Atopic Dermatitis
Conditions
Brief summary
To evaluate the safety, efficacy (dose response) and pharmacokinetics of 0.3% and 1% OPA-15406 when applied twice daily for 4 weeks in pediatric patients with atopic dermatitis.
Interventions
DRUGOPA-15406
DRUGPlacebos
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
2 Years to 14 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 |
|---|---|---|
| The Number of Subjects Experiencing AEs | Week 0-4 | The number of subjects experiencing AEs will be calculated for each treatment group. Treatment-emergent adverse events (TEAEs) occurring after the start of IMP administration are summarized. The number of subjects with events, the number of events is obtained for all the TEAEs reported. |
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 ;; 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 aged 7 to 14 years old marked the point of pruritus intensity during the last 24 hours on a 0 to 100mm VAS, with 0 being no pruritis to 100 being very severe pruritis.For subjects aged 2 to 6 years, this would not be evaluated. The negative value showed the degree of improvement. |
| 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. The negative value showed the degree of improvement. |
| 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. |
| Responder Rate of Investigator's Global Assessment(IGA) of Disease Severity at Week4 | Baseline and Week 4 | The investigator or subinvestigator assessed the skin symptoms using IGA. The investigator or subinvestigator 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. |
| Mean (SD) OPA-15406 Plasma Trough Concentrations at week1 | Week 1 | The plasma concentration of OPA-15406 was measured at Week 1. On the day of measurement, the subjects visited the trial site without morning Investigational Medicinal Product (IMP) administration. |
| Mean (SD) OPA-15406 Plasma Trough Concentrations at week4 | week4 | The plasma concentration of OPA-15406 was measured at Week 4. On the day of measurement, the subjects visited the trial site without morning Investigational Medicinal Product (IMP) administration. |
| Mean (SD) Normalized OPA-15406 Plasma Trough Concentrations by Dose Derived From %BSA at week1 | week1 | The plasma concentration of OPA-15406 was measured at Week 1. On the day of measurement, the subjects visited the trial site without morning Investigational Medicinal Product (IMP) administration.Each plasma concentration was normalized by dose. |
| Mean (SD) Normalized OPA-15406 Plasma Trough Concentrations by Dose Derived From %BSA at week4 | week4 | The plasma concentration of OPA-15406 was measured at Week 4. On the day of measurement, the subjects visited the trial site without morning Investigational Medicinal Product (IMP) administration.Each plasma concentration was normalized by dose. |
| Change From Baseline in Percentage Affected Body Surface Area | Baseline, Week 8, 16, 24 | 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. The negative value showed the degree of improvement. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 0.3% OPA-15406 Ointments Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily.
OPA-15406 | 24 |
| 1% OPA-15406 Ointments Subjects were treated with assigned 1% OPA-15406 ointment twice daily.
OPA-15406 | 25 |
| Placebo Ointments Subjects were treated with assigned 0% OPA-15406 ointment twice daily.
Placebos | 24 |
| Total | 73 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 4 |
| Overall Study | Lack of Efficacy | 0 | 0 | 1 |
| Overall Study | Withdrawal by parent/guardian | 1 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | 0.3% OPA-15406 Ointments | 1% OPA-15406 Ointments | Placebo Ointments |
|---|---|---|---|---|
| Age, Categorical <=18 years | 73 Participants | 24 Participants | 25 Participants | 24 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 8.3 years STANDARD_DEVIATION 3.4 | 8.5 years STANDARD_DEVIATION 3.8 | 7.9 years STANDARD_DEVIATION 3.5 | 8.5 years STANDARD_DEVIATION 3.1 |
| Race/Ethnicity, Customized Japanese Subjects | 73 participants | 24 participants | 25 participants | 24 participants |
| Region of Enrollment Japan | 73 Participants | 24 Participants | 25 Participants | 24 Participants |
| Sex: Female, Male Female | 21 Participants | 6 Participants | 10 Participants | 5 Participants |
| Sex: Female, Male Male | 52 Participants | 18 Participants | 15 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 25 | 0 / 24 |
| other Total, other adverse events | 6 / 24 | 8 / 25 | 8 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 25 | 0 / 24 |
Outcome results
Primary
The Number of Subjects Experiencing AEs
The number of subjects experiencing AEs will be calculated for each treatment group. Treatment-emergent adverse events (TEAEs) occurring after the start of IMP administration are summarized. The number of subjects with events, the number of events is obtained for all the TEAEs reported.
Time frame: Week 0-4
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 0.3% OPA-15406 Ointments | The Number of Subjects Experiencing AEs | 11 participants |
| 1% OPA-15406 Ointments | The Number of Subjects Experiencing AEs | 14 participants |
| Placebo Ointments | The Number of Subjects Experiencing AEs | 12 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 ;; 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 Ointments | Change From Baseline in Eczema Area and Severity Index (EASI) Score | -5.33 score on a scale | Standard Error 1.28 |
| 1% OPA-15406 Ointments | Change From Baseline in Eczema Area and Severity Index (EASI) Score | -5.52 score on a scale | Standard Error 1.26 |
| Placebo Ointments | Change From Baseline in Eczema Area and Severity Index (EASI) Score | 0.56 score on a scale | Standard Error 1.36 |
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 Ointments | Change From Baseline in Patient-Oriented Eczema Measure(POEM) Score | -4.33 score on a scale | Standard Error 1.16 |
| 1% OPA-15406 Ointments | Change From Baseline in Patient-Oriented Eczema Measure(POEM) Score | -4.37 score on a scale | Standard Error 1.14 |
| Placebo Ointments | Change From Baseline in Patient-Oriented Eczema Measure(POEM) Score | 2.26 score on a scale | Standard Error 1.24 |
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. The negative value showed the degree of improvement.
Time frame: Baseline, Week 8, 16, 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.3% OPA-15406 Ointments | Change From Baseline in Percentage Affected Body Surface Area | -6.06 percentage of Affected Body Surface Area | Standard Error 2.36 |
| 1% OPA-15406 Ointments | Change From Baseline in Percentage Affected Body Surface Area | -8.21 percentage of Affected Body Surface Area | Standard Error 2.32 |
| Placebo Ointments | Change From Baseline in Percentage Affected Body Surface Area | 1.78 percentage of Affected Body Surface Area | Standard Error 2.53 |
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. The negative value showed the degree of improvement.
Time frame: Baseline, Hour 156
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.3% OPA-15406 Ointments | Change From Baseline in Verbal Rating Scale(VRS) for Pruritus Score | -0.83 score on a scale | Standard Error 0.18 |
| 1% OPA-15406 Ointments | Change From Baseline in Verbal Rating Scale(VRS) for Pruritus Score | -0.73 score on a scale | Standard Error 0.19 |
| Placebo Ointments | Change From Baseline in Verbal Rating Scale(VRS) for Pruritus Score | 0.30 score on a scale | Standard Error 0.11 |
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 aged 7 to 14 years old marked the point of pruritus intensity during the last 24 hours on a 0 to 100mm VAS, with 0 being no pruritis to 100 being very severe pruritis.For subjects aged 2 to 6 years, this would not be evaluated. The negative value showed the degree of improvement.
Time frame: Baseline, Week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.3% OPA-15406 Ointments | Change From Baseline in Visual Analogue Scale(VAS) for Pruritus Score | -18.00 mm | Standard Error 7.27 |
| 1% OPA-15406 Ointments | Change From Baseline in Visual Analogue Scale(VAS) for Pruritus Score | -17.21 mm | Standard Error 7.29 |
| Placebo Ointments | Change From Baseline in Visual Analogue Scale(VAS) for Pruritus Score | 8.19 mm | Standard Error 7.58 |
Secondary
Mean (SD) Normalized OPA-15406 Plasma Trough Concentrations by Dose Derived From %BSA at week1
The plasma concentration of OPA-15406 was measured at Week 1. On the day of measurement, the subjects visited the trial site without morning Investigational Medicinal Product (IMP) administration.Each plasma concentration was normalized by dose.
Time frame: week1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.3% OPA-15406 Ointments | Mean (SD) Normalized OPA-15406 Plasma Trough Concentrations by Dose Derived From %BSA at week1 | 0.196 ng/mL/mg | Standard Deviation 0.201 |
| 1% OPA-15406 Ointments | Mean (SD) Normalized OPA-15406 Plasma Trough Concentrations by Dose Derived From %BSA at week1 | 0.210 ng/mL/mg | Standard Deviation 0.174 |
Secondary
Mean (SD) Normalized OPA-15406 Plasma Trough Concentrations by Dose Derived From %BSA at week4
The plasma concentration of OPA-15406 was measured at Week 4. On the day of measurement, the subjects visited the trial site without morning Investigational Medicinal Product (IMP) administration.Each plasma concentration was normalized by dose.
Time frame: week4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.3% OPA-15406 Ointments | Mean (SD) Normalized OPA-15406 Plasma Trough Concentrations by Dose Derived From %BSA at week4 | 0.150 ng/mL/mg | Standard Deviation 0.111 |
| 1% OPA-15406 Ointments | Mean (SD) Normalized OPA-15406 Plasma Trough Concentrations by Dose Derived From %BSA at week4 | 0.166 ng/mL/mg | Standard Deviation 0.148 |
Secondary
Mean (SD) OPA-15406 Plasma Trough Concentrations at week1
The plasma concentration of OPA-15406 was measured at Week 1. On the day of measurement, the subjects visited the trial site without morning Investigational Medicinal Product (IMP) administration.
Time frame: Week 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.3% OPA-15406 Ointments | Mean (SD) OPA-15406 Plasma Trough Concentrations at week1 | 0.842 ng/mL | Standard Deviation 0.577 |
| 1% OPA-15406 Ointments | Mean (SD) OPA-15406 Plasma Trough Concentrations at week1 | 2.90 ng/mL | Standard Deviation 2.74 |
Secondary
Mean (SD) OPA-15406 Plasma Trough Concentrations at week4
The plasma concentration of OPA-15406 was measured at Week 4. On the day of measurement, the subjects visited the trial site without morning Investigational Medicinal Product (IMP) administration.
Time frame: week4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.3% OPA-15406 Ointments | Mean (SD) OPA-15406 Plasma Trough Concentrations at week4 | 0.946 ng/mL | Standard Deviation 1.16 |
| 1% OPA-15406 Ointments | Mean (SD) OPA-15406 Plasma Trough Concentrations at week4 | 2.21 ng/mL | Standard Deviation 1.81 |
Secondary
Responder Rate of Investigator's Global Assessment(IGA) of Disease Severity at Week4
The investigator or subinvestigator assessed the skin symptoms using IGA. The investigator or subinvestigator 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: Baseline and Week 4
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 0.3% OPA-15406 Ointments | Responder Rate of Investigator's Global Assessment(IGA) of Disease Severity at Week4 | 37.50 Percentage of participants |
| 1% OPA-15406 Ointments | Responder Rate of Investigator's Global Assessment(IGA) of Disease Severity at Week4 | 40.00 Percentage of participants |
| Placebo Ointments | Responder Rate of Investigator's Global Assessment(IGA) of Disease Severity at Week4 | 8.33 Percentage of participants |