Trial Outcomes & Findings for Study of OPA-15406 Ointment in Patients With Atopic Dermatitis (NCT NCT02914548)

NCT ID: NCT02914548

Last Updated: 2020-07-23

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 200 participants
• Primary outcome timeframe: At Week 4
• Results posted on: 2020-07-23

Participant Flow

Participant milestones

Measure	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.	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.	Placebo Subjects were treated with assigned 0% OPA-15406 ointment twice daily. Placebo: Subjects were treated with assigned 0% OPA-15406 ointment twice daily.
Overall Study STARTED	67	67	66
Overall Study COMPLETED	46	53	46
Overall Study NOT COMPLETED	21	14	20

Reasons for withdrawal

Measure	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.	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.	Placebo Subjects were treated with assigned 0% OPA-15406 ointment twice daily. Placebo: Subjects were treated with assigned 0% OPA-15406 ointment twice daily.
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
Overall Study >40% of body surface area	0	1	1

Baseline Characteristics

Study of OPA-15406 Ointment in Patients With Atopic Dermatitis

Baseline characteristics by cohort

Measure	0.3% OPA-15406 n=67 Participants 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.	1% OPA-15406 n=67 Participants 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.	Placebo n=66 Participants Subjects were treated with assigned 0% OPA-15406 ointment twice daily. Placebo: Subjects were treated with assigned 0% OPA-15406 ointment twice daily.	Total n=200 Participants Total of all reporting groups
Age, Categorical <=18 years	2 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	65 Participants n=5 Participants	67 Participants n=7 Participants	65 Participants n=5 Participants	197 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Continuous	30.2 years STANDARD_DEVIATION 9.0 • n=5 Participants	31.0 years STANDARD_DEVIATION 10.8 • n=7 Participants	31.6 years STANDARD_DEVIATION 10.0 • n=5 Participants	30.9 years STANDARD_DEVIATION 9.9 • n=4 Participants
Sex: Female, Male Female	22 Participants n=5 Participants	25 Participants n=7 Participants	23 Participants n=5 Participants	70 Participants n=4 Participants
Sex: Female, Male Male	45 Participants n=5 Participants	42 Participants n=7 Participants	43 Participants n=5 Participants	130 Participants n=4 Participants
Race/Ethnicity, Customized Japanese	67 Participants n=5 Participants	67 Participants n=7 Participants	66 Participants n=5 Participants	200 Participants n=4 Participants
Region of Enrollment Japan	67 Participants n=5 Participants	67 Participants n=7 Participants	66 Participants n=5 Participants	200 Participants n=4 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	0.3% OPA-15406 n=67 Participants 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.	1% OPA-15406 n=67 Participants 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.	Placebo n=66 Participants Subjects were treated with assigned 0% OPA-15406 ointment twice daily. Placebo: Subjects were treated with assigned 0% OPA-15406 ointment twice daily.
Responder Rate of Investigator's Global Assessment(IGA) of Disease Severity at Week4	14.93 percentage of participants Interval 7.4 to 25.74	22.39 percentage of participants Interval 13.11 to 34.22	9.09 percentage of participants Interval 3.41 to 18.74

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	0.3% OPA-15406 n=57 Participants 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.	1% OPA-15406 n=58 Participants 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.	Placebo n=53 Participants Subjects were treated with assigned 0% OPA-15406 ointment twice daily. Placebo: Subjects were treated with assigned 0% OPA-15406 ointment twice daily.
Change From Baseline in Eczema Area and Severity Index (EASI) Score	-2.32 score on a scale Standard Error 0.75	-3.16 score on a scale Standard Error 0.75	-0.15 score on a scale Standard Error 0.77

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	0.3% OPA-15406 n=57 Participants 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.	1% OPA-15406 n=58 Participants 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.	Placebo n=53 Participants Subjects were treated with assigned 0% OPA-15406 ointment twice daily. Placebo: Subjects were treated with assigned 0% OPA-15406 ointment twice daily.
Change From Baseline in Visual Analogue Scale(VAS) for Pruritus Score	-6.76 mm Standard Error 3.31	-6.28 mm Standard Error 3.32	0.90 mm Standard Error 3.24

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	0.3% OPA-15406 n=55 Participants 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.	1% OPA-15406 n=54 Participants 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.	Placebo n=47 Participants Subjects were treated with assigned 0% OPA-15406 ointment twice daily. Placebo: Subjects were treated with assigned 0% OPA-15406 ointment twice daily.
Change From Baseline in Verbal Rating Scale(VRS) for Pruritus Score	-0.43 score on a scale Standard Error 0.10	-0.49 score on a scale Standard Error 0.10	-0.06 score on a scale Standard Error 0.10

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	0.3% OPA-15406 n=57 Participants 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.	1% OPA-15406 n=58 Participants 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.	Placebo n=53 Participants Subjects were treated with assigned 0% OPA-15406 ointment twice daily. Placebo: Subjects were treated with assigned 0% OPA-15406 ointment twice daily.
Change From Baseline in Patient-Oriented Eczema Measure(POEM) Score	-1.36 score on a scale Standard Error 0.77	-2.90 score on a scale Standard Error 0.76	-0.02 score on a scale Standard Error 0.79

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	0.3% OPA-15406 n=57 Participants 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.	1% OPA-15406 n=58 Participants 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.	Placebo n=53 Participants Subjects were treated with assigned 0% OPA-15406 ointment twice daily. Placebo: Subjects were treated with assigned 0% OPA-15406 ointment twice daily.
Change From Baseline in Percentage Affected Body Surface Area	-3.94 percentage of Affected Body Surface Area Standard Error 1.44	-3.73 percentage of Affected Body Surface Area Standard Error 1.43	-0.32 percentage of Affected Body Surface Area Standard Error 1.48

SECONDARY outcome

Timeframe: Week1, Week4, Week8

Population: All subjects who had received the IMP at least once and whose plasma drug concentration had been measured

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.

Outcome measures

Measure	0.3% OPA-15406 n=64 Participants 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.	1% OPA-15406 n=62 Participants 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.	Placebo Subjects were treated with assigned 0% OPA-15406 ointment twice daily. Placebo: Subjects were treated with assigned 0% OPA-15406 ointment twice daily.
Mean (SD) OPA-15406 Plasma Trough Concentrations Week 1	1.74 ng/mL/mg Standard Deviation 1.87	4.96 ng/mL/mg Standard Deviation 5.04	—
Mean (SD) OPA-15406 Plasma Trough Concentrations Week 4	1.71 ng/mL/mg Standard Deviation 2.50	5.22 ng/mL/mg Standard Deviation 4.70	—
Mean (SD) OPA-15406 Plasma Trough Concentrations Week 8	1.51 ng/mL/mg Standard Deviation 1.77	5.52 ng/mL/mg Standard Deviation 8.28	—

SECONDARY outcome

Timeframe: Week1, Week4, Week8

Population: All subjects who had received the IMP at least once and whose plasma drug concentration had been measured

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.

Outcome measures

Measure	0.3% OPA-15406 n=64 Participants 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.	1% OPA-15406 n=62 Participants 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.	Placebo Subjects were treated with assigned 0% OPA-15406 ointment twice daily. Placebo: Subjects were treated with assigned 0% OPA-15406 ointment twice daily.
Mean (SD) Normalized OPA-15406 Plasma Trough Concentrations by Dose Derived From %BSA Week 1	0.114 ng/mL/mg Standard Deviation 0.0991	0.113 ng/mL/mg Standard Deviation 0.0952	—
Mean (SD) Normalized OPA-15406 Plasma Trough Concentrations by Dose Derived From %BSA Week 4	0.104 ng/mL/mg Standard Deviation 0.119	0.127 ng/mL/mg Standard Deviation 0.119	—
Mean (SD) Normalized OPA-15406 Plasma Trough Concentrations by Dose Derived From %BSA Week 8	0.0910 ng/mL/mg Standard Deviation 0.103	0.137 ng/mL/mg Standard Deviation 0.242	—

SECONDARY outcome

Timeframe: Day 1 and Week 4

Population: All subjects who had received the IMP at least once and whose plasma drug concentration had been measured

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.

Outcome measures

Measure	0.3% OPA-15406 n=11 Participants 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.	1% OPA-15406 n=9 Participants 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.	Placebo Subjects were treated with assigned 0% OPA-15406 ointment twice daily. Placebo: Subjects were treated with assigned 0% OPA-15406 ointment twice daily.
OPA-15406 Plasma PK Parameters, Cmax Day 1	4.01 ng/mL Standard Deviation 5.90	7.27 ng/mL Standard Deviation 6.42	—
OPA-15406 Plasma PK Parameters, Cmax Week 4	2.07 ng/mL Standard Deviation 1.47	10.4 ng/mL Standard Deviation 3.68	—

SECONDARY outcome

Timeframe: Day 1 and Week 4

Population: All subjects who had received the IMP at least once and whose plasma drug concentration had been measured

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.

Outcome measures

Measure	0.3% OPA-15406 n=11 Participants 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.	1% OPA-15406 n=9 Participants 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.	Placebo Subjects were treated with assigned 0% OPA-15406 ointment twice daily. Placebo: Subjects were treated with assigned 0% OPA-15406 ointment twice daily.
OPA-15406 Plasma PK Parameters, AUC8h Day 1	22.0 ng・h/mL Standard Deviation 34.7	41.6 ng・h/mL Standard Deviation 37.6	—
OPA-15406 Plasma PK Parameters, AUC8h Week 4	11.6 ng・h/mL Standard Deviation 7.23	65.2 ng・h/mL Standard Deviation 26.8	—

Adverse Events

0.3% OPA-15406

Serious events: 0 serious events

Other events: 22 other events

Deaths: 0 deaths

1% OPA-15406

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	0.3% OPA-15406 n=67 participants at risk 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.	1% OPA-15406 n=67 participants at risk 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.	Placebo n=66 participants at risk Subjects were treated with assigned 0% OPA-15406 ointment twice daily. Placebo: Subjects were treated with assigned 0% OPA-15406 ointment twice daily.
Infections and infestations Viral upper respiratory tract infection	10.4% 7/67 • Treatment period (8 weeks)	6.0% 4/67 • Treatment period (8 weeks)	10.6% 7/66 • Treatment period (8 weeks)
Skin and subcutaneous tissue disorders Dermatitis atopic	16.4% 11/67 • Treatment period (8 weeks)	9.0% 6/67 • Treatment period (8 weeks)	18.2% 12/66 • Treatment period (8 weeks)
Skin and subcutaneous tissue disorders Pruritus	7.5% 5/67 • Treatment period (8 weeks)	1.5% 1/67 • Treatment period (8 weeks)	6.1% 4/66 • Treatment period (8 weeks)

Additional Information

Director of Clinical Trials

Otsuka Pharmaceutical Co., LTD.

Phone: +81-3-6361-7366

Email: CL_OPCJ_RDA_Team@otsuka.jp

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place