Psoriasis Vulgaris
Conditions
Keywords
Psoriasis vulgaris
Brief summary
The purpose of this study is to investigate the efficacy, safety, tolerability and the concentration/response relationship of E6201 in subjects with psoriasis vulgaris.
Detailed description
This is a single center, randomized, blinded, intra-individual comparison in two sequential cohorts of 15 subjects each (30 subjects in total) in an outpatient setting, in which each subject simultaneously receives five topical treatments (3 active, 1 vehicle, and 1 positive control) within one or two psoriatic plaques. Treatments consisted of 3 concentrations of E6201 gel, a negative control (gel vehicle), and a positive control (0.005% calcipotriene cream). The different concentrations of E6201 gel and vehicle control were double-blinded, while the calciprotriene cream was single-blinded. Cohort 2 participants were not dosed until all participants in Cohort 1 completed treatment and safety data were collected and evaluated.
Interventions
DRUG0.03% E6201
Topical 0.03% E6201 gel was applied once daily to individual specific regions of the psoriatic plaque.
DRUG0.1% E6201
Topical 0.1% E6201 gel was applied once daily to individual specific regions of the psoriatic plaque.
DRUG0.2% E6201
Topical 0.2% E6201 gel was applied once daily to individual specific regions of the psoriatic plaque.
DRUG0.005% E6201
Topical 0.005% E6201 gel was applied once daily to individual specific regions of the psoriatic plaque.
DRUG0.01% E6201
Topical 0.01% E6201 gel was applied once daily to individual specific regions of the psoriatic plaque.
DRUG0.05% E6201
Topical 0.05% E6201 gel was applied once daily to individual specific regions of the psoriatic plaque.
OTHERPlacebo - 0.03% gel vehicle
Topical 0.03% gel vehicle (negative control) was applied once daily to individual specific regions of the psoriatic plaque.
OTHERPlacebo - 0.1% gel vehicle
Topical 0.1% gel vehicle (negative control) was applied once daily to individual specific regions of the psoriatic plaque.
OTHERPlacebo - 0.2% gel vehicle
Topical 0.2% gel vehicle (negative control) was applied once daily to individual specific regions of the psoriatic plaque.
OTHERPlacebo - 0.05% gel vehicle
Topical 0.005% gel vehicle (negative control) was applied once daily to individual specific regions of the psoriatic plaque.
OTHERPlacebo - 0.01% gel vehicle
Topical 0.01% gel vehicle (negative control) was applied once daily to individual specific regions of the psoriatic plaque.
DRUGCalcipotriene
Topical 0.005% calcipotriene (positive control) was applied once daily to individual specific regions of the psoriatic plaque.
Sponsors
Eisai Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Inclusion: * Chronic stable plaque psoriasis with one or two stable psoriatic plaques(s) suitable in size and location for five separate treatment fields to be assessed within it. * Males and females aged between 18 and 75 years of age * The general physical examination should be normal (excluding the skin examination for psoriasis) unless the Investigator considers an abnormality not to be clinically significant with regard to the study * Females of childbearing potential must have a negative serum beta-human chorionic gonadotropin at Visit 1 (Screening) and a negative urine pregnancy test prior to starting study drug(s) (Visit 2). Female subjects of childbearing potential must agree to be abstinent or to use a highly effective method of contraception throughout the study period and for 30 days after the last dose of study drug. * Provide written informed consent * Willing and able to comply with all aspects of the protocol Exclusion: * Any clinically significant skin diseases other then chronic stable plaque psoriasis * Other types of psoriasis than chronic stable plaque variant eg, guttate, pustular, erythodermic, etc * An unstable course of the disease defined as flare(s) in the previous month * Subjects who used any concommitant topical treatment for the psoriatic plaque(s) to be studied (other than emollients or salicylic acid) within 8 weeks before the Baseline visit eg corticosteroids or topical immunomodulators, anthralin (dithranil), vitamin D derivatives, ultraviolet-light therapy including sunbathing , or retinoids. * Subjects who used any of the following systemic treatments within 12 weeks before the Baseline visit eg: corticosteroids or adrenocorticotrophic hormone analogs, retinoids such as acitretin or isotretinoin, cyclosporin, interferon, methotrexate, other immuno-suppressive/immunomodulating drugs, psoralen and ultraviolet A therapy, or biologics * Subjects planning on significant exposure to sun (sun-bathing) * Treatment with systemic or locally acting medications which might counter or influence the study aim (eg monoamine oxidase inhibitors, anti-epileptic drugs, anti-psychotic drugs) or medications which are known to provoke or aggravate psoriasis, eg Beta-blockers, antimalarial drugs, and lithium within two weeks before the Baseline visit * Subject is a dependent person, ie, a relative/family member of the Investigator and/or is a member of the Investigator's staff * Clinical study participation with any investigational drug less than 30 days prior to study entry or planning to receive an investigational drug during the study period
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Summary Statistics and Primary Pairwise Comparison (Vehicle-E6201) of Area Under the Curve (AUC) for the Baseline-Corrected Thickness of the Psoriatic Infiltrate | Day 0 (Baseline), Day 8 (Visit 10), and Day 12 (End of Treatment) | The AUC was based on the baseline-corrected thickness of the psoriatic infiltrate (20 megahertz (MHz) Sonographic measurement) at specified days for each treatment field calculated by applying the linear trapezoidal rule. Sonographic measurements were performed using a 20 MHz high-frequency sonograph. Serial A-scans were composed and represented on a monitor as a section of the skin. A lateral resolution of approximately 200 um and an axial resolution of 80 um were possible. Dependent on the echo patterns, components of the epidermis, dermis, and subcutis were represented. Therefore, exact measurement of skin thickness was possible. The inflammatory psoriatic infiltrate was seen as a clearly definable echo lucent band below the entrance echo. The thickness of the echo lucent psoriatic band was determined. The thickness was measured in micrometers (um) and was denoted as T. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Thickness of the Psoriatic Infiltrate From Baseline to End of Treatment (Day 12/Discontinuation) | Day 12/Discontinuation (Visit 14/End of Treatment) | Psoriatic infiltrate thickness was determined by 20 MHz Sonographic measurements using a 20 MHz high-frequency sonograph. Serial-A scans were composed and represented on a monitor as a section of the skin. A lateral resolution of approximately 200 um and an axial resolution of 80 um were possible. Dependent on the echo patterns, components of the epidermis, dermis, and subcutis were represented. Therefore exact measurement of the skin thickness was possible. The inflammatory psoriatic infiltrate was seen as a clearly definable echo lucent back below the entrance echo. The thickness of the echo lucent psoriatic band was determined. Comparisons were made with the untreated plaque(s) beneath the hydrocolloid dressing. Baseline was defined as Visit 2 (Day 0). Least Squares Means (LSM) and Confidence Intervals (CI) were obtained from ANCOVA model with factors for treatment and baseline psoriatic infiltrate thickness as a continuous covariate. |
| Change in Thickness of the Psoriatic Infiltrate From Baseline to Day 8 | Day 8 (Visit 10) | Psoriatic infiltrate thickness was determined by 20 MHz Sonographic measurements using a 20 MHz high-frequency sonograph. Serial-A scans were composed and represented on a monitor as a section of the skin. A lateral resolution of approximately 200 um and an axial resolution of 80 um were possible. Dependent on the echo patterns, components of the epidermis, dermis, and subcutis were represented. Therefore exact measurement of the skin thickness was possible. The inflammatory psoriatic infiltrate was seen as a clearly definable echo lucent back below the entrance echo. The thickness of the echo lucent psoriatic band was determined. Comparisons were made with the untreated plaque(s) beneath the hydrocolloid dressing. Baseline was defined as Visit 2 (Day 0). LSM and CI were obtained from ANCOVA model with factors for treatment and baseline psoriatic infiltrate thickness as a continuous covariate. |
| Clinical (Global) Assessment of Efficacy at Day 12/Discontinuation | Day 12/Discontinuation (Visit 14/End of Treatment) | Clinical (global) assessment of the test fields was performed using a 5-point score: -1 = worsened, 0 = unchanged (no effect), 1 = slight improvement, 2 = clear improvement but not completely healed, and 3 = completely healed. Comparisons were made with the untreated plaque(s) beneath the hydrocolloid dressing. Clinically apparent differences in erythema and infiltration contributed to the global assessment. Baseline was defined as Visit 2 (Day 0). |
| Clinical (Global) Assessment of Efficacy on Day 8 | Day 8 (Visit 10) | Clinical (global) assessment of the test fields was performed using a 5-point score: -1 = worsened, 0 = unchanged (no effect), 1 = slight improvement, 2 = clear improvement but not completely healed, and 3 = completely healed. Comparisons were made with the untreated plaque(s) beneath the hydrocolloid dressing. Clinically apparent differences in erythema and infiltration contributed to the global assessment. Baseline was defined as Visit 2 (Day 0). |
| Overview of Treatment-Emergent Adverse Events (TEAEs) | From first dose of study treatment up to 30 days after the last dose, or until resolution, whichever came first, or up to approximately 10 months. | TEAEs were defined as an adverse event (AE) that emerged during treatment, having been absent at pretreatment (baseline), or re-emerged during treatment, having been present at baseline but stopped prior to treatment, or worsened in severity during treatment relative to the pretreatment state, when the AE was continuous. Safety variables included TEAEs including skin reactions, diascopy and biopsy findings, clinical laboratory parameters, vital signs, and physical examinations. For Cohort 2, special attention was given to a close, daily monitoring of the application site for signs of skin irritation. Any suspected ecchymoses or petechiae were to be followed up with a diascopy test that was to be documented with digital photographs. Any positive diascopy test was to be followed up by biopsy for skin ultrastructural analysis (if agreed to by the participant, sponsor, and investigator). Few adverse events occurred in more than one treatment group. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 Three concentrations of E6201 topical gel (0.03%, 0.1%, and 0.2%) and active comparator, calcipotriene cream (0.005%), were applied once daily for 12 days to specific test fields determined at Baseline. Study treatments were applied at the research unit by designated personnel of the investigational site using separate tuberculin syringes that were filled with approximately 200 uL of each concentration of study treatment and comparator. Prior to each new application, remaining preparation residues were removed by gently cleansing each test field with a separate soft tissue. The fields to be treated were done in an occlusive manner for a treatment period of 12 days. Application time was to be kept as close as possible to the baseline application time, and was not to differ by more than +/- 4 hours. The 3 concentrations of E6201 gel were dosed first in Cohort 1 to establish the safety and tolerability prior to dosing in Cohort 2. | 15 |
| Cohort 2 Three concentrations of E6201 topical gel (0.005%, 0.01%, and 0.05%) and active comparator, calcipotriene cream (0.005%), were applied once daily for 12 days to specific test fields determined at Baseline. Study treatments were applied at the research unit by designated personnel of the investigational site in the same manner as described for Cohort 1. Cohort 2 participants were not dosed until all participants in Cohort 1 completed treatment and safety data were collected and evaluated. | 15 |
| Total | 30 |
Baseline characteristics
| Characteristic | Cohort 1 | Cohort 2 | Total |
|---|---|---|---|
| Age, Continuous | 47.4 Years STANDARD_DEVIATION 12.44 | 50.6 Years STANDARD_DEVIATION 7.01 | 49.0 Years STANDARD_DEVIATION 10.05 |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 5 Participants |
| Sex: Female, Male Male | 13 Participants | 12 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 30 | 0 / 15 | 0 / 15 | 0 / 15 | 0 / 15 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 3 / 30 | 1 / 30 | 0 / 15 | 0 / 15 | 4 / 15 | 5 / 15 | 6 / 6 | 6 / 6 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 | 0 / 15 | 0 / 15 | 0 / 15 | 0 / 15 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Summary Statistics and Primary Pairwise Comparison (Vehicle-E6201) of Area Under the Curve (AUC) for the Baseline-Corrected Thickness of the Psoriatic Infiltrate
The AUC was based on the baseline-corrected thickness of the psoriatic infiltrate (20 megahertz (MHz) Sonographic measurement) at specified days for each treatment field calculated by applying the linear trapezoidal rule. Sonographic measurements were performed using a 20 MHz high-frequency sonograph. Serial A-scans were composed and represented on a monitor as a section of the skin. A lateral resolution of approximately 200 um and an axial resolution of 80 um were possible. Dependent on the echo patterns, components of the epidermis, dermis, and subcutis were represented. Therefore, exact measurement of skin thickness was possible. The inflammatory psoriatic infiltrate was seen as a clearly definable echo lucent band below the entrance echo. The thickness of the echo lucent psoriatic band was determined. The thickness was measured in micrometers (um) and was denoted as T.
Time frame: Day 0 (Baseline), Day 8 (Visit 10), and Day 12 (End of Treatment)
Population: Full analysis population (Intent-to-treat population) included all randomized participants who received at least one application of at least one study treatment and had at least one postbaseline efficacy assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Daivonex (Calcipotriene Cream) | Summary Statistics and Primary Pairwise Comparison (Vehicle-E6201) of Area Under the Curve (AUC) for the Baseline-Corrected Thickness of the Psoriatic Infiltrate | -1449.2 um.day |
| E6201 Vehicle | Summary Statistics and Primary Pairwise Comparison (Vehicle-E6201) of Area Under the Curve (AUC) for the Baseline-Corrected Thickness of the Psoriatic Infiltrate | 17.0 um.day |
| 0.005% E6201 Gel | Summary Statistics and Primary Pairwise Comparison (Vehicle-E6201) of Area Under the Curve (AUC) for the Baseline-Corrected Thickness of the Psoriatic Infiltrate | -694.4 um.day |
| 0.01% E6201 Gel | Summary Statistics and Primary Pairwise Comparison (Vehicle-E6201) of Area Under the Curve (AUC) for the Baseline-Corrected Thickness of the Psoriatic Infiltrate | -1102.8 um.day |
| 0.03% E6201 Gel | Summary Statistics and Primary Pairwise Comparison (Vehicle-E6201) of Area Under the Curve (AUC) for the Baseline-Corrected Thickness of the Psoriatic Infiltrate | -763.1 um.day |
| 0.05% E6201 Gel | Summary Statistics and Primary Pairwise Comparison (Vehicle-E6201) of Area Under the Curve (AUC) for the Baseline-Corrected Thickness of the Psoriatic Infiltrate | -1758.2 um.day |
| 0.1% E6201 Gel | Summary Statistics and Primary Pairwise Comparison (Vehicle-E6201) of Area Under the Curve (AUC) for the Baseline-Corrected Thickness of the Psoriatic Infiltrate | -904.4 um.day |
| 0.2% E6201 Gel | Summary Statistics and Primary Pairwise Comparison (Vehicle-E6201) of Area Under the Curve (AUC) for the Baseline-Corrected Thickness of the Psoriatic Infiltrate | -920.8 um.day |
Comparison: The following hypotheses were based on the Full Analysis Population: null Hypothesis and alternative hypothesis. P values, Least Squares Means (LSM), and Confidence Intervals (CI) were obtained from ANCOVA model with factors for treatment and baseline psoriatic infiltrate thickness as a continuous covariate.p-value: 0.003895% CI: [292.5, 1130.3]ANCOVA
Comparison: The following hypotheses were based on the Full Analysis Population: null Hypothesis and alternative hypothesis. P values, LSM, and CI were obtained from ANCOVA model with factors for treatment and baseline psoriatic infiltrate thickness as a continuous covariate.p-value: <0.000195% CI: [858.9, 1380.6]ANCOVA
Comparison: The following hypotheses were based on the Full Analysis Population: null Hypothesis and alternative hypothesis. P values, LSM, and CI were obtained from ANCOVA model with factors for treatment and baseline psoriatic infiltrate thickness as a continuous covariate.p-value: 0.052395% CI: [-8.5, 1568.5]ANCOVA
Comparison: The following hypotheses were based on the Full Analysis Population: null Hypothesis and alternative hypothesis. P values, LSM, and CI were obtained from ANCOVA model with factors for treatment and baseline psoriatic infiltrate thickness as a continuous covariate.p-value: <0.000195% CI: [1392.3, 2158]ANCOVA
Comparison: The following hypotheses were based on the Full Analysis Population: null Hypothesis and alternative hypothesis. P values, LSM, and CI were obtained from ANCOVA model with factors for treatment and baseline psoriatic infiltrate thickness as a continuous covariate.p-value: 0.000295% CI: [515.7, 1327.1]ANCOVA
Comparison: The following hypotheses were based on the Full Analysis Population: null Hypothesis and alternative hypothesis. P values, LSM, and CI were obtained from ANCOVA model with factors for treatment and baseline psoriatic infiltrate thickness as a continuous covariate.p-value: 0.011595% CI: [267.6, 1607.9]ANCOVA
Secondary
Change in Thickness of the Psoriatic Infiltrate From Baseline to Day 8
Psoriatic infiltrate thickness was determined by 20 MHz Sonographic measurements using a 20 MHz high-frequency sonograph. Serial-A scans were composed and represented on a monitor as a section of the skin. A lateral resolution of approximately 200 um and an axial resolution of 80 um were possible. Dependent on the echo patterns, components of the epidermis, dermis, and subcutis were represented. Therefore exact measurement of the skin thickness was possible. The inflammatory psoriatic infiltrate was seen as a clearly definable echo lucent back below the entrance echo. The thickness of the echo lucent psoriatic band was determined. Comparisons were made with the untreated plaque(s) beneath the hydrocolloid dressing. Baseline was defined as Visit 2 (Day 0). LSM and CI were obtained from ANCOVA model with factors for treatment and baseline psoriatic infiltrate thickness as a continuous covariate.
Time frame: Day 8 (Visit 10)
Population: Full analysis population (Intent-to-treat population) included all randomized participants who received at least one application of at least one study treatment and had at least one postbaseline efficacy assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Daivonex (Calcipotriene Cream) | Change in Thickness of the Psoriatic Infiltrate From Baseline to Day 8 | -151.7 um |
| E6201 Vehicle | Change in Thickness of the Psoriatic Infiltrate From Baseline to Day 8 | 17.3 um |
| 0.005% E6201 Gel | Change in Thickness of the Psoriatic Infiltrate From Baseline to Day 8 | -63.4 um |
| 0.01% E6201 Gel | Change in Thickness of the Psoriatic Infiltrate From Baseline to Day 8 | -110.7 um |
| 0.03% E6201 Gel | Change in Thickness of the Psoriatic Infiltrate From Baseline to Day 8 | -92.9 um |
| 0.05% E6201 Gel | Change in Thickness of the Psoriatic Infiltrate From Baseline to Day 8 | -190.3 um |
| 0.1% E6201 Gel | Change in Thickness of the Psoriatic Infiltrate From Baseline to Day 8 | -108.0 um |
| 0.2% E6201 Gel | Change in Thickness of the Psoriatic Infiltrate From Baseline to Day 8 | -102.7 um |
Comparison: The following hypotheses were based on the Full Analysis Population: null Hypothesis and alternative hypothesis. P values, LSM, and CI were obtained from ANCOVA model with factors for treatment and baseline psoriatic infiltrate thickness as a continuous covariate.p-value: 0.001395% CI: [34.6, 126.7]ANCOVA
Comparison: The following hypotheses were based on the Full Analysis Population: null Hypothesis and alternative hypothesis. P values, LSM, and CI were obtained from ANCOVA model with factors for treatment and baseline psoriatic infiltrate thickness as a continuous covariate.p-value: <0.000195% CI: [92.4, 163.5]ANCOVA
Comparison: The following hypotheses were based on the Full Analysis Population: null Hypothesis and alternative hypothesis. P values, LSM, and CI were obtained from ANCOVA model with factors for treatment and baseline psoriatic infiltrate thickness as a continuous covariate.p-value: 0.045895% CI: [2.4, 218]ANCOVA
Comparison: The following hypotheses were based on the Full Analysis Population: null Hypothesis and alternative hypothesis. P values, LSM, and CI were obtained from ANCOVA model with factors for treatment and baseline psoriatic infiltrate thickness as a continuous covariate.p-value: <0.000195% CI: [155.2, 259.9]ANCOVA
Comparison: The following hypotheses were based on the Full Analysis Population: null Hypothesis and alternative hypothesis. P values, LSM, and CI were obtained from ANCOVA model with factors for treatment and baseline psoriatic infiltrate thickness as a continuous covariate.p-value: 0.000395% CI: [71.5, 179]ANCOVA
Comparison: The following hypotheses were based on the Full Analysis Population: null Hypothesis and alternative hypothesis. P values, LSM, and CI were obtained from ANCOVA model with factors for treatment and baseline psoriatic infiltrate thickness as a continuous covariate.p-value: 0.002995% CI: [93.9, 163.3]ANCOVA
Secondary
Change in Thickness of the Psoriatic Infiltrate From Baseline to End of Treatment (Day 12/Discontinuation)
Psoriatic infiltrate thickness was determined by 20 MHz Sonographic measurements using a 20 MHz high-frequency sonograph. Serial-A scans were composed and represented on a monitor as a section of the skin. A lateral resolution of approximately 200 um and an axial resolution of 80 um were possible. Dependent on the echo patterns, components of the epidermis, dermis, and subcutis were represented. Therefore exact measurement of the skin thickness was possible. The inflammatory psoriatic infiltrate was seen as a clearly definable echo lucent back below the entrance echo. The thickness of the echo lucent psoriatic band was determined. Comparisons were made with the untreated plaque(s) beneath the hydrocolloid dressing. Baseline was defined as Visit 2 (Day 0). Least Squares Means (LSM) and Confidence Intervals (CI) were obtained from ANCOVA model with factors for treatment and baseline psoriatic infiltrate thickness as a continuous covariate.
Time frame: Day 12/Discontinuation (Visit 14/End of Treatment)
Population: Full analysis population (Intent-to-treat population) included all randomized participants who received at least one application of at least one study treatment and had at least one postbaseline efficacy assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Daivonex (Calcipotriene Cream) | Change in Thickness of the Psoriatic Infiltrate From Baseline to End of Treatment (Day 12/Discontinuation) | -205.3 um |
| E6201 Vehicle | Change in Thickness of the Psoriatic Infiltrate From Baseline to End of Treatment (Day 12/Discontinuation) | 7.1 um |
| 0.005% E6201 Gel | Change in Thickness of the Psoriatic Infiltrate From Baseline to End of Treatment (Day 12/Discontinuation) | -94.4 um |
| 0.01% E6201 Gel | Change in Thickness of the Psoriatic Infiltrate From Baseline to End of Treatment (Day 12/Discontinuation) | -175.3 um |
| 0.03% E6201 Gel | Change in Thickness of the Psoriatic Infiltrate From Baseline to End of Treatment (Day 12/Discontinuation) | -162.4 um |
| 0.05% E6201 Gel | Change in Thickness of the Psoriatic Infiltrate From Baseline to End of Treatment (Day 12/Discontinuation) | -239.5 um |
| 0.1% E6201 Gel | Change in Thickness of the Psoriatic Infiltrate From Baseline to End of Treatment (Day 12/Discontinuation) | -125.2 um |
| 0.2% E6201 Gel | Change in Thickness of the Psoriatic Infiltrate From Baseline to End of Treatment (Day 12/Discontinuation) | -137.9 um |
Comparison: The following hypotheses were based on the Full Analysis Population: null Hypothesis and alternative hypothesis. P values, LSM, and CI were obtained from ANCOVA model with factors for treatment and baseline psoriatic infiltrate thickness as a continuous covariate.p-value: 0.004295% CI: [36, 167]ANCOVA
Comparison: The following hypotheses were based on the Full Analysis Population: null Hypothesis and alternative hypothesis. P values, LSM, and CI were obtained from ANCOVA model with factors for treatment and baseline psoriatic infiltrate thickness as a continuous covariate.p-value: <0.000195% CI: [140.3, 224.4]ANCOVA
Comparison: The following hypotheses were based on the Full Analysis Population: null Hypothesis and alternative hypothesis. P values, LSM, and CI were obtained from ANCOVA model with factors for treatment and baseline psoriatic infiltrate thickness as a continuous covariate.p-value: <0.000195% CI: [127.4, 211.5]ANCOVA
Comparison: The following hypotheses were based on the Full Analysis Population: null Hypothesis and alternative hypothesis. P values, LSM, and CI were obtained from ANCOVA model with factors for treatment and baseline psoriatic infiltrate thickness as a continuous covariate.p-value: <0.000195% CI: [185, 308.1]ANCOVA
Comparison: The following hypotheses were based on the Full Analysis Population: null Hypothesis and alternative hypothesis. P values, LSM, and CI were obtained from ANCOVA model with factors for treatment and baseline psoriatic infiltrate thickness as a continuous covariate.p-value: 0.004395% CI: [53.9, 210.7]ANCOVA
Comparison: The following hypotheses were based on the Full Analysis Population: null Hypothesis and alternative hypothesis. P values, LSM) and CI were obtained from ANCOVA model with factors for treatment and baseline psoriatic infiltrate thickness as a continuous covariate.p-value: 0.003695% CI: [64.2, 225.8]ANCOVA
Secondary
Clinical (Global) Assessment of Efficacy at Day 12/Discontinuation
Clinical (global) assessment of the test fields was performed using a 5-point score: -1 = worsened, 0 = unchanged (no effect), 1 = slight improvement, 2 = clear improvement but not completely healed, and 3 = completely healed. Comparisons were made with the untreated plaque(s) beneath the hydrocolloid dressing. Clinically apparent differences in erythema and infiltration contributed to the global assessment. Baseline was defined as Visit 2 (Day 0).
Time frame: Day 12/Discontinuation (Visit 14/End of Treatment)
Population: Full analysis population (Intent-to-treat population) included all randomized participants who received at least one application of at least one study treatment and had at least one postbaseline efficacy assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Daivonex (Calcipotriene Cream) | Clinical (Global) Assessment of Efficacy at Day 12/Discontinuation | Clear improvement but not completely healed | 33.3 Percentage of participants |
| Daivonex (Calcipotriene Cream) | Clinical (Global) Assessment of Efficacy at Day 12/Discontinuation | Completely healed | 3.3 Percentage of participants |
| Daivonex (Calcipotriene Cream) | Clinical (Global) Assessment of Efficacy at Day 12/Discontinuation | Worsened | 0 Percentage of participants |
| Daivonex (Calcipotriene Cream) | Clinical (Global) Assessment of Efficacy at Day 12/Discontinuation | Slight improvement | 56.7 Percentage of participants |
| Daivonex (Calcipotriene Cream) | Clinical (Global) Assessment of Efficacy at Day 12/Discontinuation | Unchanged (no effect) | 6.7 Percentage of participants |
| E6201 Vehicle | Clinical (Global) Assessment of Efficacy at Day 12/Discontinuation | Unchanged (no effect) | 90.0 Percentage of participants |
| E6201 Vehicle | Clinical (Global) Assessment of Efficacy at Day 12/Discontinuation | Clear improvement but not completely healed | 0 Percentage of participants |
| E6201 Vehicle | Clinical (Global) Assessment of Efficacy at Day 12/Discontinuation | Worsened | 0 Percentage of participants |
| E6201 Vehicle | Clinical (Global) Assessment of Efficacy at Day 12/Discontinuation | Slight improvement | 10.0 Percentage of participants |
| E6201 Vehicle | Clinical (Global) Assessment of Efficacy at Day 12/Discontinuation | Completely healed | 0 Percentage of participants |
| 0.005% E6201 Gel | Clinical (Global) Assessment of Efficacy at Day 12/Discontinuation | Worsened | 0 Percentage of participants |
| 0.005% E6201 Gel | Clinical (Global) Assessment of Efficacy at Day 12/Discontinuation | Completely healed | 0 Percentage of participants |
| 0.005% E6201 Gel | Clinical (Global) Assessment of Efficacy at Day 12/Discontinuation | Unchanged (no effect) | 20.0 Percentage of participants |
| 0.005% E6201 Gel | Clinical (Global) Assessment of Efficacy at Day 12/Discontinuation | Clear improvement but not completely healed | 13.3 Percentage of participants |
| 0.005% E6201 Gel | Clinical (Global) Assessment of Efficacy at Day 12/Discontinuation | Slight improvement | 66.7 Percentage of participants |
| 0.01% E6201 Gel | Clinical (Global) Assessment of Efficacy at Day 12/Discontinuation | Slight improvement | 33.3 Percentage of participants |
| 0.01% E6201 Gel | Clinical (Global) Assessment of Efficacy at Day 12/Discontinuation | Completely healed | 0 Percentage of participants |
| 0.01% E6201 Gel | Clinical (Global) Assessment of Efficacy at Day 12/Discontinuation | Worsened | 0 Percentage of participants |
| 0.01% E6201 Gel | Clinical (Global) Assessment of Efficacy at Day 12/Discontinuation | Unchanged (no effect) | 0 Percentage of participants |
| 0.01% E6201 Gel | Clinical (Global) Assessment of Efficacy at Day 12/Discontinuation | Clear improvement but not completely healed | 66.7 Percentage of participants |
| 0.03% E6201 Gel | Clinical (Global) Assessment of Efficacy at Day 12/Discontinuation | Slight improvement | 46.7 Percentage of participants |
| 0.03% E6201 Gel | Clinical (Global) Assessment of Efficacy at Day 12/Discontinuation | Worsened | 0 Percentage of participants |
| 0.03% E6201 Gel | Clinical (Global) Assessment of Efficacy at Day 12/Discontinuation | Unchanged (no effect) | 6.7 Percentage of participants |
| 0.03% E6201 Gel | Clinical (Global) Assessment of Efficacy at Day 12/Discontinuation | Clear improvement but not completely healed | 46.7 Percentage of participants |
| 0.03% E6201 Gel | Clinical (Global) Assessment of Efficacy at Day 12/Discontinuation | Completely healed | 0 Percentage of participants |
| 0.05% E6201 Gel | Clinical (Global) Assessment of Efficacy at Day 12/Discontinuation | Slight improvement | 13.3 Percentage of participants |
| 0.05% E6201 Gel | Clinical (Global) Assessment of Efficacy at Day 12/Discontinuation | Clear improvement but not completely healed | 86.7 Percentage of participants |
| 0.05% E6201 Gel | Clinical (Global) Assessment of Efficacy at Day 12/Discontinuation | Unchanged (no effect) | 0 Percentage of participants |
| 0.05% E6201 Gel | Clinical (Global) Assessment of Efficacy at Day 12/Discontinuation | Worsened | 0 Percentage of participants |
| 0.05% E6201 Gel | Clinical (Global) Assessment of Efficacy at Day 12/Discontinuation | Completely healed | 0 Percentage of participants |
| 0.1% E6201 Gel | Clinical (Global) Assessment of Efficacy at Day 12/Discontinuation | Slight improvement | 83.3 Percentage of participants |
| 0.1% E6201 Gel | Clinical (Global) Assessment of Efficacy at Day 12/Discontinuation | Worsened | 0 Percentage of participants |
| 0.1% E6201 Gel | Clinical (Global) Assessment of Efficacy at Day 12/Discontinuation | Unchanged (no effect) | 0 Percentage of participants |
| 0.1% E6201 Gel | Clinical (Global) Assessment of Efficacy at Day 12/Discontinuation | Completely healed | 0 Percentage of participants |
| 0.1% E6201 Gel | Clinical (Global) Assessment of Efficacy at Day 12/Discontinuation | Clear improvement but not completely healed | 16.7 Percentage of participants |
| 0.2% E6201 Gel | Clinical (Global) Assessment of Efficacy at Day 12/Discontinuation | Completely healed | 16.7 Percentage of participants |
| 0.2% E6201 Gel | Clinical (Global) Assessment of Efficacy at Day 12/Discontinuation | Clear improvement but not completely healed | 0 Percentage of participants |
| 0.2% E6201 Gel | Clinical (Global) Assessment of Efficacy at Day 12/Discontinuation | Worsened | 0 Percentage of participants |
| 0.2% E6201 Gel | Clinical (Global) Assessment of Efficacy at Day 12/Discontinuation | Slight improvement | 83.3 Percentage of participants |
| 0.2% E6201 Gel | Clinical (Global) Assessment of Efficacy at Day 12/Discontinuation | Unchanged (no effect) | 0 Percentage of participants |
Secondary
Clinical (Global) Assessment of Efficacy on Day 8
Clinical (global) assessment of the test fields was performed using a 5-point score: -1 = worsened, 0 = unchanged (no effect), 1 = slight improvement, 2 = clear improvement but not completely healed, and 3 = completely healed. Comparisons were made with the untreated plaque(s) beneath the hydrocolloid dressing. Clinically apparent differences in erythema and infiltration contributed to the global assessment. Baseline was defined as Visit 2 (Day 0).
Time frame: Day 8 (Visit 10)
Population: Full analysis population (Intent-to-treat population) included all randomized participants who received at least one application of at least one study treatment and had at least one postbaseline efficacy assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Daivonex (Calcipotriene Cream) | Clinical (Global) Assessment of Efficacy on Day 8 | Completely healed | 0 Percentage of participants |
| Daivonex (Calcipotriene Cream) | Clinical (Global) Assessment of Efficacy on Day 8 | Slight improvement | 46.7 Percentage of participants |
| Daivonex (Calcipotriene Cream) | Clinical (Global) Assessment of Efficacy on Day 8 | Clear improvement but not completely healed | 30.0 Percentage of participants |
| Daivonex (Calcipotriene Cream) | Clinical (Global) Assessment of Efficacy on Day 8 | Worsened | 3.3 Percentage of participants |
| Daivonex (Calcipotriene Cream) | Clinical (Global) Assessment of Efficacy on Day 8 | Unchanged (no effect) | 20.0 Percentage of participants |
| E6201 Vehicle | Clinical (Global) Assessment of Efficacy on Day 8 | Slight improvement | 6.7 Percentage of participants |
| E6201 Vehicle | Clinical (Global) Assessment of Efficacy on Day 8 | Completely healed | 0 Percentage of participants |
| E6201 Vehicle | Clinical (Global) Assessment of Efficacy on Day 8 | Clear improvement but not completely healed | 0 Percentage of participants |
| E6201 Vehicle | Clinical (Global) Assessment of Efficacy on Day 8 | Unchanged (no effect) | 90.0 Percentage of participants |
| E6201 Vehicle | Clinical (Global) Assessment of Efficacy on Day 8 | Worsened | 3.3 Percentage of participants |
| 0.005% E6201 Gel | Clinical (Global) Assessment of Efficacy on Day 8 | Completely healed | 0 Percentage of participants |
| 0.005% E6201 Gel | Clinical (Global) Assessment of Efficacy on Day 8 | Unchanged (no effect) | 33.3 Percentage of participants |
| 0.005% E6201 Gel | Clinical (Global) Assessment of Efficacy on Day 8 | Slight improvement | 66.7 Percentage of participants |
| 0.005% E6201 Gel | Clinical (Global) Assessment of Efficacy on Day 8 | Clear improvement but not completely healed | 0 Percentage of participants |
| 0.005% E6201 Gel | Clinical (Global) Assessment of Efficacy on Day 8 | Worsened | 0 Percentage of participants |
| 0.01% E6201 Gel | Clinical (Global) Assessment of Efficacy on Day 8 | Worsened | 0 Percentage of participants |
| 0.01% E6201 Gel | Clinical (Global) Assessment of Efficacy on Day 8 | Clear improvement but not completely healed | 40.0 Percentage of participants |
| 0.01% E6201 Gel | Clinical (Global) Assessment of Efficacy on Day 8 | Completely healed | 0 Percentage of participants |
| 0.01% E6201 Gel | Clinical (Global) Assessment of Efficacy on Day 8 | Slight improvement | 53.3 Percentage of participants |
| 0.01% E6201 Gel | Clinical (Global) Assessment of Efficacy on Day 8 | Unchanged (no effect) | 6.7 Percentage of participants |
| 0.03% E6201 Gel | Clinical (Global) Assessment of Efficacy on Day 8 | Unchanged (no effect) | 6.7 Percentage of participants |
| 0.03% E6201 Gel | Clinical (Global) Assessment of Efficacy on Day 8 | Completely healed | 0 Percentage of participants |
| 0.03% E6201 Gel | Clinical (Global) Assessment of Efficacy on Day 8 | Slight improvement | 60.0 Percentage of participants |
| 0.03% E6201 Gel | Clinical (Global) Assessment of Efficacy on Day 8 | Clear improvement but not completely healed | 26.7 Percentage of participants |
| 0.03% E6201 Gel | Clinical (Global) Assessment of Efficacy on Day 8 | Worsened | 6.7 Percentage of participants |
| 0.05% E6201 Gel | Clinical (Global) Assessment of Efficacy on Day 8 | Clear improvement but not completely healed | 86.7 Percentage of participants |
| 0.05% E6201 Gel | Clinical (Global) Assessment of Efficacy on Day 8 | Unchanged (no effect) | 0 Percentage of participants |
| 0.05% E6201 Gel | Clinical (Global) Assessment of Efficacy on Day 8 | Slight improvement | 13.3 Percentage of participants |
| 0.05% E6201 Gel | Clinical (Global) Assessment of Efficacy on Day 8 | Worsened | 0 Percentage of participants |
| 0.05% E6201 Gel | Clinical (Global) Assessment of Efficacy on Day 8 | Completely healed | 0 Percentage of participants |
| 0.1% E6201 Gel | Clinical (Global) Assessment of Efficacy on Day 8 | Completely healed | 0 Percentage of participants |
| 0.1% E6201 Gel | Clinical (Global) Assessment of Efficacy on Day 8 | Worsened | 0 Percentage of participants |
| 0.1% E6201 Gel | Clinical (Global) Assessment of Efficacy on Day 8 | Slight improvement | 83.3 Percentage of participants |
| 0.1% E6201 Gel | Clinical (Global) Assessment of Efficacy on Day 8 | Unchanged (no effect) | 16.7 Percentage of participants |
| 0.1% E6201 Gel | Clinical (Global) Assessment of Efficacy on Day 8 | Clear improvement but not completely healed | 0 Percentage of participants |
| 0.2% E6201 Gel | Clinical (Global) Assessment of Efficacy on Day 8 | Completely healed | 0 Percentage of participants |
| 0.2% E6201 Gel | Clinical (Global) Assessment of Efficacy on Day 8 | Worsened | 0 Percentage of participants |
| 0.2% E6201 Gel | Clinical (Global) Assessment of Efficacy on Day 8 | Unchanged (no effect) | 0 Percentage of participants |
| 0.2% E6201 Gel | Clinical (Global) Assessment of Efficacy on Day 8 | Clear improvement but not completely healed | 0 Percentage of participants |
| 0.2% E6201 Gel | Clinical (Global) Assessment of Efficacy on Day 8 | Slight improvement | 100 Percentage of participants |
Secondary
Overview of Treatment-Emergent Adverse Events (TEAEs)
TEAEs were defined as an adverse event (AE) that emerged during treatment, having been absent at pretreatment (baseline), or re-emerged during treatment, having been present at baseline but stopped prior to treatment, or worsened in severity during treatment relative to the pretreatment state, when the AE was continuous. Safety variables included TEAEs including skin reactions, diascopy and biopsy findings, clinical laboratory parameters, vital signs, and physical examinations. For Cohort 2, special attention was given to a close, daily monitoring of the application site for signs of skin irritation. Any suspected ecchymoses or petechiae were to be followed up with a diascopy test that was to be documented with digital photographs. Any positive diascopy test was to be followed up by biopsy for skin ultrastructural analysis (if agreed to by the participant, sponsor, and investigator). Few adverse events occurred in more than one treatment group.
Time frame: From first dose of study treatment up to 30 days after the last dose, or until resolution, whichever came first, or up to approximately 10 months.
Population: Safety population included all participants who received at least one application of at least one study treatment and had at least one postdose safety assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Daivonex (Calcipotriene Cream) | Overview of Treatment-Emergent Adverse Events (TEAEs) | TEAEs leading to study treatment withdrawal | 1 Percentage of participants |
| Daivonex (Calcipotriene Cream) | Overview of Treatment-Emergent Adverse Events (TEAEs) | TEAEs leading to study treatment dose decrease | 0 Percentage of participants |
| Daivonex (Calcipotriene Cream) | Overview of Treatment-Emergent Adverse Events (TEAEs) | Severe TEAEs | 0 Percentage of participants |
| Daivonex (Calcipotriene Cream) | Overview of Treatment-Emergent Adverse Events (TEAEs) | TEAEs | 3 Percentage of participants |
| Daivonex (Calcipotriene Cream) | Overview of Treatment-Emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 3 Percentage of participants |
| Daivonex (Calcipotriene Cream) | Overview of Treatment-Emergent Adverse Events (TEAEs) | Serious TEAEs | 0 Percentage of participants |
| Daivonex (Calcipotriene Cream) | Overview of Treatment-Emergent Adverse Events (TEAEs) | TEAEs leading to study treatment interruption | 0 Percentage of participants |
| E6201 Vehicle | Overview of Treatment-Emergent Adverse Events (TEAEs) | TEAEs leading to study treatment interruption | 0 Percentage of participants |
| E6201 Vehicle | Overview of Treatment-Emergent Adverse Events (TEAEs) | TEAEs leading to study treatment withdrawal | 1 Percentage of participants |
| E6201 Vehicle | Overview of Treatment-Emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 1 Percentage of participants |
| E6201 Vehicle | Overview of Treatment-Emergent Adverse Events (TEAEs) | Severe TEAEs | 0 Percentage of participants |
| E6201 Vehicle | Overview of Treatment-Emergent Adverse Events (TEAEs) | Serious TEAEs | 0 Percentage of participants |
| E6201 Vehicle | Overview of Treatment-Emergent Adverse Events (TEAEs) | TEAEs | 1 Percentage of participants |
| E6201 Vehicle | Overview of Treatment-Emergent Adverse Events (TEAEs) | TEAEs leading to study treatment dose decrease | 0 Percentage of participants |
| 0.005% E6201 Gel | Overview of Treatment-Emergent Adverse Events (TEAEs) | TEAEs leading to study treatment withdrawal | 0 Percentage of participants |
| 0.005% E6201 Gel | Overview of Treatment-Emergent Adverse Events (TEAEs) | TEAEs leading to study treatment interruption | 0 Percentage of participants |
| 0.005% E6201 Gel | Overview of Treatment-Emergent Adverse Events (TEAEs) | Serious TEAEs | 0 Percentage of participants |
| 0.005% E6201 Gel | Overview of Treatment-Emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 0 Percentage of participants |
| 0.005% E6201 Gel | Overview of Treatment-Emergent Adverse Events (TEAEs) | TEAEs | 0 Percentage of participants |
| 0.005% E6201 Gel | Overview of Treatment-Emergent Adverse Events (TEAEs) | TEAEs leading to study treatment dose decrease | 0 Percentage of participants |
| 0.005% E6201 Gel | Overview of Treatment-Emergent Adverse Events (TEAEs) | Severe TEAEs | 0 Percentage of participants |
| 0.01% E6201 Gel | Overview of Treatment-Emergent Adverse Events (TEAEs) | Serious TEAEs | 0 Percentage of participants |
| 0.01% E6201 Gel | Overview of Treatment-Emergent Adverse Events (TEAEs) | TEAEs leading to study treatment interruption | 0 Percentage of participants |
| 0.01% E6201 Gel | Overview of Treatment-Emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 0 Percentage of participants |
| 0.01% E6201 Gel | Overview of Treatment-Emergent Adverse Events (TEAEs) | TEAEs leading to study treatment dose decrease | 0 Percentage of participants |
| 0.01% E6201 Gel | Overview of Treatment-Emergent Adverse Events (TEAEs) | Severe TEAEs | 0 Percentage of participants |
| 0.01% E6201 Gel | Overview of Treatment-Emergent Adverse Events (TEAEs) | TEAEs | 0 Percentage of participants |
| 0.01% E6201 Gel | Overview of Treatment-Emergent Adverse Events (TEAEs) | TEAEs leading to study treatment withdrawal | 0 Percentage of participants |
| 0.03% E6201 Gel | Overview of Treatment-Emergent Adverse Events (TEAEs) | Serious TEAEs | 0 Percentage of participants |
| 0.03% E6201 Gel | Overview of Treatment-Emergent Adverse Events (TEAEs) | TEAEs | 4 Percentage of participants |
| 0.03% E6201 Gel | Overview of Treatment-Emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 4 Percentage of participants |
| 0.03% E6201 Gel | Overview of Treatment-Emergent Adverse Events (TEAEs) | Severe TEAEs | 0 Percentage of participants |
| 0.03% E6201 Gel | Overview of Treatment-Emergent Adverse Events (TEAEs) | TEAEs leading to study treatment withdrawal | 1 Percentage of participants |
| 0.03% E6201 Gel | Overview of Treatment-Emergent Adverse Events (TEAEs) | TEAEs leading to study treatment dose decrease | 0 Percentage of participants |
| 0.03% E6201 Gel | Overview of Treatment-Emergent Adverse Events (TEAEs) | TEAEs leading to study treatment interruption | 0 Percentage of participants |
| 0.05% E6201 Gel | Overview of Treatment-Emergent Adverse Events (TEAEs) | Serious TEAEs | 0 Percentage of participants |
| 0.05% E6201 Gel | Overview of Treatment-Emergent Adverse Events (TEAEs) | TEAEs leading to study treatment interruption | 0 Percentage of participants |
| 0.05% E6201 Gel | Overview of Treatment-Emergent Adverse Events (TEAEs) | TEAEs leading to study treatment withdrawal | 0 Percentage of participants |
| 0.05% E6201 Gel | Overview of Treatment-Emergent Adverse Events (TEAEs) | Severe TEAEs | 0 Percentage of participants |
| 0.05% E6201 Gel | Overview of Treatment-Emergent Adverse Events (TEAEs) | TEAEs leading to study treatment dose decrease | 0 Percentage of participants |
| 0.05% E6201 Gel | Overview of Treatment-Emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 5 Percentage of participants |
| 0.05% E6201 Gel | Overview of Treatment-Emergent Adverse Events (TEAEs) | TEAEs | 5 Percentage of participants |
| 0.1% E6201 Gel | Overview of Treatment-Emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 6 Percentage of participants |
| 0.1% E6201 Gel | Overview of Treatment-Emergent Adverse Events (TEAEs) | TEAEs | 6 Percentage of participants |
| 0.1% E6201 Gel | Overview of Treatment-Emergent Adverse Events (TEAEs) | TEAEs leading to study treatment dose decrease | 0 Percentage of participants |
| 0.1% E6201 Gel | Overview of Treatment-Emergent Adverse Events (TEAEs) | TEAEs leading to study treatment withdrawal | 0 Percentage of participants |
| 0.1% E6201 Gel | Overview of Treatment-Emergent Adverse Events (TEAEs) | TEAEs leading to study treatment interruption | 0 Percentage of participants |
| 0.1% E6201 Gel | Overview of Treatment-Emergent Adverse Events (TEAEs) | Severe TEAEs | 0 Percentage of participants |
| 0.1% E6201 Gel | Overview of Treatment-Emergent Adverse Events (TEAEs) | Serious TEAEs | 0 Percentage of participants |
| 0.2% E6201 Gel | Overview of Treatment-Emergent Adverse Events (TEAEs) | TEAEs leading to study treatment interruption | 0 Percentage of participants |
| 0.2% E6201 Gel | Overview of Treatment-Emergent Adverse Events (TEAEs) | Serious TEAEs | 0 Percentage of participants |
| 0.2% E6201 Gel | Overview of Treatment-Emergent Adverse Events (TEAEs) | TEAEs leading to study treatment dose decrease | 0 Percentage of participants |
| 0.2% E6201 Gel | Overview of Treatment-Emergent Adverse Events (TEAEs) | TEAEs | 6 Percentage of participants |
| 0.2% E6201 Gel | Overview of Treatment-Emergent Adverse Events (TEAEs) | Severe TEAEs | 0 Percentage of participants |
| 0.2% E6201 Gel | Overview of Treatment-Emergent Adverse Events (TEAEs) | TEAEs leading to study treatment withdrawal | 0 Percentage of participants |
| 0.2% E6201 Gel | Overview of Treatment-Emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 6 Percentage of participants |