Oral Health
Conditions
Brief summary
This study investigated the ability of two zinc-containing toothpaste formulations (Zinc A and Zinc B) to reduce the level of bacteria in saliva in the two-hour period after their use, compared to the effect of rinsing with water alone.
Detailed description
This was a single centre, three treatment, randomized, blinded, cross-over study which involved rinsing with slurries of two sodium fluoride-silica dentifrices containing zinc chloride and sodium citrate, and with water alone. The study consisted of four Visits: Visit 1 (Screening), Visit 2 (Treatment 1), Visit 3 (Treatment 2), Visit 4 (Treatment 3). There was a minimum two days wash out period before the first treatment visit and between treatment visits to avoid any treatment carry-over effect. During that time participants brushed as normal (twice-daily) at home with a washout toothpaste and a toothbrush which was provided at screening. Participants were required not to brush their teeth on the morning of the treatment visits and not to eat or drink for 2 hours prior to the treatment visits.
Interventions
DRUGZinc-A toothpaste
Participants received 6.0 grams (g) \[± 0.3g\] of the Zinc-A toothpaste in the form of slurry, one day per treatment (with at least 2 \[generally 7\] days between treatments. Participants emptied the contents of the dosing cup into their mouth, swilled the product around their mouth for 2 timed minutes then they expectorated into a sink.
DRUGZinc-B toothpaste
Participants received 6.0 grams (g) \[± 0.3g\] of the Zinc-B toothpaste in the form of slurry, one day per treatment (with at least 2 \[generally 7\] days between treatments. Participants emptied the contents of the dosing cup into their mouth, swilled the product around their mouth for 2 timed minutes then they expectorated into a sink.
OTHERMineral water
Participants received 6.0g (±0.3g) of mineral water (by weighing out), one day per treatment (with at least 2 \[generally 7\] days between treatments). Participants emptied the contents of the dosing cup into their mouth, swilled the product around their mouth for 2 timed minutes then they expectorated into a sink.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
* Personnel: GSKCH permanent and contract/contingency workers. * Consent: Demonstrated understanding of the study and was willing to participate and had received a signed and dated copy of the informed consent form. * Compliance: Understood, was willing and able and complied with all study procedures and restrictions. * General Health: Good general health * Oral Health: Good oral health * Salivary Flow Rate: Had a salivary flow rate in the range of normal values (unstimulated whole saliva flow rate ≥ 0.2milliliter per minute (ml/min); stimulated whole saliva flow rate ≥ 0.8ml/min)
Exclusion criteria
* Study personnel: Members of the clinical study staff. * Pregnancy: Pregnant Women * Breast-feeding: Women who were breast-feeding. * Allergy/Intolerance: Had Known or suspected intolerance or hypersensitivity to the study materials (or closely related compounds) or any of their stated ingredients. * Medication: a) Used an antimicrobial mouthwash within 48 hours of the test visit e.g. Listerine, Corsodyl etc. b) had taken, antibiotics within 2 weeks of the test visit. * Oral Surgery and Dental Conditions: a)Had an on-going dental treatment b) Had any oral surgery or extraction within 6 weeks of screening c) Symptoms of oral pain or any self-reported oral ulcers or herpetic lesions * Clinical Study Participation: a) Participation in a clinical study where they received an investigational drug within 2 weeks of the screening visit b) Previously participated in this study. * Substance Abstinence: Participant who were unwilling to abstain from smoking for at least 2 hours prior to treatment visits.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Area Under the Curve Between 0 and 2 Hours (AUC [0-2] Hours) for Total Viable Counts (TVCs) of Bacteria in Saliva Using Traditional Plating Technique | Change from baseline in log10-transformed AUC 0-2hr | Area Under the Curve (AUC) between 0 and 2 hours (hr) was assessed using traditional plating technique which provides the total viable counts (TVCs) of anaerobic bacteria. This outcome measure is AUC of change from baseline in log TVC. AUC for each time-point were calculated individually for each participant for each treatment and were aggregated into an AUC measurement. The aggregated AUC measurement was calculated in the order that first the collected data is logged which is further analyzed by change in log. Then, AUC 0-2hr change in log was calculated using the trapezoidal rule. The resulted values were then divided by 2hr to take out time units and are logged to calculate bacteria count. Hence, the outcome measure calculates change from baseline in log10-transformed AUC 0-2hr over the range from pre-treatment time point (0hr) to the concentration at 120 minutes (min) i.e., 2hr. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in AUC (0-2) Hours for the Ratio of Live:Dead Bacteria Using Live-dead Staining Technique | Baseline up to 2 hours | Anaerobic bacteria were counted using live:dead staining technique. Change from baseline in AUC (0-2)hr was calculated for the ratio of live and dead bacteria. Viable bacterial counts for each time-point were calculated individually for each participant for each treatment and were aggregated into an AUC measurement. AUC was calculated using the trapezoidal rule and using nominal time points. The resulted values were then divided by 2hr to take out time units. The AUC was calculated over the range from pre-treatment time point (0hr) to 2hr. In this outcome measure, the change from baseline is calculated in log ratio of live: dead. |
| Change From Baseline in log10-transformed Total Viable Bacterial Count Using Traditional Bacterial Plating Technique | At Baseline, 5 minutes, 15 minutes, 30 minutes, 1 hour and 2 hours post-treatment | Anaerobic bacteria were counted using traditional plating technique. Total viable bacterial counts for each time-point was calculated individually for each participant for each treatment. Change from baseline in log 10 transformed total viable bacterial values was calculated. |
| Change From Baseline in Live:Dead Bacteria Ratio in Saliva Using Staining Technique | At Baseline, 30 minutes, 1 hour and 2 hours post-treatment | Anaerobic bacteria were counted using live:dead staining technique. Change from baseline was calculated for the ratio of live to dead bacteria. |
Countries
United Kingdom
Participant flow
Recruitment details
All the participants were recruited from one center in United Kingdom.
Pre-assignment details
A total of 16 participants were screened, out of which 1 did not met the study criteria. Total of 15 participants were randomized to study treatments.
Participants by arm
| Arm | Count |
|---|---|
| Overall Includes participants that were given interventions: Zinc-A toothpaste or Zinc-B toothpaste or Mineral Water | 15 |
| Total | 15 |
Baseline characteristics
| Characteristic | Overall |
|---|---|
| Age, Continuous | 37.1 Years STANDARD_DEVIATION 10.15 |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 0 / 15 | 0 / 15 | 0 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 | 0 / 15 |
Outcome results
Primary
Change From Baseline in Area Under the Curve Between 0 and 2 Hours (AUC [0-2] Hours) for Total Viable Counts (TVCs) of Bacteria in Saliva Using Traditional Plating Technique
Area Under the Curve (AUC) between 0 and 2 hours (hr) was assessed using traditional plating technique which provides the total viable counts (TVCs) of anaerobic bacteria. This outcome measure is AUC of change from baseline in log TVC. AUC for each time-point were calculated individually for each participant for each treatment and were aggregated into an AUC measurement. The aggregated AUC measurement was calculated in the order that first the collected data is logged which is further analyzed by change in log. Then, AUC 0-2hr change in log was calculated using the trapezoidal rule. The resulted values were then divided by 2hr to take out time units and are logged to calculate bacteria count. Hence, the outcome measure calculates change from baseline in log10-transformed AUC 0-2hr over the range from pre-treatment time point (0hr) to the concentration at 120 minutes (min) i.e., 2hr.
Time frame: Change from baseline in log10-transformed AUC 0-2hr
Population: The efficacy analysis was performed on Intent to Treat (ITT) population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Zinc-A Toothpaste | Change From Baseline in Area Under the Curve Between 0 and 2 Hours (AUC [0-2] Hours) for Total Viable Counts (TVCs) of Bacteria in Saliva Using Traditional Plating Technique | At Baseline | 8.818 Log10 (cells/ml) | Standard Deviation 1.3909 |
| Zinc-A Toothpaste | Change From Baseline in Area Under the Curve Between 0 and 2 Hours (AUC [0-2] Hours) for Total Viable Counts (TVCs) of Bacteria in Saliva Using Traditional Plating Technique | Change from Baseline in AUC at 120 minutes | -0.037 Log10 (cells/ml) | Standard Deviation 2.4945 |
| Zinc-B Toothpaste | Change From Baseline in Area Under the Curve Between 0 and 2 Hours (AUC [0-2] Hours) for Total Viable Counts (TVCs) of Bacteria in Saliva Using Traditional Plating Technique | At Baseline | 8.785 Log10 (cells/ml) | Standard Deviation 1.3643 |
| Zinc-B Toothpaste | Change From Baseline in Area Under the Curve Between 0 and 2 Hours (AUC [0-2] Hours) for Total Viable Counts (TVCs) of Bacteria in Saliva Using Traditional Plating Technique | Change from Baseline in AUC at 120 minutes | -0.348 Log10 (cells/ml) | Standard Deviation 2.8109 |
| Mineral Water | Change From Baseline in Area Under the Curve Between 0 and 2 Hours (AUC [0-2] Hours) for Total Viable Counts (TVCs) of Bacteria in Saliva Using Traditional Plating Technique | At Baseline | 8.845 Log10 (cells/ml) | Standard Deviation 0.7271 |
| Mineral Water | Change From Baseline in Area Under the Curve Between 0 and 2 Hours (AUC [0-2] Hours) for Total Viable Counts (TVCs) of Bacteria in Saliva Using Traditional Plating Technique | Change from Baseline in AUC at 120 minutes | 0.193 Log10 (cells/ml) | Standard Deviation 1.6106 |
p-value: 0.178795% CI: [-0.8101, 0.1596]ANCOVA
p-value: 0.006395% CI: [-1.1886, -0.2187]ANCOVA
Secondary
Change From Baseline in AUC (0-2) Hours for the Ratio of Live:Dead Bacteria Using Live-dead Staining Technique
Anaerobic bacteria were counted using live:dead staining technique. Change from baseline in AUC (0-2)hr was calculated for the ratio of live and dead bacteria. Viable bacterial counts for each time-point were calculated individually for each participant for each treatment and were aggregated into an AUC measurement. AUC was calculated using the trapezoidal rule and using nominal time points. The resulted values were then divided by 2hr to take out time units. The AUC was calculated over the range from pre-treatment time point (0hr) to 2hr. In this outcome measure, the change from baseline is calculated in log ratio of live: dead.
Time frame: Baseline up to 2 hours
Population: The efficacy analysis was performed on ITT population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Zinc-A Toothpaste | Change From Baseline in AUC (0-2) Hours for the Ratio of Live:Dead Bacteria Using Live-dead Staining Technique | At Baseline | 0.758 Ratio (unitless) | Standard Deviation 0.3961 |
| Zinc-A Toothpaste | Change From Baseline in AUC (0-2) Hours for the Ratio of Live:Dead Bacteria Using Live-dead Staining Technique | Change from Baseline in AUC at 120 minutes | -7.612 Ratio (unitless) | Standard Deviation 5.5419 |
| Zinc-B Toothpaste | Change From Baseline in AUC (0-2) Hours for the Ratio of Live:Dead Bacteria Using Live-dead Staining Technique | At Baseline | 0.946 Ratio (unitless) | Standard Deviation 0.1495 |
| Zinc-B Toothpaste | Change From Baseline in AUC (0-2) Hours for the Ratio of Live:Dead Bacteria Using Live-dead Staining Technique | Change from Baseline in AUC at 120 minutes | -10.927 Ratio (unitless) | Standard Deviation 4.6267 |
| Mineral Water | Change From Baseline in AUC (0-2) Hours for the Ratio of Live:Dead Bacteria Using Live-dead Staining Technique | At Baseline | 0.906 Ratio (unitless) | Standard Deviation 0.1856 |
| Mineral Water | Change From Baseline in AUC (0-2) Hours for the Ratio of Live:Dead Bacteria Using Live-dead Staining Technique | Change from Baseline in AUC at 120 minutes | -1.024 Ratio (unitless) | Standard Deviation 3.7681 |
Secondary
Change From Baseline in Live:Dead Bacteria Ratio in Saliva Using Staining Technique
Anaerobic bacteria were counted using live:dead staining technique. Change from baseline was calculated for the ratio of live to dead bacteria.
Time frame: At Baseline, 30 minutes, 1 hour and 2 hours post-treatment
Population: The efficacy analysis was performed on ITT population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Zinc-A Toothpaste | Change From Baseline in Live:Dead Bacteria Ratio in Saliva Using Staining Technique | At 2 hour | -3.236 Ratio (unitless) | Standard Deviation 3.1452 |
| Zinc-A Toothpaste | Change From Baseline in Live:Dead Bacteria Ratio in Saliva Using Staining Technique | At 1 hour | -4.259 Ratio (unitless) | Standard Deviation 3.1983 |
| Zinc-A Toothpaste | Change From Baseline in Live:Dead Bacteria Ratio in Saliva Using Staining Technique | At 30 minutes | -4.701 Ratio (unitless) | Standard Deviation 3.3349 |
| Zinc-B Toothpaste | Change From Baseline in Live:Dead Bacteria Ratio in Saliva Using Staining Technique | At 2 hour | -5.419 Ratio (unitless) | Standard Deviation 2.6849 |
| Zinc-B Toothpaste | Change From Baseline in Live:Dead Bacteria Ratio in Saliva Using Staining Technique | At 1 hour | -6.153 Ratio (unitless) | Standard Deviation 2.6444 |
| Zinc-B Toothpaste | Change From Baseline in Live:Dead Bacteria Ratio in Saliva Using Staining Technique | At 30 minutes | -6.728 Ratio (unitless) | Standard Deviation 2.7295 |
| Mineral Water | Change From Baseline in Live:Dead Bacteria Ratio in Saliva Using Staining Technique | At 1 hour | -0.820 Ratio (unitless) | Standard Deviation 2.4004 |
| Mineral Water | Change From Baseline in Live:Dead Bacteria Ratio in Saliva Using Staining Technique | At 30 minutes | -0.049 Ratio (unitless) | Standard Deviation 1.8977 |
| Mineral Water | Change From Baseline in Live:Dead Bacteria Ratio in Saliva Using Staining Technique | At 2 hour | -0.769 Ratio (unitless) | Standard Deviation 2.7484 |
Secondary
Change From Baseline in log10-transformed Total Viable Bacterial Count Using Traditional Bacterial Plating Technique
Anaerobic bacteria were counted using traditional plating technique. Total viable bacterial counts for each time-point was calculated individually for each participant for each treatment. Change from baseline in log 10 transformed total viable bacterial values was calculated.
Time frame: At Baseline, 5 minutes, 15 minutes, 30 minutes, 1 hour and 2 hours post-treatment
Population: The efficacy analysis was performed on ITT population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Zinc-A Toothpaste | Change From Baseline in log10-transformed Total Viable Bacterial Count Using Traditional Bacterial Plating Technique | At 1 hour | -0.032 Log10 (cells/ml) | Standard Deviation 1.2486 |
| Zinc-A Toothpaste | Change From Baseline in log10-transformed Total Viable Bacterial Count Using Traditional Bacterial Plating Technique | At 30 minutes | 0.092 Log10 (cells/ml) | Standard Deviation 1.4285 |
| Zinc-A Toothpaste | Change From Baseline in log10-transformed Total Viable Bacterial Count Using Traditional Bacterial Plating Technique | At 5 minutes | -0.364 Log10 (cells/ml) | Standard Deviation 1.341 |
| Zinc-A Toothpaste | Change From Baseline in log10-transformed Total Viable Bacterial Count Using Traditional Bacterial Plating Technique | At 15 minutes | -0.030 Log10 (cells/ml) | Standard Deviation 1.2444 |
| Zinc-A Toothpaste | Change From Baseline in log10-transformed Total Viable Bacterial Count Using Traditional Bacterial Plating Technique | At 2 hour | 0.009 Log10 (cells/ml) | Standard Deviation 1.4097 |
| Zinc-B Toothpaste | Change From Baseline in log10-transformed Total Viable Bacterial Count Using Traditional Bacterial Plating Technique | At 30 minutes | -0.130 Log10 (cells/ml) | Standard Deviation 1.5997 |
| Zinc-B Toothpaste | Change From Baseline in log10-transformed Total Viable Bacterial Count Using Traditional Bacterial Plating Technique | At 5 minutes | -0.474 Log10 (cells/ml) | Standard Deviation 1.4832 |
| Zinc-B Toothpaste | Change From Baseline in log10-transformed Total Viable Bacterial Count Using Traditional Bacterial Plating Technique | At 15 minutes | -0.214 Log10 (cells/ml) | Standard Deviation 1.5142 |
| Zinc-B Toothpaste | Change From Baseline in log10-transformed Total Viable Bacterial Count Using Traditional Bacterial Plating Technique | At 1 hour | -0.175 Log10 (cells/ml) | Standard Deviation 1.4857 |
| Zinc-B Toothpaste | Change From Baseline in log10-transformed Total Viable Bacterial Count Using Traditional Bacterial Plating Technique | At 2 hour | -0.129 Log10 (cells/ml) | Standard Deviation 1.5035 |
| Mineral Water | Change From Baseline in log10-transformed Total Viable Bacterial Count Using Traditional Bacterial Plating Technique | At 2 hour | 0.127 Log10 (cells/ml) | Standard Deviation 0.8379 |
| Mineral Water | Change From Baseline in log10-transformed Total Viable Bacterial Count Using Traditional Bacterial Plating Technique | At 1 hour | 0.193 Log10 (cells/ml) | Standard Deviation 0.7781 |
| Mineral Water | Change From Baseline in log10-transformed Total Viable Bacterial Count Using Traditional Bacterial Plating Technique | At 5 minutes | 0.144 Log10 (cells/ml) | Standard Deviation 0.5679 |
| Mineral Water | Change From Baseline in log10-transformed Total Viable Bacterial Count Using Traditional Bacterial Plating Technique | At 30 minutes | -0.177 Log10 (cells/ml) | Standard Deviation 1.078 |
| Mineral Water | Change From Baseline in log10-transformed Total Viable Bacterial Count Using Traditional Bacterial Plating Technique | At 15 minutes | 0.161 Log10 (cells/ml) | Standard Deviation 0.9736 |