A 12-Day Randomized, Blinded, Vehicle and Active Comparator-Controlled Study to Determine the Efficacy and Safety of Six Concentrations of Topical E6201 Gel in Subjects With Psoriasis Vulgaris
Sponsor
Eisai Limited (Industry)
Overall Status
Completed
CT.gov ID
NCT01268527
Collaborator
(none)
30
1
2
8.9
3.4
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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.
Study Design
Study Type:
Interventional
Actual Enrollment
:
30 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Primary Purpose:
Treatment
Official Title:
A 12-Day Randomized, Blinded, Vehicle and Active Comparator-Controlled Study to Determine the Efficacy and Safety of Six Concentrations of Topical E6201 Gel in Subjects With Psoriasis Vulgaris
Actual Study Start Date
:
Mar 15, 2010
Actual Primary Completion Date
:
Dec 11, 2010
Actual Study Completion Date
:
Dec 11, 2010
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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. The 3 concentrations of E6201 gel were dosed first in Cohort 1 to establish the safety and tolerability prior to dosing in Cohort 2. |
Drug: 0.03% E6201
Topical 0.03% E6201 gel was applied once daily to individual specific regions of the psoriatic plaque.
Drug: 0.1% E6201
Topical 0.1% E6201 gel was applied once daily to individual specific regions of the psoriatic plaque.
Drug: 0.2% E6201
Topical 0.2% E6201 gel was applied once daily to individual specific regions of the psoriatic plaque.
Other: Placebo - 0.03% gel vehicle
Topical 0.03% gel vehicle (negative control) was applied once daily to individual specific regions of the psoriatic plaque.
Other: Placebo - 0.1% gel vehicle
Topical 0.1% gel vehicle (negative control) was applied once daily to individual specific regions of the psoriatic plaque.
Other: Placebo - 0.2% gel vehicle
Topical 0.2% gel vehicle (negative control) was applied once daily to individual specific regions of the psoriatic plaque.
Drug: Calcipotriene
Topical 0.005% calcipotriene (positive control) was applied once daily to individual specific regions of the psoriatic plaque.
Other Names:
|
| Experimental: 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. Cohort 2 participants were not dosed until all participants in Cohort 1 completed treatment and safety data were collected and evaluated. |
Drug: 0.005% E6201
Topical 0.005% E6201 gel was applied once daily to individual specific regions of the psoriatic plaque.
Drug: 0.01% E6201
Topical 0.01% E6201 gel was applied once daily to individual specific regions of the psoriatic plaque.
Drug: 0.05% E6201
Topical 0.05% E6201 gel was applied once daily to individual specific regions of the psoriatic plaque.
Other: Placebo - 0.05% gel vehicle
Topical 0.005% gel vehicle (negative control) was applied once daily to individual specific regions of the psoriatic plaque.
Other: Placebo - 0.01% gel vehicle
Topical 0.01% gel vehicle (negative control) was applied once daily to individual specific regions of the psoriatic plaque.
Other: Placebo - 0.05% gel vehicle
Topical 0.05% gel vehicle (negative control) was applied once daily to individual specific regions of the psoriatic plaque.
Drug: Calcipotriene
Topical 0.005% calcipotriene (positive control) was applied once daily to individual specific regions of the psoriatic plaque.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Bioskin GmbH | Berlin | Germany |
Sponsors and Collaborators
- Eisai Limited
Investigators
- Study Director: Joseph Mercer, Eisai Limited
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Eisai Limited
ClinicalTrials.gov Identifier:
NCT01268527
Other Study ID Numbers:
- E6201-E044-204
- 2009-014815-11
First Posted:
Dec 31, 2010
Last Update Posted:
Jun 11, 2021
Last Verified:
May 1, 2021
Keywords provided by Eisai Limited
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Cohort 1 | Cohort 2 |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Period Title: Overall Study | ||
| STARTED | 15 | 15 |
| COMPLETED | 15 | 15 |
| NOT COMPLETED | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Cohort 1 | Cohort 2 | Total |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | Total of all reporting groups |
| Overall Participants | 15 | 15 | 30 |
| Age (Years) [Geometric Mean (Standard Deviation) ] | |||
| Geometric Mean (Standard Deviation) [Years] |
47.4
(12.44)
|
50.6
(7.01)
|
49.0
(10.05)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
2
13.3%
|
3
20%
|
5
16.7%
|
| Male |
13
86.7%
|
12
80%
|
25
83.3%
|
Outcome Measures
| Title | Summary Statistics and Primary Pairwise Comparison (Vehicle-E6201) of Area Under the Curve (AUC) for the Baseline-Corrected Thickness of the Psoriatic Infiltrate |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Daivonex (Calcipotriene Cream) | E6201 Vehicle | 0.005% E6201 Gel | 0.01% E6201 Gel | 0.03% E6201 Gel | 0.05% E6201 Gel | 0.1% E6201 Gel | 0.2% E6201 Gel |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Daivonex (calcipotriene cream) at 0.005% was 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 a tuberculin syringe that was filled with approximately 200 uL of Daivonex. 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. | E6201 vehicle was 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 earlier. | E6201 gel (0.005%) was 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 earlier. | E6201 gel (0.01%) was 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 earlier. | E6201 gel (0.03%) was 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 earlier. | E6201 gel (0.05%) was 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 earlier. | E6201 gel (0.1%) was 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 earlier. | E6201 gel (0.2%) was 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 earlier. |
| Measure Participants | 30 | 30 | 15 | 15 | 15 | 15 | 6 | 6 |
| Least Squares Mean (95% Confidence Interval) [um.day] |
-1449.2
|
17.0
|
-694.4
|
-1102.8
|
-763.1
|
-1758.2
|
-904.4
|
-920.8
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | E6201 Vehicle, 0.005% E6201 Gel |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0038 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in LSM (vehicle - E6201 gel) |
| Estimated Value | 711.4 | |
| Confidence Interval |
(2-Sided) 95% 292.5 to 1130.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | E6201 Vehicle, 0.01% E6201 Gel |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in LSM (vehicle - E6201 gel) |
| Estimated Value | 1119.8 | |
| Confidence Interval |
(2-Sided) 95% 858.9 to 1380.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | E6201 Vehicle, 0.03% E6201 Gel |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0523 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in LSM (vehicle - E6201 gel) |
| Estimated Value | 780.0 | |
| Confidence Interval |
(2-Sided) 95% -8.5 to 1568.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | E6201 Vehicle, 0.05% E6201 Gel |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in LSM (vehicle - E6201 gel) |
| Estimated Value | 1775.1 | |
| Confidence Interval |
(2-Sided) 95% 1392.3 to 2158.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | E6201 Vehicle, 0.1% E6201 Gel |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0002 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in LSM (vehicle - E6201 gel) |
| Estimated Value | 921.4 | |
| Confidence Interval |
(2-Sided) 95% 515.7 to 1327.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | E6201 Vehicle, 0.2% E6201 Gel |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0115 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in LSM (vehicle - E6201 gel) |
| Estimated Value | 937.8 | |
| Confidence Interval |
(2-Sided) 95% 267.6 to 1607.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change in Thickness of the Psoriatic Infiltrate From Baseline to End of Treatment (Day 12/Discontinuation) |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Daivonex (Calcipotriene Cream) | E6201 Vehicle | 0.005% E6201 Gel | 0.01% E6201 Gel | 0.03% E6201 Gel | 0.05% E6201 Gel | 0.1% E6201 Gel | 0.2% E6201 Gel |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Daivonex (calcipotriene cream) at 0.005% was 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 a tuberculin syringe that was filled with approximately 200 uL of Daivonex. 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. | E6201-vehicle was 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 earlier. | E6201 gel (0.005%) was 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 earlier. | E6201 gel (0.01%) was 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 earlier. | E6201 gel (0.03%) was 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 earlier. | E6201 gel (0.05%) was 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 earlier. | E6201 gel (0.1%) was 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 earlier. | E6201 gel (0.2%) was 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 earlier. |
| Measure Participants | 30 | 30 | 15 | 15 | 15 | 15 | 6 | 6 |
| Least Squares Mean (95% Confidence Interval) [um] |
-205.3
|
7.1
|
-94.4
|
-175.3
|
-162.4
|
-239.5
|
-125.2
|
-137.9
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | E6201 Vehicle, 0.005% E6201 Gel |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0042 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in LSM (vehicle - E6201 gel) |
| Estimated Value | 101.5 | |
| Confidence Interval |
(2-Sided) 95% 36.0 to 167.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | E6201 Vehicle, 0.01% E6201 Gel |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in LSM (vehicle - E6201 gel) |
| Estimated Value | 182.4 | |
| Confidence Interval |
(2-Sided) 95% 140.3 to 224.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | E6201 Vehicle, 0.03% E6201 Gel |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in LSM (vehicle - E6201 gel) |
| Estimated Value | 169.5 | |
| Confidence Interval |
(2-Sided) 95% 127.4 to 211.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | E6201 Vehicle, 0.05% E6201 Gel |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in LSM (vehicle - E6201 gel) |
| Estimated Value | 246.6 | |
| Confidence Interval |
(2-Sided) 95% 185.0 to 308.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | E6201 Vehicle, 0.1% E6201 Gel |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0043 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in LSM (vehicle - E6201 gel) |
| Estimated Value | 132.3 | |
| Confidence Interval |
(2-Sided) 95% 53.9 to 210.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | E6201 Vehicle, 0.2% E6201 Gel |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0036 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in LSM (vehicle - E6201 gel) |
| Estimated Value | 145.0 | |
| Confidence Interval |
(2-Sided) 95% 64.2 to 225.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change in Thickness of the Psoriatic Infiltrate From Baseline to Day 8 |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Daivonex (Calcipotriene Cream) | E6201 Vehicle | 0.005% E6201 Gel | 0.01% E6201 Gel | 0.03% E6201 Gel | 0.05% E6201 Gel | 0.1% E6201 Gel | 0.2% E6201 Gel |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Daivonex (calcipotriene cream) at 0.005% was 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 a tuberculin syringe that was filled with approximately 200 uL of Daivonex. 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. | E6201-vehicle was 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 earlier. | E6201 gel (0.005%) was 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 earlier. | E6201 gel (0.01%) was 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 earlier. | E6201 gel (0.03%) was 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 earlier. | E6201 gel (0.05%) was 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 earlier. | E6201 gel (0.1%) was 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 earlier. | E6201 gel (0.2%) was 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 earlier. |
| Measure Participants | 30 | 30 | 15 | 15 | 15 | 15 | 6 | 6 |
| Least Squares Mean (95% Confidence Interval) [um] |
-151.7
|
17.3
|
-63.4
|
-110.7
|
-92.9
|
-190.3
|
-108.0
|
-102.7
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | E6201 Vehicle, 0.005% E6201 Gel |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0013 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in LSM (vehicle - E6201 gel) |
| Estimated Value | 80.7 | |
| Confidence Interval |
(2-Sided) 95% 34.6 to 126.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | E6201 Vehicle, 0.01% E6201 Gel |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in LSM (vehicle - E6201 gel) |
| Estimated Value | 127.9 | |
| Confidence Interval |
(2-Sided) 95% 92.4 to 163.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | E6201 Vehicle, 0.03% E6201 Gel |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0458 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in LSM (vehicle - E6201 gel) |
| Estimated Value | 110.2 | |
| Confidence Interval |
(2-Sided) 95% 2.4 to 218.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | E6201 Vehicle, 0.05% E6201 Gel |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in LSM (vehicle - E6201 gel) |
| Estimated Value | 207.5 | |
| Confidence Interval |
(2-Sided) 95% 155.2 to 259.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | E6201 Vehicle, 0.1% E6201 Gel |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0003 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in LSM (vehicle - E6201 gel) |
| Estimated Value | 125.3 | |
| Confidence Interval |
(2-Sided) 95% 71.5 to 179.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | E6201 Vehicle, 0.2% E6201 Gel |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0029 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in LSM (vehicle - E6201 gel) |
| Estimated Value | 128.6 | |
| Confidence Interval |
(2-Sided) 95% 93.9 to 163.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Clinical (Global) Assessment of Efficacy at Day 12/Discontinuation |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Daivonex (Calcipotriene Cream) | E6201 Vehicle | 0.005% E6201 Gel | 0.01% E6201 Gel | 0.03% E6201 Gel | 0.05% E6201 Gel | 0.1% E6201 Gel | 0.2% E6201 Gel |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Daivonex (calcipotriene cream) at 0.005% was 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 a tuberculin syringe that was filled with approximately 200 uL of Daivonex. 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. | E6201-vehicle was 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 earlier. | E6201 gel (0.005%) was 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 earlier. | E6201 gel (0.01%) was 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 earlier. | E6201 gel (0.03%) was 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 earlier. | E6201 gel (0.05%) was 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 earlier. | E6201 gel (0.1%) was 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 earlier. | E6201 gel (0.2%) was 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 earlier. |
| Measure Participants | 30 | 30 | 15 | 15 | 15 | 15 | 6 | 6 |
| Worsened |
0
0%
|
0
0%
|
0
0%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Unchanged (no effect) |
6.7
44.7%
|
90.0
600%
|
20.0
66.7%
|
0
NaN
|
6.7
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Slight improvement |
56.7
378%
|
10.0
66.7%
|
66.7
222.3%
|
33.3
NaN
|
46.7
NaN
|
13.3
NaN
|
83.3
NaN
|
83.3
NaN
|
| Clear improvement but not completely healed |
33.3
222%
|
0
0%
|
13.3
44.3%
|
66.7
NaN
|
46.7
NaN
|
86.7
NaN
|
16.7
NaN
|
0
NaN
|
| Completely healed |
3.3
22%
|
0
0%
|
0
0%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
16.7
NaN
|
| Title | Clinical (Global) Assessment of Efficacy on Day 8 |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Daivonex (Calcipotriene Cream) | E6201 Vehicle | 0.005% E6201 Gel | 0.01% E6201 Gel | 0.03% E6201 Gel | 0.05% E6201 Gel | 0.1% E6201 Gel | 0.2% E6201 Gel |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Daivonex (calcipotriene cream) at 0.005% was 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 a tuberculin syringe that was filled with approximately 200 uL of Daivonex. 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. | E6201-vehicle was 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 earlier. | E6201 gel (0.005%) was 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 earlier. | E6201 gel (0.01%) was 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 earlier. | E6201 gel (0.03%) was 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 earlier. | E6201 gel (0.05%) was 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 earlier. | E6201 gel (0.1%) was 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 earlier. | E6201 gel (0.2%) was 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 earlier. |
| Measure Participants | 30 | 30 | 15 | 15 | 15 | 15 | 6 | 6 |
| Worsened |
3.3
22%
|
3.3
22%
|
0
0%
|
0
NaN
|
6.7
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Unchanged (no effect) |
20.0
133.3%
|
90.0
600%
|
33.3
111%
|
6.7
NaN
|
6.7
NaN
|
0
NaN
|
16.7
NaN
|
0
NaN
|
| Slight improvement |
46.7
311.3%
|
6.7
44.7%
|
66.7
222.3%
|
53.3
NaN
|
60.0
NaN
|
13.3
NaN
|
83.3
NaN
|
100
NaN
|
| Clear improvement but not completely healed |
30.0
200%
|
0
0%
|
0
0%
|
40.0
NaN
|
26.7
NaN
|
86.7
NaN
|
0
NaN
|
0
NaN
|
| Completely healed |
0
0%
|
0
0%
|
0
0%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Title | Overview of Treatment-Emergent Adverse Events (TEAEs) |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Daivonex (Calcipotriene Cream) | E6201 Vehicle | 0.005% E6201 Gel | 0.01% E6201 Gel | 0.03% E6201 Gel | 0.05% E6201 Gel | 0.1% E6201 Gel | 0.2% E6201 Gel |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Daivonex (calcipotriene cream) at 0.005% was 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 a tuberculin syringe that was filled with approximately 200 uL of Daivonex. 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. | E6201 vehicle was 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 earlier. | E6201 gel (0.005%) was 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 earlier. | E6201 gel (0.01%) was 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 earlier. | E6201 gel (0.03%) was 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 earlier. | E6201 gel (0.05%) was 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 earlier. | E6201 gel (0.1%) was 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 earlier. | E6201 gel (0.2%) was 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 earlier. |
| Measure Participants | 30 | 30 | 15 | 15 | 15 | 15 | 6 | 6 |
| TEAEs |
3
20%
|
1
6.7%
|
0
0%
|
0
NaN
|
4
NaN
|
5
NaN
|
6
NaN
|
6
NaN
|
| Treatment-related TEAEs |
3
20%
|
1
6.7%
|
0
0%
|
0
NaN
|
4
NaN
|
5
NaN
|
6
NaN
|
6
NaN
|
| Severe TEAEs |
0
0%
|
0
0%
|
0
0%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Serious TEAEs |
0
0%
|
0
0%
|
0
0%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| TEAEs leading to study treatment withdrawal |
1
6.7%
|
1
6.7%
|
0
0%
|
0
NaN
|
1
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| TEAEs leading to study treatment dose decrease |
0
0%
|
0
0%
|
0
0%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| TEAEs leading to study treatment interruption |
0
0%
|
0
0%
|
0
0%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
Adverse Events
| 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. | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Treatment-emergent adverse events (TEAEs) were collected and defined as an AE that emerged during treatment, having been absent at pretreatment, 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. Few adverse events occurred in more than one treatment group. | |||||||||||||||
| Arm/Group Title | Daivonex (Calcipotriene Cream) | E6201 Vehicle | 0.005% E6201 Gel | 0.01% E6201 Gel | 0.03% E6201 Gel | 0.05% E6201 Gel | 0.1% E6201 Gel | 0.2% E6201 Gel | ||||||||
| Arm/Group Description | Daivonex (calcipotriene cream) at 0.005% was 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 a tuberculin syringe that was filled with approximately 200 uL of Daivonex. 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. | E6201 vehicle was 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 earlier. | E6201 gel (0.005%) was 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 earlier. | E6201 gel (0.01%) was 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 earlier. | E6201 gel (0.03%) was 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 earlier. | E6201 gel (0.05%) was 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 earlier. | E6201 gel (0.1%) was 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 earlier. | E6201 gel (0.2%) was 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 earlier. | ||||||||
All Cause Mortality |
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| Daivonex (Calcipotriene Cream) | E6201 Vehicle | 0.005% E6201 Gel | 0.01% E6201 Gel | 0.03% E6201 Gel | 0.05% E6201 Gel | 0.1% E6201 Gel | 0.2% E6201 Gel | |||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/30 (0%) | 0/30 (0%) | 0/15 (0%) | 0/15 (0%) | 0/15 (0%) | 0/15 (0%) | 0/6 (0%) | 0/6 (0%) | ||||||||
Serious Adverse Events |
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| Daivonex (Calcipotriene Cream) | E6201 Vehicle | 0.005% E6201 Gel | 0.01% E6201 Gel | 0.03% E6201 Gel | 0.05% E6201 Gel | 0.1% E6201 Gel | 0.2% E6201 Gel | |||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/30 (0%) | 0/30 (0%) | 0/15 (0%) | 0/15 (0%) | 0/15 (0%) | 0/15 (0%) | 0/6 (0%) | 0/6 (0%) | ||||||||
Other (Not Including Serious) Adverse Events |
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| Daivonex (Calcipotriene Cream) | E6201 Vehicle | 0.005% E6201 Gel | 0.01% E6201 Gel | 0.03% E6201 Gel | 0.05% E6201 Gel | 0.1% E6201 Gel | 0.2% E6201 Gel | |||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/30 (10%) | 1/30 (3.3%) | 0/15 (0%) | 0/15 (0%) | 4/15 (26.7%) | 5/15 (33.3%) | 6/6 (100%) | 6/6 (100%) | ||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||
| Pain in extremity | 0/30 (0%) | 0/30 (0%) | 0/15 (0%) | 0/15 (0%) | 0/15 (0%) | 0/15 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | ||||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||||
| Rash erythematous | 2/30 (6.7%) | 0/30 (0%) | 0/15 (0%) | 0/15 (0%) | 2/15 (13.3%) | 0/15 (0%) | 5/6 (83.3%) | 4/6 (66.7%) | ||||||||
| Erythema | 0/30 (0%) | 0/30 (0%) | 0/15 (0%) | 0/15 (0%) | 0/15 (0%) | 5/15 (33.3%) | 0/6 (0%) | 0/6 (0%) | ||||||||
| Scab | 0/30 (0%) | 0/30 (0%) | 0/15 (0%) | 0/15 (0%) | 0/15 (0%) | 0/15 (0%) | 3/6 (50%) | 5/6 (83.3%) | ||||||||
| Lividity | 0/30 (0%) | 0/30 (0%) | 0/15 (0%) | 0/15 (0%) | 1/15 (6.7%) | 0/15 (0%) | 1/6 (16.7%) | 2/6 (33.3%) | ||||||||
| Dermatitis contact | 1/30 (3.3%) | 1/30 (3.3%) | 0/15 (0%) | 0/15 (0%) | 1/15 (6.7%) | 0/15 (0%) | 0/6 (0%) | 0/6 (0%) | ||||||||
| Skin erosion | 1/30 (3.3%) | 0/30 (0%) | 0/15 (0%) | 0/15 (0%) | 1/15 (6.7%) | 0/15 (0%) | 1/6 (16.7%) | 0/6 (0%) | ||||||||
| Skin haemorrhage | 0/30 (0%) | 0/30 (0%) | 0/15 (0%) | 0/15 (0%) | 0/15 (0%) | 0/15 (0%) | 0/6 (0%) | 1/6 (16.7%) | ||||||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Results Point of Contact
| Name/Title | Eisai Medical Information |
|---|---|
| Organization | Eisai Medical Research Inc. |
| Phone | 1-888-274-2378 |
| esi_medinfo@eisai.com |
Responsible Party:
Eisai Limited
ClinicalTrials.gov Identifier:
NCT01268527
Other Study ID Numbers:
- E6201-E044-204
- 2009-014815-11
First Posted:
Dec 31, 2010
Last Update Posted:
Jun 11, 2021
Last Verified:
May 1, 2021