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This study is to evaluate the effect of fluoride dentifrices on enamel with artificial caries lesions in an in situ model
In situ models represent an acceptable approach for testing the anti-caries potential of fluoride products. This study is to evaluate the effect of fluoride dentifrice containing 1450 parts per million fluoride (ppm F) on enamel with artificial caries lesions in an in situ model. The study toothpaste containing sodium fluoride (NaF) and 0.4% carbopol will be compared to 4 other dentifrices. Comparator toothpastes include NaF toothpaste (1400 ppm F), NaF toothpaste (675 ppm F), sodium monofluorophosphate (NaMFP) and NaF toothpaste (1450 ppm F) and placebo toothpaste (0 ppm F).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| NaF toothpaste(1450 ppmF) | Experimental | Study toothpaste containing 1450 ppm F as NaF and 0.4% carbopol as excipient. |
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| NaF toothpaste (1400 ppmF) | Active Comparator | Study toothpaste containing 1400 ppm F as NaF |
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| NaMFP/NaF toothpaste (1450 ppmF) | Active Comparator | Reference toothpaste containing 1000 ppm F as NaMFP and 450 ppm F as NaF |
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| NaF toothpaste (675 ppmF) | Active Comparator | Study toothpaste containing 675 ppm F as NaF |
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| Placebo toothpaste (0 ppmF) | Placebo Comparator | Fluoride free placebo toothpaste (0 ppm F) |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| NaF | Drug | Fluoride |
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| Measure | Description | Time Frame |
|---|---|---|
| Percentage Surface Microhardness Recovery (%SMHR) of Sound Enamel Specimens Exposed to NaF Toothpaste (1450ppmF) and NaF Toothpaste (1400ppmF) | SMH test was used to assess mineral status of partially demineralized enamel specimens using Wilson 2100 Hardness tester. SMH was determined by measuring the length of the indentations of enamel specimens. An increase in the indentation length compared to the baseline indicates softening/demineralization while decrease in the indentation represents rehardening/ remineralization of enamel surface. Percent SMHR was calculated from indentation values of enamel specimens at baseline(B); after intra-oral exposure(R) on Day 14; and after in-vitro demineralization(D) on Day 14 using formula [(D-R)/(D-B)]*100. | Baseline to 14 days |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage SMHR of Sound Enamel Specimens Exposed to NaF Toothpaste (1450ppmF), NaF Toothpaste (1400ppmF), NaMFP/NaF Toothpaste (1450ppmF), NaF Toothpaste (675ppmF) and Placebo Toothpaste (0ppmF) | SMH test was used to assess mineral status of partially demineralized enamel specimens using Wilson 2100 Hardness tester. SMH was determined by measuring the length of the indentations of enamel specimens. An increase in the indentation length compared to the baseline indicates softening/demineralization while decrease in the indentation represents rehardening/ remineralization of enamel surface. Percent SMHR was calculated from indentation values of enamel specimens at baseline(B); after intra-oral exposure(R) on Day 14; and after in-vitro demineralization(D) on Day 14 using formula [(D-R)/(D-B)]*100. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Indiana University School of Dentistry | Indianapolis | Indiana | 46202 | United States |
Two days before the start of each treatment period, participants received a professional dental cleaning of their natural teeth, then brushed at home with the fluoride-free toothpaste.
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| ID | Title | Description |
|---|---|---|
| FG000 | Sodium Fluoride (NaF) Toothpaste(1450 Parts Per Million(Ppm)F) | Participants brushed their natural teeth for one timed minute with NaF and 0.4% carbopol toothpaste (1450ppmF as NaF), followed by rinsing with 10 milliliters (mL) water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days. During the treatment period, participants wore their partial dentures 24-hours a day, except when cleaning their dentures. |
| FG001 | NaF Toothpaste (1400ppmF) | Participants brushed their natural teeth for one timed minute with NaF toothpaste (1400ppmF as NaF), followed by rinsing with 10mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days. During the treatment period, participants wore their partial dentures 24-hours a day, except when cleaning their dentures. |
| FG002 | Sodium Monofluorophosphate (NaMFP)/NaF Toothpaste (1450ppmF) | Participants brushed their natural teeth for one timed minute with NaMFP and NaF toothpaste (1450ppmF - 1000ppmF as NaMFP and 450ppmF as NaF), followed by rinsing with 10mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days. During the treatment period, participants wore their partial dentures 24-hours a day, except when cleaning their dentures. |
| FG003 | NaF Toothpaste (675ppmF) | Participants brushed their natural teeth for one timed minute with sodium fluoride and silica toothpaste (675ppmF as NaF), followed by rinsing with 10mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days. During the treatment period, participants wore their partial dentures 24-hours a day, except when cleaning their dentures. |
| FG004 | Placebo Toothpaste (0ppmF) | Participants brushed their natural teeth for one timed minute with fluoride free toothpaste (0ppmF), followed by rinsing with 10mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days. During the treatment period, participants wore their partial dentures 24-hours a day, except when cleaning their dentures. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
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| Period 1 |
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| ID | Title | Description |
|---|---|---|
| BG000 | All Randomized Participants | All randomized participants who received at least one of the treatment dentifrices during the study and had at least one safety assessment after using the treatment dentifrice. |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage Surface Microhardness Recovery (%SMHR) of Sound Enamel Specimens Exposed to NaF Toothpaste (1450ppmF) and NaF Toothpaste (1400ppmF) | SMH test was used to assess mineral status of partially demineralized enamel specimens using Wilson 2100 Hardness tester. SMH was determined by measuring the length of the indentations of enamel specimens. An increase in the indentation length compared to the baseline indicates softening/demineralization while decrease in the indentation represents rehardening/ remineralization of enamel surface. Percent SMHR was calculated from indentation values of enamel specimens at baseline(B); after intra-oral exposure(R) on Day 14; and after in-vitro demineralization(D) on Day 14 using formula [(D-R)/(D-B)]*100. | Intent to Treat (ITT) population: All randomized participants who had at least one post baseline efficacy assessment. Missing data was not imputed. Due to drop outs there were differences in the number of participants (N) per treatment group. | Posted | Least Squares Mean | Standard Error | Percentage SMHR | Baseline to 14 days |
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All AEs encountered or spontaneously reported following administration of any investigational product (including washout product), or for up to 5 days after the last administration of investigational product were recorded.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | NaF Toothpaste(1450ppmF) | Participants brushed their natural teeth for one timed minute with NaF and 0.4% carbopol toothpaste (1450ppmF as NaF), followed by rinsing with 10 mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days. During the treatment period, participants wore their partial dentures 24-hours a day, except when cleaning their dentures. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gingival erythema | Gastrointestinal disorders |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 |
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| ID | Term |
|---|---|
| D005459 | Fluorides |
| ID | Term |
|---|---|
| D000838 | Anions |
| D007477 | Ions |
| D004573 | Electrolytes |
| D007287 | Inorganic Chemicals |
| D006858 |
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| Placebo | Drug | Placebo |
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| NaMFP | Drug | Fluoride |
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| Baseline to 14 days |
| Percentage SMHR of Demineralized Enamel Specimens Exposed to NaF Toothpaste (1450ppmF), NaF Toothpaste (1400ppmF), NaF Toothpaste (675ppmF), NaMFP/NaF Toothpaste(1450ppmF) and Placebo Toothpaste (0ppmF) | SMH test was used to assess mineral status of partially demineralized enamel specimens using Wilson 2100 Hardness tester. SMH was determined by measuring the length of the indentations of enamel specimens. An increase in the indentation length compared to the baseline indicates softening/demineralization while decrease in the indentation represents rehardening/ remineralization of enamel surface. Percent SMHR was calculated from indentation values of enamel specimens at baseline(B); after intra-oral exposure(R) on Day 14; and after in-vitro demineralization(D) on Day 14 using formula [(D-R)/(D-B)]*100. | Baseline to 14 days |
| Enamel Fluoride Uptake (Sound Enamel Specimens) | Enamel fluoride uptake was determined using the microdrill enamel biopsy technique. The amount of fluoride uptake by enamel was calculated based on the amount of fluoride (F) divided by the area of the enamel cores. The difference between treatments was calculated with respect to fluoride uptake by enamel. | Baseline to 14 days |
| Enamel Fluoride Uptake (Demineralized Specimens) | Enamel fluoride uptake was determined using the microdrill enamel biopsy technique. The amount of fluoride uptake by enamel was calculated based on the amount of fluoride (F) divided by the area of the enamel cores. The difference between treatments was calculated with respect to fluoride uptake by enamel. | Baseline to 14 days |
| Other Reason |
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| COMPLETED |
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| COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| OG000 | NaF Toothpaste (1450ppmF) | Participants brushed their natural teeth for one timed minute with NaF and 0.4% carbopol toothpaste (1450ppmF as NaF), followed by rinsing with 10 mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days. During the treatment period, participants wore their partial dentures 24-hours a day, except when cleaning their dentures. |
| OG001 | NaF Toothpaste (1400ppmF) | Participants brushed their natural teeth for one timed minute with NaF toothpaste (1400ppmF as NaF), followed by rinsing with 10mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days. During the treatment period, participants wore their partial dentures 24-hours a day, except when cleaning their dentures. |
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| Secondary | Percentage SMHR of Sound Enamel Specimens Exposed to NaF Toothpaste (1450ppmF), NaF Toothpaste (1400ppmF), NaMFP/NaF Toothpaste (1450ppmF), NaF Toothpaste (675ppmF) and Placebo Toothpaste (0ppmF) | SMH test was used to assess mineral status of partially demineralized enamel specimens using Wilson 2100 Hardness tester. SMH was determined by measuring the length of the indentations of enamel specimens. An increase in the indentation length compared to the baseline indicates softening/demineralization while decrease in the indentation represents rehardening/ remineralization of enamel surface. Percent SMHR was calculated from indentation values of enamel specimens at baseline(B); after intra-oral exposure(R) on Day 14; and after in-vitro demineralization(D) on Day 14 using formula [(D-R)/(D-B)]*100. | ITT population: All randomized participants who had at least one post baseline efficacy assessment. Missing data was not imputed. Due to drop out there were differences in the number of participants analyzed per treatment group. | Posted | Least Squares Mean | Standard Error | Percentage SMHR | Baseline to 14 days |
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| Secondary | Percentage SMHR of Demineralized Enamel Specimens Exposed to NaF Toothpaste (1450ppmF), NaF Toothpaste (1400ppmF), NaF Toothpaste (675ppmF), NaMFP/NaF Toothpaste(1450ppmF) and Placebo Toothpaste (0ppmF) | SMH test was used to assess mineral status of partially demineralized enamel specimens using Wilson 2100 Hardness tester. SMH was determined by measuring the length of the indentations of enamel specimens. An increase in the indentation length compared to the baseline indicates softening/demineralization while decrease in the indentation represents rehardening/ remineralization of enamel surface. Percent SMHR was calculated from indentation values of enamel specimens at baseline(B); after intra-oral exposure(R) on Day 14; and after in-vitro demineralization(D) on Day 14 using formula [(D-R)/(D-B)]*100. | ITT population. All randomized participants who had at least one post baseline efficacy assessment. Missing data was not imputed. Due to drop out there were differences in the number of participants analyzed per treatment group. | Posted | Least Squares Mean | Standard Error | Percentage SMHR | Baseline to 14 days |
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| Secondary | Enamel Fluoride Uptake (Sound Enamel Specimens) | Enamel fluoride uptake was determined using the microdrill enamel biopsy technique. The amount of fluoride uptake by enamel was calculated based on the amount of fluoride (F) divided by the area of the enamel cores. The difference between treatments was calculated with respect to fluoride uptake by enamel. | ITT population:. All randomized participants who had at least one post baseline efficacy assessment. Missing data was not imputed. Due to drop out there are differences in the number of participants analyzed per treatment group. | Posted | Least Squares Mean | Standard Error | micrograms (μg)*F/centimeters(cm)^2] | Baseline to 14 days |
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| Secondary | Enamel Fluoride Uptake (Demineralized Specimens) | Enamel fluoride uptake was determined using the microdrill enamel biopsy technique. The amount of fluoride uptake by enamel was calculated based on the amount of fluoride (F) divided by the area of the enamel cores. The difference between treatments was calculated with respect to fluoride uptake by enamel. | ITT population: All randomized participants with at least one post baseline efficacy assessment. Missing data was not imputed. Due to drop out there are differences in the number of participants analyzed per treatment group. | Posted | Least Squares Mean | Standard Error | μg*F/cm^2 | Baseline to 14 days |
|
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| 0 |
| 50 |
| 3 |
| 50 |
| EG001 | NaF Toothpaste (1400ppmF) | Participants brushed their natural teeth for one timed minute with NaF toothpaste (1400ppmF as NaF), followed by rinsing with 10mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days. During the treatment period, participants wore their partial dentures 24-hours a day, except when cleaning their dentures. | 0 | 52 | 1 | 52 |
| EG002 | NaMFP/NaF Toothpaste (1450ppmF) | Participants brushed their natural teeth for one timed minute with NaMFP and NaF toothpaste (1450ppmF - 1000ppmF as NaMFP and 450ppmF as NaF), followed by rinsing with 10mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days. During the treatment period, participants wore their partial dentures 24-hours a day, except when cleaning their dentures. | 0 | 53 | 3 | 53 |
| EG003 | NaF Toothpaste (675ppmF) | Participants brushed their natural teeth for one timed minute with sodium fluoride and silica toothpaste (675ppmF as NaF), followed by rinsing with 10mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days. During the treatment period, participants wore their partial dentures 24-hours a day, except when cleaning their dentures. | 0 | 53 | 4 | 53 |
| EG004 | Placebo Toothpaste (0ppmF) | Participants brushed their natural teeth for one timed minute with fluoride free toothpaste (0ppmF), followed by rinsing with 10mL water for 10 seconds. Participants continued the study brushing/rinsing regimen at home twice daily for 14 days. During the treatment period, participants wore their partial dentures 24-hours a day, except when cleaning their dentures. | 0 | 51 | 1 | 51 |
| EG005 | Overall | All participants received all treatments during the study | 0 | 57 | 10 | 57 |
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.
| Hydrofluoric Acid |
| D017611 | Fluorine Compounds |
| Superiority or Other |
| Null hypothesis considered population means of the treatments in comparison, to be equal with respect to percent SMH. Statistical tests were 2-sided with a significance level of 0.05. | ANOVA | ANOVA with factors for treatment and period with subject as a random effect. | 0.4306 | No adjustment made for multiple comparisons as the primary comparison was pre-specified. | Adjusted Mean Difference | 2.79 | 2-Sided | 95 | -4.18 | 9.77 | Difference is first named treatment minus second named treatment such that a negative difference favors the first named treatment. | No | Superiority or Other |
| Null hypothesis considered population means of the treatments in comparison, to be equal with respect to percent SMH. Statistical tests were 2-sided with a significance level of 0.05. | ANOVA | ANOVA with factors for treatment and period with subject as a random effect. | <0.0001 | No adjustment made for multiple comparisons as the primary comparison was pre-specified. | Adjusted Mean Difference | -25.07 | 2-Sided | 95 | -32.09 | -18.06 | Difference is first named treatment minus second named treatment such that a negative difference favors the first named treatment. | No | Superiority or Other |
| Null hypothesis considered population means of the treatments in comparison, to be equal with respect to percent SMH. Statistical tests were 2-sided with a significance level of 0.05. | ANOVA | ANOVA with factors for treatment and period with subject as a random effect. | 0.9567 | No adjustment made for multiple comparisons as the primary comparison was pre-specified. | Adjusted Mean Difference | 0.19 | 2-Sided | 95 | -6.71 | 7.09 | Difference is first named treatment minus second named treatment such that a negative difference favors the first named treatment. | No | Superiority or Other |
| Null hypothesis considered population means of the treatments in comparison, to be equal with respect to percent SMH. Statistical tests were 2-sided with a significance level of 0.05. | ANOVA | ANOVA with factors for treatment and period with subject as a random effect. | 0.8188 | No adjustment made for multiple comparisons as the primary comparison was pre-specified. | Adjusted Mean Difference | 0.81 | 2-Sided | 95 | -6.14 | 7.76 | Difference is first named treatment minus second named treatment such that a negative difference favors the first named treatment. | No | Superiority or Other |
| Null hypothesis considered population means of the treatments in comparison, to be equal with respect to percent SMH. Statistical tests were 2-sided with a significance level of 0.05. | ANOVA | ANOVA with factors for treatment and period with subject as a random effect. | <0.0001 | No adjustment made for multiple comparisons as the primary comparison was pre-specified. | Adjusted Mean Difference | -27.06 | 2-Sided | 95 | -34.03 | -20.08 | Difference is first named treatment minus second named treatment such that a negative difference favors the first named treatment. | No | Superiority or Other |
| Null hypothesis considered population means of the treatments in comparison, to be equal with respect to percent SMH. Statistical tests were 2-sided with a significance level of 0.05. | ANOVA | ANOVA with factors for treatment and period with subject as a random effect. | 0.8599 | No adjustment made for multiple comparisons as the primary comparison was pre-specified. | Adjusted Mean Difference | 0.62 | 2-Sided | 95 | -6.28 | 7.51 | Difference is first named treatment minus second named treatment such that a negative difference favors the first named treatment. | No | Superiority or Other |
| Null hypothesis considered population means of the treatments in comparison, to be equal with respect to percent SMH. Statistical tests were 2-sided with a significance level of 0.05. | ANOVA | ANOVA with factors for treatment and period with subject as a random effect. | <0.0001 | No adjustment made for multiple comparisons as the primary comparison was pre-specified. | Adjusted Mean Difference | -27.25 | 2-Sided | 95 | -34.20 | -20.30 | Difference is first named treatment minus second named treatment such that a negative difference favors the first named treatment. | No | Superiority or Other |
| Null hypothesis considered population means of the treatments in comparison, to be equal with respect to percent SMH. Statistical tests were 2-sided with a significance level of 0.05. | ANOVA | ANOVA with factors for treatment and period with subject as a random effect. | <0.0001 | No adjustment made for multiple comparisons as the primary comparison was pre-specified. | Adjusted Mean Difference | -27.87 | 2-Sided | 95 | -34.84 | -20.89 | Difference is first named treatment minus second named treatment such that a negative difference favors the first named treatment. | No | Superiority or Other |
| Superiority or Other |
| Null hypothesis considered population means of the treatments in comparison, to be equal with respect to percent SMH. Statistical tests were 2-sided with a significance level of 0.05. | ANOVA | ANOVA with factors for treatment and period with subject as a random effect. | 0.1433 | No adjustment made for multiple comparisons as the primary comparison was pre-specified. | Adjusted Mean Difference | 3.50 | 2-Sided | 95 | -1.20 | 8.19 | Difference is first named treatment minus second named treatment such that a negative difference favors the first named treatment. | No | Superiority or Other |
| Null hypothesis considered population means of the treatments in comparison, to be equal with respect to percent SMH. Statistical tests were 2-sided with a significance level of 0.05. | ANOVA | ANOVA with factors for treatment and period with subject as a random effect. | 0.0020 | No adjustment made for multiple comparisons as the primary comparison was pre-specified. | Adjusted Mean Difference | 7.47 | 2-Sided | 95 | 2.78 | 12.16 | Difference is first named treatment minus second named treatment such that a negative difference favors the first named treatment. | No | Superiority or Other |
| Null hypothesis considered population means of the treatments in comparison, to be equal with respect to percent SMH. Statistical tests were 2-sided with a significance level of 0.05. | ANOVA | ANOVA with factors for treatment and period with subject as a random effect. | <0.0001 | No adjustment made for multiple comparisons as the primary comparison was pre-specified. | Adjusted Mean Difference | 23.52 | 2-Sided | 95 | 18.79 | 28.25 | Difference is first named treatment minus second named treatment such that a negative difference favors the first named treatment. | No | Superiority or Other |
| Null hypothesis considered population means of the treatments in comparison, to be equal with respect to percent SMH. Statistical tests were 2-sided with a significance level of 0.05. | ANOVA | ANOVA with factors for treatment and period with subject as a random effect. | 0.0373 | No adjustment made for multiple comparisons as the primary comparison was pre-specified. | Adjusted Mean Difference | 4.94 | 2-Sided | 95 | 0.29 | 9.59 | Difference is first named treatment minus second named treatment such that a negative difference favors the first named treatment. | No | Superiority or Other |
| Null hypothesis considered population means of the treatments in comparison, to be equal with respect to percent SMH. Statistical tests were 2-sided with a significance level of 0.05. | ANOVA | ANOVA with factors for treatment and period with subject as a random effect. | 0.0002 | No adjustment made for multiple comparisons as the primary comparison was pre-specified. | Adjusted Mean Difference | 8.92 | 2-Sided | 95 | 4.24 | 13.59 | Difference is first named treatment minus second named treatment such that a negative difference favors the first named treatment. | No | Superiority or Other |
| Null hypothesis considered population means of the treatments in comparison, to be equal with respect to percent SMH. Statistical tests were 2-sided with a significance level of 0.05. | ANOVA | ANOVA with factors for treatment and period with subject as a random effect. | <0.0001 | No adjustment made for multiple comparisons as the primary comparison was pre-specified. | Adjusted Mean Difference | 24.97 | 2-Sided | 95 | 20.27 | 29.66 | Difference is first named treatment minus second named treatment such that a negative difference favors the first named treatment. | No | Superiority or Other |
| Null hypothesis considered population means of the treatments in comparison, to be equal with respect to percent SMH. Statistical tests were 2-sided with a significance level of 0.05. | ANOVA | ANOVA with factors for treatment and period with subject as a random effect. | 0.0925 | No adjustment made for multiple comparisons as the primary comparison was pre-specified. | Adjusted Mean Difference | 3.98 | 2-Sided | 95 | -0.66 | 8.61 | Difference is first named treatment minus second named treatment such that a negative difference favors the first named treatment. | No | Superiority or Other |
| Null hypothesis considered population means of the treatments in comparison, to be equal with respect to percent SMH. Statistical tests were 2-sided with a significance level of 0.05. | ANOVA | ANOVA with factors for treatment and period with subject as a random effect. | <0.0001 | No adjustment made for multiple comparisons as the primary comparison was pre-specified. | Adjusted Mean Difference | 20.03 | 2-Sided | 95 | 15.35 | 24.70 | Difference is first named treatment minus second named treatment such that a negative difference favors the first named treatment. | No | Superiority or Other |
| Null hypothesis considered population means of the treatments in comparison, to be equal with respect to percent SMH. Statistical tests were 2-sided with a significance level of 0.05. | ANOVA | ANOVA with factors for treatment and period with subject as a random effect. | <0.0001 | No adjustment made for multiple comparisons as the primary comparison was pre-specified. | Adjusted Mean Difference | 16.05 | 2-Sided | 95 | 11.36 | 20.74 | Difference is first named treatment minus second named treatment such that a negative difference favors the first named treatment. | No | Superiority or Other |
| Superiority or Other |
| Null hypothesis considered population means of the treatments in comparison, to be equal with respect to EFU. Statistical tests were 2-sided with a significance level of 0.05. | ANOVA | ANOVA with factors for treatment and period with subject as a random effect. | 0.0440 | No adjustment made for multiple comparisons as the primary comparison was pre-specified. | Adjusted Mean Difference | 106.90 | 2-Sided | 95 | 2.92 | 210.87 | Difference is first named treatment minus second named treatment such that a positive difference favors the first named treatment. | No | Superiority or Other |
| Null hypothesis considered population means of the treatments in comparison, to be equal with respect to EFU. Statistical tests were 2-sided with a significance level of 0.05. | ANOVA | ANOVA with factors for treatment and period with subject as a random effect. | 0.0026 | No adjustment made for multiple comparisons as the primary comparison was pre-specified. | Adjusted Mean Difference | 160.92 | 2-Sided | 95 | 56.96 | 264.88 | Difference is first named treatment minus second named treatment such that a positive difference favors the first named treatment. | No | Superiority or Other |
| Null hypothesis considered population means of the treatments in comparison, to be equal with respect to EFU. Statistical tests were 2-sided with a significance level of 0.05. | ANOVA | ANOVA with factors for treatment and period with subject as a random effect. | <0.0001 | No adjustment made for multiple comparisons as the primary comparison was pre-specified. | Adjusted Mean Difference | 222.47 | 2-Sided | 95 | 117.58 | 327.36 | Difference is first named treatment minus second named treatment such that a positive difference favors the first named treatment. | No | Superiority or Other |
| Null hypothesis considered population means of the treatments in comparison, to be equal with respect to EFU. Statistical tests were 2-sided with a significance level of 0.05. | ANOVA | ANOVA with factors for treatment and period with subject as a random effect. | 0.0382 | No adjustment made for multiple comparisons as the primary comparison was pre-specified. | Adjusted Mean Difference | 108.91 | 2-Sided | 95 | 5.98 | 211.83 | Difference is first named treatment minus second named treatment such that a positive difference favors the first named treatment. | No | Superiority or Other |
| Null hypothesis considered population means of the treatments in comparison, to be equal with respect to EFU. Statistical tests were 2-sided with a significance level of 0.05. | ANOVA | ANOVA with factors for treatment and period with subject as a random effect. | 0.0021 | No adjustment made for multiple comparisons as the primary comparison was pre-specified. | Adjusted Mean Difference | 162.93 | 2-Sided | 95 | 59.68 | 266.18 | Difference is first named treatment minus second named treatment such that a positive difference favors the first named treatment. | No | Superiority or Other |
| Null hypothesis considered population means of the treatments in comparison, to be equal with respect to EFU. Statistical tests were 2-sided with a significance level of 0.05. | ANOVA | ANOVA with factors for treatment and period with subject as a random effect. | <0.0001 | No adjustment made for multiple comparisons as the primary comparison was pre-specified. | Adjusted Mean Difference | 224.48 | 2-Sided | 95 | 120.51 | 328.46 | Difference is first named treatment minus second named treatment such that a positive difference favors the first named treatment. | No | Superiority or Other |
| Null hypothesis considered population means of the treatments in comparison, to be equal with respect to EFU. Statistical tests were 2-sided with a significance level of 0.05. | ANOVA | ANOVA with factors for treatment and period with subject as a random effect. | 0.3003 | No adjustment made for multiple comparisons as the primary comparison was pre-specified. | Adjusted Mean Difference | 54.03 | 2-Sided | 95 | -48.56 | 156.61 | Difference is first named treatment minus second named treatment such that a positive difference favors the first named treatment. | No | Superiority or Other |
| Null hypothesis considered population means of the treatments in comparison, to be equal with respect to EFU. Statistical tests were 2-sided with a significance level of 0.05. | ANOVA | ANOVA with factors for treatment and period with subject as a random effect. | 0.2432 | No adjustment made for multiple comparisons as the primary comparison was pre-specified. | Adjusted Mean Difference | 61.55 | 2-Sided | 95 | -42.14 | 165.24 | Difference is first named treatment minus second named treatment such that a positive difference favors the first named treatment. | No | Superiority or Other |
| Null hypothesis considered population means of the treatments in comparison, to be equal with respect to EFU. Statistical tests were 2-sided with a significance level of 0.05. | ANOVA | ANOVA with factors for treatment and period with subject as a random effect. | 0.0289 | No adjustment made for multiple comparisons as the primary comparison was pre-specified. | Adjusted Mean Difference | 115.58 | 2-Sided | 95 | 12.02 | 219.13 | Difference is first named treatment minus second named treatment such that a positive difference favors the first named treatment. | No | Superiority or Other |
| Superiority or Other |
| Null hypothesis considered population means of the treatments in comparison, to be equal with respect to EFU. Statistical tests were 2-sided with a significance level of 0.05. | ANOVA | ANOVA with factors for treatment and period with subject as a random effect. | 0.0003 | No adjustment made for multiple comparisons as the primary comparison was pre-specified. | Adjusted Mean Difference | 575.71 | 2-Sided | 95 | 268.24 | 883.17 | Difference is first named treatment minus second named treatment such that a positive difference favors the first named treatment. | No | Superiority or Other |
| Null hypothesis considered population means of the treatments in comparison, to be equal with respect to EFU. Statistical tests were 2-sided with a significance level of 0.05. | ANOVA | ANOVA with factors for treatment and period with subject as a random effect. | <0.0001 | No adjustment made for multiple comparisons as the primary comparison was pre-specified. | Adjusted Mean Difference | 637.67 | 2-Sided | 95 | 330.30 | 945.03 | Difference is first named treatment minus second named treatment such that a positive difference favors the first named treatment. | No | Superiority or Other |
| Null hypothesis considered population means of the treatments in comparison, to be equal with respect to EFU. Statistical tests were 2-sided with a significance level of 0.05. | ANOVA | ANOVA with factors for treatment and period with subject as a random effect. | <0.0001 | No adjustment made for multiple comparisons as the primary comparison was pre-specified. | Adjusted Mean Difference | 1813.29 | 2-Sided | 95 | 1503.03 | 2123.54 | Difference is first named treatment minus second named treatment such that a positive difference favors the first named treatment. | No | Superiority or Other |
| Null hypothesis considered population means of the treatments in comparison, to be equal with respect to EFU. Statistical tests were 2-sided with a significance level of 0.05. | ANOVA | ANOVA with factors for treatment and period with subject as a random effect. | 0.0002 | Adjusted Mean Difference | 589.61 | 2-Sided | 95 | 285.31 | 893.92 | Difference is first named treatment minus second named treatment such that a positive difference favors the first named treatment. | No | Superiority or Other |
| Null hypothesis considered population means of the treatments in comparison, to be equal with respect to EFU. Statistical tests were 2-sided with a significance level of 0.05. | ANOVA | ANOVA with factors for treatment and period with subject as a random effect. | <0.0001 | No adjustment made for multiple comparisons as the primary comparison was pre-specified. | Adjusted Mean Difference | 651.57 | 2-Sided | 95 | 346.44 | 956.70 | Difference is first named treatment minus second named treatment such that a positive difference favors the first named treatment. | No | Superiority or Other |
| Null hypothesis considered population means of the treatments in comparison, to be equal with respect to EFU. Statistical tests were 2-sided with a significance level of 0.05. | ANOVA | ANOVA with factors for treatment and period with subject as a random effect. | <0.0001 | No adjustment made for multiple comparisons as the primary comparison was pre-specified. | Adjusted Mean Difference | 1827.19 | 2-Sided | 95 | 1519.78 | 2134.60 | Difference is first named treatment minus second named treatment such that a positive difference favors the first named treatment. | No | Superiority or Other |
| Null hypothesis considered population means of the treatments in comparison, to be equal with respect to EFU. Statistical tests were 2-sided with a significance level of 0.05. | ANOVA | ANOVA with factors for treatment and period with subject as a random effect. | 0.6874 | No adjustment made for multiple comparisons as the primary comparison was pre-specified. | Adjusted Mean Difference | 61.96 | 2-Sided | 95 | -241.25 | 365.17 | Difference is first named treatment minus second named treatment such that a positive difference favors the first named treatment. | No | Superiority or Other |
| Null hypothesis considered population means of the treatments in comparison, to be equal with respect to EFU. Statistical tests were 2-sided with a significance level of 0.05. | ANOVA | ANOVA with factors for treatment and period with subject as a random effect. | <0.0001 | Adjusted Mean Difference | 1237.58 | 2-Sided | 95 | 931.46 | 1543.70 | Difference is first named treatment minus second named treatment such that a positive difference favors the first named treatment. | No | Superiority or Other |
| Null hypothesis considered population means of the treatments in comparison, to be equal with respect to EFU. Statistical tests were 2-sided with a significance level of 0.05. | ANOVA | ANOVA with factors for treatment and period with subject as a random effect. | <0.0001 | No adjustment made for multiple comparisons as the primary comparison was pre-specified. | Adjusted Mean Difference | 1175.62 | 2-Sided | 95 | 869.15 | 1482.10 | Difference is first named treatment minus second named treatment such that a positive difference favors the first named treatment. | No | Superiority or Other |