Trial Outcomes & Findings for Pharmacokinetics of Advantage Arrest in Children (NCT NCT04186663)

NCT ID: NCT04186663

Last Updated: 2022-03-10

Results Overview

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).

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 59 participants
• Primary outcome timeframe: Based on data collected at 2, 4, 6, 24, 48, 96, and 168 hours post-SDF application
• Results posted on: 2022-03-10

Participant Flow

Participant milestones

Measure	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
Overall Study STARTED	59
Overall Study COMPLETED	55
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Measure	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
Overall Study Lost to Follow-up	1
Overall Study Unable to complete blood draw	3

Baseline Characteristics

Pharmacokinetics of Advantage Arrest in Children

Baseline characteristics by cohort

Measure	Advantage Arrest n=55 Participants 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
Age, Continuous	7.7 years STANDARD_DEVIATION 2.9 • n=5 Participants
Sex: Female, Male Female	25 Participants n=5 Participants
Sex: Female, Male Male	30 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	24 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	25 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	6 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	11 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	8 Participants n=5 Participants
Race (NIH/OMB) White	11 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	25 Participants n=5 Participants
Region of Enrollment United States	55 participants n=5 Participants
Weight (kg)	32.6 kg STANDARD_DEVIATION 16.5 • n=5 Participants

PRIMARY outcome

Timeframe: Based on data collected at 2, 4, 6, 24, 48, 96, and 168 hours post-SDF application

Population: Children who completed including blood draw

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).

Outcome measures

Measure	Advantage Arrest n=55 Participants 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
Predicted Peak Serum Silver Concentration (Cmax)	17.8 ng/ml Standard Deviation 10.6

PRIMARY outcome

Timeframe: Based on data collected at 2, 4, 6, 24, 48, 96, and 168 hours post-SDF application

Population: Children who completed including blood draw

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).

Outcome measures

Measure	Advantage Arrest n=55 Participants 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
Predicted Time to Peak Serum Silver Concentration (Tmax)	5.1 hours Standard Deviation 0.9

PRIMARY outcome

Timeframe: 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).

Outcome measures

Measure	Advantage Arrest n=55 Participants 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
Silver Half-life	5.9 days Standard Deviation 4.7

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Advantage Arrest n=55 Participants 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
Apparent Oral Clearance of Silver (CL/F)	498 Liters/day Standard Deviation 496

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Advantage Arrest n=55 Participants 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
Apparent Volume of Distribution of Silver (V/F)	2294 Liters/day Standard Deviation 1253

SECONDARY outcome

Timeframe: 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).

Outcome measures

Measure	Advantage Arrest n=55 Participants 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
Serum Silver Exposure (AUC)	149 ng*day/mL Standard Deviation 140

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Measure	Advantage Arrest n=55 Participants 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
Average Serum Fluoride Concentrations	15 ng/ml Interval 6.0 to 36.0

Adverse Events

Advantage Arrest

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Hellene Ellenikiotis

University of California San Francisco

Phone: 408-313-0166

Email: hellene.ellenikiotis@ucsf.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place