cm^2). Higher values of EFU indicate greater incorporation of fluoride into the enamel and are thus more favorable.
measure: % SMHR (Comparison of 1150 Ppm Fluoride and 5% KNO3 Dentifrice Relative to Comparator Containing 1100 Ppm Fluoride)
time frame: After 4 hrs following single exposure of treatment
description: The %SMHR was calculated to assess the changes in mineralization status of enamel specimens. The mean indent length (micrometer) from five Knoop microindentations within each specimen was measured at baseline (B), after the first erosive challenge (E1), and after 2 and 4 hours intraoral phase (R). An increase in the indentation length compared to the baseline indicates softening of the enamel surface while decrease in the indentation length represents re-hardening of enamel surface. The %SMHR was calculated as: %SMHR = [(E1-R)/(E1-B)]*100. Greater values of %SMHR indicate that greater remineralization has occurred, thus higher values are more favorable.
measure: % RER (Comparison of 1150 Ppm Fluoride and 5% KNO3 Dentifrice Relative to Comparator Containing 1100 Ppm Fluoride)
time frame: After 4 hrs following single exposure of treatment
description: The %RER was calculated to assess the ability of treated enamel specimens to provide a combined benefit in terms of enhanced remineralization and acid resistance of the enamel. The mean indent length (micrometer) from five Knoop microindentations within each specimen was measured at baseline (B), after the first erosive challenge (E1), and after the second erosive challenge (E2) (E2 is measured for after both 2 and 4 hours of remineralization). An increase in the indentation length compared to the baseline indicates softening of the enamel surface while decrease in the indentation length represents re-hardening of enamel surface. The %RER was calculated as : %RER = [(E1-E2)/ (E1-B)]*100. Higher values of %RER indicate greater resistance to erosion, thus higher values are more favorable.
measure: EFU (Comparison of 1150 Ppm Fluoride and 5% KNO3 Dentifrice Relative to Comparator Containing 1100 Ppm Fluoride)
time frame: After 4 hrs following single exposure of treatment
description: The EFU was measured to determine the amount of fluoride incorporation into the model erosive lesions. Each enamel specimen drilled to a depth of approximately 100 μm using a microdrill, through the entire lesion (four cores per specimen). The enamel powder pooled from four drilling samples was then, dissolved in a known volume of perchloric acid and immediately analyzed for fluoride content using a calibrated fluoride specific electrode. The amount of fluoride-uptake by enamel was calculated based on the amount of fluoride divided by the area of the enamel cores and expressed as microgram fluoride per square centimeter (μgF/cm^2). Higher values of EFU indicate greater incorporation of fluoride into the enamel and are thus more favorable.
arm group label: Test product
arm group type: Experimental
description: Participants will apply a full ribbon of the test product (1.5 grams [g]) containing 0.254% w/w sodium fluoride and 5% KNO3.
arm group label: Comparator Product
arm group type: Active Comparator
description: Participants will apply a full ribbon of the comparator product (1.5 g orally) containing 0.454% w/w stannous fluoride.
arm group label: Placebo Product
arm group type: Placebo Comparator
description: Participants will apply a full ribbon of the placebo (1.5 g orally) containing 5% KNO3.
intervention type: Drug
intervention name: 0.254% w/w sodium fluoride and 5% KNO3
description: Dentifrice containing 0.254% w/w sodium fluoride (1150 ppm fluoride) and 5% KNO3; plus 0.25% PVM/MA copolymer and 2.5% sodium lactate. Participants will brush it on the buccal surfaces of their natural teeth for 25 timed seconds and then swish the resulting toothpaste slurry around the mouth, without further brushing, for a timed period of 95 seconds. After expectorating the slurry, the participants will gently rinse their mouths with 15 millilitres [mL] of tap water for 10 seconds before expectorating again.
arm group label: Test product
intervention type: Drug
intervention name: 0.454% w/w stannous fluoride
description: Dentifrice containing 0.454% w/w stannous fluoride (1100 ppm fluoride). Participants will brush it on the buccal surfaces of their natural teeth for 25 timed seconds and then swish the resulting toothpaste slurry around the mouth, without further brushing, for a timed period of 95 seconds. After expectorating the slurry, the participants will gently rinse their mouths with 15 mL of tap water for 10 seconds before expectorating again.
arm group label: Comparator Product
intervention type: Drug
intervention name: 5% KNO3
description: Fluoride free placebo dentifrice containing 5% KNO3 (0 ppm fluoride), 0.25% PVM/MA copolymer and 2.5% lactate. Participants will brush it on the buccal surfaces of their natural teeth for 25 timed seconds and then swish the resulting toothpaste slurry around the mouth, without further brushing, for a timed period of 95 seconds. After expectorating the slurry, the participants will gently rinse their mouths with 15 mL of tap water for 10 seconds before expectorating again.
arm group label: Placebo Product
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: GSK Clinical Trials
role: Study Director
affiliation: GlaxoSmithKline
facility: 
country: United States
url: https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217381&amp;parentIdentifier=208166&amp;attachmentIdentifier=2023405a-a4d3-4a83-81a3-646cce348c22&amp;fileName=gsk-208166-protocol-redact.pdf&amp;versionIdentifier=
description: Related Info
url: https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217381&amp;parentIdentifier=208166&amp;attachmentIdentifier=6d21b0dc-6a7f-469f-9dd7-40aeb2f0005d&amp;fileName=gsk-208166-reporting-and-analysis-plan-redact.pdf&amp;versionIdentifier=
description: Related Info
responsible party type: Sponsor
mesh term: Tooth Erosion
mesh term: Listerine
mesh term: Fluorides
mesh term: Sodium Fluoride
mesh term: Tin Fluorides
sharing ipd: Yes
ipd description: IPD for this study will be made available via the Clinical Study Data Request site.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd time frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
ipd access criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
ipd url: https://clinicalstudydatarequest.com/Posting.aspx?ID=20365
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 