NCT02751320

Efficacy of Three Toothpastes Using an in Situ Caries Model

Completed NA Results posted Last updated 13 October 2017

What this trial tests

NA trial testing 0.425 % w/w phytate,1150ppm F in Dental Caries in 58 participants. Completed in 11 August 2016.

Timeline

1 February 2016

Primary endpoint
1 July 2016

11 August 2016

Quick facts

Lead sponsor	GlaxoSmithKline
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	single
Primary purpose	basic science
Enrollment	58
Start date	1 February 2016
Primary completion	1 July 2016
Estimated completion	11 August 2016
Sites	1 location across United States

Drugs / interventions tested

• 0.425 % w/w phytate,1150ppm F — full drug profile →
• 0.85 % w/w phytate,1150ppm F — full drug profile →
• 0.85 % w/w phytate,0.3%ZnCl2 0.5% sodium citrate, 1150ppm F
• 0 ppm F — full drug profile →
• 1150ppm F — full drug profile →
• 0.3%ZnCl2, 0.5% sodium citrate, 1150ppm F — full drug profile →

Conditions studied

• Dental Caries — all drugs for Dental Caries →

Sponsor

GlaxoSmithKline — full company profile →

Who can join

Adults 18 to 85, any sex, with Dental Caries. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage Surface Microhardness Recovery (SMHR) of Phyte (0% 0.425% and 0.85%) at 2 Weeks Primary · Baseline upto 2 weeks

SMHR test was used to assess the changes in mineralization status of partially demineralized enamel specimens using a Wilson 2100 Hardness tester. SMH was determined by measuring the length of the indentations of enamel specimens. % SMHR was calculated from indentation length (micrometer \[μm\]) of sound enamel specimen at baseline (B), indentation length (μm) after in vitro demineralization(D), indentation length (μm) after intra-oral exposure (R): \[D-R/D-B\]\*100.

Group	Value	95% CI
Test Product 1	25.53	± 21.513
Test Product 2	26.81	± 18.059
Reference Product 1	7.41	± 18.648
Reference Product 2	28.88	± 21.046

% SMHR of 0.85% Phytate Compared to 0% Phytate, in Presence of 1150ppm Fluoride and 0.3% ZnCl2, 0.3% ZnCl2 Compared to 0% ZnCl2 in the Presence of 1150ppm Fluoride and 0.3% ZnCl2 Compared to 0% ZnCl2 in the Presence of 1150ppm Fluoride and 0.85% Phytate Secondary · Baseline upto 2 weeks

SMHR test was used to assess the changes in mineralization status of partially demineralized enamel specimens using a Wilson 2100 Hardness tester. SMH was determined by measuring the length of the indentations of enamel specimens. % SMHR was calculated from indentation length (μm) of sound enamel specimen at baseline (B), indentation length (μm) after in vitro demineralization(D), indentation length (μm) after intra-oral exposure (R): \[D-R/D-B\]\*100.

Group	Value	95% CI
Test Product 2	26.81	± 18.059
Test Product 3	23.38	± 20.177
Reference Product 2	28.88	± 21.046
Reference Product 3	28.80	± 20.830

Transverse Microradiography (TMR) Net Remineralization Change (ΔM) Value of Phytate (0% 0.452% and 0.85%) at 4 Weeks Secondary · Baseline upto 4 weeks

TMR was used to assess changes in the mineral status of partially demineralized enamel specimens. Lesions were analyzed at baseline and Integrated Mineral Loss (∆Z): (∆Z =(lesion depth x 87) - area under the curve \[Area under the curve which relates volume % mineral at distances from the specimen surface with respect to section thickness\]). After treatment a further section was taken from each lesion specimen for radiography assessment; ∆Z was calculated. The change which occurred in mineral content (∆M) of the lesions as a result of treatment was calculated by: ∆M= (baseline ∆Z - Post-treat

Group	Value	95% CI
Test Product 1	3055.36	± 1459.283
Test Product 2	2772.96	± 989.567
Reference Product 1	3849.83	± 1978.088
Reference Product 2	2720.00	± 1151.914

TMR Δm Value of 0.85% Phytate Compared to 0% Phytate, in the Presence of 1150ppm F and 0.3% ZnCl2, 0.3% ZnCl2 Compared to 0% ZnCl2 in the Presence of 1150ppm F and 0.3% ZnCl2 Compared to 0% ZnCl2 in the Presence of 1150ppm F and 0.85% Phytate Secondary · Baseline upto 4 weeks

TMR was used to assess changes in the mineral status of partially demineralized enamel specimens. Lesions were analyzed at baseline and Integrated Mineral Loss (∆Z): (∆Z =(lesion depth x 87) - area under the curve \[Area under the curve which relates volume % mineral at distances from the specimen surface with respect to section thickness\]). After treatment a further section was taken from each lesion specimen for radiography assessment; ∆Z was calculated. The change which occurred in mineral content (∆M) of the lesions as a result of treatment was calculated by: ∆M= (baseline ∆Z - Post-treat

Group	Value	95% CI
Test Product 2	2772.96	± 989.567
Test Product 3	2733.33	± 1051.738
Reference Product 2	2720.00	± 1151.914
Reference Product 3	2421.25	± 677.286

Enamel Fluoride Uptake (EFU) of All Study Formulation Variables Secondary · At Week 2

The microdrill enamel biopsy technique was used to analyze the fluoride uptake by enamel. Each enamel specimen was mounted on the long axis of a drill attached to a microdrill and drilled to a depth of approximately 100 μm through the entire lesion (four cores per specimen). The enamel powder pooled from four drilling samples was then immediately analyzed for fluoride content using fluoride specific electrode and pH/ion meter. The amount of fluoride-uptake by enamel was calculated based on the amount of fluoride divided by the area of the enamel cores and expressed as μg/cm\^2.

Group	Value	95% CI
Test Product 1	5.35	± 2.038
Test Product 2	4.78	± 2.655
Test Product 3	5.02	± 2.499
Reference Product 1	1.09	± 0.397
Reference Product 2	5.87	± 2.772
Reference Product 3	5.37	± 2.384

Enamel Fluoride Uptake (EFU) of All Study Formulation Variables Secondary · At Week 4

The microdrill enamel biopsy technique was used to analyze the fluoride uptake by enamel. Each enamel specimen was mounted on the long axis of a drill attached to a microdrill and drilled to a depth of approximately 100 μm through the entire lesion (four cores per specimen). The enamel powder pooled from four drilling samples was then immediately analyzed for fluoride content using fluoride specific electrode and pH/ion meter. The amount of fluoride-uptake by enamel was calculated based on the amount of fluoride divided by the area of the enamel cores and expressed as μg/cm\^2.

Group	Value	95% CI
Test Product 1	12.28	± 6.756
Test Product 2	11.09	± 6.336
Test Product 3	14.16	± 12.851
Reference Product 1	1.64	± 0.974
Reference Product 2	15.29	± 10.177
Reference Product 3	15.11	± 10.180

Adverse events — posted to ClinicalTrials.gov

Reporting threshold: 1%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Test Product 1

Serious: 1/28 (4%)

Deaths: 0/28

Test Product 2

Serious: 0/28 (0%)

Deaths: 0/28

Test Product 3

Serious: 0/28 (0%)

Deaths: 0/28

Reference Product 1

Serious: 0/29 (0%)

Deaths: 0/29

Reference Product 2

Serious: 0/27 (0%)

Deaths: 0/27

Reference Product 3

Serious: 0/28 (0%)

Deaths: 0/28

Serious adverse events (1 terms)

Reaction	System	Test Product 1	Test Product 2	Test Product 3	Reference Product 1	Reference Product 2	Reference Product 3
INVASIVE DUCTAL BREAST CARCINOMA	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—

Other adverse events (38 terms — click to expand)

Reaction	System	Test Product 1	Test Product 2	Test Product 3	Reference Product 1	Reference Product 2	Reference Product 3
GINGIVAL ERYTHEMA	Gastrointestinal disorders	—	—	—	—	—	—
Mouth ulceration	Gastrointestinal disorders	—	—	—	—	—	—
Gingival ulceration	Gastrointestinal disorders	—	—	—	—	—	—
Oral mucosal erythema	Gastrointestinal disorders	—	—	—	—	—	—
Dry mouth	Gastrointestinal disorders	—	—	—	—	—	—
Toothache	Gastrointestinal disorders	—	—	—	—	—	—
Gastrooesophageal reflux disease	Gastrointestinal disorders	—	—	—	—	—	—
Gingival oedema	Gastrointestinal disorders	—	—	—	—	—	—
Gingival pain	Gastrointestinal disorders	—	—	—	—	—	—
Gingival swelling	Gastrointestinal disorders	—	—	—	—	—	—
Leukoplakia oral	Gastrointestinal disorders	—	—	—	—	—	—
Lip dry	Gastrointestinal disorders	—	—	—	—	—	—
Noninfective gingivitis	Gastrointestinal disorders	—	—	—	—	—	—
Tongue coated	Gastrointestinal disorders	—	—	—	—	—	—
Tongue oedema	Gastrointestinal disorders	—	—	—	—	—	—
Thermal burn	Injury, poisoning and procedural complications	—	—	—	—	—	—
Laceration	Injury, poisoning and procedural complications	—	—	—	—	—	—
Lip injury	Injury, poisoning and procedural complications	—	—	—	—	—	—
Muscle strain	Injury, poisoning and procedural complications	—	—	—	—	—	—
Traumatic ulcer	Injury, poisoning and procedural complications	—	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—	—
Migraine	Nervous system disorders	—	—	—	—	—	—
Device Failure	Product Issues	—	—	—	—	—	—
Injury Associated With Device	General disorders	—	—	—	—	—	—
Seasonal Allergy	Immune system disorders	—	—	—	—	—	—
Angular cheilitis	Infections and infestations	—	—	—	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—	—	—	—
Oral herpes	Infections and infestations	—	—	—	—	—	—
Pneumonia	Infections and infestations	—	—	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—	—	—
Glucose Tolerance Impaired	Metabolism and nutrition disorders	—	—	—	—	—	—
Musculoskeletal Pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—
Allergic sinusitis	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Asthma	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Pharyngeal erythema	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Skin cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—

Most-reported serious reactions: INVASIVE DUCTAL BREAST CARCINOMA.

Data from ClinicalTrials.gov NCT02751320 adverse events section.

Sponsor's own description

This will be a single-centre, randomized, blinded, placebo-controlled, 6-treatment, 4-period crossover, incomplete block design, in situ caries study in healthy adults who wear a removable bilateral mandibular partial denture. The denture will be modified to accommodate 4 gauze-covered specimens of human dental enamel (4x3mm) that have been previously demineralized in vitro to form either S or low-R lesions (2 specimens of each lesion type will be used with each participant). After 14 days of twice daily product use off-site, the 2 S lesion specimens will be removed at the study site, with the remaining 2 low-R lesion specimens removed at the study site after a further 14 days of product use. To determine the remineralization ability of the treatments, all specimens will be analyzed by transverse microradiography (TMR) and enamel fluoride uptake (EFU), with the S lesions additionally analyzed by surface micro hardness (SMH) and the low-R lesions additionally analyzed by quantitative light fluorescence (QLF).

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.