Skip to main content
OpenTrials
Completed

NCT Number: NCT04186663

Pharmacokinetics of Advantage Arrest in Children

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).

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Dental Caries Stomatognathic Diseases Tooth Demineralization Tooth Diseases

Age range

3 year–13 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

University of California San Francisco Clinical and Translational Science Institute

San Francisco, California, 94158, United States

About this study

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 Subjects will be treated with Advantage Arrest and have one blood sample withdrawn at a randomly assigned time point.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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Silver diamine fluoride

Drug

38% aqueous silver diamine fluoride [Ag(NH3)]2F, CAS RN 33040-28-7

Other names: Advantage Arrest

Primary outcomes

  1. 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).

  2. 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).

  3. 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).

Secondary outcomes

  1. 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.

  2. 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.

  3. 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).

Other outcomes

  1. 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.

Sponsors and collaborators

Lead sponsor

Advantage Silver Dental Arrest, LLC

Industry

Collaborators

  • University of California, San Francisco

Registry information

Important dates

Study start
2019
Primary completion
2020
Study completion
2020
First posted
Dec 5, 2019
Registry last updated
Mar 10, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.