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Anti-caries Potential of a Sodium Monofluorophosphate and Calcium Sodium Phosphosilicate Dentifrice

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ClinicalTrials.gov Identifier: NCT01657877
Recruitment Status : Completed
First Posted : August 6, 2012
Results First Posted : July 24, 2014
Last Update Posted : October 1, 2014
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Double (Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Caries
Interventions Drug: Calcium sodium phosphosilicate
Drug: Sodium monoflurophosphate
Drug: Placebo
Enrollment 100

Recruitment Details Participants were recruited at one clinical site (US).
Pre-assignment Details A total of 95 participants were screened, of which 79 were randomized. Of the subjects who were not randomized, 11 did not meet the study criteria; 3 had protocol violations; 2 withdrew consent.
Arm/Group Title Overall Participants
Hide Arm/Group Description

In this cross-over study, participant partial dentures were modified to hold two enamel specimens. Denture was modified at the start of the first treatment period to hold the enamel specimens. The participants were randomized using a computer generated program to receive following dentifrices:

  1. Dentifrice containing 1500 parts per million (ppm) as sodium monofluorophosphate (SMFP) + 5% calcium sodium phosphosilicate (CSP)
  2. Dentifrice containing 1500 ppm fluoride as SMFP + 0% CSP
  3. Dentifrice containing 500 ppm fluoride as SMFP + 0% CSP
  4. Dentifrice containing 0 ppm fluoride + 0% CSP
  5. Dentifrice containing 0 ppm fluoride + 5% CSP. The participants applied the given dentifrice as per their treatment group to a toothbrush and brushed their natural teeth twice daily for one timed minute. There was a washout period of 6 days between each treatment period.
Period Title: Overall Study
Started 79
Received 500ppm Fluoride as SMFP+ 0% CSP 70 [1]
Received 1500ppm Fluoride as SMFP+5% CSP 75 [2]
Received 0ppm Fluoride+ 5% CSP 71 [3]
Received 0ppm Fluoride+ 0% CSP 69 [4]
Received 1500ppm Fluoride as SMFP+0% CSP 71 [5]
Completed 65
Not Completed 14
Reason Not Completed
Withdrawal by Subject             4
Protocol Violation             6
Adverse Event             2
Other Reason             2
[1]
Discontinuations: 1 due to other reason in P2 and 1 protocol violation in P4
[2]
Discontinuations:2 withdrawal of consent in period (P) 1; 1 AE in P2;1 protocol violation in P3 & P4
[3]
Discontinuations: 1 protocol violation in P1 and P2 each and 1 withdrawal of consent in P1.
[4]
Discontinuation: 1 in P4 due to other reasons
[5]
Discontinuations: 1 protocol violation in P1 and 1 withdrawal of consent and AE in P3
Arm/Group Title All Randomized Participants
Hide Arm/Group Description All randomized participants were evaluated for baseline characteristics.
Overall Number of Baseline Participants 79
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 79 participants
63.5  (9.60)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 79 participants
Female
46
  58.2%
Male
33
  41.8%
1.Primary Outcome
Title Percentage (%) Change in Surface Microhardness (SMH) Following 21 Days of Twice Daily Treatment With the 1500 Ppm Fluoride + 5% CSP Dentifrice and With the 1500 Ppm Fluoride Dentifrice.
Hide Description Percent SMH recovery (SMHR) was calculated from hardness 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. A greater percentage change in SMHR represents a better remineralisation and hence a better outcome.
Time Frame Baseline to 21 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Per protocol (PP) population: The per protocol (PP) population was defined as those subjects in the intention to treat population who did not have protocol violations leading to exclusion of all efficacy data from analyses. Missing data was not imputed.
Arm/Group Title Dentifrice Containing 1500ppm Fluoride as SMFP + 0% CSP Dentifrice Containing 1500ppm Fluoride as SMFP + 5 % CSP
Hide Arm/Group Description:
Participants applied a full ribbon of the dentifrice (approximately 1.5 g) containing 1500 ppm fluoride as SMFP and 0 % CSP, to a toothbrush and brushed their natural teeth twice daily for one timed minute.
Participants applied a full ribbon of the dentifrice (approximately 1.5 g) containing 1500 ppm fluoride as SMFP and 5 % CSP, to a toothbrush and brushed their natural teeth twice daily for one timed minute.
Overall Number of Participants Analyzed 70 75
Mean (Standard Error)
Unit of Measure: Percentage SMHR
30.15  (2.447) 32.32  (2.673)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dentifrice Containing 1500ppm Fluoride as SMFP + 0% CSP, Dentifrice Containing 1500ppm Fluoride as SMFP + 5 % CSP
Comments The null hypothesis states that the population mean for the 1500 ppm fluoride as SMFP + 0% CSP minus the population mean for the 1500 ppm fluoride as SMFP and 5% CSP dentifrice is more than 6 %.
Type of Statistical Test Non-Inferiority or Equivalence
Comments The success criterion for this study was to observe the upper bound of the 2-sided 95% confidence interval for difference in % change in SMHR to be <= 6 units SMHR i.e. 1500 ppm fluoride as SMFP + 5% CSP is no more than 6 units inferior to the 1500 ppm fluoride as SMFP + 0 % CSP dentifrice.
Statistical Test of Hypothesis P-Value 0.2601
Comments [Not Specified]
Method ANOVA
Comments Based on the mixed effects ANOVA considering treatment and study period as factors, and subject as random effect
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -2.23
Confidence Interval (2-Sided) 95%
-6.11 to 1.66
Estimation Comments Difference is 1500 ppm fluoride as SMFP and 0 % CSP minus 1500 ppm fluoride as SMFP and 5 % CSP such that a positive difference favors 1500 ppm fluoride as SMFP and 0 % CSP
2.Secondary Outcome
Title Percentage (%) Change in SMH Following 21 Days of Twice Daily Treatment With 500 Ppm Fluoride as SMFP and 0 % CSP Dentifrice, 0 Ppm Fluoride and 0% CSP, and 0 Ppm Fluoride and 5 % CSP.
Hide Description Percent SMH recovery (SMHR) was calculated from hardness 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. A greater percentage change in SMHR represents a better remineralisation and hence a better outcome.
Time Frame Baseline to 21 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PP population:all randomized participants in the ITT population who had no protocol violations leading to exclusion of all efficacy data from analyses.
Arm/Group Title Dentifrice Containing 500 Ppm Fluoride as SMFP + 0% CSP Dentifrice Containing 0 Ppm Fluoride + 0% CSP Dentifrice Containing 0 Ppm Fluoride + 5% CSP
Hide Arm/Group Description:
Participants applied a full ribbon of the dentifrice (approximately 1.5 g) containing 500 ppm fluoride as SMFP and 0 % CSP, to a toothbrush and brushed their natural teeth twice daily for one timed minute.
Participants applied a full ribbon of the dentifrice (approximately 1.5 g) containing 0 ppm fluoride and 0 % CSP, to a toothbrush and brushed their natural teeth twice daily for one timed minute.
Participants applied a full ribbon of the dentifrice (approximately 1.5 g) containing 0 ppm fluoride and 5 % CSP, to a toothbrush and brushed their natural teeth twice daily for one timed minute.
Overall Number of Participants Analyzed 70 69 70
Mean (Standard Error)
Unit of Measure: Percentage SMHR
18.72  (1.649) 14.74  (1.362) 14.01  (1.392)
3.Secondary Outcome
Title Enamel Fluoride Uptake (EFU)
Hide Description Change to EFU was determine using a microdrill enamel biopsy of the in situ enamel specimens.
Time Frame Baseline to 21 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PP population: all randomized participants in the ITT population who had no protocol violations leading to exclusion of all efficacy data from analyses. Missing data was not imputed. Due to drop out there were differences in the number of participants analyzed per treatment group.
Arm/Group Title Dentifrice Containing 1500 Ppm Fluoride as SMFP + 5% CSP Dentifrice Containing 1500 Ppm Fluoride as SMFP + 0% CSP Dentifrice Containing 500 Ppm Fluoride as SMFP + 0% CSP Dentifrice Containing 0 Ppm Fluoride + 0% CSP Dentifrice Containing 0 Ppm Fluoride + 5% CSP
Hide Arm/Group Description:
Participants applied a full ribbon of the dentifrice (approximately 1.5 g) containing 1500 ppm fluoride as SMFP and 5 % CSP, to a toothbrush and brushed their natural teeth twice daily for one timed minute.
Participants applied a full ribbon of the dentifrice (approximately 1.5 g) containing 1500 ppm fluoride as SMFP and 0 % CSP, to a toothbrush and brushed their natural teeth twice daily for one timed minute.
Participants applied a full ribbon of the dentifrice (approximately 1.5 g) containing 500 ppm fluoride as SMFP and 0 % CSP, to a toothbrush and brushed their natural teeth twice daily for one timed minute.
Participants applied a full ribbon of the dentifrice (approximately 1.5 g) containing no fluoride and no CSP, to a toothbrush and brushed their natural teeth twice daily for one timed minute.
Participants applied a full ribbon of the dentifrice (approximately 1.5 g) containing no fluoride and 5 % CSP, to a toothbrush and brushed their natural teeth twice daily for one timed minute.
Overall Number of Participants Analyzed 75 70 70 69 70
Mean (Standard Error)
Unit of Measure: ppm EFU
15.58  (0.784) 14.85  (0.729) 9.23  (0.440) 4.17  (0.241) 4.54  (0.291)
Time Frame Adverse events were collected from the start of the investigational product (or washout product), and until 5 days following last administration of the investigational product.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Dentifrice Containing 1500 Ppm Fluoride as SMFP + 5% CSP Dentifrice Containing 1500 Ppm Fluoride as SMFP + 0% CSP Dentifrice Containing 500 Ppm Fluoride as SMFP + 0% CSP Dentifrice Containing 0 Ppm Fluoride + 0% CSP Dentifrice Containing 0 Ppm Fluoride + 5% CSP
Hide Arm/Group Description Participants applied a full ribbon of the dentifrice (approximately 1.5 g) containing 1500 ppm fluoride as SMFP and 5 % CSP, to a toothbrush and brushed their natural teeth twice daily for one timed minute. Participants applied a full ribbon of the dentifrice (approximately 1.5 g) containing 1500 ppm fluoride as SMFP and 0 % CSP, to a toothbrush and brushed their natural teeth twice daily for one timed minute. Participants applied a full ribbon of the dentifrice (approximately 1.5 g) containing 500 ppm fluoride as SMFP and 0 % CSP, to a toothbrush and brushed their natural teeth twice daily for one timed minute. Participants applied a full ribbon of the dentifrice (approximately 1.5 g) containing no fluoride and no CSP, to a toothbrush and brushed their natural teeth twice daily for one timed minute. Participants applied a full ribbon of the dentifrice (approximately 1.5 g) containing no fluoride and 5 % CSP, to a toothbrush and brushed their natural teeth twice daily for one timed minute.
All-Cause Mortality
Dentifrice Containing 1500 Ppm Fluoride as SMFP + 5% CSP Dentifrice Containing 1500 Ppm Fluoride as SMFP + 0% CSP Dentifrice Containing 500 Ppm Fluoride as SMFP + 0% CSP Dentifrice Containing 0 Ppm Fluoride + 0% CSP Dentifrice Containing 0 Ppm Fluoride + 5% CSP
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Dentifrice Containing 1500 Ppm Fluoride as SMFP + 5% CSP Dentifrice Containing 1500 Ppm Fluoride as SMFP + 0% CSP Dentifrice Containing 500 Ppm Fluoride as SMFP + 0% CSP Dentifrice Containing 0 Ppm Fluoride + 0% CSP Dentifrice Containing 0 Ppm Fluoride + 5% CSP
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/75 (1.33%)      0/71 (0.00%)      2/70 (2.86%)      0/69 (0.00%)      0/71 (0.00%)    
Cardiac disorders           
Unstable angina pectoris   0/75 (0.00%)  0 0/71 (0.00%)  0 1/70 (1.43%)  1 0/69 (0.00%)  0 0/71 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Invasive lobular carcinoma of left breast   1/75 (1.33%)  1 0/71 (0.00%)  0 0/70 (0.00%)  0 0/69 (0.00%)  0 0/71 (0.00%)  0
Multiple myeloma of bones   0/75 (0.00%)  0 0/71 (0.00%)  0 1/70 (1.43%)  1 0/69 (0.00%)  0 0/71 (0.00%)  0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
Dentifrice Containing 1500 Ppm Fluoride as SMFP + 5% CSP Dentifrice Containing 1500 Ppm Fluoride as SMFP + 0% CSP Dentifrice Containing 500 Ppm Fluoride as SMFP + 0% CSP Dentifrice Containing 0 Ppm Fluoride + 0% CSP Dentifrice Containing 0 Ppm Fluoride + 5% CSP
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   18/75 (24.00%)      13/71 (18.31%)      14/70 (20.00%)      11/69 (15.94%)      13/71 (18.31%)    
Blood and lymphatic system disorders           
Anaemia   0/75 (0.00%)  0 0/71 (0.00%)  0 1/70 (1.43%)  1 0/69 (0.00%)  0 0/71 (0.00%)  0
Endocrine disorders           
Hypothyroidism   0/75 (0.00%)  0 0/71 (0.00%)  0 0/70 (0.00%)  0 0/69 (0.00%)  0 1/71 (1.41%)  1
Eye disorders           
Conjunctivitis   0/75 (0.00%)  0 1/71 (1.41%)  1 0/70 (0.00%)  0 0/69 (0.00%)  0 0/71 (0.00%)  0
Eyelid irritation   1/75 (1.33%)  1 0/71 (0.00%)  0 0/70 (0.00%)  0 0/69 (0.00%)  0 0/71 (0.00%)  0
Eyelid ptosis   0/75 (0.00%)  0 0/71 (0.00%)  0 0/70 (0.00%)  0 1/69 (1.45%)  1 0/71 (0.00%)  0
Gastrointestinal disorders           
Gingival erythema   1/75 (1.33%)  1 1/71 (1.41%)  1 3/70 (4.29%)  3 1/69 (1.45%)  1 4/71 (5.63%)  4
Mouth ulceration   0/75 (0.00%)  0 1/71 (1.41%)  1 1/70 (1.43%)  3 0/69 (0.00%)  0 1/71 (1.41%)  1
Cheilitis   0/75 (0.00%)  0 1/71 (1.41%)  1 1/70 (1.43%)  1 0/69 (0.00%)  0 0/71 (0.00%)  0
Constipation   1/75 (1.33%)  1 0/71 (0.00%)  0 0/70 (0.00%)  0 0/69 (0.00%)  0 0/71 (0.00%)  0
Oral mucosal exfoliation   0/75 (0.00%)  0 0/71 (0.00%)  0 0/70 (0.00%)  0 1/69 (1.45%)  2 0/71 (0.00%)  0
Gingival inflammation   1/75 (1.33%)  1 0/71 (0.00%)  0 0/70 (0.00%)  0 0/69 (0.00%)  0 0/71 (0.00%)  0
Gingival pain   0/75 (0.00%)  0 0/71 (0.00%)  0 1/70 (1.43%)  1 0/69 (0.00%)  0 0/71 (0.00%)  0
Glossitis   1/75 (1.33%)  1 0/71 (0.00%)  0 0/70 (0.00%)  0 0/69 (0.00%)  0 0/71 (0.00%)  0
Lip blister   0/75 (0.00%)  0 0/71 (0.00%)  0 1/70 (1.43%)  1 0/69 (0.00%)  0 0/71 (0.00%)  0
Loose tooth   1/75 (1.33%)  1 0/71 (0.00%)  0 0/70 (0.00%)  0 0/69 (0.00%)  0 0/71 (0.00%)  0
Sensitivity of teeth   0/75 (0.00%)  0 0/71 (0.00%)  0 1/70 (1.43%)  1 0/69 (0.00%)  0 0/71 (0.00%)  0
Tongue ulceration   0/75 (0.00%)  0 0/71 (0.00%)  0 0/70 (0.00%)  0 1/69 (1.45%)  1 0/71 (0.00%)  0
Tooth deposit   0/75 (0.00%)  0 0/71 (0.00%)  0 1/70 (1.43%)  1 0/69 (0.00%)  0 0/71 (0.00%)  0
Tooth disorder   0/75 (0.00%)  0 1/71 (1.41%)  1 0/70 (0.00%)  0 0/69 (0.00%)  0 0/71 (0.00%)  0
Urinary tract infection   1/75 (1.33%)  1 1/71 (1.41%)  1 1/70 (1.43%)  1 0/69 (0.00%)  0 0/71 (0.00%)  0
Diarrhoea   0/75 (0.00%)  0 0/71 (0.00%)  0 0/70 (0.00%)  0 0/69 (0.00%)  0 1/71 (1.41%)  2
Gingival ulceration   2/75 (2.67%)  2 2/71 (2.82%)  2 0/70 (0.00%)  0 0/69 (0.00%)  0 0/71 (0.00%)  0
General disorders           
Dental caries   0/75 (0.00%)  0 0/71 (0.00%)  0 1/70 (1.43%)  1 0/69 (0.00%)  0 0/71 (0.00%)  0
Nodule   0/75 (0.00%)  0 0/71 (0.00%)  0 1/70 (1.43%)  1 1/69 (1.45%)  1 0/71 (0.00%)  0
Infections and infestations           
Nasopharyngitis   0/75 (0.00%)  0 2/71 (2.82%)  2 2/70 (2.86%)  2 1/69 (1.45%)  1 1/71 (1.41%)  1
Gastroenteritis viral   1/75 (1.33%)  1 0/71 (0.00%)  0 0/70 (0.00%)  0 1/69 (1.45%)  1 0/71 (0.00%)  0
Herpes zoster   0/75 (0.00%)  0 0/71 (0.00%)  0 0/70 (0.00%)  0 1/69 (1.45%)  1 0/71 (0.00%)  0
Pneumonia   1/75 (1.33%)  1 0/71 (0.00%)  0 0/70 (0.00%)  0 0/69 (0.00%)  0 0/71 (0.00%)  0
Vulvovaginal mycotic infection   1/75 (1.33%)  1 0/71 (0.00%)  0 0/70 (0.00%)  0 0/69 (0.00%)  0 0/71 (0.00%)  0
Injury, poisoning and procedural complications           
Gingival injury   1/75 (1.33%)  1 1/71 (1.41%)  1 2/70 (2.86%)  2 1/69 (1.45%)  1 0/71 (0.00%)  0
Foot fracture   0/75 (0.00%)  0 0/71 (0.00%)  0 0/70 (0.00%)  0 0/69 (0.00%)  0 1/71 (1.41%)  1
Tooth fracture   0/75 (0.00%)  0 1/71 (1.41%)  1 0/70 (0.00%)  0 0/69 (0.00%)  0 0/71 (0.00%)  0
Investigations           
Blood cholesterol increased   0/75 (0.00%)  0 0/71 (0.00%)  0 0/70 (0.00%)  0 1/69 (1.45%)  1 1/71 (1.41%)  1
Musculoskeletal and connective tissue disorders           
Arthritis   1/75 (1.33%)  1 1/71 (1.41%)  1 0/70 (0.00%)  0 0/69 (0.00%)  0 2/71 (2.82%)  2
Joint swelling   1/75 (1.33%)  1 0/71 (0.00%)  0 0/70 (0.00%)  0 0/69 (0.00%)  0 0/71 (0.00%)  0
Musculoskeletal pain   0/75 (0.00%)  0 0/71 (0.00%)  0 0/70 (0.00%)  0 1/69 (1.45%)  1 0/71 (0.00%)  0
Neck pain   0/75 (0.00%)  0 0/71 (0.00%)  0 0/70 (0.00%)  0 1/69 (1.45%)  1 0/71 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Oral fibroma   1/75 (1.33%)  1 0/71 (0.00%)  0 0/70 (0.00%)  0 0/69 (0.00%)  0 0/71 (0.00%)  0
Nervous system disorders           
Headache   0/75 (0.00%)  0 0/71 (0.00%)  0 0/70 (0.00%)  0 2/69 (2.90%)  2 0/71 (0.00%)  0
Amnesia   0/75 (0.00%)  0 1/71 (1.41%)  1 0/70 (0.00%)  0 0/69 (0.00%)  0 0/71 (0.00%)  0
Dizziness   1/75 (1.33%)  1 0/71 (0.00%)  0 0/70 (0.00%)  0 0/69 (0.00%)  0 0/71 (0.00%)  0
Respiratory, thoracic and mediastinal disorders           
Nasal ulcer   0/75 (0.00%)  0 1/71 (1.41%)  1 0/70 (0.00%)  0 0/69 (0.00%)  0 0/71 (0.00%)  0
Oropharyngeal pain   0/75 (0.00%)  0 0/71 (0.00%)  0 1/70 (1.43%)  1 0/69 (0.00%)  0 0/71 (0.00%)  0
Tonsillar inflammation   0/75 (0.00%)  0 1/71 (1.41%)  1 0/70 (0.00%)  0 0/69 (0.00%)  0 0/71 (0.00%)  0
Surgical and medical procedures           
Tooth repair   2/75 (2.67%)  2 0/71 (0.00%)  0 0/70 (0.00%)  0 0/69 (0.00%)  0 1/71 (1.41%)  1
Vascular disorders           
Hypertension   0/75 (0.00%)  0 0/71 (0.00%)  0 0/70 (0.00%)  0 0/69 (0.00%)  0 1/71 (1.41%)  1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01657877     History of Changes
Other Study ID Numbers: RH01381
First Submitted: August 2, 2012
First Posted: August 6, 2012
Results First Submitted: June 19, 2014
Results First Posted: July 24, 2014
Last Update Posted: October 1, 2014