Pharmacokinetics of Advantage Arrest in Children

Dental Caries Clinical Trial

Official title:

Pharmacokinetics of Advantage Arrest in Children

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04186663
• Other study ID #: 2019-06-23
• Status: Completed
• Phase: Phase 2
• Start date: August 1, 2019
• Est. completion date: March 31, 2020

Study information

• Verified date: May 2021
• Source: Advantage Silver Dental Arrest, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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 Subjects will be treated with Advantage Arrest and have one blood sample withdrawn at a randomly assigned time point.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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 59
• Est. completion date: March 31, 2020
• Est. primary completion date: March 31, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 3 Years to 13 Years

Eligibility

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.

Related Conditions & MeSH terms

• Dental Caries

Intervention

Drug:
• Silver Diamine Fluoride
38% aqueous silver diamine fluoride [Ag(NH3)]2F, CAS RN 33040-28-7

Locations

Country	Name	City	State
United States	University of California San Francisco Clinical and Translational Science Institute	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
Advantage Silver Dental Arrest, LLC	University of California, San Francisco

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Average Serum Fluoride Concentrations	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
Primary	Predicted Peak Serum Silver Concentration (Cmax)	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
Primary	Predicted Time to Peak Serum Silver Concentration (Tmax)	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
Primary	Silver Half-life	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	Apparent Oral Clearance of Silver (CL/F)	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
Secondary	Apparent Volume of Distribution of Silver (V/F)	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
Secondary	Serum Silver Exposure (AUC)	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