To Assess the Mildness of a Cosmetic Cleanser in Healthy Participants Using the Forearm-Controlled Application Technique (FCAT)

• ClinicalTrials.gov Identifier: NCT03119688
• Recruitment Status: Completed
• First Posted: April 18, 2017
• Results First Posted: May 2, 2019
• Last Update Posted: May 2, 2019
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Investigator, Outcomes Assessor); Primary Purpose: Basic Science
• Condition: Skin Care
• Interventions: Other: Test Product; Other: Positive Control; Other: Reference Product; Other: No Treatment
• Enrollment: 50

Participant Flow

Recruitment Details	Participants were recruited from one center in Brazil.
Pre-assignment Details	A total of 89 participants were screened, out of which 39 participants did not meet the study criteria. Remaining 50 participants were enrolled in the study, out of which 2 participants were not randomized to the study due to adverse events (AEs).

Arm/Group Title	Overall Participants
Arm/Group Description	All participants enrolled in the study received all the study products and received at least 1 wash procedure. Each participant received 9 controlled wash applications over 5 days of test product (0.09 mL), positive control (soap bar) and negative control (0.09 mL) at each allocated test site. Therefore, each participant received a total of 27 applications of study products. Each wash procedure included a 10-second application of the test product, followed by a 90-second wait and a 15-second rinse-off with sterile water.
Period Title: Overall Study
Started	48
Completed	44
Not Completed	4
Reason Not Completed
Adverse Event	4

Baseline Characteristics

Arm/Group Title		Overall Participants
Arm/Group Description		All participants enrolled in the study received all the study products and received at least 1 wash procedure. Each participant received 9 controlled wash applications over 5 days of test product (0.09 mL), positive control (soap bar) and negative control (0.09 mL) at each allocated test site. Therefore, each participant received a total of 27 applications of study products. Each wash procedure included a 10-second application of the test product, followed by a 90-second wait and a 15-second rinse-off with sterile water.
Overall Number of Baseline Participants		48
Baseline Analysis Population Description		Baseline parameters were reported for safety population. The safety population (N=48) included all participants who had received at least one wash procedure.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	48 participants
		39.1 (13.69)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	48 participants
	Female	47 97.9%
	Male	1 2.1%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	48 participants
	American Indian or Alaska Native	1 2.1%
	Asian	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	8 16.7%
	White	39 81.3%
	More than one race	0 0.0%
	Unknown or Not Reported	0 0.0%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Visual Assessment of Dryness at Day 5
Description	Skin dryness was assessed by a trained examiner according to following the scoring scale: 0 (No dryness); 1 (Patches of slight powederiness and occasional patches of small scales may be seen, distribution generalized.); 2 (Generalised slight powederiness, early cracking or occasional small lifting scales may be present); 3 (Generalised moderate powederiness and/or heavy cracking and lifting scales; 4 (Generalised heavy powederiness and/or heavy cracking and lifting scales); 5 (Generalised high cracking and lifting scales, eczematous change may be present, powederiness may be present but not prominent, may see bleeding crack); 6 (Generalised severe cracking, eczematous change may be present, bleeding cracks may be present, scale large may be beginning to disappear). Lower scores reflect less dry skin.
Time Frame	At Baseline and Day 5 (3 hours post last wash procedure)

Outcome Measure Data

Analysis Population Description

ITT population (N=48) was the primary population of analysis, which included all participants who were randomized and received at least one wash procedure, including sterile water, and had at least one post-baseline clinical assessment. Number of participants analyzed for this endpoint were part of the ITT population, evaluated on Day 5.

Arm/Group Title	Test	Positive Control	Negative Control	No Treatment
Arm/Group Description:	Data of this arm included all allotted sides of the forearms of the participants where test product (0.09 ml of the cleanser) was applied during the study.	Data of this arm included all allotted sides of the forearms of the participants where positive control (Soap bar) was applied during the study.	Data of this arm included all allotted sides of the forearms of the participants where Negative control (0.09 ml of sterile water) was applied during the study.	Data of this arm included all allotted sides of the forearms of the participants which were left untreated during the study.
Overall Number of Participants Analyzed	44	44	44	44
Mean (Standard Deviation); Unit of Measure: Score on a scale
	0.48 (0.284)	0.91 (0.291)	0.56 (0.290)	0.63 (0.307)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test, Negative Control
	Comments	The null hypothesis (non-inferiority setting) is that the population mean dryness for Test minus Baxter Sterile Water (negative control) is at least 0.25.
	Type of Statistical Test	Non-Inferiority
	Comments	The non-Inferiority margin is set at 0.25. The upper limit of the 90% CI is less than this and hence NI is met.
Statistical Test of Hypothesis	P-Value	0.1769
	Comments	No adjustment for multiple comparisons was made.
	Method	ANOVA
	Comments	ANOVA model with change from baseline in examiner assessment on dryness as response and treatment, site as fixed effects; participant as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.077
	Confidence Interval	(2-Sided) 90%; -0.1707 to 0.0169
	Estimation Comments	Difference is first named treatment minus second named treatment such that a negative difference favors first named treatment.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Positive Control, Negative Control
	Comments	The null hypothesis is that the difference in population mean dryness is zero.
	Type of Statistical Test	Superiority
	Comments	This is a superiority test setting.
Statistical Test of Hypothesis	P-Value	<.0001
	Comments	No adjustment for multiple comparisons was made.
	Method	ANOVA
	Comments	ANOVA model with change from baseline in examiner assessment on dryness as response and treatment, site as fixed effects;participant as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.350
	Confidence Interval	(2-Sided) 90%; 0.2565 to 0.4441
	Estimation Comments	Difference is first named treatment minus second named treatment such that a negative difference favors first named treatment.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Test, Positive Control
	Comments	The null hypothesis is that the difference in population mean dryness is zero.
	Type of Statistical Test	Superiority
	Comments	This is a superiority test setting.
Statistical Test of Hypothesis	P-Value	<.0001
	Comments	No adjustment for multiple comparisons was made.
	Method	ANOVA
	Comments	ANOVA model with change from baseline in examiner assessment on dryness as response and treatment, site as fixed effects; participant as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.427
	Confidence Interval	(2-Sided) 90%; 0.3333 to 0.5211
	Estimation Comments	Difference is first named treatment minus second named treatment such that a negative difference favors first named treatment.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Negative Control, No Treatment
	Comments	The null hypothesis is that the difference in population mean dryness is zero.
	Type of Statistical Test	Superiority
	Comments	This is a superiority test setting.
Statistical Test of Hypothesis	P-Value	0.2518
	Comments	No adjustment for multiple comparisons was made.
	Method	ANOVA
	Comments	ANOVA model with change from baseline in examiner assessment on dryness as response and treatment, site as fixed effects;participant as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.065
	Confidence Interval	(2-Sided) 90%; -0.0287 to 0.1592
	Estimation Comments	Difference is first named treatment minus second named treatment such that a negative difference favors first named treatment.

2. Secondary Outcome

Title	Change From Baseline in Visual Assessment of Redness at Day 5
Description	Skin redness was assessed by a trained examiner according to following the scoring scale: 0 (No redness); 1(Barely detectable redness); 2(Slight redness); 3 (Moderate redness); 4 (Heavy or substantial redness); 5 (Extreme redness); 6 (Severe Redness). Lower scores reflect less skin redness.
Time Frame	At Baseline and Day 5 (3 hours post last wash procedure)

Outcome Measure Data

Analysis Population Description

ITT population (N=48) was the primary population of analysis, which included all participants who were randomized and received at least one wash procedure, including sterile water, and had at least one post-baseline clinical assessment. Number of participants analyzed for this endpoint were part of the ITT population, evaluated on Day 5.

Arm/Group Title	Test	Positive Control	Negative Control	No Treatment
Arm/Group Description:	Data of this arm included all allotted sides of the forearms of the participants where test product (0.09 ml of the cleanser)was applied during the study.	Data of this arm included all allotted sides of the forearms of the participants where positive control (Soap bar) was applied during the study.	Data of this arm included all allotted sides of the forearms of the participants where Negative control (0.09 ml of sterile water ) was applied during the study.	Data of this arm included all allotted sides of the forearms of the participants which were left untreated during the study.
Overall Number of Participants Analyzed	44	44	44	44
Mean (Standard Deviation); Unit of Measure: Score on a scale
	0.01 (0.075)	0.00 (0.00)	0.00 (0.00)	0.00 (0.00)

3. Secondary Outcome

Title	Change From Baseline in Visual Assessment of Dryness at Day 2, 3, and 4
Description	Skin dryness was assessed by a trained examiner according to following the scoring scale: 0 (No dryness); 1 (Patches of slight powederiness and occasional patches of small scales may be seen, distribution generalized.); 2 (Generalised slight powederiness, early cracking or occasional small lifting scales may be present); 3 (Generalised moderate powederiness and/or heavy cracking and lifting scales; 4 (Generalised heavy powederiness and/or heavy cracking and lifting scales); 5 (Generalised high cracking and lifting scales, eczematous change may be present, powederiness may be present but not prominent, may see bleeding crack); 6 (Generalised severe cracking, eczematous change may be present, bleeding cracks may be present, scale large may be beginning to disappear). Lower scores reflect less dry skin.
Time Frame	At Baseline and Day 2, 3, and 4 (3 hours post last wash procedure)

Outcome Measure Data

Analysis Population Description

ITT population (N=48) was the primary population of analysis, which included all participants who were randomized and received at least one wash procedure, including sterile water, and had at least one post-baseline clinical assessment.

Arm/Group Title		Test	Positive Control	Negative Control	Reference (Unwashed Area)
Arm/Group Description:		Data of this arm included all allotted sides of the forearms of the participants where test product (0.09 ml of the cleanser)was applied during the study.	Data of this arm included all allotted sides of the forearms of the participants where positive control (Soap bar) was applied during the study.	Data of this arm included all allotted sides of the forearms of the participants where Negative control (0.09 ml of sterile water) was applied during the study.	Data of this arm included all allotted sides of the forearms of the participants which were left untreated during the study.
Overall Number of Participants Analyzed		48	48	48	48
Mean (Standard Deviation); Unit of Measure: Score on a scale
Day 2	Number Analyzed	48 participants	48 participants	48 participants	48 participants
		0.25 (0.253)	0.46 (0.307)	0.28 (0.251)	0.31 (0.265)
Day 3	Number Analyzed	45 participants	45 participants	45 participants	45 participants
		0.37 (0.248)	0.66 (0.298)	0.38 (0.285)	0.42 (0.260)
Day 4	Number Analyzed	44 participants	44 participants	44 participants	44 participants
		0.43 (0.255)	0.76 (0.314)	0.42 (0.240)	0.55 (0.302)

4. Secondary Outcome

Title	Change From Baseline in Visual Assessment of Redness at Day 2, 3, and 4
Description	Skin redness was assessed by a trained examiner according to following the scoring scale: 0 (No redness); 1(Barely detectable redness); 2(Slight redness); 3 (Moderate redness); 4 (Heavy or substantial redness); 5 (Extreme redness); 6 (Severe Redness). Lower scores reflect less skin redness.
Time Frame	At Baseline and Day 2, 3, and 4 (3 hours post last wash procedure)

Outcome Measure Data

Analysis Population Description

ITT population (N=48) was the primary population of analysis, which included all participants who were randomized and received at least one wash procedure, including sterile water, and had at least one post-baseline clinical assessment.

Arm/Group Title		Test	Positive Control	Negative Control	Reference (Unwashed Area)
Arm/Group Description:		Data of this arm included all allotted sides of the forearms of the participants where test product (0.09 ml of the cleanser) was applied during the study.	Data of this arm included all allotted sides of the forearms of the participants where positive control (Soap bar) was applied during the study.	Data of this arm included all allotted sides of the forearms of the participants where Negative control (0.09 ml of sterile water ) was applied during the study.	Data of this arm included all allotted sides of the forearms of the participants which were left untreated during the study
Overall Number of Participants Analyzed		48	48	48	48
Mean (Standard Deviation); Unit of Measure: Score on a scale
Day 2	Number Analyzed	48 participants	48 participants	48 participants	48 participants
		0.06 (0.167)	0.05 (0.154)	0.01 (0.072)	0.01 (0.072)
Day 3	Number Analyzed	45 participants	45 participants	45 participants	48 participants
		0.00 (0.00)	0.00 (0.00)	0.00 (0.00)	0.00 (0.00)
Day 4	Number Analyzed	44 participants	44 participants	44 participants	48 participants
		0.00 (0.00)	0.01 (0.075)	0.00 (0.00)	0.02 (0.151)

5. Secondary Outcome

Title	Change From Baseline in Transepidermal Water Loss (TEWL) at Day 5
Description	TEWL was measured using Tewameter. TEWL measuring principle was based on water vapour gradient determination between two pairs of sensors placed at different distances perpendicularly to the skin. The probe was held in place on the skin for one measurement, for approximately 40 seconds (sec), to ensure that a stable value has been established. The first part of the measurement belonged to the equilibration phase. The values of the last 10 sec were averaged as the actual measurement values. An increase in TEWL values shows damage to the skin barrier function.
Time Frame	At Baseline and Day 5 (3 hours post last wash procedure)

Outcome Measure Data

Analysis Population Description

ITT population (N=48) was the primary population of analysis, which included all participants who were randomized and received at least one wash procedure, including sterile water, and had at least one post-baseline clinical assessment. Number of participants analyzed for this endpoint were part of the ITT population, evaluated on Day 5.

Arm/Group Title	Test Product	Positive Control	Negative Control	No Treatment
Arm/Group Description:	Data of this arm included all allotted sides of the forearms of the participants where test product (0.09 ml of the cleanser)was applied during the study..	Data of this arm included all allotted sides of the forearms of the participants where positive control (Soap bar) was applied during the study.	Data of this arm included all allotted sides of the forearms of the participants where Negative control (0.09 ml of sterile water ) was applied during the study.	Data of this arm included all allotted sides of the forearms of the participants which were left untreated during the study.
Overall Number of Participants Analyzed	44	44	44	44
Mean (Standard Deviation); Unit of Measure: g/m^2/hr
	0.91 (2.118)	1.95 (2.025)	0.94 (1.714)	0.53 (1.682)

6. Secondary Outcome

Title	Change From Baseline in Skin Moisturisation at Day 5
Description	Corneometry was used to measure moisture content of stratum corneum using corneometer. The measuring principle was based on changes in the capacitance of the measuring head, functioning as a condensator. Between the gold conductors of the probe an electrical field was built which allowed the dielectricity of the stratum corneum to be measured. Because the dielectricity of the skin varies as a function of its water content, the stratum corneum moisturisation can be measured. The Corneometer probe was placed in contact with the skin of the paarticipant's test site for 1-2 seconds per measurement. The Corneometer measurements were taken and an average (mean) reading was calculated for each site and time point. Corneometer values lower than 30 instrumental units (i.u.) represents very dry skin, while values between 30 und 50 i.u are typically for dry skin on the forearm. An increase in Corneometer values, therefore, corresponds to a skin-moisturising effect.
Time Frame	At Baseline and Day 5 (3 hours post last wash procedure)

Outcome Measure Data

Analysis Population Description

ITT population (N=48) was the primary population of analysis, which included all participants who were randomized and received at least one wash procedure, including sterile water, and had at least one post-baseline clinical assessment. Number of participants analyzed for this endpoint were part of the ITT population, evaluated on Day 5.

Arm/Group Title	Test	Positive Control	Negative Control	No Treatment
Arm/Group Description:	Data of this arm included all allotted sides of the forearms of the participants where test product (0.09 ml of the cleanser)was applied during the study.	Data of this arm included all allotted sides of the forearms of the participants where positive control (Soap bar) was applied during the study.	Data of this arm included all allotted sides of the forearms of the participants where Negative control (0.09 ml of sterile water) was applied during the study	Data of this arm included all allotted sides of the forearms of the participants which were left untreated during the study.
Overall Number of Participants Analyzed	44	44	44	44
Mean (Standard Deviation); Unit of Measure: i.u.
	2.35 (5.341)	-4.57 (5.368)	2.13 (4.803)	0.34 (3.729)

Adverse Events

Time Frame	Approximately 5 days
Adverse Event Reporting Description	All treatment emergent adverse events (AEs) were reported.
Arm/Group Title	Test	Positive Control	Negative Control	No Treatment	Overall Participants
Arm/Group Description	Data of this arm included all allotted sides of the forearms of the participants where test product (0.09 ml of the cleanser) was applied during the study..	Data of this arm included all allotted sides of the forearms of the participants where positive control (Soap bar) was applied during the study.	Data of this arm included all allotted sides of the forearms of the participants where Negative control (0.09 ml of sterile water) was applied during the study.	Data of this arm included all allotted sides of the forearms of the participants which were left untreated during the study.	Included all participants who applied any of the study products.
All-Cause Mortality
	Test	Positive Control	Negative Control	No Treatment	Overall Participants
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/48 (0.00%)	0/48 (0.00%)	0/48 (0.00%)	0/48 (0.00%)	0/48 (0.00%)
Serious Adverse Events
	Test	Positive Control	Negative Control	No Treatment	Overall Participants
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/48 (0.00%)	0/48 (0.00%)	0/48 (0.00%)	0/48 (0.00%)	0/48 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	1%
	Test	Positive Control	Negative Control	No Treatment	Overall Participants
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	4/48 (8.33%)	4/48 (8.33%)	4/48 (8.33%)	2/48 (4.17%)	6/48 (12.50%)
Gastrointestinal disorders
FOOD POISONING †	1/48 (2.08%)	1/48 (2.08%)	1/48 (2.08%)	1/48 (2.08%)	1/48 (2.08%)
TOOTHACHE †	1/48 (2.08%)	1/48 (2.08%)	1/48 (2.08%)	1/48 (2.08%)	1/48 (2.08%)
General disorders
APPLICATION SITE PRURITUS †	1/48 (2.08%)	0/48 (0.00%)	0/48 (0.00%)	0/48 (0.00%)	1/48 (2.08%)
APPLICATION SITE PAIN †	0/48 (0.00%)	1/48 (2.08%)	2/48 (4.17%)	0/48 (0.00%)	2/48 (4.17%)
Injury, poisoning and procedural complications
THERMAL BURN †	1/48 (2.08%)	0/48 (0.00%)	0/48 (0.00%)	0/48 (0.00%)	1/48 (2.08%)
ARTHROPOD BITE †	0/48 (0.00%)	1/48 (2.08%)	0/48 (0.00%)	0/48 (0.00%)	1/48 (2.08%)
† Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

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
• EMail: GSKClinicalSupportHD@gsk.com

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT03119688
• Other Study ID Numbers: 207619
• First Submitted: April 5, 2017
• First Posted: April 18, 2017
• Results First Submitted: April 20, 2018
• Results First Posted: May 2, 2019
• Last Update Posted: May 2, 2019