Atopic Dermatitis
Conditions
Brief summary
The purpose of this study is to assess the efficacy and safety of OPA-15406 ointment in patients with atopic dermatitis.
Interventions
DRUGOPA-15406
Subjects were treated with assigned 0.3% or 1% OPA-15406 ointment twice daily.
DRUGPlacebo
Subjects were treated with assigned 0% OPA-15406 ointment twice daily.
Sponsors
Otsuka Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
15 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of atopic dermatitis based on the criteria of Hanifin and Rajka
Exclusion criteria
* Subjects who have an atopic dermatitis or contact dermatitis flare-up defined as a sudden intensification of atopic dermatitis. * Subjects who have an active viral skin infection. * Subjects with a current or history of malignancy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Responder Rate of Investigator's Global Assessment(IGA) of Disease Severity at Week4 | At Week 4 | The investigator or sub investigator assessed the skin symptoms using IGA. The investigator or sub investigator scored the severity (0 = clear, 1 = almost clear, 2 =mild, 3 = moderate, 4 = severe/very severe) of the overall symptoms of the treatment area (erythema, infiltration, papules, effusion and scab formation) from baseline to Week4. Incidence of success in IGA was defined as the rate of subjects whose IGA score was 0 (clear) or 1 (almost clear) and had improved by at least 2 grades (responders) from baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Eczema Area and Severity Index (EASI) Score | Baseline, Week 4 | The investigator or sub investigator assessed the symptoms of AD using EASI. EASI's minimum and maximum scores are 0 and 72 scores respectively. The higher the EASI score is, the more severe the symptoms of AD, and a negative change from the baseline means improvement and a positive change means worsening. The investigator or sub investigator scored the severity (0-3 points) and affected BSA (%) based on the 4 symptoms (erythema, infiltration/papules, excoriation, and lichenification) on the 4 body regions (face, neck and head ; upper limbs ;trunk; and lower limbs). Number of participants analyzed represents number of participants with data at both Baseline and Week4. Participants who have no data were excluded. |
| Change From Baseline in Visual Analogue Scale(VAS) for Pruritus Score | Baseline, Week 4 | The investigator or subinvestigator evaluated the level of pruritus based on VAS. The subjects will mark the point of pruritus intensity during the last 24 hours on the line of a 100- mm VAS sheet between the left end (no pruritus: the score is 0 ) and the right end (very severe pruritus: the score is 100), and a negative change from the baseline means improvement and a positive change means worsening. Number of participants analyzed represents number of participants with data at both Baseline and Week4. Participants who have no data were excluded |
| Change From Baseline in Patient-Oriented Eczema Measure(POEM) Score | Baseline, Week 4 | The investigator or sub investigator evaluated eczema according to the POEM. The subjects answered 7 questions about their eczema by 0-4 points per question. The POEMS's minimum and maximum scores are 0 and 28 scores respectively. The higher the POEM score is, the more severe the symptoms are, and a negative change from the baseline means improvement and a positive change means worsening. If it is difficult for subjects to answer the questions, their parents answered them instead. Number of participants analyzed represents number of participants with data at both Baseline and Week4. Participants who have no data were excluded. |
| Change From Baseline in Percentage Affected Body Surface Area | Baseline, Week 4 | The investigator or subinvestigator drew the affected BSA (range of skin eruption at the time of examination) on the human body drawing to determine the affected areas (%) on the respective 4 body regions (face, neck, and head; upper limbs; trunk; and lower limbs). One palm of the subject corresponds to 1% BSA. |
| Change From Baseline in Verbal Rating Scale(VRS) for Pruritus Score | Baseline, Hour 156 | The investigator or subinvestigator evaluated the pruritus intensity based on VRS. The subjects aged 7 to 14 years old evaluated the pruritus intensity according to the following criteria. The subjects recorded the level of pruritus and the time and date of evaluation in a pruritus diary. 0 : None 1. : Mild 2. : Moderate 3. : Severe For subjects aged 2 to 6 years, this would not be evaluated. Number of participants analyzed represents number of participants with data at both Baseline and Week4. Participants who have no data were excluded. |
| Mean (SD) Normalized OPA-15406 Plasma Trough Concentrations by Dose Derived From %BSA | Week1, Week4, Week8 | The plasma concentration of OPA-15406 was measured at Week1, Week4 and Week8. On the day of measurement, the subjects visited the trial site without morning Investigational Medicinal Product (IMP) administration.Number of participants analyzed represents number of participants with data at each point. Participants who have no effective data were excluded. |
| OPA-15406 Plasma PK Parameters, Cmax | Day 1 and Week 4 | OPA-15406 plasma PK parameter (Cmax) was measured on Day 1 and at Week 4 following topical administration of OPA-15406 0.3% and 1% ointment to adult subjects with AD.Number of participants analyzed represents number of participants with effective data at each point. Participants who have no effective data were excluded. |
| OPA-15406 Plasma PK Parameters, AUC8h | Day 1 and Week 4 | OPA-15406 plasma PK parameter (AUC8h) was measured on Day 1 and at Week 4 following topical administration of OPA-15406 0.3% and 1% ointment to adult subjects with AD.Number of participants analyzed represents number of participants with effective data at each point. Participants who have no effective data were excluded. |
| Mean (SD) OPA-15406 Plasma Trough Concentrations | Week1, Week4, Week8 | The plasma concentration of OPA-15406 was measured at Week1, Week4 and Week8. On the day of measurement, the subjects visited the trial site without morning Investigational Medicinal Product (IMP) administration. Number of participants analyzed represents number of participants with data at each point. Participants who have no effective data were excluded. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 0.3% OPA-15406 Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily.
OPA-15406: Subjects were treated with assigned 0.3% or 1% OPA-15406 ointment twice daily. | 67 |
| 1% OPA-15406 Subjects were treated with assigned 1% OPA-15406 ointment twice daily.
OPA-15406: Subjects were treated with assigned 0.3% or 1% OPA-15406 ointment twice daily. | 67 |
| Placebo Subjects were treated with assigned 0% OPA-15406 ointment twice daily.
Placebo: Subjects were treated with assigned 0% OPA-15406 ointment twice daily. | 66 |
| Total | 200 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | >40% of body surface area | 0 | 1 | 1 |
| Overall Study | Adverse Event | 15 | 7 | 15 |
| Overall Study | Physician Decision | 2 | 2 | 0 |
| Overall Study | Protocol Violation | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 4 | 4 |
Baseline characteristics
| Characteristic | 0.3% OPA-15406 | 1% OPA-15406 | Placebo | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 2 Participants | 0 Participants | 1 Participants | 3 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 65 Participants | 67 Participants | 65 Participants | 197 Participants |
| Age, Continuous | 30.2 years STANDARD_DEVIATION 9 | 31.0 years STANDARD_DEVIATION 10.8 | 31.6 years STANDARD_DEVIATION 10 | 30.9 years STANDARD_DEVIATION 9.9 |
| Race/Ethnicity, Customized Japanese | 67 Participants | 67 Participants | 66 Participants | 200 Participants |
| Region of Enrollment Japan | 67 Participants | 67 Participants | 66 Participants | 200 Participants |
| Sex: Female, Male Female | 22 Participants | 25 Participants | 23 Participants | 70 Participants |
| Sex: Female, Male Male | 45 Participants | 42 Participants | 43 Participants | 130 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 67 | 0 / 67 | 0 / 66 |
| other Total, other adverse events | 22 / 67 | 11 / 67 | 20 / 66 |
| serious Total, serious adverse events | 0 / 67 | 0 / 67 | 0 / 66 |
Outcome results
Primary
Responder Rate of Investigator's Global Assessment(IGA) of Disease Severity at Week4
The investigator or sub investigator assessed the skin symptoms using IGA. The investigator or sub investigator scored the severity (0 = clear, 1 = almost clear, 2 =mild, 3 = moderate, 4 = severe/very severe) of the overall symptoms of the treatment area (erythema, infiltration, papules, effusion and scab formation) from baseline to Week4. Incidence of success in IGA was defined as the rate of subjects whose IGA score was 0 (clear) or 1 (almost clear) and had improved by at least 2 grades (responders) from baseline.
Time frame: At Week 4
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 0.3% OPA-15406 | Responder Rate of Investigator's Global Assessment(IGA) of Disease Severity at Week4 | 14.93 percentage of participants |
| 1% OPA-15406 | Responder Rate of Investigator's Global Assessment(IGA) of Disease Severity at Week4 | 22.39 percentage of participants |
| Placebo | Responder Rate of Investigator's Global Assessment(IGA) of Disease Severity at Week4 | 9.09 percentage of participants |
Secondary
Change From Baseline in Eczema Area and Severity Index (EASI) Score
The investigator or sub investigator assessed the symptoms of AD using EASI. EASI's minimum and maximum scores are 0 and 72 scores respectively. The higher the EASI score is, the more severe the symptoms of AD, and a negative change from the baseline means improvement and a positive change means worsening. The investigator or sub investigator scored the severity (0-3 points) and affected BSA (%) based on the 4 symptoms (erythema, infiltration/papules, excoriation, and lichenification) on the 4 body regions (face, neck and head ; upper limbs ;trunk; and lower limbs). Number of participants analyzed represents number of participants with data at both Baseline and Week4. Participants who have no data were excluded.
Time frame: Baseline, Week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.3% OPA-15406 | Change From Baseline in Eczema Area and Severity Index (EASI) Score | -2.32 score on a scale | Standard Error 0.75 |
| 1% OPA-15406 | Change From Baseline in Eczema Area and Severity Index (EASI) Score | -3.16 score on a scale | Standard Error 0.75 |
| Placebo | Change From Baseline in Eczema Area and Severity Index (EASI) Score | -0.15 score on a scale | Standard Error 0.77 |
Secondary
Change From Baseline in Patient-Oriented Eczema Measure(POEM) Score
The investigator or sub investigator evaluated eczema according to the POEM. The subjects answered 7 questions about their eczema by 0-4 points per question. The POEMS's minimum and maximum scores are 0 and 28 scores respectively. The higher the POEM score is, the more severe the symptoms are, and a negative change from the baseline means improvement and a positive change means worsening. If it is difficult for subjects to answer the questions, their parents answered them instead. Number of participants analyzed represents number of participants with data at both Baseline and Week4. Participants who have no data were excluded.
Time frame: Baseline, Week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.3% OPA-15406 | Change From Baseline in Patient-Oriented Eczema Measure(POEM) Score | -1.36 score on a scale | Standard Error 0.77 |
| 1% OPA-15406 | Change From Baseline in Patient-Oriented Eczema Measure(POEM) Score | -2.90 score on a scale | Standard Error 0.76 |
| Placebo | Change From Baseline in Patient-Oriented Eczema Measure(POEM) Score | -0.02 score on a scale | Standard Error 0.79 |
Secondary
Change From Baseline in Percentage Affected Body Surface Area
The investigator or subinvestigator drew the affected BSA (range of skin eruption at the time of examination) on the human body drawing to determine the affected areas (%) on the respective 4 body regions (face, neck, and head; upper limbs; trunk; and lower limbs). One palm of the subject corresponds to 1% BSA.
Time frame: Baseline, Week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.3% OPA-15406 | Change From Baseline in Percentage Affected Body Surface Area | -3.94 percentage of Affected Body Surface Area | Standard Error 1.44 |
| 1% OPA-15406 | Change From Baseline in Percentage Affected Body Surface Area | -3.73 percentage of Affected Body Surface Area | Standard Error 1.43 |
| Placebo | Change From Baseline in Percentage Affected Body Surface Area | -0.32 percentage of Affected Body Surface Area | Standard Error 1.48 |
Secondary
Change From Baseline in Verbal Rating Scale(VRS) for Pruritus Score
The investigator or subinvestigator evaluated the pruritus intensity based on VRS. The subjects aged 7 to 14 years old evaluated the pruritus intensity according to the following criteria. The subjects recorded the level of pruritus and the time and date of evaluation in a pruritus diary. 0 : None 1. : Mild 2. : Moderate 3. : Severe For subjects aged 2 to 6 years, this would not be evaluated. Number of participants analyzed represents number of participants with data at both Baseline and Week4. Participants who have no data were excluded.
Time frame: Baseline, Hour 156
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.3% OPA-15406 | Change From Baseline in Verbal Rating Scale(VRS) for Pruritus Score | -0.43 score on a scale | Standard Error 0.1 |
| 1% OPA-15406 | Change From Baseline in Verbal Rating Scale(VRS) for Pruritus Score | -0.49 score on a scale | Standard Error 0.1 |
| Placebo | Change From Baseline in Verbal Rating Scale(VRS) for Pruritus Score | -0.06 score on a scale | Standard Error 0.1 |
Secondary
Change From Baseline in Visual Analogue Scale(VAS) for Pruritus Score
The investigator or subinvestigator evaluated the level of pruritus based on VAS. The subjects will mark the point of pruritus intensity during the last 24 hours on the line of a 100- mm VAS sheet between the left end (no pruritus: the score is 0 ) and the right end (very severe pruritus: the score is 100), and a negative change from the baseline means improvement and a positive change means worsening. Number of participants analyzed represents number of participants with data at both Baseline and Week4. Participants who have no data were excluded
Time frame: Baseline, Week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.3% OPA-15406 | Change From Baseline in Visual Analogue Scale(VAS) for Pruritus Score | -6.76 mm | Standard Error 3.31 |
| 1% OPA-15406 | Change From Baseline in Visual Analogue Scale(VAS) for Pruritus Score | -6.28 mm | Standard Error 3.32 |
| Placebo | Change From Baseline in Visual Analogue Scale(VAS) for Pruritus Score | 0.90 mm | Standard Error 3.24 |
Secondary
Mean (SD) Normalized OPA-15406 Plasma Trough Concentrations by Dose Derived From %BSA
The plasma concentration of OPA-15406 was measured at Week1, Week4 and Week8. On the day of measurement, the subjects visited the trial site without morning Investigational Medicinal Product (IMP) administration.Number of participants analyzed represents number of participants with data at each point. Participants who have no effective data were excluded.
Time frame: Week1, Week4, Week8
Population: All subjects who had received the IMP at least once and whose plasma drug concentration had been measured
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 0.3% OPA-15406 | Mean (SD) Normalized OPA-15406 Plasma Trough Concentrations by Dose Derived From %BSA | Week 1 | 0.114 ng/mL/mg | Standard Deviation 0.0991 |
| 0.3% OPA-15406 | Mean (SD) Normalized OPA-15406 Plasma Trough Concentrations by Dose Derived From %BSA | Week 4 | 0.104 ng/mL/mg | Standard Deviation 0.119 |
| 0.3% OPA-15406 | Mean (SD) Normalized OPA-15406 Plasma Trough Concentrations by Dose Derived From %BSA | Week 8 | 0.0910 ng/mL/mg | Standard Deviation 0.103 |
| 1% OPA-15406 | Mean (SD) Normalized OPA-15406 Plasma Trough Concentrations by Dose Derived From %BSA | Week 1 | 0.113 ng/mL/mg | Standard Deviation 0.0952 |
| 1% OPA-15406 | Mean (SD) Normalized OPA-15406 Plasma Trough Concentrations by Dose Derived From %BSA | Week 4 | 0.127 ng/mL/mg | Standard Deviation 0.119 |
| 1% OPA-15406 | Mean (SD) Normalized OPA-15406 Plasma Trough Concentrations by Dose Derived From %BSA | Week 8 | 0.137 ng/mL/mg | Standard Deviation 0.242 |
Secondary
Mean (SD) OPA-15406 Plasma Trough Concentrations
The plasma concentration of OPA-15406 was measured at Week1, Week4 and Week8. On the day of measurement, the subjects visited the trial site without morning Investigational Medicinal Product (IMP) administration. Number of participants analyzed represents number of participants with data at each point. Participants who have no effective data were excluded.
Time frame: Week1, Week4, Week8
Population: All subjects who had received the IMP at least once and whose plasma drug concentration had been measured
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 0.3% OPA-15406 | Mean (SD) OPA-15406 Plasma Trough Concentrations | Week 1 | 1.74 ng/mL/mg | Standard Deviation 1.87 |
| 0.3% OPA-15406 | Mean (SD) OPA-15406 Plasma Trough Concentrations | Week 4 | 1.71 ng/mL/mg | Standard Deviation 2.5 |
| 0.3% OPA-15406 | Mean (SD) OPA-15406 Plasma Trough Concentrations | Week 8 | 1.51 ng/mL/mg | Standard Deviation 1.77 |
| 1% OPA-15406 | Mean (SD) OPA-15406 Plasma Trough Concentrations | Week 1 | 4.96 ng/mL/mg | Standard Deviation 5.04 |
| 1% OPA-15406 | Mean (SD) OPA-15406 Plasma Trough Concentrations | Week 4 | 5.22 ng/mL/mg | Standard Deviation 4.7 |
| 1% OPA-15406 | Mean (SD) OPA-15406 Plasma Trough Concentrations | Week 8 | 5.52 ng/mL/mg | Standard Deviation 8.28 |
Secondary
OPA-15406 Plasma PK Parameters, AUC8h
OPA-15406 plasma PK parameter (AUC8h) was measured on Day 1 and at Week 4 following topical administration of OPA-15406 0.3% and 1% ointment to adult subjects with AD.Number of participants analyzed represents number of participants with effective data at each point. Participants who have no effective data were excluded.
Time frame: Day 1 and Week 4
Population: All subjects who had received the IMP at least once and whose plasma drug concentration had been measured
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 0.3% OPA-15406 | OPA-15406 Plasma PK Parameters, AUC8h | Day 1 | 22.0 ng・h/mL | Standard Deviation 34.7 |
| 0.3% OPA-15406 | OPA-15406 Plasma PK Parameters, AUC8h | Week 4 | 11.6 ng・h/mL | Standard Deviation 7.23 |
| 1% OPA-15406 | OPA-15406 Plasma PK Parameters, AUC8h | Day 1 | 41.6 ng・h/mL | Standard Deviation 37.6 |
| 1% OPA-15406 | OPA-15406 Plasma PK Parameters, AUC8h | Week 4 | 65.2 ng・h/mL | Standard Deviation 26.8 |
Secondary
OPA-15406 Plasma PK Parameters, Cmax
OPA-15406 plasma PK parameter (Cmax) was measured on Day 1 and at Week 4 following topical administration of OPA-15406 0.3% and 1% ointment to adult subjects with AD.Number of participants analyzed represents number of participants with effective data at each point. Participants who have no effective data were excluded.
Time frame: Day 1 and Week 4
Population: All subjects who had received the IMP at least once and whose plasma drug concentration had been measured
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 0.3% OPA-15406 | OPA-15406 Plasma PK Parameters, Cmax | Day 1 | 4.01 ng/mL | Standard Deviation 5.9 |
| 0.3% OPA-15406 | OPA-15406 Plasma PK Parameters, Cmax | Week 4 | 2.07 ng/mL | Standard Deviation 1.47 |
| 1% OPA-15406 | OPA-15406 Plasma PK Parameters, Cmax | Day 1 | 7.27 ng/mL | Standard Deviation 6.42 |
| 1% OPA-15406 | OPA-15406 Plasma PK Parameters, Cmax | Week 4 | 10.4 ng/mL | Standard Deviation 3.68 |