Dental CariesPhase 2NCT04186663
Pharmacokinetics of Advantage Arrest in Children
A Phase 2 study testing Silver Diamine Fluoride in people with Dental Caries, run by Advantage Silver Dental Arrest, LLC at 1 site in United States.
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). Read more about this study
- Who is it for?
- Ages 3 to 13 yearsHealthy volunteers can take part
- Conditions the study is for
- Dental Caries
- What is being tested?
- Silver Diamine Fluoride
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 59 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Aug 2019to 31 Mar 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 13 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Healthy.
- At least one carious lesion.
Who cannot join
- Oral mucositis
- Any ulcerative lesions
- Hypersensitivity to silver
- Hypersensitivity to fluoride.
- SDF treatment within 3 months.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California San Francisco Clinical and Translational Science Institute
San Francisco, California, 94158
About this study
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).
Read the 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 Subjects will be treated with Advantage Arrest and have one blood sample withdrawn at a randomly assigned time point.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.
- Conditions
- Dental Caries
- Being tested
- Silver Diamine Fluoride
- Keywords
- child, pharmacokinetics, silver diamine fluoride
- Medical subject headings
- Dental Caries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Silver Diamine FluorideDrug
Also called Advantage Arrest
38% aqueous silver diamine fluoride [Ag(NH3)]2F, CAS RN 33040-28-7
| Study group | Role | What they receive |
|---|---|---|
| Advantage Arrest | Experimental | 38% silver diamine fluoride, topical, 1 drop, single application Receives: Drug: Silver Diamine Fluoride |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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).
Measured: 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).
Measured: Based on data collected at 2, 4, 6, 24, 48, 96, and 168 hours post-SDF application
Secondary outcomes (3)
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.
Measured: 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)
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.
Measured: 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).
Measured: Based on data collected at 2, 4, 6, 24, 48, 96, and 168 hours post-SDF application
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2019
- Study start1 Aug 2019
- Primary completion31 Mar 2020
- Study completion31 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Dental CariesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Open label exposure--response study
- Masking
- None (open label)
- Enrolment
- 59 participants (actual)
Sponsor and investigators
- Lead sponsor
- Advantage Silver Dental Arrest, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- University of California, San Francisco
- Responsible party
- Sponsor
- Investigators
- Hellene Ellenikiotis, DDS, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04186663
- Sponsor's protocol ID
- 2019-06-23
- Status last verified
- May 2021
- First submitted
- 28 Nov 2019
- Last updated
- 10 Mar 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics of Advantage Arrest in Children
- ClinicalTrials.gov ID
- NCT04186663
- Acronym / sponsor ID
- 2019-06-23
- Conditions
- Dental Caries
- Keywords
- child, pharmacokinetics, silver diamine fluoride
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 59 participants (actual)
- Lead sponsor
- Advantage Silver Dental Arrest, LLCIndustry (pharma, biotech, devices)
- Collaborators
- University of California, San Francisco
- Study start
- 1 Aug 2019 (actual)
- Primary completion
- 31 Mar 2020 (actual)
- Study completion
- 31 Mar 2020 (actual)
- First posted
- 5 Dec 2019 (actual)
- Results
- Posted 10 Mar 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Open label exposure--response study
| Arm | Type | Receives |
|---|---|---|
| Advantage Arrest | Experimental | Drug: Silver Diamine Fluoride38% silver diamine fluoride, topical, 1 drop, single application |
Who may qualify
- Ages
- 3 to 13 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- Healthy.
- At least one carious lesion.
Key exclusion criteria (5 listed)
- Oral mucositis
- Any ulcerative lesions
- Hypersensitivity to silver
- Hypersensitivity to fluoride.
- SDF treatment within 3 months.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Silver Diamine FluorideAlso: Advantage Arrest38% aqueous silver diamine fluoride [Ag(NH3)]2F, CAS RN 33040-28-7 | Drug | Advantage Arrest |
Primary outcome
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).
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).
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).
3 secondary outcomes
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
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
Serum Silver Exposure (AUC)
Time frame: Based on data collected at 2, 4, 6, 24, 48, 96, and 168 hours post-SDF application
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hellene Ellenikiotis, DDS principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Silver Diamine Fluoride in people with Dental Caries, run by Advantage Silver Dental Arrest, LLC at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Mar 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2022.