Phase 2 Study of OPA-15406 Ointment in Pediatric Patients With Atopic Dermatitis

• Sponsor: Otsuka Pharmaceutical Co., Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03018691
• Collaborator: (none)
• Enrollment: 73
• Locations: 4
• Arms: 3
• Actual Duration (Months): 5
• Patients Per Site: 18.3
• Patients Per Site Per Month: 3.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Atopic Dermatitis	Drug: OPA-15406; Drug: Placebos	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 73 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-blind, Vehicle-controlled, Parallel-group Trial to Assess the Safety and Efficacy of 0.3% and 1% OPA-15406 Ointments When Administered for 4 Weeks in Pediatric Patients With Atopic Dermatitis
• Actual Study Start Date: Jan 1, 2017
• Actual Primary Completion Date: Jun 1, 2017
• Actual Study Completion Date: Jun 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 0.3% OPA-15406 Ointments Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily.	Drug: OPA-15406
Experimental: 1% OPA-15406 Ointments Subjects were treated with assigned 1% OPA-15406 ointment twice daily.	Drug: OPA-15406
Placebo Comparator: Placebo Ointments Subjects were treated with assigned 0% OPA-15406 ointment twice daily.	Drug: Placebos

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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 : Mild : Moderate : Severe For subjects aged 2 to 6 years, this would not be evaluated. The negative value showed the degree of improvement.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 14 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Hokkaido Region		Japan
2		Kanto Region		Japan
3		Kinki Region		Japan
4		Kyushu Region		Japan

Sponsors and Collaborators

• Otsuka Pharmaceutical Co., Ltd.

Investigators

• Study Director: Hiroaki Ono, Mr, Otsuka Pharmaceutical Co., Ltd.

Study Documents (Full-Text)

• Study Protocol - Nov 14, 2016
• Statistical Analysis Plan - Aug 9, 2017

More Information

Publications

None provided.

• Responsible Party: Otsuka Pharmaceutical Co., Ltd.
• ClinicalTrials.gov Identifier: NCT03018691
• Other Study ID Numbers: 271-102-00002; JapicCTI-173484
• First Posted: Jan 12, 2017
• Last Update Posted: Jul 23, 2020
• Last Verified: Jun 1, 2020

• Additional relevant MeSH terms: Dermatitis, Atopic; Dermatitis; Eczema

Study Results

Participant Flow

Arm/Group Title	0.3% OPA-15406 Ointments	1% OPA-15406 Ointments	Placebo Ointments
Arm/Group Description	Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily. OPA-15406	Subjects were treated with assigned 1% OPA-15406 ointment twice daily. OPA-15406	Subjects were treated with assigned 0% OPA-15406 ointment twice daily. Placebos
Period Title: Overall Study
STARTED	24	25	24
COMPLETED	22	24	17
NOT COMPLETED	2	1	7

Baseline Characteristics

Arm/Group Title	0.3% OPA-15406 Ointments	1% OPA-15406 Ointments	Placebo Ointments	Total
Arm/Group Description	Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily. OPA-15406	Subjects were treated with assigned 1% OPA-15406 ointment twice daily. OPA-15406	Subjects were treated with assigned 0% OPA-15406 ointment twice daily. Placebos	Total of all reporting groups
Overall Participants	24	25	24	73
Age (Count of Participants)
<=18 years	24 100%	25 100%	24 100%	73 100%
Between 18 and 65 years	0 0%	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	8.5 (3.8)	7.9 (3.5)	8.5 (3.1)	8.3 (3.4)
Sex: Female, Male (Count of Participants)
Female	6 25%	10 40%	5 20.8%	21 28.8%
Male	18 75%	15 60%	19 79.2%	52 71.2%
Race/Ethnicity, Customized (participants) [Number]
Japanese Subjects	24 100%	25 100%	24 100%	73 100%
Region of Enrollment (Count of Participants)
Japan	24 100%	25 100%	24 100%	73 100%

Outcome Measures

1. Primary Outcome

Title	The Number of Subjects Experiencing AEs
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	0.3% OPA-15406 Ointments	1% OPA-15406 Ointments	Placebo Ointments
Arm/Group Description	Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily. OPA-15406	Subjects were treated with assigned 1% OPA-15406 ointment twice daily. OPA-15406	Subjects were treated with assigned 0% OPA-15406 ointment twice daily. Placebos
Measure Participants	24	25	24
Number [participants]	11 45.8%	14 56%	12 50%

2. Secondary Outcome

Title	Responder Rate of Investigator's Global Assessment(IGA) of Disease Severity at Week4
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	0.3% OPA-15406 Ointments	1% OPA-15406 Ointments	Placebo Ointments
Arm/Group Description	Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily. OPA-15406	Subjects were treated with assigned 1% OPA-15406 ointment twice daily. OPA-15406	Subjects were treated with assigned 0% OPA-15406 ointment twice daily. Placebos
Measure Participants	24	25	24
Number (95% Confidence Interval) [Percentage of participants]	37.50 156.3%	40.00 160%	8.33 34.7%

3. Secondary Outcome

Title	Change From Baseline in Eczema Area and Severity Index (EASI) Score
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	0.3% OPA-15406 Ointments	1% OPA-15406 Ointments	Placebo Ointments
Arm/Group Description	Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily. OPA-15406	Subjects were treated with assigned 1% OPA-15406 ointment twice daily. OPA-15406	Subjects were treated with assigned 0% OPA-15406 ointment twice daily. Placebos
Measure Participants	23	24	18
Mean (Standard Error) [score on a scale]	-5.33 (1.28)	-5.52 (1.26)	0.56 (1.36)

4. Secondary Outcome

Title	Change From Baseline in Visual Analogue Scale(VAS) for Pruritus Score
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	0.3% OPA-15406 Ointments	1% OPA-15406 Ointments	Placebo Ointments
Arm/Group Description	Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily. OPA-15406	Subjects were treated with assigned 1% OPA-15406 ointment twice daily. OPA-15406	Subjects were treated with assigned 0% OPA-15406 ointment twice daily. Placebos
Measure Participants	16	16	14
Mean (Standard Error) [mm]	-18.00 (7.27)	-17.21 (7.29)	8.19 (7.58)

5. Secondary Outcome

Title	Change From Baseline in Verbal Rating Scale(VRS) for Pruritus Score
Description	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 : Mild : Moderate : 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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	0.3% OPA-15406 Ointments	1% OPA-15406 Ointments	Placebo Ointments
Arm/Group Description	Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily. OPA-15406	Subjects were treated with assigned 1% OPA-15406 ointment twice daily. OPA-15406	Subjects were treated with assigned 0% OPA-15406 ointment twice daily. Placebos
Measure Participants	15	17	14
Mean (Standard Error) [score on a scale]	-0.83 (0.18)	-0.73 (0.19)	0.30 (0.11)

6. Secondary Outcome

Title	Change From Baseline in Patient-Oriented Eczema Measure(POEM) Score
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	0.3% OPA-15406 Ointments	1% OPA-15406 Ointments	Placebo Ointments
Arm/Group Description	Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily. OPA-15406	Subjects were treated with assigned 1% OPA-15406 ointment twice daily. OPA-15406	Subjects were treated with assigned 0% OPA-15406 ointment twice daily. Placebos
Measure Participants	23	24	18
Mean (Standard Error) [score on a scale]	-4.33 (1.16)	-4.37 (1.14)	2.26 (1.24)

7. Secondary Outcome

Title	Change From Baseline in Percentage Affected Body Surface Area
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	0.3% OPA-15406 Ointments	1% OPA-15406 Ointments	Placebo Ointments
Arm/Group Description	Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily. OPA-15406	Subjects were treated with assigned 1% OPA-15406 ointment twice daily. OPA-15406	Subjects were treated with assigned 0% OPA-15406 ointment twice daily. Placebos
Measure Participants	23	24	18
Mean (Standard Error) [percentage of Affected Body Surface Area]	-6.06 (2.36)	-8.21 (2.32)	1.78 (2.53)

8. Secondary Outcome

Title	Mean (SD) OPA-15406 Plasma Trough Concentrations at week1
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	0.3% OPA-15406	1% OPA-15406
Arm/Group Description	Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily.	Subjects were treated with assigned 1% OPA-15406 ointment twice daily.
Measure Participants	18	21
Mean (Standard Deviation) [ng/mL]	0.842 (0.577)	2.90 (2.74)

9. Secondary Outcome

Title	Mean (SD) OPA-15406 Plasma Trough Concentrations at week4
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	0.3% OPA-15406	1% OPA-15406
Arm/Group Description	Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily.	Subjects were treated with assigned 1% OPA-15406 ointment twice daily.
Measure Participants	20	22
Mean (Standard Deviation) [ng/mL]	0.946 (1.16)	2.21 (1.81)

10. Secondary Outcome

Title	Mean (SD) Normalized OPA-15406 Plasma Trough Concentrations by Dose Derived From %BSA at week1
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	0.3% OPA-15406	1% OPA-15406
Arm/Group Description	Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily.	Subjects were treated with assigned 1% OPA-15406 ointment twice daily.
Measure Participants	18	21
Mean (Standard Deviation) [ng/mL/mg]	0.196 (0.201)	0.210 (0.174)

11. Secondary Outcome

Title	Mean (SD) Normalized OPA-15406 Plasma Trough Concentrations by Dose Derived From %BSA at week4
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	0.3% OPA-15406	1% OPA-15406
Arm/Group Description	Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily.	Subjects were treated with assigned 1% OPA-15406 ointment twice daily.
Measure Participants	20	22
Mean (Standard Deviation) [ng/mL/mg]	0.150 (0.111)	0.166 (0.148)

Adverse Events

Time Frame	Treatment period
Arm/Group Title	0.3% OPA-15406 Ointments		1% OPA-15406 Ointments		Placebo Ointments
Arm/Group Description	Subjects were treated with assigned 0.3% OPA-15406 ointment twice daily. OPA-15406		Subjects were treated with assigned 1% OPA-15406 ointment twice daily. OPA-15406		Subjects were treated with assigned 0% OPA-15406 ointment twice daily. Placebos
All Cause Mortality
	0.3% OPA-15406 Ointments		1% OPA-15406 Ointments		Placebo Ointments
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/25 (0%)		0/24 (0%)
Serious Adverse Events
	0.3% OPA-15406 Ointments		1% OPA-15406 Ointments		Placebo Ointments
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/25 (0%)		0/24 (0%)
Other (Not Including Serious) Adverse Events
	0.3% OPA-15406 Ointments		1% OPA-15406 Ointments		Placebo Ointments
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/24 (25%)		8/25 (32%)		8/24 (33.3%)
Infections and infestations
Influenza	2/24 (8.3%)		1/25 (4%)		0/24 (0%)
Viral upper respiratory tract infection	1/24 (4.2%)		0/25 (0%)		2/24 (8.3%)
Investigations
Blood alkaline phosphatase increased	0/24 (0%)		2/25 (8%)		0/24 (0%)
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract inflammation	1/24 (4.2%)		6/25 (24%)		2/24 (8.3%)
Skin and subcutaneous tissue disorders
Dermatitis atopic	2/24 (8.3%)		1/25 (4%)		4/24 (16.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.