Atopic Dermatitis
Conditions
Keywords
Atopic Dermatitis, Pruritus
Brief summary
The purpose and (primary) objectives of this study are to evaluate the efficacy, safety, and tolerability of TS-022 in adults with atopic dermatitis who have moderate to very severe pruritus (itching), following a 28-day regimen of twice-daily topical application.
Detailed description
(none provided)
Interventions
DRUGTS022
Lotion
DRUGVehicle
Lotion
Sponsors
Taisho Pharmaceutical R&D Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Adults, males or females, 18 - 65 years of age at the time of obtaining the written Informed Consent 2. Generally healthy subjects, who have no past or present history of any significant and/or newly-diagnosed disease or condition 3. A score of 2 (Mild Disease), 3 (Moderate Disease) or 4 (Severe Disease) on the Investigator's Global Assessment of Atopic Dermatitis (IGA) Scale 4. A score of 2 (Moderate Pruritus), 3 (Severe Pruritus) or 4 (Very Severe Pruritus) on the Five-Point Pruritus Scale 5. Patient satisfies the diagnostic criteria for AD as determined by the criteria of Hanifin and Rajka 6. Patient understands the study procedures and agrees to participate in the study by giving written Informed Consent 7. Ability to read and understand English and to provide written informed consent and authorization for protected health information disclosure
Exclusion criteria
1. Concurrent skin pathology or recent history (within the past 5 years) of a chronic skin disease other than AD 2. Use of phototherapy, including exposure to tanning beds, within 28 days of Study Drug application 3. Taking systemic immunosuppressive drugs, biologicals, or corticosteroids therapy within (14 days), or topical immunosuppressive drugs or corticosteroid therapy (within 7 days) of Study Drug application 4. Females who are planning a pregnancy, who are pregnant, or who are breastfeeding 5. Inability or unwillingness to discontinue current AD treatment(s) 6. Inability or unwillingness to comply with study visit schedule and/or other study activities as required by the study protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Pruritis Visual Analog Scale (VAS) | Baseline through Study Day 36 (Visit 7) | Patient reported outcome of pruritis measurement (0-100 mm/min-max)on a change in visual analog scale |
| Safety and Tolerability of TS-022 Topical Lotion as Measured by Participants Who Demonstrated Adverse Events | Baseline through Study Day 36 (Visit 7) | Safety assessment of all subjects who received investigational product. Outcome measure is number of subjects with an adverse event. Measures of adverse events in participants included vital signs, laboratory findings, physical exams, electrocardiograms |
| Investigator's Global Assessment (IGA) Based on a Dermatologist's Evalution of the Change in Subject's Score of Target Treatment Areas | baseline through Study Day 36 (Visit 7) | investigator assessment of disease status rated on 0-5 scale (0 = clear to 5 = very severe) based on a change in score from baseline to Study Day 36 (Visit 7) |
| Five Point Pruritus Scale for Self-Assessment of Target Treatment Area Based on a Change in Score | Baseline, which is Day -7 (Visit 2), through Day 36 (Visit 7) | self-assessment using a five point scale of pruritus state based on a change in scale from none (0) to very severe (4), interfering with daily or sleep activities. Subjects will complete the Five-Point Pruritus Scale once at Screening (Visit 1), then twice daily beginning at baseline, which occurs on the morning of Study Day -7 (Visit 2), through Study Day 36 (Visit 7) |
| Eczema Area and Severity Index (EASI) Based on a Change in Score of Eruption in Proportionate Body Surface Areas | baseline through Study Day 36 (Visit 7) | The head and neck \[10%\], trunk \[30%\], upper extremities \[20%\] and lower extremities \[40%\] were assessed separately for erythema (E), infiltration/papulation (I), excoriation (Ex) and lichenification (L) represented by a numeric coded value of (0, No eruption) to (6, 90% - 100% eruption). One score given to each part of the body on a scale from 1-6 based on the four attributes (E, I, Ex, L) and then a proportional average is taken to get a total score of 1-6. |
| Skindex-29 Questionnaire to Measure the Subject's Overall Quality of Life Based on Activities of Daily Living That Affect Change in Emotion (10 to 50 Points), Symptoms (7 to 35 Points) and Functioning (12 to 60 Points) to Skin Over One Week Period. | Study Day -7 through Study Day 22 | Assessment of subject's activities of daily living using the SKINDEX-29 questionnaire to measure the subject's overall quality of life based on a change in scale from baseline. The SKINDEX scoring scale has a range of 29-145. The smaller the number the better the patient feels. The results are the difference of the SKINDEX scoring scale at treatment discharge (day 22) minus baseline (day-7). Hence the results should be negative, as the patient's emotion, symptoms and functioning of the skin should feel better at treatment discharge as opposed to baseline. |
| Number of Participants Who Had Measurable Pruritis Based on a Visual Horizontal Analog Scale | Baseline through Study Day 36 (Visit 7) | Pruritis Visual Analog Scale (VAS) based on patient reported outcome of pruritis measurement on a VAS indicating the amount of pruritus (itchiness) experienced from the time of last dose application through the time just before current dose application. Change in pruritus is assessed twice daily beginning at baseline, Study Day -7 (Visit 2), through Study Day 36 (Visit 7). Subjects determine measurable pruritis using a visual horizontal analog scale ranging from No Itch, even the slightest itch or Slight Itch, to Worst Itch Imaginable to denote the increase in severity of itching. |
Countries
United States
Participant flow
Recruitment details
Recruitment period for the study started 03Jun09. It was the responsibility of the PI for advertisement and recruitment of the study.
Pre-assignment details
There was a seven day run-in-period in which subjects self-applied the Vehicle control twice daily.
Participants by arm
| Arm | Count |
|---|---|
| Vehicle once daily | 31 |
| TS-022 0.005% lotion/once daily | 30 |
| TS-022 0.010% lotion/once daily | 31 |
| TS-022 0.020% lotion/once daily | 30 |
| Total | 122 |
Baseline characteristics
| Characteristic | TS-022 0.005% | TS-022 0.010% | Vehicle | TS-022 0.020% | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 30 Participants | 31 Participants | 31 Participants | 30 Participants | 122 Participants |
| Age Continuous | 38.0 years STANDARD_DEVIATION 11.63 | 35.1 years STANDARD_DEVIATION 13.78 | 37.5 years STANDARD_DEVIATION 13.53 | 39.0 years STANDARD_DEVIATION 13.89 | 36.4 years STANDARD_DEVIATION 13.23 |
| Region of Enrollment United States | 30 participants | 31 participants | 31 participants | 30 participants | 122 participants |
| Sex: Female, Male Female | 21 Participants | 17 Participants | 19 Participants | 20 Participants | 77 Participants |
| Sex: Female, Male Male | 9 Participants | 14 Participants | 12 Participants | 10 Participants | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 9 / 31 | 11 / 30 | 10 / 31 | 11 / 30 |
| serious Total, serious adverse events | 0 / 31 | 0 / 30 | 0 / 31 | 0 / 30 |
Outcome results
Primary
Change in Pruritis Visual Analog Scale (VAS)
Patient reported outcome of pruritis measurement (0-100 mm/min-max)on a change in visual analog scale
Time frame: Baseline through Study Day 36 (Visit 7)
Population: Intent To Treat (ITT) analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vehicle | Change in Pruritis Visual Analog Scale (VAS) | -12.4 mm | Standard Deviation 14.09 |
| TS-022 0.005% | Change in Pruritis Visual Analog Scale (VAS) | -15.5 mm | Standard Deviation 18.38 |
| TS-022 0.010% | Change in Pruritis Visual Analog Scale (VAS) | -13.9 mm | Standard Deviation 21.11 |
| TS-022 0.020% | Change in Pruritis Visual Analog Scale (VAS) | -6.2 mm | Standard Deviation 18.82 |
Primary
Eczema Area and Severity Index (EASI) Based on a Change in Score of Eruption in Proportionate Body Surface Areas
The head and neck \[10%\], trunk \[30%\], upper extremities \[20%\] and lower extremities \[40%\] were assessed separately for erythema (E), infiltration/papulation (I), excoriation (Ex) and lichenification (L) represented by a numeric coded value of (0, No eruption) to (6, 90% - 100% eruption). One score given to each part of the body on a scale from 1-6 based on the four attributes (E, I, Ex, L) and then a proportional average is taken to get a total score of 1-6.
Time frame: baseline through Study Day 36 (Visit 7)
Population: ITT analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vehicle | Eczema Area and Severity Index (EASI) Based on a Change in Score of Eruption in Proportionate Body Surface Areas | -3.1 units on a scale | Standard Deviation 4.75 |
| TS-022 0.005% | Eczema Area and Severity Index (EASI) Based on a Change in Score of Eruption in Proportionate Body Surface Areas | -2.1 units on a scale | Standard Deviation 5.09 |
| TS-022 0.010% | Eczema Area and Severity Index (EASI) Based on a Change in Score of Eruption in Proportionate Body Surface Areas | -2.7 units on a scale | Standard Deviation 3.87 |
| TS-022 0.020% | Eczema Area and Severity Index (EASI) Based on a Change in Score of Eruption in Proportionate Body Surface Areas | -2.3 units on a scale | Standard Deviation 4.5 |
Primary
Five Point Pruritus Scale for Self-Assessment of Target Treatment Area Based on a Change in Score
self-assessment using a five point scale of pruritus state based on a change in scale from none (0) to very severe (4), interfering with daily or sleep activities. Subjects will complete the Five-Point Pruritus Scale once at Screening (Visit 1), then twice daily beginning at baseline, which occurs on the morning of Study Day -7 (Visit 2), through Study Day 36 (Visit 7)
Time frame: Baseline, which is Day -7 (Visit 2), through Day 36 (Visit 7)
Population: ITT
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Vehicle | Five Point Pruritus Scale for Self-Assessment of Target Treatment Area Based on a Change in Score | -0.4 units on a scale |
| TS-022 0.005% | Five Point Pruritus Scale for Self-Assessment of Target Treatment Area Based on a Change in Score | -0.5 units on a scale |
| TS-022 0.010% | Five Point Pruritus Scale for Self-Assessment of Target Treatment Area Based on a Change in Score | -0.6 units on a scale |
| TS-022 0.020% | Five Point Pruritus Scale for Self-Assessment of Target Treatment Area Based on a Change in Score | -0.2 units on a scale |
Primary
Investigator's Global Assessment (IGA) Based on a Dermatologist's Evalution of the Change in Subject's Score of Target Treatment Areas
investigator assessment of disease status rated on 0-5 scale (0 = clear to 5 = very severe) based on a change in score from baseline to Study Day 36 (Visit 7)
Time frame: baseline through Study Day 36 (Visit 7)
Population: ITT
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Vehicle | Investigator's Global Assessment (IGA) Based on a Dermatologist's Evalution of the Change in Subject's Score of Target Treatment Areas | -0.6 units on a scale |
| TS-022 0.005% | Investigator's Global Assessment (IGA) Based on a Dermatologist's Evalution of the Change in Subject's Score of Target Treatment Areas | -0.5 units on a scale |
| TS-022 0.010% | Investigator's Global Assessment (IGA) Based on a Dermatologist's Evalution of the Change in Subject's Score of Target Treatment Areas | -0.6 units on a scale |
| TS-022 0.020% | Investigator's Global Assessment (IGA) Based on a Dermatologist's Evalution of the Change in Subject's Score of Target Treatment Areas | -0.6 units on a scale |
Primary
Number of Participants Who Had Measurable Pruritis Based on a Visual Horizontal Analog Scale
Pruritis Visual Analog Scale (VAS) based on patient reported outcome of pruritis measurement on a VAS indicating the amount of pruritus (itchiness) experienced from the time of last dose application through the time just before current dose application. Change in pruritus is assessed twice daily beginning at baseline, Study Day -7 (Visit 2), through Study Day 36 (Visit 7). Subjects determine measurable pruritis using a visual horizontal analog scale ranging from No Itch, even the slightest itch or Slight Itch, to Worst Itch Imaginable to denote the increase in severity of itching.
Time frame: Baseline through Study Day 36 (Visit 7)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vehicle | Number of Participants Who Had Measurable Pruritis Based on a Visual Horizontal Analog Scale | 29 participants |
| TS-022 0.005% | Number of Participants Who Had Measurable Pruritis Based on a Visual Horizontal Analog Scale | 78 participants |
Primary
Safety and Tolerability of TS-022 Topical Lotion as Measured by Participants Who Demonstrated Adverse Events
Safety assessment of all subjects who received investigational product. Outcome measure is number of subjects with an adverse event. Measures of adverse events in participants included vital signs, laboratory findings, physical exams, electrocardiograms
Time frame: Baseline through Study Day 36 (Visit 7)
Population: total number of subjects who received study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vehicle | Safety and Tolerability of TS-022 Topical Lotion as Measured by Participants Who Demonstrated Adverse Events | 9 participants |
| TS-022 0.005% | Safety and Tolerability of TS-022 Topical Lotion as Measured by Participants Who Demonstrated Adverse Events | 11 participants |
| TS-022 0.010% | Safety and Tolerability of TS-022 Topical Lotion as Measured by Participants Who Demonstrated Adverse Events | 10 participants |
| TS-022 0.020% | Safety and Tolerability of TS-022 Topical Lotion as Measured by Participants Who Demonstrated Adverse Events | 11 participants |
Primary
Skindex-29 Questionnaire to Measure the Subject's Overall Quality of Life Based on Activities of Daily Living That Affect Change in Emotion (10 to 50 Points), Symptoms (7 to 35 Points) and Functioning (12 to 60 Points) to Skin Over One Week Period.
Assessment of subject's activities of daily living using the SKINDEX-29 questionnaire to measure the subject's overall quality of life based on a change in scale from baseline. The SKINDEX scoring scale has a range of 29-145. The smaller the number the better the patient feels. The results are the difference of the SKINDEX scoring scale at treatment discharge (day 22) minus baseline (day-7). Hence the results should be negative, as the patient's emotion, symptoms and functioning of the skin should feel better at treatment discharge as opposed to baseline.
Time frame: Study Day -7 through Study Day 22
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vehicle | Skindex-29 Questionnaire to Measure the Subject's Overall Quality of Life Based on Activities of Daily Living That Affect Change in Emotion (10 to 50 Points), Symptoms (7 to 35 Points) and Functioning (12 to 60 Points) to Skin Over One Week Period. | -11.7 units on a scale | Standard Deviation 11.61 |
| TS-022 0.005% | Skindex-29 Questionnaire to Measure the Subject's Overall Quality of Life Based on Activities of Daily Living That Affect Change in Emotion (10 to 50 Points), Symptoms (7 to 35 Points) and Functioning (12 to 60 Points) to Skin Over One Week Period. | -12.1 units on a scale | Standard Deviation 14.79 |
| TS-022 0.010% | Skindex-29 Questionnaire to Measure the Subject's Overall Quality of Life Based on Activities of Daily Living That Affect Change in Emotion (10 to 50 Points), Symptoms (7 to 35 Points) and Functioning (12 to 60 Points) to Skin Over One Week Period. | -12.3 units on a scale | Standard Deviation 17.56 |
| TS-022 0.020% | Skindex-29 Questionnaire to Measure the Subject's Overall Quality of Life Based on Activities of Daily Living That Affect Change in Emotion (10 to 50 Points), Symptoms (7 to 35 Points) and Functioning (12 to 60 Points) to Skin Over One Week Period. | -4.1 units on a scale | Standard Deviation 12.43 |