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Evaluation of Plaque Fluid Fluoride Retention From Fluoride Toothpastes

Evaluation of Plaque Fluid Fluoride Retention From Fluoride Toothpastes

Status
Completed
Phases
Phase 3
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00708305
Enrollment
65
Registered
2008-07-02
Start date
2008-06-30
Completion date
2008-10-31
Last updated
2015-01-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Dental Caries

Keywords

toothpaste, plaque fluid, fluoride

Brief summary

The purpose of this study is to investigate the efficacy of different sodium fluoride (NaF) containing toothpastes in prevention of dental caries. Change from baseline fluoride data at various time points up to four hours after a single brushing with NaF containing toothpastes will be evaluated.

Detailed description

Topical fluorides in a wide variety of delivery systems have been proven to be clinically effective in the prevention of dental caries. It is generally agreed that fluoride has its anti-caries effect mainly by decreasing the rate of enamel demineralization and enhancing the rate of enamel remineralization. There is a general consensus that level of fluoride in plaque fluid, may be directly related to the anti caries effects of fluoride. Also, fluoride levels in the oral fluids decrease rapidly after topical fluoride application, mainly due to the diluting and washing effect of saliva followed by periodic swallowing. To evaluate fluoride content, plaque samples will be collected from the interproximal surfaces of the posterior teeth of participants using a standardized approach. Plaque fluid fluoride will be calculated using a micro analytical method and in comparison to a standard fluoride curve constructed on the same day of the analysis.

Interventions

DRUGSodium Fluoride (NaF)

Different fluoride toothpastes containing between 1400ppmF - 1450ppmF of fluoride as NaF

DRUGPlacebo

Fluoride free toothpaste (0ppmF)

Sponsors

GlaxoSmithKline
Lead SponsorINDUSTRY

Study design

Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes

Inclusion criteria

1. Age:Age 18 through 65 years. 2. General Health: Good general health with (in the opinion of the investigator) no clinically significant and/or relevant abnormalities of medical history or oral examination, specifically including diabetes or hypoglycemia. 3. Compliance: Understands and is willing, able and likely to comply with all study procedures and restrictions. 4. Consent: Demonstrates understanding of the study and willingness to participate as evidenced by voluntary written informed consent and has received a signed and dated copy of the informed consent form. 5. Oral: a) Currently living in the Indianapolis, Indiana area and not taking fluoride supplements. b) Have a normal stimulated (= 0.8 ml/min) and unstimulated (= 0.2 ml/min) salivary flow rate. c) Have a full complement of natural teeth with the exception of third molars and teeth extracted for orthodontic reasons. Participants natural teeth must have at least one surface free of restoration in each interproximal embrasure. d) Produce at least 6mg of plaque at Screening Visit 2.

Exclusion criteria

1. Pregnancy:Women who are known to be pregnant or who are intending to become pregnant over the duration of the study. No pregnancy test will be required. 2. Breast-feeding:Women who are breast-feeding. 3. Medical History:Current or relevant history of any serious, severe or unstable physical or psychiatric illness that would make the subject unlikely to fully complete the study or any that increases the risk to the subject. 4. Allergy/Intolerance: Known or suspected intolerance or hypersensitivity to the study materials (or closely related compounds) or any of their stated ingredients. 5. Clinical Study/Experimental Medication:Participation in another clinical study or receipt of an investigational drug within 30 days of the screening visit 1 at the start of the study with the exception of those participating in GSKCH study Z3170476. 6. Medication: a) Currently taking antibiotics or have taken antibiotics in the two weeks prior to any treatment visit or during the study. b) Has a medical condition that would require prophylactic antibiotics prior to a dental cleaning. 7. Dental: a) Current active caries or moderate to severe periodontal disease that may compromise the health of the participants or the study. b) Current use of chlorhexidine mouthrinse. 8. Personnel: An employee of the sponsor or the study site who is directly involved in the conduct of the study.

Design outcomes

Primary

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

Secondary

MeasureTime frameDescription
Natural Log Transformed AUC for Fluoride Concentration in Plaque Fluid Between 0-4 HoursPlaque samples collected at 15 minutes, 30 minutes, 1 hour, 2 hours and 4 hours post single application of treatmentTo 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 0-4 hours using trapezoidal rule and natural log transformation was applied.due to failure of assumption of normal distribution of data.
Change From Baseline in Fluoride Concentration at 15 Minutes After Brushing With Study TreatmentsPlaque samples were collected at baseline, 15 minutes post single application of study treatmentChange from baseline at any time point for a treatment period was calculated as the median post brushing fluoride value at a time point minus the median baseline (pre-brushing) fluoride value for a treatment period.
Change From Baseline in Fluoride Concentration at 30 Minutes Post Brushing With Study TreatmentsPlaque samples were collected at baseline, 30 minutes post single application of study treatmentChange from baseline at any time point for a treatment period was calculated as the median post brushing fluoride value at a time point minus the median baseline (pre-brushing) fluoride value for a treatment period.
Change From Baseline in Fluoride Concentration at 1 Hour Post Brushing With Study TreatmentsPlaque samples were collected at baseline, 1 hour post single application of study treatmentChange from baseline at any time point for a treatment period was calculated as the median post brushing fluoride value at a time point minus the median baseline (pre-brushing) fluoride value for a treatment period.
Change From Baseline in Fluoride Concentration at 2 Hours Post Brushing With Study TreatmentsPlaque samples were collected at baseline, 2 hour post single application of study treatmentChange from baseline at any time point for a treatment period was calculated as the median post brushing fluoride value at a time point minus the median baseline (pre-brushing) fluoride value for a treatment period.
Change From Baseline in Fluoride Concentration at 4 Hours Post Brushing With Study TreatmentsPlaque samples were collected at baseline, 4 hours post single application of study treatmentChange from baseline at any time point for a treatment period was calculated as the median post brushing fluoride value at a time point minus the median baseline (pre-brushing) fluoride value for a treatment period.

Countries

United States

Participant flow

Recruitment details

Participants were recruited at the clinical site.

Pre-assignment details

There was a four-day wash out prior to each treatment period during which participants used the study fluoride-free toothpaste. Two to three days prior to the start of each treatment visit, participants attended the study site for a dental prophylaxis then discontinued all oral hygiene prior to study treatment visit.

Participants by arm

ArmCount
Overall Study
All randomized participants
65
Total65

Withdrawals & dropouts

PeriodReasonFG000FG001FG002FG003
Period 1Other Reason0002
Period 1Protocol Violation1010
Period 2Lost to Follow-up0100
Period 2Other Reason1001
Period 2Protocol Violation0100
Period 3Other Reason1000
Period 3Protocol Violation0200

Baseline characteristics

CharacteristicOverall Study
Age, Continuous26.4 years
STANDARD_DEVIATION 6.97
Region of Enrollment
United States
65 participants
Sex: Female, Male
Female
31 Participants
Sex: Female, Male
Male
34 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
deaths
Total, all-cause mortality
— / —— / —— / —— / —
other
Total, other adverse events
0 / 580 / 590 / 610 / 59
serious
Total, serious adverse events
0 / 580 / 590 / 610 / 59

Outcome results

Primary

Natural Log Transformed Area Under the Fluoride Concentration in Plaque Fluid by Time Curve (AUC) Between 0-4 Hours

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.

Time frame: Plaque samples collected at 15 minutes, 30 minutes, 1 hour, 2 hours and 4 hours post single application of treatment

Population: Per-Protocol (PP) population: All participants who had at least one post-baseline efficacy assessment but did not have any major protocol deviations. Due to drop outs, there were differences in the n per treatment group. Missing data was not imputed.

ArmMeasureValue (LEAST_SQUARES_MEAN)Dispersion
NaF Toothpaste(1450 Ppm F)Natural Log Transformed Area Under the Fluoride Concentration in Plaque Fluid by Time Curve (AUC) Between 0-4 Hours0.54 ln(μg*F*minutes/cm^2)Standard Error 0.086
NaF Toothpaste (1400 Ppm F)Natural Log Transformed Area Under the Fluoride Concentration in Plaque Fluid by Time Curve (AUC) Between 0-4 Hours0.54 ln(μg*F*minutes/cm^2)Standard Error 0.087
Comparison: Null hypothesis is no difference between treatments in comparison. Tests were 2-sided at 5% significance levels.p-value: 0.976295% CI: [-0.21, 0.2]ANCOVA
Secondary

Change From Baseline in Fluoride Concentration at 15 Minutes After Brushing With Study Treatments

Change from baseline at any time point for a treatment period was calculated as the median post brushing fluoride value at a time point minus the median baseline (pre-brushing) fluoride value for a treatment period.

Time frame: Plaque samples were collected at baseline, 15 minutes post single application of study treatment

Population: PP population: All participants who had at least one post-baseline efficacy assessment but did not have any major protocol deviations. Due to drop outs, there were differences in the n per treatment group. Missing data was not imputed.

ArmMeasureValue (MEDIAN)Dispersion
NaF Toothpaste(1450 Ppm F)Change From Baseline in Fluoride Concentration at 15 Minutes After Brushing With Study Treatments2.00 μg*F/gFull Range 4.586
NaF Toothpaste (1400 Ppm F)Change From Baseline in Fluoride Concentration at 15 Minutes After Brushing With Study Treatments1.56 μg*F/gFull Range 2.806
NaMFP/NaF Toothpaste (1450ppmF)Change From Baseline in Fluoride Concentration at 15 Minutes After Brushing With Study Treatments0.76 μg*F/gFull Range 1.633
Placebo Toothpaste (0ppmF)Change From Baseline in Fluoride Concentration at 15 Minutes After Brushing With Study Treatments0.03 μg*F/gFull Range 0.083
Comparison: Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.p-value: 0.015195% CI: [0.12, 1.72]Wilcoxon Signed Rank Test
Comparison: Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.p-value: <0.000195% CI: [0.69, 2.36]Wilcoxon Signed Rank Test
Comparison: Null hypothesis is no difference between treatments. Tests were 2-sided.p-value: <0.000195% CI: [2.06, 4.05]Wilcoxon Signed Rank Test
Comparison: Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.p-value: <0.000195% CI: [0.41, 1.27]Wilcoxon Signed Rank Test
Comparison: Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.p-value: <0.000195% CI: [1.5, 2.74]Wilcoxon Signed Rank Test
Comparison: Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.p-value: <0.000195% CI: [0.73, 1.35]Wilcoxon Signed Rank Test
Secondary

Change From Baseline in Fluoride Concentration at 1 Hour Post Brushing With Study Treatments

Change from baseline at any time point for a treatment period was calculated as the median post brushing fluoride value at a time point minus the median baseline (pre-brushing) fluoride value for a treatment period.

Time frame: Plaque samples were collected at baseline, 1 hour post single application of study treatment

Population: PP population: All participants who had at least one post-baseline efficacy assessment but did not have any major protocol deviations. Due to drop outs, there were differences in the n per treatment group. Missing data was not imputed.

ArmMeasureValue (MEDIAN)
NaF Toothpaste(1450 Ppm F)Change From Baseline in Fluoride Concentration at 1 Hour Post Brushing With Study Treatments0.20 μg*F/g
NaF Toothpaste (1400 Ppm F)Change From Baseline in Fluoride Concentration at 1 Hour Post Brushing With Study Treatments0.22 μg*F/g
NaMFP/NaF Toothpaste (1450ppmF)Change From Baseline in Fluoride Concentration at 1 Hour Post Brushing With Study Treatments0.12 μg*F/g
Placebo Toothpaste (0ppmF)Change From Baseline in Fluoride Concentration at 1 Hour Post Brushing With Study Treatments0.01 μg*F/g
Comparison: Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.p-value: 0.686595% CI: [-0.13, 0.08]Wilcoxon Signed Rank Test
Comparison: Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.p-value: 0.175695% CI: [-0.02, 0.12]Wilcoxon Signed Rank Test
Comparison: Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.p-value: <0.000195% CI: [0.16, 0.38]Wilcoxon Signed Rank Test
Comparison: Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.p-value: 0.002395% CI: [0.04, 0.22]Wilcoxon Signed Rank Test
Comparison: Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.p-value: <0.000195% CI: [0.22, 0.51]Wilcoxon Signed Rank Test
Comparison: Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.p-value: <0.000195% CI: [0.12, 0.25]Wilcoxon Signed Rank Test
Secondary

Change From Baseline in Fluoride Concentration at 2 Hours Post Brushing With Study Treatments

Change from baseline at any time point for a treatment period was calculated as the median post brushing fluoride value at a time point minus the median baseline (pre-brushing) fluoride value for a treatment period.

Time frame: Plaque samples were collected at baseline, 2 hour post single application of study treatment

Population: PP population: All participants who had at least one post-baseline efficacy assessment but did not have any major protocol deviations. Due to drop outs, there were differences in the n per treatment group. Missing data was not imputed.

ArmMeasureValue (MEDIAN)
NaF Toothpaste(1450 Ppm F)Change From Baseline in Fluoride Concentration at 2 Hours Post Brushing With Study Treatments0.09 μg*F/g
NaF Toothpaste (1400 Ppm F)Change From Baseline in Fluoride Concentration at 2 Hours Post Brushing With Study Treatments0.09 μg*F/g
NaMFP/NaF Toothpaste (1450ppmF)Change From Baseline in Fluoride Concentration at 2 Hours Post Brushing With Study Treatments0.07 μg*F/g
Placebo Toothpaste (0ppmF)Change From Baseline in Fluoride Concentration at 2 Hours Post Brushing With Study Treatments0.00 μg*F/g
Comparison: Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.p-value: 0.078395% CI: [-0.08, 0]Wilcoxon Signed Rank Test
Comparison: Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.p-value: 0.053195% CI: [0, 0.07]Wilcoxon Signed Rank Test
Comparison: Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.p-value: <0.000195% CI: [0.07, 0.14]Wilcoxon Signed Rank Test
Comparison: Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.p-value: 0.000595% CI: [0.03, 0.15]Wilcoxon Signed Rank Test
Comparison: Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.p-value: <0.000195% CI: [0.08, 0.2]Wilcoxon Signed Rank Test
Comparison: Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.p-value: <0.000195% CI: [0.04, 0.1]Wilcoxon Signed Rank Test
Secondary

Change From Baseline in Fluoride Concentration at 30 Minutes Post Brushing With Study Treatments

Change from baseline at any time point for a treatment period was calculated as the median post brushing fluoride value at a time point minus the median baseline (pre-brushing) fluoride value for a treatment period.

Time frame: Plaque samples were collected at baseline, 30 minutes post single application of study treatment

Population: PP population: All participants who had at least one post-baseline efficacy assessment but did not have any major protocol deviations. Due to drop outs, there were differences in the n per treatment group. Missing data was not imputed.

ArmMeasureValue (MEDIAN)
NaF Toothpaste(1450 Ppm F)Change From Baseline in Fluoride Concentration at 30 Minutes Post Brushing With Study Treatments0.71 μg*F/g
NaF Toothpaste (1400 Ppm F)Change From Baseline in Fluoride Concentration at 30 Minutes Post Brushing With Study Treatments0.72 μg*F/g
NaMFP/NaF Toothpaste (1450ppmF)Change From Baseline in Fluoride Concentration at 30 Minutes Post Brushing With Study Treatments0.28 μg*F/g
Placebo Toothpaste (0ppmF)Change From Baseline in Fluoride Concentration at 30 Minutes Post Brushing With Study Treatments0.02 μg*F/g
Comparison: Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.p-value: 0.554595% CI: [-0.22, 0.47]Wilcoxon Signed Rank Test
Comparison: Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.p-value: 0.000395% CI: [0.15, 0.71]Wilcoxon Signed Rank Test
Comparison: Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.p-value: <0.000195% CI: [0.58, 1.56]Wilcoxon Signed Rank Test
Comparison: Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.p-value: <0.000195% CI: [0.15, 0.68]Wilcoxon Signal Rank Test
Comparison: Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.p-value: <0.000195% CI: [0.58, 1.35]Wilcoxon Signed Rank Test
Comparison: Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.p-value: <0.000195% CI: [0.26, 0.56]Wilcoxon Signed Rank Test
Secondary

Change From Baseline in Fluoride Concentration at 4 Hours Post Brushing With Study Treatments

Change from baseline at any time point for a treatment period was calculated as the median post brushing fluoride value at a time point minus the median baseline (pre-brushing) fluoride value for a treatment period.

Time frame: Plaque samples were collected at baseline, 4 hours post single application of study treatment

Population: PP population: All participants who had at least one post-baseline efficacy assessment but did not have any major protocol deviations. Due to drop outs, there were differences in the n per treatment group. Missing data was not imputed.

ArmMeasureValue (MEDIAN)
NaF Toothpaste(1450 Ppm F)Change From Baseline in Fluoride Concentration at 4 Hours Post Brushing With Study Treatments0.04 μg*F/g
NaF Toothpaste (1400 Ppm F)Change From Baseline in Fluoride Concentration at 4 Hours Post Brushing With Study Treatments0.04 μg*F/g
NaMFP/NaF Toothpaste (1450ppmF)Change From Baseline in Fluoride Concentration at 4 Hours Post Brushing With Study Treatments0.02 μg*F/g
Placebo Toothpaste (0ppmF)Change From Baseline in Fluoride Concentration at 4 Hours Post Brushing With Study Treatments-0.01 μg*F/g
Comparison: Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.p-value: 0.430995% CI: [-0.03, 0.01]Wilcoxon Signed Rank Test
Comparison: Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.p-value: 0.072695% CI: [0, 0.04]Wilcoxon Signed Rank Test
Comparison: Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.p-value: <0.000195% CI: [0.03, 0.06]Wilcoxon Signed Rank Test
Comparison: Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.p-value: 0.010795% CI: [0.01, 0.06]Wilcoxon Signed Rank Test
Comparison: Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.p-value: <0.000195% CI: [0.03, 0.07]Wilcoxon Signed Rank Test
Comparison: Null hypothesis was no difference between treatments, being compared. Statistical tests were 2-sided at 5% significance level.p-value: 0.001295% CI: [0.01, 0.04]Wilcoxon Signed Rank Test
Secondary

Natural Log Transformed AUC for Fluoride Concentration in Plaque Fluid Between 0-4 Hours

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 0-4 hours using trapezoidal rule and natural log transformation was applied.due to failure of assumption of normal distribution of data.

Time frame: Plaque samples collected at 15 minutes, 30 minutes, 1 hour, 2 hours and 4 hours post single application of treatment

Population: Per-Protocol (PP) population: All participants who had at least one post-baseline efficacy assessment but did not have any major protocol deviations. Due to drop outs, there were differences in the n per treatment group. Missing data was not imputed.

ArmMeasureValue (LOG_MEAN)Dispersion
NaF Toothpaste(1450 Ppm F)Natural Log Transformed AUC for Fluoride Concentration in Plaque Fluid Between 0-4 Hours0.54 ln(μg*F*minutes/cm^2)Standard Error 0.086
NaF Toothpaste (1400 Ppm F)Natural Log Transformed AUC for Fluoride Concentration in Plaque Fluid Between 0-4 Hours0.54 ln(μg*F*minutes/cm^2)Standard Error 0.087
NaMFP/NaF Toothpaste (1450ppmF)Natural Log Transformed AUC for Fluoride Concentration in Plaque Fluid Between 0-4 Hours0.05 ln(μg*F*minutes/cm^2)Standard Error 0.086
Placebo Toothpaste (0ppmF)Natural Log Transformed AUC for Fluoride Concentration in Plaque Fluid Between 0-4 Hours-0.90 ln(μg*F*minutes/cm^2)Standard Error 0.087
Comparison: Null hypothesis is no difference between treatments being compared. Tests were 2 sided at 5% significance levels.p-value: <0.000195% CI: [0.28, 0.7]ANCOVA
Comparison: Null hypothesis was no difference between treatments, being compared. Tests were 2 sided at 5% significance levels.p-value: <0.000195% CI: [1.23, 1.65]ANCOVA
Comparison: Null hypothesis was no difference between treatments, being compared. Tests were 2 sided at 5% significance levels.p-value: <0.000195% CI: [0.28, 0.7]ANCOVA
Comparison: Null hypothesis was no difference between treatments, being compared. Tests were 2 sided at 5% significance levels.p-value: <0.000195% CI: [1.23, 1.65]ANCOVA
Comparison: Null hypothesis was no difference between treatments, being compared. Tests were 2 sided at 5% significance levels.p-value: <0.000195% CI: [0.74, 1.16]ANCOVA

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026