Testing if Tartarase Can Remove Dental Tartar
Condition: Dental Calculus
MeSH terms: Dental Calculus; Calculi
Study type: Interventional

Summary: 
      This study was designed to find our whether a novel toothpaste containing safe digestive
      enzymes (Tartarase) was able to remove pre-existing dental tartar when compared to a
      well-known toothpaste (Crest). A group of 40 test subjects that had at lease 9 mm of tartar
      on the tongue side of the 6 lower front teeth, were randomly divided into 3 groups unknown to
      the the team overseeing the measurements. All the groups brushed with a toothbrush approved
      by the American Dental Association. Group A (20 subject) was the control group. They brushed
      in the morning and before bed with Crest for 2 minutes. Group B (10 subjects) brushed in the
      morning and before bed using the same procedure, first with Tartarase for 30 seconds, spit,
      but did not rinse, then repeated. After 30 minutes then brushed with Crest. Group C (10
      subjects) brushed for 30 seconds with Tartarase, spit but did not rinse, then filled a dental
      tray with Tartarase and covered the 6 lower front teeth and waited 30 minutes, spit but did
      not rinse and brushed for ann additional 30 seconds with Tartarase. After 30 minutes they
      brushed with Crest. They brushed with crest before bed, without another Tartarase treatment.
      The study was a 4-week study, with tartar measured at the start (baseline), again after 2
      weeks and again at the final study point of 4 weeks.

      If any of the study subjects experienced anything unpleasant, they were to inform the team
      overseeing the study. The tartar measurements were compiled into the 3 groups and
      statistically analyzed to determine if there were any changes in the amount of tartar within
      the groups and between the groups.
    

Detailed description: 
      Quality assurance All raw data (Case Report Forms) were screened for quality assurance by the
      Investigators' Quality Assurance officer (QA) and found to be in compliance with protocol
      requirements before being sent to the Sponsor.

      Data checks Not applicable Source data verification Not applicable Data dictionary

      The Volpe-Manhold Index (V-MI) measures, in millimeters, calculus present on the lingual
      surfaces of the lower six anterior teeth. The measurement from the most inferior border of
      visible calculus obtained in three planes:

        1. Bisecting the center of the lingual surface;

        2. Diagonally through the mesial-incisal point angle of the tooth through the area of
           greatest calculus height; and

        3. Diagonally through the distal point angle of the tooth through the area of greatest
           calculus height.

      The primary outcome was calculus using the V-MI, all other variables are considered
      secondary. The calculus scores are summed to provide a total score at each clinical
      examination. The primary time points were at the baseline and at the after 4 weeks of product
      use.

      Standard operating procedures Patient recruitment Subjects were recruited from site's
      database. Data collection During the course of the trial, the clinical site allowed
      monitoring by the Sponsor to check compliance with Protocol, regulations and guidelines,
      adequacy of the equipment and facilities, and satisfactory data collection.

      Data Management Data was transferred from the case report forms (scoring charts) and entered
      into a database (Excel Spreadsheet) for analysis. The data was tabulated according to
      clinical scoring index and examination using a spreadsheet program.

      Case Report Forms, questionnaires, and Subjects Diaries were entered into spreadsheets at the
      research site after source data verification and resolution of monitoring queries. The
      spreadsheets were electronically delivered to research site subcontractor for data analysis.

      Data was entered using a double entry method and controlled by periodic and random validation
      check programming. Immediately following data validation, a data transfer was conducted to
      prevent modification to the spreadsheets.

      Data Analysis A safety analysis set was conducted, including all subjects using the
      experimental gel at least a single time. A Performance analysis set consisted of all subjects
      providing at least one post treatment performance measurement. Only observed data was used;
      missing data was not imputed.

      STATISTICAL ANALYSIS Subject Disposition The safety analysis set was used for describing
      subject disposition. Subject disposition was tabulated; the number of enrolled, exposed,
      prematurely terminated and completed subjects were summarized. A list of
      dropouts/terminations was prepared including reason for discontinuation, and time of
      discontinuation.

      Safety Analyses Safety analyses was descriptive in nature, with SAE's and AEs tabulated by
      body system, preferred term, severity and relation to investigational gel. Where relevant,
      events were related to remote log file data. In addition, safety complaints, as described by
      the subjects were described and investigated.

      Performance Analyses Efficacy was determined by reduction of dental calculus within treatment
      groups (longitudinal analysis) and between groups as compared to the control group following
      4 weeks of treatment.

      The primary outcome was calculus using the V-MI, as described in the Data Dictionary.

      Statistical significance of mean data for age and scoring index was determined parametrically
      by analysis of variance for testing of differences between the product groups. Intergroup
      comparisons for each parameter were made by means of multiple range tests with compensation
      for gender, if necessary. Data from all subjects who completed the final assessment were used
      in the analysis.

      The data for each scoring index was also analyzed by analysis of covariance using the
      baseline data as the covariate. The covariate (baseline data) was included in the statistics
      model for increased precision in determining the effect of the test products on the scores.
      The adjusted means generated by this procedure compensate for any variations between
      treatment groups that existed in the baseline data.

      Longitudinal (i.e., within-treatment) comparisons were performed for V-MI means using a
      one-sample t-test on the changes from baseline to the final examination.

      All comparisons were tested at an overall 0.05 level of significance using 2-sided tests.
      Summary statistics were provided at all timepoints. Safety data was summarized. Adverse
      events experienced by all subjects receiving test products were included in the safety
      analyses. All cases were checked for compliance with the study protocol, and for accuracy and
      completeness. Those cases which did not meet these requirements were excluded from primary
      analyses.

      Post-power analyses for those endpoints that were determined to not be statistically
      significant were undertaken. Thus, sample sizes needed for a properly powered study were
      determined.

      All adverse events reported were listed, documenting course, outcome, severity, and possible
      relationship to study products. Comparisons among the treatment groups were made by
      tabulating the frequency of subjects with one or more adverse events during the trial. If
      required, likelihood ratio chi square tests were used to compare the frequency of subjects
      experiencing adverse events among treatment groups.

      Reporting for adverse events A subject may have discontinued the trial at any time for any
      reason. The investigator could have withdrawn a subject if, in his judgment, it was in the
      best interest of the subject, if the subject could not comply with the protocol, or if a
      Serious Adverse Event occurred. If a subject withdrew, the reason was recorded in the CRF End
      of Study Statement and signed by the Investigator.

      Risk Assessment Risk is the product of the likelihood that an adverse medical event will
      occur, times the severity of the event. A comprehensive Risk Analysis was conducted for the
      Tartarase gel to indicate it was safe for human use. The risk analysis report was available
      upon request.

      Adverse Events Definitions An Adverse Event (AE) is any untoward medical occurrence (sign,
      symptom, illness, abnormal laboratory value, or other medical event) in a subject. This
      definition does not imply that there is a relationship between the adverse event and the
      device under investigation. (Significant device failure may constitute an adverse event if an
      undesirable experience occurs).

      An Adverse Device Effect (ADE) is any untoward and unanticipated response to a medical
      device. This definition includes any event resulting from insufficiencies or inadequacies in
      the instructions for use or the deployment of the device, or any event that is a result of a
      user error.

      Serious Adverse Event (SAE)

      A serious adverse event (SAE) is any adverse event that:

      Led to death Led to a serious deterioration in the health of the subject that resulted in a
      life-threatening illness or injury Resulted in a permanent impairment of a body structure or
      a body function Required in-subject hospitalization or prolongation of existing
      hospitalization Resulted in medical or surgical intervention to prevent permanent impairment
      to body structure or a body function Led to fatal distress, a congenital abnormality, birth
      defect or death An unanticipated adverse event is any serious, study product related adverse
      event, if that event was not previously identified in the risk analysis and informed consent
      form in nature, severity, or frequency.

      Adverse events are graded according to severity as follows: Mild: Sign or symptom, usually
      transient, requiring no special treatment and generally not interfering with usual
      activities. Moderate: Sign or symptom, which may be ameliorated by simple therapeutic
      measures; yet, may interfere with usual activity. Severe: Sign or symptom that are intense or
      debilitating and that interfere with usual activities. Recovery is usually aided by
      therapeutic measures.

      The Investigator reported all Adverse Events which occurred with each subject throughout the
      study and follow-up period and recorded them in the CRF Adverse Events Investigation Form.
      The Investigator categorized Adverse Events according to:

      Serious or non-serious Severity Anticipated or unanticipated Relationship to device use
      INVESTIGATOR REPORTING OF AES

      The Investigator would have reported all serious adverse events (SAEs) to Pontis Biologics by
      telephone as soon as becoming aware of them. A written follow-up report would have been
      emailed or faxed to Pontic Biologics and the reviewing IRB within 24 hours and would have
      included the following information:

      Nature of SAE Statement regarding the degree to which it is considered device related, and
      rationale Results of any diagnostic tests that were performed Description of any treatment
      implemented Statement of subject's current clinical status Investigator's signature and date

      Non-serious adverse events that were unanticipated and may have been study product related
      were reported to the Pontic Biologics by telephone within 24 hours. A written follow-up
      report was emailed or faxed to Pontis Biologics within 5 working days and included the
      following information:

      Nature of adverse effect (AE) Statement as to why it is considered unanticipated Statement as
      to the degree to which it is considered device related, and rationale Results of any
      diagnostic tests that were performed Description of any treatment implemented Statement of
      subject's current clinical status Change Management Not applicable Sample size assessment See
      statistical analysis Plan for missing data Not applicable Statistical Analysis The primary
      outcome was calculus using the V-MI, and all other variables are considered secondary.
      Statistical significance of mean data for age and scoring index was determined parametrically
      by analysis of variance for testing of differences between the product groups. Intergroup
      comparisons for each parameter were made by means of multiple range tests with compensation
      for gender, if necessary. Data from all subjects who completed the final assessment were used
      in the analysis.

      The data for each scoring index was also analyzed by analysis of covariance using the
      baseline data as the covariate. The covariate (baseline data) was included in the statistics
      model for increased precision in determining the effect of the test products on the scores.
      The adjusted means generated by this procedure compensate for any variations between
      treatment groups that existed in the baseline data.

      Longitudinal (i.e., within-treatment) comparisons were performed for V-MI means using a
      one-sample t-test on the changes from baseline to the final examination.

      All comparisons were tested at an overall 0.05 level of significance using 2-sided tests.
      Summary statistics were provided at all timepoints. Safety data was summarized. Adverse
      events experienced by all subjects receiving test products were included in the safety
      analyses. All cases were checked for compliance with the study protocol, and for accuracy and
      completeness. Those cases which did not meet these requirements were excluded from primary
      analyses.

      Post-power analyses for those endpoints that were determined to not be statistically
      significant were undertaken. Thus, sample sizes needed for a properly powered study were
      determined.

      All adverse events reported were listed, documenting course, outcome, severity, and possible
      relationship to study products. Comparisons among the treatment groups were made by
      tabulating the frequency of subjects with one or more adverse events during the trial. If
      required, likelihood ratio chi square tests were used to compare the frequency of subjects
      experiencing adverse events among treatment groups.
    

Intervention name(s): Tartarase
Intervention type(s): Biological
Intervention description(s): Brushing with a formulation containing DNase 1 and chymotrypsin to assess its efficacy at removing accumulated calculus
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Comparison of the change in calculus abundance of two treatment groups, using the same dentifrice with two different methods of application with a control group using a popular standard dentifrice.
Masking: Single (Care Provider)
Primary purpose: Treatment
Keywords: gingivitis; dentifrice; plaque