Pharmacokinetics of Advantage Arrest in Children

March 9, 2022 updated by: Advantage Silver Dental Arrest, LLC
The purpose of this study is to characterize basic PK parameters (Cmax, t1/2, AUC) in healthy children to contribute to evidence for the safety of Advantage Arrest, consistent with Guidance for Industry--Exposure--Response Relationships (April 2003).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a topical agent where the active ingredients are applied to the teeth and eventually swallowed and may be absorbed through the GI tract or excreted. Minimal amounts are absorbed through the oral mucosa. Serum concentrations of silver and fluoride will be be proportional to the dose of silver and fluoride administered topically to the teeth as part of Advantage Arrest. This is an open label exposure-response study with up to 50 healthy children ages 3-13 years of age. Subjects will be treated with Advantage Arrest and have one blood sample withdrawn at a randomly assigned time point. A minimum of 3 subjects per time point at 2,4,6,24,48,96 and 168 hours. Serum samples will be analyzed for F and Ag.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
59

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94158
        • University of California San Francisco Clinical and Translational Science Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

3 years to 13 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Healthy.
  • At least one carious lesion.

Exclusion Criteria:

  • Oral mucositis
  • Any ulcerative lesions
  • Hypersensitivity to silver
  • Hypersensitivity to fluoride.
  • SDF treatment within 3 months.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Advantage Arrest
38% silver diamine fluoride, topical, 1 drop, single application
Drug: Silver Diamine Fluoride
38% aqueous silver diamine fluoride [Ag(NH3)]2F, CAS RN 33040-28-7
Other Names:
  • Advantage Arrest

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Predicted Peak Serum Silver Concentration (Cmax)
Time Frame: Based on data collected at 2, 4, 6, 24, 48, 96, and 168 hours post-SDF application
As only a single blood sample was obtained from each child, serum silver concentration versus time data were analyzed simultaneously using population pharmacokinetic analysis with nonlinear mixed effects modeling. The parameters estimated were the apparent volume of distribution (V/F) and apparent oral clearance (CL/F). The rate constant of absorption (ka) was fixed to 23.7 day-1. The predicted peak serum silver Cmax was calculated using Cmax = Dose/(V/F)*exp^(-k⋅tmax ), where k = (CL/F)/(V/F) and tmax = [ln(ka/k)]/(ka-k).
Based on data collected at 2, 4, 6, 24, 48, 96, and 168 hours post-SDF application
Predicted Time to Peak Serum Silver Concentration (Tmax)
Time Frame: Based on data collected at 2, 4, 6, 24, 48, 96, and 168 hours post-SDF application
As only a single blood sample was obtained from each child, serum silver concentration versus time data were analyzed simultaneously using population pharmacokinetic analysis with nonlinear mixed effects modeling. The parameters estimated were the apparent volume of distribution (V/F) and apparent oral clearance (CL/F). The rate constant of absorption (ka) was fixed to 23.7 day-1. The predicted time to peak concentration was calculated using tmax = [ln(ka/k)]/(ka-k), where k = (CL/F)/(V/F).
Based on data collected at 2, 4, 6, 24, 48, 96, and 168 hours post-SDF application
Silver Half-life
Time Frame: Based on data collected at 2, 4, 6, 24, 48, 96, and 168 hours post-SDF application
As only a single blood sample was obtained from each child, serum silver concentration versus time data were analyzed simultaneously using population pharmacokinetic analysis with nonlinear mixed effects modeling. The parameters estimated were the apparent volume of distribution (V/F) and apparent oral clearance (CL/F). The rate constant of absorption (ka) was fixed to 23.7 day-1. The half-life of silver was calculated using half-life = ln(2)/k, where k = (CL/F)/(V/F).
Based on data collected at 2, 4, 6, 24, 48, 96, and 168 hours post-SDF application

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Apparent Oral Clearance of Silver (CL/F)
Time Frame: Based on data collected at 2, 4, 6, 24, 48, 96, and 168 hours post-SDF application
As only a single blood sample was obtained from each child, serum silver concentration versus time data were analyzed simultaneously using population pharmacokinetic analysis with nonlinear mixed effects modeling. The apparent oral clearance of silver (CL/F) was an estimated parameter.
Based on data collected at 2, 4, 6, 24, 48, 96, and 168 hours post-SDF application
Apparent Volume of Distribution of Silver (V/F)
Time Frame: Based on data collected at 2, 4, 6, 24, 48, 96, and 168 hours post-SDF application
As only a single blood sample was obtained from each child, serum silver concentration versus time data were analyzed simultaneously using population pharmacokinetic analysis with nonlinear mixed effects modeling. The apparent volume of distribution (V/F) was an estimated parameter.
Based on data collected at 2, 4, 6, 24, 48, 96, and 168 hours post-SDF application
Serum Silver Exposure (AUC)
Time Frame: Based on data collected at 2, 4, 6, 24, 48, 96, and 168 hours post-SDF application
Area under the curve of silver. As only a single blood sample was obtained from each child, serum silver concentration versus time data were analyzed simultaneously using population pharmacokinetic analysis with nonlinear mixed effects modeling. The parameters estimated were the apparent volume of distribution (V/F) and apparent oral clearance (CL/F). The rate constant of absorption (ka) was fixed to 23.7 day-1. The area under the curve was calculated using AUC = Dose/(CL/F).
Based on data collected at 2, 4, 6, 24, 48, 96, and 168 hours post-SDF application

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Average Serum Fluoride Concentrations
Time Frame: Collected at 2, 4, 6, 24, 48, 96, and 168 hours post-SDF application
Overall average of measured serum fluoride concentrations at the various timepoints.
Collected at 2, 4, 6, 24, 48, 96, and 168 hours post-SDF application

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Advantage Silver Dental Arrest, LLC

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
University of California, San Francisco

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Hellene Ellenikiotis, DDS, University of California, San Francisco

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 31, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 31, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 28, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 4, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 5, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 10, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 9, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2019-06-23

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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