Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| University of California, San Francisco | OTHER |
Not provided
Not provided
Not provided
Not provided
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).
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 Subjects will be treated with Advantage Arrest and have one blood sample withdrawn at a randomly assigned time point.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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Advantage Arrest | Experimental | 38% silver diamine fluoride, topical, 1 drop, single application |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Silver Diamine Fluoride | Drug | 38% aqueous silver diamine fluoride [Ag(NH3)]2F, CAS RN 33040-28-7 |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| 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 |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Hellene Ellenikiotis, DDS | University of California, San Francisco | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California San Francisco Clinical and Translational Science Institute | San Francisco | California | 94158 | United States |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Advantage Arrest | 38% silver diamine fluoride, topical, 1 drop, single application Silver Diamine Fluoride: 38% aqueous silver diamine fluoride [Ag(NH3)]2F, CAS RN 33040-28-7 |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Advantage Arrest | 38% silver diamine fluoride, topical, 1 drop, single application Silver Diamine Fluoride: 38% aqueous silver diamine fluoride [Ag(NH3)]2F, CAS RN 33040-28-7 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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). | Children who completed including blood draw | Posted | Mean | Standard Deviation | ng/ml | Based on data collected at 2, 4, 6, 24, 48, 96, and 168 hours post-SDF application |
|
168 h
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Advantage Arrest | 38% silver diamine fluoride, topical, 1 drop, single application Silver Diamine Fluoride: 38% aqueous silver diamine fluoride [Ag(NH3)]2F, CAS RN 33040-28-7 |
Not provided
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Hellene Ellenikiotis | University of California San Francisco | 408-313-0166 | hellene.ellenikiotis@ucsf.edu |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jun 23, 2019 | Dec 2, 2019 | Prot_SAP_000.pdf |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D003731 | Dental Caries |
| ID | Term |
|---|---|
| D017001 | Tooth Demineralization |
| D014076 | Tooth Diseases |
| D009057 | Stomatognathic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C024633 | silver diamine fluoride |
Not provided
Not provided
Not provided
Open label exposure--response study
Not provided
Not provided
Not provided
Not provided
| 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 |
| 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 |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Weight (kg) | Mean | Standard Deviation | kg |
|
|
|
| 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). | Children who completed including blood draw | Posted | Mean | Standard Deviation | hours | 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). | Posted | Mean | Standard Deviation | days | 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. | Posted | Mean | Standard Deviation | Liters/day | 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. | Posted | Mean | Standard Deviation | Liters/day | 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). | Posted | Mean | Standard Deviation | ng*day/mL | Based on data collected at 2, 4, 6, 24, 48, 96, and 168 hours post-SDF application |
|
|
|
| Other Pre-specified | Average Serum Fluoride Concentrations | Overall average of measured serum fluoride concentrations at the various timepoints. | Posted | Mean | Full Range | ng/ml | Collected at 2, 4, 6, 24, 48, 96, and 168 hours post-SDF application |
|
|
|
| 0 |
| 55 |
| 0 |
| 55 |
| 0 |
| 55 |
Not provided
Not provided