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fluoride

Phase 3

Dental Caries | Small molecule | ENT |GSK plc|Trials Updated: Nov 14, 2018

fluoride development status

Highest phase Phase 3
Registered trials 8 across 3 sponsors since Jul 2008

fluoride target and mechanism

ModalitySmall molecule

Also known as Sodium fluoride, Sodium Fluoride (NaF), Sodium fluoride toothpaste, NaF

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLED
Total Trials7
Total Enrollment810

FDA Designations

No designations recorded

fluoride clinical trials

fluoride · 7 trials · 5 indications

Phase 3 3Phase 2 4
NCT01641237Effect of Fluoride in a Dentifrice on Remineralization of Erosive LesionsEnamel Erosion
COMPLETED72 Analytics
NCT01607411A Clinical Study to Evaluate Experimental Children's Toothpastes in an In-Situ Caries ModelDental Caries
COMPLETED55 Analytics
NCT00708305Evaluation of Plaque Fluid Fluoride Retention From Fluoride ToothpastesDental Caries
COMPLETED65 Analytics
PHASE3COMPLETED
Effect of Fluoride in a Dentifrice on Remineralization of Erosive Lesions
Enamel ErosionUnlock trial analytics
PHASE3COMPLETED
A Clinical Study to Evaluate Experimental Children's Toothpastes in an In-Situ Caries Model
Dental CariesUnlock trial analytics
PHASE3COMPLETED
Evaluation of Plaque Fluid Fluoride Retention From Fluoride Toothpastes
Dental CariesUnlock trial analytics

Study Endpoints

Primary Endpoints

Percentage Surface Microhardness Recovery (%SMHR) Dose Response Relationship
Baseline to 4 hours

SMHR test was used to assess the changes in mineralization status of enamel specimens using a Wilson 2100 Hardness tester. SMHR was determined by measuring the length of the indentations of enamel specimens. An increase in the indentation length compared to the baseline indicates softening while decrease in the indentation length represents rehardening of enamel surface. Percent SMHR was calculated from indentation values of enamel specimens at baseline (B), after in-situ hardening (R) and after first erosive challenge (E1) using formula: \[(E1-R)/ (E1-B)\]\*100.

Percentage Surface Microhardness Recovery of Test Dentifrices Relative to Placebo Dentifrice
Baseline to 4 hours

Surface microhardness recovery (SMHR) test was used to assess the changes in mineralization status of enamel specimens using a Wilson 2100 Hardness tester. SMHR was determined by measuring the length of the indentations of enamel specimens. An increase in the indentation length compared to the baseline indicates softening while decrease in the indentation length represents rehardening of enamel surface. Percent SMHR was calculated from indentation values of enamel specimens at baseline (B), after in-situ hardening (R) and after first demineralization challenge (D1) using formula: \[(D1-R)/ (D1-B)\]\*100.

Natural Log Transformed Area Under the Fluoride Concentration in Plaque Fluid by Time Curve (AUC) Between 0-4 Hours
Plaque samples collected at 15 minutes, 30 minutes, 1 hour, 2 hours and 4 hours post single application of treatment

To evaluate fluoride content, plaque samples were collected from the interproximal surfaces of the posterior teeth of participants using a standardized approach. Plaque fluid fluoride were calculated using a micro analytical method and in comparison to a standard fluoride curve constructed on the same day of the analysis. AUC was determined from 0-4hours using trapezoidal rule and natural log transformation was applied due to failure of assumption of normal distribution of data.

Change From Baseline in Schiff Sensitivity Score
Week 8

The examiner assessed the participant's response to an evaporative air stimulus for each tooth using the Schiff Sensitivity Scale which was scored as follows - 0: Participant did not respond to air stimulation; 1: Participant responded to air stimulus but does not request discontinuation of stimulus; 2: Participant responded to air stimulus and requested discontinuation or moves from stimulus; 3: Participant responded to stimulus, considered stimulus to be painful, and requested discontinuation of the stimulus. A reduction in Schiff Sensitivity score will be indicative of an improvement in sensitivity.

Number of Gingival Bleeding Sites at 24 Weeks
24 weeks

The Bleeding Index was performed by a single examiner using a color coded periodontal probe. The probe was engaged approximately 1 millimetre (mm) into the gingival crevice. A moderate pressure was used whilst sweeping from interproximal to interproximal along the sulcular epithelium. The BI scoring system used is as follows: 0= No bleeding after 30 seconds; 1= Bleeding upon probing after 30 seconds; 2= Immediate bleeding observed

Modified Gingival Index (MGI) at 24 Weeks
24 weeks

MGI was assessed on facial and lingual surfaces at two sites on each tooth (papillae and margin). The scoring of the MGI was performed under dental office conditions using a standard dental light for illuminating the oral cavity. Compressed air, water and mouth mirrors were available to each examiner. This procedure was performed by a single examiner. The MGI scoring system is as follows: 0 = absence of inflammation; 1 = mild inflammation; slight change in color, little change in color; little change in texture of any portion of the marginal or papillary gingival unit; 2 = mild inflammation; criteria as above but involving the entire marginal or papillar gingival units; 3= moderate inflammation; glazing, redness, edema, and/ or hypertrophy of the marginal or papillary gingival unit; 4 = severe inflammation; marked redness, edema and/or hypertrophy of the marginal or papillary gingival unit, spontaneous bleeding, congestion, or ulceration

Adjusted Mean Percent Net Erosion Resistance (NER) of Enamel Specimens Exposed to Test Dentifrice + Test MR Relative to: 1) Test Dentifrice+ Sterile Water Rinse 2) Reference Dentifrice+ Sterile Water Rinse 3) Placebo Dentifrice+ Sterile Water Rinse
Baseline, 4 hours post treatment in each treatment period

Enamel specimens were exposed to dietary erosive challenge and set of five indentations within each specimen was measured. Decrease in the indentation length compared to the baseline indicates hardening of enamel surface. Enamel specimens were exposed to second erosion challenge to determine NER which compared the indentations values of enamel specimens at baseline (B), first erosive (E1) and second erosive challenge (E2). Percent NER was calculated by formula: \[(E1-E2)/ (E1-B)\]\*100. Smaller the negative NER, better is treatment regimen in imparting resistance to enamel.

Secondary Endpoints

%SMHR
Baseline to 4 hours
Percentage Relative Erosion Resistance
Baseline to 4 hours
Enamel Fluoride Uptake (Corrected Data)
Baseline to 4 hours
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Study Design & Arms

AllocationRANDOMIZED
MaskingTRIPLE
ModelCROSSOVER
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Low ppm fluoride dentifriceEXPERIMENTALLow ppm fluoride as sodium fluoride in a silica base dentifrice
Medium ppm fluoride dentifriceEXPERIMENTALMedium ppm fluoride as sodium fluoride in a silica base dentifrice
High ppm fluoride dentifriceEXPERIMENTALHigh ppm fluoride as sodium fluoride in a silica base dentifrice
No fluoride dentifricePLACEBO_COMPARATORno added fluoride in a silica base dentifrice
Fluoride free toothpastePLACEBO_COMPARATORtoothpaste with no fluoride
1426ppm Fluoride ToothpasteEXPERIMENTALExperimental toothpaste containing 1426 ppm Fluoride
1000 ppm Fluoride ToothpasteEXPERIMENTALExperimental toothpaste containing 1000 ppm Fluoride
500 ppm ToothpasteEXPERIMENTALExperimental toothpaste containing 500 ppm Fluoride
NaF toothpaste (1450 parts per million [ppm] fluoride [F])EXPERIMENTALParticipants brushed for one timed minute with 1.6g of NaF/silica and 0.4 percent carbopol toothpaste containing 1450ppmF as NaF. Participants then swished the slurry around their mouth for 10 seconds, expectorated, then rinsed with water for 10 seconds.
NaF toothpaste (1400ppmF)ACTIVE_COMPARATORParticipants brushed for one timed minute with 1.6g of NaF toothpaste containing 1400ppmF as NaF. Participants then swished the slurry around their mouth for 10 seconds, expectorated, then rinsed with water for 10 seconds.
Sodium monofluorophosphate (NaMFP)/ NaF toothpaste (1450ppmF))ACTIVE_COMPARATORParticipants brushed for one timed minute with 1.6g of NaMFP/NaF toothpaste containing 1450ppmF from NaMFP and NaF. Participants then swished the slurry around their mouth for 10 seconds, expectorated, then rinsed with water for 10 seconds.
Placebo toothpaste (0ppmF)PLACEBO_COMPARATORParticipants brushed for one timed minute with 1.6g of fluoride free toothpaste. Participants then swished the slurry around their mouth for 10 seconds, expectorated, then rinsed with water for 10 seconds.
Test ProductEXPERIMENTALParticipants will rinse twice daily (morning and evening) with 10 milliliters (mL) of oral rinse for 60 timed seconds and expectorate. No further rinsing with water will be permitted after use of the oral rinse.
Negative ControlOTHERParticipants will rinse twice daily (morning and evening) with 10 mL of oral rinse for 60 timed seconds and expectorate. No further rinsing with water will be permitted after use of the oral rinse.
PlaceboPLACEBO_COMPARATORParticipants will rinse twice daily (morning and evening) with 10 mL of oral rinse for 60 timed seconds and expectorate. No further rinsing with water will be permitted after use of the oral rinse.
Experimental DentifriceEXPERIMENTALParticipants were advised to brush their teeth with experimental dentifrice containing sodium bicarbonate plus 1150 parts per million (ppm) fluoride as sodium fluoride
Reference DentifriceACTIVE_COMPARATORParticipants were advised to brush their teeth with reference dentifrice containing 1100ppm fluoride as sodium fluoride
Sodium bicarbonate plus sodium fluorideEXPERIMENTALExperimental dentifrice containing sodium bicarbonate plus 1150 parts per million (ppm) fluoride as sodium fluoride
Sodium fluorideACTIVE_COMPARATORToothpaste containing 1100 ppm fluoride as sodium fluoride
Test Dentifrice + Test Mouth Rinse (MR)EXPERIMENTALTest fluoride dentifrice and test fluoride MR
Test Dentifrice + Sterile Water RinseEXPERIMENTALTest fluoride dentifrice and sterile water rinse
Placebo Dentifrice + Test MREXPERIMENTALPlacebo dentifrice and test fluoride rinse
Reference Dentifrice + Sterile Water RinseACTIVE_COMPARATORMarketed fluoride dentifrice with sterile water rinse
Placebo Dentifrice + Sterile Water RinsePLACEBO_COMPARATORPlacebo dentifrice and sterile water rinse

Interventions

NameTypeDescription
sodium fluorideDRUGfluoride as sodium fluoride
no added fluoride in a silica baseDRUGno added fluoride
FluorideDRUGFluoride Toothpaste
PlaceboDRUGFluoride free toothpaste
Sodium Fluoride (NaF)DRUGDifferent fluoride toothpastes containing between 1400ppmF - 1450ppmF of fluoride as NaF
Potassium oxalateDEVICEOral rinse containing 1.5 percent (%) KOX and 0 ppm fluoride
Sodium bicarbonate and sodium fluorideDRUGExperimental toothpaste containing sodium bicarbonate experimental dentifrice plus 1150 parts per million (ppm) fluoride as sodium fluoride
Sodium bicarbonate plus sodium fluorideDRUGExperimental dentifrice containing sodium bicarbonate plus 1150 parts per million (ppm) fluoride as sodium fluoride
Sodium monoflurophosphateDRUGUnited Kingdom marketed fluoride toothpaste
Sterile waterDRUGSterile water rinse
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Eligibility Criteria

Age Range18 Years to 65 Years
SexALL
Healthy VolunteersYes
Study Sites1

Inclusion Criteria: * intact maxillary dental arch suitable to retain a palatal appliance, an intact mandibular dental arch and a stimulated/unstimulated saliva flow rate of ≥ 0.8 milliliter/minute (ml/min) and ≥ 0.2 ml/min respectively.

Countries:United States
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Frequently asked questions about fluoride

What is fluoride used for?

Fluoride is used in oral care products to help prevent dental caries and to manage dentin sensitivity, enamel erosion, tooth erosion, and general oral hygiene. It is a small molecule developed by GSK plc for these dental and ENT applications.

Who makes fluoride?

GSK plc, which trades under the ticker GSK, is the developer of fluoride for oral care indications. The company has sponsored clinical trials evaluating fluoride-containing formulations such as dentifrices and oral rinses.

What phase is fluoride in?

Fluoride has been studied in Phase 3 clinical development. A Phase 3 trial, NCT01641237, evaluated the effect of fluoride in a dentifrice on remineralization of erosive lesions. The program also includes completed Phase 2 trials.

What clinical trials is fluoride in?

Fluoride has been evaluated in completed clinical trials including NCT01641237, a Phase 3 study of a fluoride dentifrice for enamel erosion, and NCT03238352, a Phase 2 oral rinse study for dentin sensitivity. Phase 2 trials NCT02207907 and NCT02207400 assessed sodium bicarbonate toothpaste for oral hygiene.

Is fluoride the same as sodium fluoride?

Yes, fluoride is also known as sodium fluoride or Sodium Fluoride (NaF). These names refer to the same active ingredient used in the oral care formulations studied by GSK plc.