A Proof of Concept Clinical Study to Investigate the Effects of an Experimental Cosmetic Moisturiser on the Barrier Function of Human Skin on the Face and Forearm

Study Overview
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Brief Summary
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The objective of this POC clinical study is to investigate the impact of the test product (Developmental Cosmetic Moisturising Cream) on skin barrier function and skin moisturisation on the forearm and face after 4 weeks of twice daily application compared to no treatment in participants with dry sensitive skin.

Detailed Description
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Areas on the volar forearm and each side of the face, will be selected for measurements of transepidermal water loss (TEWL) and corneometry to be conducted . A physical challenge and a regression period of 5 days is also included to evaluate skin barrier function and moisturisation. A regression period of 5 days (Days 30, 31, 32, 33 and 34) of no study product use following the 4 week treatment phase is also included to evaluate skin barrier function and moisturisation.

Official Title
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A Proof of Concept (POC) Clinical Study to Investigate the Effects of a Developmental Cosmetic Moisturising Cream on the Barrier Function of Human Skin on the Face and Forearm

Conditions
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Skin Care

Intervention / Treatment
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* Other: Test product (Moisturising cream)
* Other: Positive control (Commercial market place moisturising cream)
* Other: No treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Demonstrates understanding of the study procedures, restrictions and willingness to participate as evidenced by voluntary written informed consent and has received a signed and dated copy of the informed consent form. Good general and mental health with, in the opinion of the investigator or medically qualified designee no clinically significant and relevant abnormalities in medical history or upon physical examination. Self-reported dry, sensitive skin on the face and body. Agreement to comply with the procedures and requirements of the study and to attend the scheduled assessment visits. Trained examiner visual grading assessment score (including subject self-assessment of tightness) of overall dryness ≥ 3 with a score of at least 1 in the roughness parameter and 4 (for any individual parameter) on each of the forearms and each side of the face at the Screening visit (Visit 1) and Baseline visit (Visit 2). In addition, there will be no greater than 0.5 point difference between trained examiner visual grading scores of each volar forearm and each side of the face at the Screening and Baseline visits. Fitzpatrick skin type I-IV Exclusion Criteria: Women who are known to be pregnant or who are intending to become pregnant over the duration of the study. Women who are breast-feeding. Any history of significant dermatological diseases or conditions or medical conditions known to alter skin appearance or physiologic response (e.g. diabetes) which could, in the opinion of the Investigator, preclude topical application of the investigational products and/or interfere with the evaluations. Presence of open sores, pimples, or cysts at the application site. Active dermatosis (local or disseminated) that might interfere with the results of the study. Considered immune compromised. Currently using any medication which in the opinion of the investigator, may affect the evaluation of the study product, or place the subject at undue risk. Use of the following topical or systemic medications: immunosuppressants, antihistamines, non-hormonal anti-inflammatory drugs, and corticosteroids up to 2 weeks before screening visit. Intention of using any oral or topical steroids. Regular use of inhaled steroids (occasional use is permitted). Regular use of topical anti-itch medications (occasional use permitted; the product should be applied with an applicator but not to the proposed application areas. Use of any topical drug or medication in the proposed application areas. Intention of being vaccinated during the study period or has been vaccinated within 3 weeks of the screening visit. Currently receiving allergy injections, or received an allergy injection within 7 days prior to Visit 1, or expects to begin injections during study participation. Previous history of atopy, allergic reactions, irritation or intense discomfort feelings to topical-use products, cosmetics or medication. Known or suspected intolerance or hypersensitivity to any of the study materials (or closely related compounds) or any of their stated ingredients. Participation in another clinical study (including cosmetic studies) or receipt of an investigational drug within 14 days of the screening visit. Previous participation in this study. Recent history (within the last 5 years) of alcohol or other substance abuse. Smoker (including e-cigarettes) Moles, tattoos, scars, hairs, etc. at the test areas if it is likely that they could affect the assessments. Subject has visible sunburn on the test sites. Use of self-tanning products on the test areas (face and arms) within 2 weeks prior to the screening visit. Any individual parameter score 4 on any test areas of the face or either of the forearms as assessed by a trained examiner. Any Subject who, in the judgment of the Investigator, should not participate in the study. An employee of the sponsor or the study site or members of their immediate family.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Test product/ No treatment<br>Participants randomized to this arm will apply Test product at allocated sites and leave other sites untreated. | Other: Test product (Moisturising cream)<br>* Participants will be instructed to apply their assigned product to the randomly assigned sites twice daily (in the morning and evening).<br>Other: No treatment<br>* No treatment.<br>|
| Other: Test product/positive control<br>Participants randomized to this arm will apply Test and positive product at allocated sites. | Other: Test product (Moisturising cream)<br>* Participants will be instructed to apply their assigned product to the randomly assigned sites twice daily (in the morning and evening).<br>Other: Positive control (Commercial market place moisturising cream)<br>* Participants will be instructed to apply their assigned product to the randomly assigned sites twice daily (in the morning and evening).<br>|
| Other: Positive control /no treatment<br>Participants randomized to this arm will apply Positive product at allocated sites and leave other sites untreated. | Other: Positive control (Commercial market place moisturising cream)<br>* Participants will be instructed to apply their assigned product to the randomly assigned sites twice daily (in the morning and evening).<br>Other: No treatment<br>* No treatment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Transepidermal Water Loss (TEWL) Measurements on Day 29, Test Product Treated Versus (vs.) Untreated Sites on the Forearm | TEWL measuring principle is 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 belongs to the equilibration phase. The values of the last 10 secs were averaged as the actual measurement values. An increase in TEWL values shows damage to the skin barrier function. | At Baseline and Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Transepidermal Water Loss (TEWL) Measurements on Day 29, Test Product Treated vs. Untreated Sites on the Face | TEWL measuring principle is 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 secs, to ensure that a stable value has been established. The first part of the measurement belongs to the equilibration phase. The values of the last 10 secs were averaged as the actual measurement values. An increase in TEWL values shows damage to the skin barrier function. | At Baseline and Day 29 | 
| Change From Baseline in Corneometry on the Forearm and Face, Test Product Treated vs. Untreated Sites | Corneometry was used to measure moisture content of stratum corneum using corneometer. The measuring principle is based on changes in the capacitance of the measuring head, functioning as a condensator. Between the conductors of the probe an electrical field was built which allows the dielectricity of the stratum corneum to be measured. Because the dielectricity of the skin varies as a function of its water content. The Corneometer measurements was taken 5 times in total and then an average reading was calculated for each site and time point. An increase in corneometry values indicates an increase in the hydration status of the skin and vice versa. | At Baseline, Day 1 (30 minutes and 6 hours post study product application), Day 2, 15, and 29 | 
| Change From Baseline in Transepidermal Water Loss (TEWL) on the Forearm and Face, Test Product Treated vs. Untreated Sites at Day 2 and 15 | TEWL measuring principle is 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 secs, to ensure that a stable value has been established. The first part of the measurement belongs to the equilibration phase. The values of the last 10 secs were averaged as the actual measurement values. An increase in TEWL values shows damage to the skin barrier function. | At Baseline, Day 2, and 15 | 
| Standardised Area Under Curve (AUC1-29) of Change From Baseline in Corneometry Over Treatment Period | Standardised AUC1-29 was calculated for each participant for change from baseline in corneometry on forearms and face over the treatment period; i.e. up to Day 29 using the trapezoidal rule and dividing by the number of days in the period. Corneometry was used to measure moisture content of stratum corneum using corneometer. The measuring principle is based on changes in the capacitance of the measuring head, functioning as a condensator. Between the conductors of the probe an electrical field was built which allows the dielectricity of the stratum corneum to be measured. Because the dielectricity of the skin varies as a function of its water content. The Corneometer measurements was taken 5 times in total and then an average reading was calculated for each site and time point. An increase in corneometry values indicates an increase in the hydration status of the skin and vice versa. | Up to Day 29 | 
| Standardised Area Under Curve (AUC1-29) of Change From Baseline in Transepidermal Water Loss (TEWL) Over Treatment Period | Standardised AUC1-29 was calculated for each participant for change from baseline in TEWL on forearms and face over the treatment period; i.e. up to Day 29 using the trapezoidal rule and dividing by the number of days in the period. TEWL measuring principle is 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 secs, to ensure that a stable value has been established. The first part of the measurement belongs to the equilibration phase. The values of the last 10 secs were averaged as the actual measurement values. An increase in TEWL values shows damage to the skin barrier function. | Up to Day 29 | 
| Change From Pre-challenge in Transepidermal Water Loss (TEWL) Measurements of D-Squame Discs Following 4, 8 and 12 Adhesive Discs Removal From Skin of Both Test Product Treated and Untreated Sites on the Forearm on Day 29 | A series of D-Squame discs were gently smoothed over the designated D-Squame Areas by applying a uniform pressure for 5 secs with a stamp to ensure consistent adhesion to the skin. Each disc was pulled off the skin with one fluent and decisive movement. There were maximum of 12 D-Squame discs (in groups of 4) removed from each forearm repeatedly. TEWL measuring principle is 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 secs, to ensure that a stable value has been established. The first part of the measurement belongs to the equilibration phase. The values of the last 10 secs were averaged as the actual measurement values. TEWL was measured pre-challenge and after 4, 8 and 12 discs have been removed from the forearms. An increase in TEWL values shows damage to the skin barrier function. | On Day 29 (including Pre-challenge) | 
| Change From Pre-challenge in Transepidermal Water Loss (TEWL) Measurements of D-Squame Discs Following 3, 6 and 9 Adhesive Discs Removal From Skin of Both Test Product Treated and Untreated Sites on the Face on Day 29 | A series of D-Squame discs were gently smoothed over the designated D-Squame Areas by applying a uniform pressure for 5 secs with a stamp to ensure consistent adhesion to the skin. Each disc was pulled off the skin with one fluent and decisive movement. There were maximum of 9 D-Squame discs (in groups of 3) removed from the face repeatedly. TEWL measuring principle is 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 secs, to ensure that a stable value has been established. The first part of the measurement belongs to the equilibration phase. The values of the last 10 secs were averaged as the actual measurement values. TEWL was measured pre-challenge and after 3, 6 and 9 discs have been removed from the face. An increase in TEWL values shows damage to the skin barrier function. | On Day 29 (including Pre-challenge) | 
| Protein Analysis (SquameScan) of D-Squame Discs (Total of 12 Adhesive Discs) From Skin of Both Test Product Treated and Untreated Sites on the Forearm on Day 29 | The protein content of each D-Squame disc was analysed using a SquameScan. SquameScan is the instrument used to indirectly measure the protein content extracted from the skin by D-squame tape strips. The determination was performed by measuring the optical absorption of the strip at about 850 nanometres (nm) (infrared light). The value displayed in % was proportionally related to the protein content. The protein content was analysed for each of the discs obtained the D-Squame stripping on the forearms and reported to 2 decimal places. | On Day 29 | 
| Protein Analysis of D-Squame Discs (Total of 9 Adhesive Discs) From Skin of Both Test Product Treated and Untreated Sites on the Face on Day 29 | The protein content of each D-Squame disc was analysed using a SquameScan. SquameScan is the instrument used to indirectly measure the protein content extracted from the skin by D-squame tape strips. The determination was performed by measuring the optical absorption of the strip at about 850 nm (infrared light). The value displayed in % was proportionally related to the protein content. The protein content was analysed for each of the discs obtained the D-Squame stripping on the face and reported to 2 decimal places. | On Day 29 | 
| Change From Baseline in Transepidermal Water Loss (TEWL) Measurements on Days 30, 31, 32, 33 and 34 in Test Product Treated vs. Untreated Sites on the Forearm and Face | TEWL measuring principle is 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 secs, to ensure that a stable value was established. The first part of the measurement belongs to the equilibration phase. The values of the last 10 secs were averaged as the actual measurement values. An increase in TEWL values shows damage to the skin barrier function. | At Baseline, Day 30, 31, 32, 33 and 34 | 
| Change From Day 29 in Transepidermal Water Loss (TEWL) Measurements on Days 30, 31, 32, 33 and 34 in Test Product Treated vs. Untreated Sites on the Forearm and Face | TEWL measuring principle is 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 secs, to ensure that a stable value was established. The first part of the measurement belongs to the equilibration phase. The values of the last 10 secs were averaged as the actual measurement values. An increase in TEWL values shows damage to the skin barrier function. | At Day 30, 31, 32, 33, and 34 | 
| Change From Baseline in Standardised Area Under Curve (AUCday 29-34) of Transepidermal Water Loss (TEWL) Over Regression Period (Days 30, 31, 32, 33 and 34) of Forearm and Face, Test Product Treated vs. Untreated Sites | Standardised AUCday29-34 was calculated for each participant for change from baseline in TEWL on forearms and face over the regression period (Day31, 32, 33 and 34) using the trapezoidal rule and dividing by the number of days in the period. TEWL measuring principle is 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 secs, to ensure that a stable value was established. The first part of the measurement belongs to the equilibration phase. The values of the last 10 secs were averaged as the actual measurement values. An increase in TEWL values shows damage to the skin barrier function. | Up to Day 34 | 
| Change From Day 29 in Standardised Area Under Curve (AUCday 29-34) of Transepidermal Water Loss (TEWL) Over Regression Period (Days 30, 31, 32, 33 and 34) of Forearm and Face, Test Product Treated vs. Untreated Sites | Standardised AUCday29-34 was calculated for each participant for change from Day 29 in TEWL on forearms and face over the regression period (Day31, 32, 33 and 34) using the trapezoidal rule and dividing by the number of days in the period. TEWL measuring principle is 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 secs, to ensure that a stable value was established. The first part of the measurement belongs to the equilibration phase. The values of the last 10 secs were averaged as the actual measurement values. An increase in TEWL values shows damage to the skin barrier function. | Up to Day 34 | 
| Change From Baseline in Corneometry Measurements on Days 30, 31, 32, 33 and 34 in Test Product Treated Site vs. Untreated Site on the Forearm and Face | Corneometry was used to measure the moisture content of stratum corneum using corneometer. The measuring principle is based on changes in the capacitance of the measuring head, functioning as a condensator. Between the conductors of the probe an electrical field was built which allows the dielectricity of the stratum corneum to be measured. Because the dielectricity of the skin varies as a function of its water content. The Corneometer measurements were taken 5 times in total and then an average reading was calculated for each site and time point. An increase in corneometry values indicates an increase in the hydration status of the skin and vice versa. | At Baseline, Day 30, 31, 32, 33, and 34 | 
| Change From Day 29 in Corneometry Measurements on Days 30, 31, 32, 33 and 34 in Test Product Treated Site vs. Untreated Site on the Forearm and Face | Corneometry was used to measure the moisture content of stratum corneum using corneometer. The measuring principle is based on changes in the capacitance of the measuring head, functioning as a condensator. Between the conductors of the probe an electrical field was built which allows the dielectricity of the stratum corneum to be measured. Because the dielectricity of the skin varies as a function of its water content. The Corneometer measurements were taken 5 times in total and then an average reading was calculated for each site and time point. An increase in corneometry values indicates an increase in the hydration status of the skin and vice versa. | At Day 29, 30, 31, 32, 33, and 34 | 
| Standardised Area Under Curve (AUCday29-34) Calculated Using Change From Baseline in Corneometry Over Regression Period (Days 30, 31, 32, 33 and 34) on the Forearm and Face | Standardised AUCday29-34 was calculated for each participant for change from baseline in corneometry on forearms and face over the regression period using the trapezoidal rule and dividing by the number of days in the period. Corneometry was used to measure moisture content of stratum corneum using corneometer. The measuring principle is based on changes in the capacitance of the measuring head, functioning as a condensator. Between the conductors of the probe an electrical field was built which allows the dielectricity of the stratum corneum to be measured. Because the dielectricity of the skin varies as a function of its water content. The Corneometer measurements was taken 5 times in total and then an average reading was calculated for each site and time point. An increase in corneometry values indicates an increase in the hydration status of the skin and vice versa. | Up to Day 34 | 
| Standardised AUC Calculated Using Change From Day 29 in Corneometry Over Regression Period (Days 30, 31, 32, 33 and 34) on the Forearm and Face | Standardised AUCday29-34 was calculated for each participant for change from day 29 in corneometry on forearms and face over the regression period using the trapezoidal rule and dividing by the number of days in the period. Corneometry was used to measure the moisture content of stratum corneum using corneometer. The measuring principle is based on changes in the capacitance of the measuring head, functioning as a condensator. Between the conductors of the probe an electrical field was built which allows the dielectricity of the stratum corneum to be measured. Because the dielectricity of the skin varies as a function of its water content. The Corneometer measurements were taken 5 times in total and then an average reading was calculated for each site and time point. An increase in corneometry values indicates an increase in the hydration status of the skin and vice versa. | Up to Day 34 | 
| Change From Baseline in Transepidermal Water Loss (TEWL) Measurements on Day 29 of Positive Control Treated Site vs. Untreated Site on the Forearm. | TEWL measuring principle is 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 secs, to ensure that a stable value has been established. The first part of the measurement belongs to the equilibration phase. The values of the last 10 seconds were averaged as the actual measurement values. An increase in TEWL values shows damage to the skin barrier function. | At Baseline and Day 29 |