Pharmacokinetics of Advantage Arrest in Children

Phase 2

Completed

Conditions: Dental Caries

Interventions: Drug: Silver Diamine Fluoride

Registration Number: NCT04186663

Lead Sponsor: Advantage Silver Dental Arrest, LLC

Brief 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).

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 Subjects will be treated with Advantage Arrest and have one blood sample withdrawn at a randomly assigned time point.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

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 59

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Advantage Arrest	Silver Diamine Fluoride	38% silver diamine fluoride, topical, 1 drop, single application

Primary Outcome Measures

Name	Time	Method
Predicted Peak Serum Silver Concentration (Cmax)	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).
Predicted Time to Peak Serum Silver Concentration (Tmax)	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).
Silver Half-life	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 Outcome Measures

Name	Time	Method
Apparent Volume of Distribution of Silver (V/F)	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.
Apparent Oral Clearance of Silver (CL/F)	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.
Serum Silver Exposure (AUC)	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).