Trial Outcomes & Findings for Safety, Tolerability, and PK of AN2728 in Adolescents With Atopic Dermatitis (NCT NCT01652885)

NCT ID: NCT01652885

Last Updated: 2017-04-24

Results Overview

Local tolerability symptoms, burning or stinging, were classified according to severity as: 1) none = no stinging or burning, 2) mild = slight warm, tingling sensation; not really troublesome, 3) moderate = definite warm; tingling or stinging sensation; troublesome and 4) severe = hot, tingling or stinging sensation that caused definite discomfort. Number of participants with local tolerability symptoms according to severity on Baseline were reported in this outcome measure.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 23 participants
• Primary outcome timeframe: Baseline
• Results posted on: 2017-04-24

Participant Flow

Participant milestones

Measure	AN2728 Topical Ointment 2 Percent AN2728 ointment 2 percent was applied topically to treatment-targeted lesions in participant with mild to moderate atopic dermatitis (AD), twice daily for up to 28 days, except on Day 1 and 8 applied once daily. Lesions were identified at Baseline (Day 1) by investigator.
Overall Study STARTED	23
Overall Study COMPLETED	22
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure	AN2728 Topical Ointment 2 Percent AN2728 ointment 2 percent was applied topically to treatment-targeted lesions in participant with mild to moderate atopic dermatitis (AD), twice daily for up to 28 days, except on Day 1 and 8 applied once daily. Lesions were identified at Baseline (Day 1) by investigator.
Overall Study Adverse Event	1

Baseline Characteristics

Safety, Tolerability, and PK of AN2728 in Adolescents With Atopic Dermatitis

Baseline characteristics by cohort

Measure	AN2728 Topical Ointment 2 Percent n=23 Participants AN2728 ointment 2 percent was applied topically to treatment-targeted lesions in participant with mild to moderate AD, twice daily for up to 28 days, except on Day 1 and 8 applied once daily. Lesions were identified at Baseline (Day 1) by investigator.
Age, Continuous	15.0 years STANDARD_DEVIATION 1.55 • n=93 Participants
Sex: Female, Male Female	19 Participants n=93 Participants
Sex: Female, Male Male	4 Participants n=93 Participants

PRIMARY outcome

Timeframe: Baseline

Population: Safety population included all participants who were enrolled and had received any amount of the study drug.

Local tolerability symptoms, burning or stinging, were classified according to severity as: 1) none = no stinging or burning, 2) mild = slight warm, tingling sensation; not really troublesome, 3) moderate = definite warm; tingling or stinging sensation; troublesome and 4) severe = hot, tingling or stinging sensation that caused definite discomfort. Number of participants with local tolerability symptoms according to severity on Baseline were reported in this outcome measure.

Outcome measures

Measure	AN2728 Topical Ointment 2 Percent n=23 Participants AN2728 ointment 2 percent was applied topically to treatment-targeted lesions in participant with mild to moderate AD, twice daily for up to 28 days, except on Day 1 and 8 applied once daily. Lesions were identified at Baseline (Day 1) by investigator.
Number of Participants With Local Tolerability Symptoms According to Severity on Baseline None	10 participants
Number of Participants With Local Tolerability Symptoms According to Severity on Baseline Mild	7 participants
Number of Participants With Local Tolerability Symptoms According to Severity on Baseline Moderate	6 participants
Number of Participants With Local Tolerability Symptoms According to Severity on Baseline Severe	0 participants

PRIMARY outcome

Timeframe: Day 2

Population: Safety population included all participants who were enrolled and had received any amount of the study drug.

Local tolerability symptoms, burning or stinging, were classified according to severity as: 1) none = no stinging or burning, 2) mild = slight warm, tingling sensation; not really troublesome, 3) moderate = definite warm; tingling or stinging sensation; troublesome and 4) severe = hot, tingling or stinging sensation that caused definite discomfort. Number of participants with local tolerability symptoms according to severity on Day 2 were reported in this outcome measure.

Outcome measures

Measure	AN2728 Topical Ointment 2 Percent n=23 Participants AN2728 ointment 2 percent was applied topically to treatment-targeted lesions in participant with mild to moderate AD, twice daily for up to 28 days, except on Day 1 and 8 applied once daily. Lesions were identified at Baseline (Day 1) by investigator.
Number of Participants With Local Tolerability Symptoms According to Severity on Day 2 None	17 participants
Number of Participants With Local Tolerability Symptoms According to Severity on Day 2 Mild	5 participants
Number of Participants With Local Tolerability Symptoms According to Severity on Day 2 Moderate	1 participants
Number of Participants With Local Tolerability Symptoms According to Severity on Day 2 Severe	0 participants

PRIMARY outcome

Timeframe: Day 4

Population: Safety population included all participants who were enrolled and had received any amount of the study drug.

Local tolerability symptoms, burning or stinging, were classified according to severity as: 1) none = no stinging or burning, 2) mild = slight warm, tingling sensation; not really troublesome, 3) moderate = definite warm; tingling or stinging sensation; troublesome and 4) severe = hot, tingling or stinging sensation that caused definite discomfort. Number of participants with local tolerability symptoms according to severity on Day 4 were reported in this outcome measure.

Outcome measures

Measure	AN2728 Topical Ointment 2 Percent n=23 Participants AN2728 ointment 2 percent was applied topically to treatment-targeted lesions in participant with mild to moderate AD, twice daily for up to 28 days, except on Day 1 and 8 applied once daily. Lesions were identified at Baseline (Day 1) by investigator.
Number of Participants With Local Tolerability Symptoms According to Severity on Day 4 None	18 participants
Number of Participants With Local Tolerability Symptoms According to Severity on Day 4 Mild	3 participants
Number of Participants With Local Tolerability Symptoms According to Severity on Day 4 Moderate	2 participants
Number of Participants With Local Tolerability Symptoms According to Severity on Day 4 Severe	0 participants

PRIMARY outcome

Timeframe: Day 6

Population: Safety population included all participants who were enrolled and had received any amount of the study drug.

Local tolerability symptoms, burning or stinging, were classified according to severity as: 1) none = no stinging or burning, 2) mild = slight warm, tingling sensation; not really troublesome, 3) moderate = definite warm; tingling or stinging sensation; troublesome and 4) severe = hot, tingling or stinging sensation that caused definite discomfort. Number of participants with local tolerability symptoms according to severity on Day 6 were reported in this outcome measure.

Outcome measures

Measure	AN2728 Topical Ointment 2 Percent n=23 Participants AN2728 ointment 2 percent was applied topically to treatment-targeted lesions in participant with mild to moderate AD, twice daily for up to 28 days, except on Day 1 and 8 applied once daily. Lesions were identified at Baseline (Day 1) by investigator.
Number of Participants With Local Tolerability Symptoms According to Severity on Day 6 None	18 participants
Number of Participants With Local Tolerability Symptoms According to Severity on Day 6 Mild	4 participants
Number of Participants With Local Tolerability Symptoms According to Severity on Day 6 Moderate	1 participants
Number of Participants With Local Tolerability Symptoms According to Severity on Day 6 Severe	0 participants

PRIMARY outcome

Timeframe: Day 8

Population: Safety population included all participants who were enrolled and had received any amount of the study drug.

Local tolerability symptoms, burning or stinging, were classified according to severity as: 1) none = no stinging or burning, 2) mild = slight warm, tingling sensation; not really troublesome, 3) moderate = definite warm; tingling or stinging sensation; troublesome and 4) severe = hot, tingling or stinging sensation that caused definite discomfort. Number of participants with local tolerability symptoms according to severity on Day 8 were reported in this outcome measure.

Outcome measures

Measure	AN2728 Topical Ointment 2 Percent n=23 Participants AN2728 ointment 2 percent was applied topically to treatment-targeted lesions in participant with mild to moderate AD, twice daily for up to 28 days, except on Day 1 and 8 applied once daily. Lesions were identified at Baseline (Day 1) by investigator.
Number of Participants With Local Tolerability Symptoms According to Severity on Day 8 None	20 participants
Number of Participants With Local Tolerability Symptoms According to Severity on Day 8 Mild	3 participants
Number of Participants With Local Tolerability Symptoms According to Severity on Day 8 Moderate	0 participants
Number of Participants With Local Tolerability Symptoms According to Severity on Day 8 Severe	0 participants

PRIMARY outcome

Timeframe: Day 9

Population: Safety population included all participants who were enrolled and had received any amount of the study drug.

Local tolerability symptoms, burning or stinging, were classified according to severity as: 1) none = no stinging or burning, 2) mild = slight warm, tingling sensation; not really troublesome, 3) moderate = definite warm; tingling or stinging sensation; troublesome and 4) severe = hot, tingling or stinging sensation that caused definite discomfort. Number of participants with local tolerability symptoms according to severity on Day 9 were reported in this outcome measure.

Outcome measures

Measure	AN2728 Topical Ointment 2 Percent n=23 Participants AN2728 ointment 2 percent was applied topically to treatment-targeted lesions in participant with mild to moderate AD, twice daily for up to 28 days, except on Day 1 and 8 applied once daily. Lesions were identified at Baseline (Day 1) by investigator.
Number of Participants With Local Tolerability Symptoms According to Severity on Day 9 None	18 participants
Number of Participants With Local Tolerability Symptoms According to Severity on Day 9 Mild	4 participants
Number of Participants With Local Tolerability Symptoms According to Severity on Day 9 Moderate	1 participants
Number of Participants With Local Tolerability Symptoms According to Severity on Day 9 Severe	0 participants

PRIMARY outcome

Timeframe: Day 15

Population: Safety population included all participants who were enrolled and had received any amount of the study drug.

Local tolerability symptoms, burning or stinging, were classified according to severity as: 1) none = no stinging or burning, 2) mild = slight warm, tingling sensation; not really troublesome, 3) moderate = definite warm; tingling or stinging sensation; troublesome and 4) severe = hot, tingling or stinging sensation that caused definite discomfort. Number of participants with local tolerability symptoms according to severity on Day 15 were reported in this outcome measure.

Outcome measures

Measure	AN2728 Topical Ointment 2 Percent n=23 Participants AN2728 ointment 2 percent was applied topically to treatment-targeted lesions in participant with mild to moderate AD, twice daily for up to 28 days, except on Day 1 and 8 applied once daily. Lesions were identified at Baseline (Day 1) by investigator.
Number of Participants With Local Tolerability Symptoms According to Severity on Day 15 None	19 participants
Number of Participants With Local Tolerability Symptoms According to Severity on Day 15 Mild	4 participants
Number of Participants With Local Tolerability Symptoms According to Severity on Day 15 Moderate	0 participants
Number of Participants With Local Tolerability Symptoms According to Severity on Day 15 Severe	0 participants

PRIMARY outcome

Timeframe: Day 22

Population: Safety population included all participants who were enrolled and had received any amount of the study drug.

Local tolerability symptoms, burning or stinging, were classified according to severity as: 1) none = no stinging or burning, 2) mild = slight warm, tingling sensation; not really troublesome, 3) moderate = definite warm; tingling or stinging sensation; troublesome and 4) severe = hot, tingling or stinging sensation that caused definite discomfort. Number of participants with local tolerability symptoms according to severity on Day 22 were reported in this outcome measure.

Outcome measures

Measure	AN2728 Topical Ointment 2 Percent n=23 Participants AN2728 ointment 2 percent was applied topically to treatment-targeted lesions in participant with mild to moderate AD, twice daily for up to 28 days, except on Day 1 and 8 applied once daily. Lesions were identified at Baseline (Day 1) by investigator.
Number of Participants With Local Tolerability Symptoms According to Severity on Day 22 None	21 participants
Number of Participants With Local Tolerability Symptoms According to Severity on Day 22 Mild	2 participants
Number of Participants With Local Tolerability Symptoms According to Severity on Day 22 Moderate	0 participants
Number of Participants With Local Tolerability Symptoms According to Severity on Day 22 Severe	0 participants

PRIMARY outcome

Timeframe: Day 29

Population: Safety population included all participants who were enrolled and had received any amount of the study drug.

Local tolerability symptoms, burning or stinging, were classified according to severity as: 1) none = no stinging or burning, 2) mild = slight warm, tingling sensation; not really troublesome, 3) moderate = definite warm; tingling or stinging sensation; troublesome and 4) severe = hot, tingling or stinging sensation that caused definite discomfort. Number of participants with local tolerability symptoms according to severity on Day 29 were reported in this outcome measure.

Outcome measures

Measure	AN2728 Topical Ointment 2 Percent n=23 Participants AN2728 ointment 2 percent was applied topically to treatment-targeted lesions in participant with mild to moderate AD, twice daily for up to 28 days, except on Day 1 and 8 applied once daily. Lesions were identified at Baseline (Day 1) by investigator.
Number of Participants With Local Tolerability Symptoms According to Severity on Day 29 None	20 participants
Number of Participants With Local Tolerability Symptoms According to Severity on Day 29 Mild	2 participants
Number of Participants With Local Tolerability Symptoms According to Severity on Day 29 Moderate	0 participants
Number of Participants With Local Tolerability Symptoms According to Severity on Day 29 Severe	1 participants

PRIMARY outcome

Timeframe: Baseline (Day 1) up to Day 29

Population: Safety population included all participants who were enrolled and had received any amount of the study drug.

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death;initial or prolonged inpatient hospitalization; life- threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to Day 29 that were absent before treatment or that worsened relative to pretreatment state.

Outcome measures

Measure	AN2728 Topical Ointment 2 Percent n=23 Participants AN2728 ointment 2 percent was applied topically to treatment-targeted lesions in participant with mild to moderate AD, twice daily for up to 28 days, except on Day 1 and 8 applied once daily. Lesions were identified at Baseline (Day 1) by investigator.
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	10 participants
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	0 participants

PRIMARY outcome

Timeframe: Baseline (Day 1) up to Day 29

Population: Safety population included all participants who were enrolled and had received any amount of the study drug.

Vital signs (temperature, respiratory rate, pulse, systolic and diastolic blood pressure) were obtained with participant in the seated position, after having sat calmly for at least 5 minutes. Clinical significance of vital signs was determined at the investigator's discretion.

Outcome measures

Measure	AN2728 Topical Ointment 2 Percent n=23 Participants AN2728 ointment 2 percent was applied topically to treatment-targeted lesions in participant with mild to moderate AD, twice daily for up to 28 days, except on Day 1 and 8 applied once daily. Lesions were identified at Baseline (Day 1) by investigator.
Number of Participants With Clinically Significant Vital Signs Abnormalities	0 participants

PRIMARY outcome

Timeframe: Baseline (Day 1) up to Day 29

Population: Safety population included all participants who were enrolled and had received any amount of the study drug.

Laboratory parameters included: hematology (hemoglobin, hematocrit, red blood cell, platelet and white blood cell count, neutrophils, eosinophils, monocytes, basophils and lymphocytes), chemistry (blood urea nitrogen, creatinine, sodium, potassium, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, albumin, total protein and serum pregnancy test [for all female participants]) and urine (urine pregnancy test [for all female participants]). Clinical significance of laboratory parameters was determined at the investigator's discretion.

Outcome measures

Measure	AN2728 Topical Ointment 2 Percent n=23 Participants AN2728 ointment 2 percent was applied topically to treatment-targeted lesions in participant with mild to moderate AD, twice daily for up to 28 days, except on Day 1 and 8 applied once daily. Lesions were identified at Baseline (Day 1) by investigator.
Number of Participants With Clinically Significant Laboratory Test Abnormalities	0 participants

PRIMARY outcome

Timeframe: Pre-dose (0 hour), 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 1

Population: Pharmacokinetic (PK) population included participants from the safety population who had completed any portion of the PK day procedures and evaluations.

Maximum observed plasma concentration of AN2728 and its two identified oxidative metabolites, AN7602 and AN8323 on Day 1 was reported in the outcome measure.

Outcome measures

Measure	AN2728 Topical Ointment 2 Percent n=23 Participants AN2728 ointment 2 percent was applied topically to treatment-targeted lesions in participant with mild to moderate AD, twice daily for up to 28 days, except on Day 1 and 8 applied once daily. Lesions were identified at Baseline (Day 1) by investigator.
Maximum Observed Plasma Concentration (Cmax) of AN2728 and Major Oxidative Metabolites of AN2728: Day 1 AN2728	105 nanogram per milliliter Standard Deviation 160
Maximum Observed Plasma Concentration (Cmax) of AN2728 and Major Oxidative Metabolites of AN2728: Day 1 AN7602	28.2 nanogram per milliliter Standard Deviation 37.0
Maximum Observed Plasma Concentration (Cmax) of AN2728 and Major Oxidative Metabolites of AN2728: Day 1 AN8323	998 nanogram per milliliter Standard Deviation 1220

PRIMARY outcome

Timeframe: Pre-dose (0 hour), 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 1

Population: PK population included participants from the safety population who had completed any portion of the PK day procedures and evaluations.

Time to reach maximum plasma concentration of AN2728 and its two identified oxidative metabolites, AN7602 and AN8323 on Day 1 was reported in the outcome measure.

Outcome measures

Measure	AN2728 Topical Ointment 2 Percent n=23 Participants AN2728 ointment 2 percent was applied topically to treatment-targeted lesions in participant with mild to moderate AD, twice daily for up to 28 days, except on Day 1 and 8 applied once daily. Lesions were identified at Baseline (Day 1) by investigator.
Time to Reach Maximum Observed Plasma Concentration (Tmax) of AN2728 and Major Oxidative Metabolites of AN2728: Day 1 AN2728	2.37 hour Interval 1.0 to 24.0
Time to Reach Maximum Observed Plasma Concentration (Tmax) of AN2728 and Major Oxidative Metabolites of AN2728: Day 1 AN7602	2.08 hour Interval 1.0 to 24.0
Time to Reach Maximum Observed Plasma Concentration (Tmax) of AN2728 and Major Oxidative Metabolites of AN2728: Day 1 AN8323	6.25 hour Interval 3.95 to 25.0

PRIMARY outcome

Timeframe: Pre-dose (0 hour), 1, 2, 4, 6, 8 and 12 hours post-dose on Day 1

Population: PK population included participants from the safety population who had completed any portion of the PK day procedures and evaluations.

Area under the concentration-time curve from hour zero to the 12 hour post-dose measurable concentration, of AN2728 and its two identified oxidative metabolites, AN7602 and AN8323 on Day 1 was reported in the outcome measure.

Outcome measures

Measure	AN2728 Topical Ointment 2 Percent n=23 Participants AN2728 ointment 2 percent was applied topically to treatment-targeted lesions in participant with mild to moderate AD, twice daily for up to 28 days, except on Day 1 and 8 applied once daily. Lesions were identified at Baseline (Day 1) by investigator.
Area Under the Concentration-Time Curve From Hour Zero To the 12 Hour Post-Dose Measurable Concentration of AN2728 and Major Oxidative Metabolites of AN2728: Day 1 AN2728	448 nanogram*hour per milliliter Standard Deviation 527
Area Under the Concentration-Time Curve From Hour Zero To the 12 Hour Post-Dose Measurable Concentration of AN2728 and Major Oxidative Metabolites of AN2728: Day 1 AN7602	142 nanogram*hour per milliliter Standard Deviation 172
Area Under the Concentration-Time Curve From Hour Zero To the 12 Hour Post-Dose Measurable Concentration of AN2728 and Major Oxidative Metabolites of AN2728: Day 1 AN8323	8900 nanogram*hour per milliliter Standard Deviation 11600

PRIMARY outcome

Timeframe: Pre-dose (0 hour), 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 1

Population: PK population included participants from the safety population who had completed any portion of the PK day procedures and evaluations. Here, "n" signifies number of participants who were evaluable for specific categories.

Apparent terminal half-life, of AN2728 and its two identified oxidative metabolites, AN7602 and AN8323 on Day 1 was reported in the outcome measure. Apparent terminal half-life is the time measured for the drug concentration to decrease by one-half in plasma.

Outcome measures

Measure	AN2728 Topical Ointment 2 Percent n=23 Participants AN2728 ointment 2 percent was applied topically to treatment-targeted lesions in participant with mild to moderate AD, twice daily for up to 28 days, except on Day 1 and 8 applied once daily. Lesions were identified at Baseline (Day 1) by investigator.
Apparent Terminal Half-Life of AN2728 and Major Oxidative Metabolites of AN2728: Day 1 AN2728 (n =16)	7.17 hour Standard Deviation 2.30
Apparent Terminal Half-Life of AN2728 and Major Oxidative Metabolites of AN2728: Day 1 AN7602 (n =18)	8.19 hour Standard Deviation 5.13
Apparent Terminal Half-Life of AN2728 and Major Oxidative Metabolites of AN2728: Day 1 AN8323 (n =6)	17.7 hour Standard Deviation 1.63

PRIMARY outcome

Timeframe: Pre-dose (0 hour), 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 8

Population: PK population included participants from the safety population who had completed any portion of the PK day procedures and evaluations. Here, "Number of Participants Analyzed" (N) signifies evaluable participants for this outcome measure.

Maximum observed plasma concentration of AN2728 and its two identified oxidative metabolites, AN7602 and AN8323 on Day 8 was reported in the outcome measure.

Outcome measures

Measure	AN2728 Topical Ointment 2 Percent n=22 Participants AN2728 ointment 2 percent was applied topically to treatment-targeted lesions in participant with mild to moderate AD, twice daily for up to 28 days, except on Day 1 and 8 applied once daily. Lesions were identified at Baseline (Day 1) by investigator.
Maximum Observed Plasma Concentration (Cmax) of AN2728 and Major Oxidative Metabolites of AN2728: Day 8 AN2728	94.6 nanogram per milliliter Standard Deviation 189
Maximum Observed Plasma Concentration (Cmax) of AN2728 and Major Oxidative Metabolites of AN2728: Day 8 AN7602	26.3 nanogram per milliliter Standard Deviation 43.9
Maximum Observed Plasma Concentration (Cmax) of AN2728 and Major Oxidative Metabolites of AN2728: Day 8 AN8323	1850 nanogram per milliliter Standard Deviation 1830

PRIMARY outcome

Timeframe: Pre-dose (0 hour), 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 8

Population: PK population included participants from the safety population who had completed any portion of the PK day procedures and evaluations. Here, 'N' signifies evaluable participants for this outcome measure.

Time to reach maximum plasma concentration of AN2728 and its two identified oxidative metabolites, AN7602 and AN8323 on Day 8 was reported in the outcome measure.

Outcome measures

Measure	AN2728 Topical Ointment 2 Percent n=22 Participants AN2728 ointment 2 percent was applied topically to treatment-targeted lesions in participant with mild to moderate AD, twice daily for up to 28 days, except on Day 1 and 8 applied once daily. Lesions were identified at Baseline (Day 1) by investigator.
Time to Reach Maximum Observed Plasma Concentration (Tmax) of AN2728 and Major Oxidative Metabolites of AN2728: Day 8 AN2728	2.17 hour Interval 1.0 to 7.93
Time to Reach Maximum Observed Plasma Concentration (Tmax) of AN2728 and Major Oxidative Metabolites of AN2728: Day 8 AN7602	3.94 hour Interval 1.0 to 6.15
Time to Reach Maximum Observed Plasma Concentration (Tmax) of AN2728 and Major Oxidative Metabolites of AN2728: Day 8 AN8323	6.00 hour Interval 0.0 to 25.1

PRIMARY outcome

Timeframe: Pre-dose (0 hour), 1, 2, 4, 6, 8 and 12 hours post-dose on Day 8

Population: PK population included participants from the safety population who had completed any portion of the PK day procedures and evaluations. Here, 'N' signifies evaluable participants for this outcome measure.

Area under the concentration-time curve from hour zero to the 12 hour post-dose measurable concentration, of AN2728 and its two identified oxidative metabolites, AN7602 and AN8323 on Day 8 was reported in the outcome measure.

Outcome measures

Measure	AN2728 Topical Ointment 2 Percent n=22 Participants AN2728 ointment 2 percent was applied topically to treatment-targeted lesions in participant with mild to moderate AD, twice daily for up to 28 days, except on Day 1 and 8 applied once daily. Lesions were identified at Baseline (Day 1) by investigator.
Area Under the Concentration-Time Curve From Hour Zero To the 12 Hour Post-Dose Measurable Concentration of AN2728 and Major Oxidative Metabolites of AN2728: Day 8 AN2728	462 nanogram*hour per milliliter Standard Deviation 506
Area Under the Concentration-Time Curve From Hour Zero To the 12 Hour Post-Dose Measurable Concentration of AN2728 and Major Oxidative Metabolites of AN2728: Day 8 AN7602	142 nanogram*hour per milliliter Standard Deviation 154
Area Under the Concentration-Time Curve From Hour Zero To the 12 Hour Post-Dose Measurable Concentration of AN2728 and Major Oxidative Metabolites of AN2728: Day 8 AN8323	18200 nanogram*hour per milliliter Standard Deviation 18100

PRIMARY outcome

Timeframe: Pre-dose (0 hour), 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 8

Population: PK population included participants from the safety population who had completed any portion of the PK day procedures and evaluations. Here, "n" signifies number of participants who were evaluable for specific categories.

Apparent terminal half-life, of AN2728 and its two identified oxidative metabolites, AN7602 and AN8323 on Day 8 was reported in the outcome measure. Apparent terminal half-life is the time measured for the drug concentration to decrease by one-half in plasma.

Outcome measures

Measure	AN2728 Topical Ointment 2 Percent n=23 Participants AN2728 ointment 2 percent was applied topically to treatment-targeted lesions in participant with mild to moderate AD, twice daily for up to 28 days, except on Day 1 and 8 applied once daily. Lesions were identified at Baseline (Day 1) by investigator.
Apparent Terminal Half-Life of AN2728 and Major Oxidative Metabolites of AN2728: Day 8 AN2728 (n =17)	11.9 hour Standard Deviation 8.28
Apparent Terminal Half-Life of AN2728 and Major Oxidative Metabolites of AN2728: Day 8 AN7602 (n =16)	10.5 hour Standard Deviation 6.38
Apparent Terminal Half-Life of AN2728 and Major Oxidative Metabolites of AN2728: Day 8 AN8323 (n =6)	33.5 hour Standard Deviation 10.1

SECONDARY outcome

Timeframe: Baseline up to Day 29

Population: Safety population included all participants who were enrolled and had received any amount of the study drug.

ISGA assess severity of atopic dermatitis on a 5 point scale ranged from 0 (clear) to 4 (maximum severe), where higher scores indicate higher degree of atopic dermatitis. Grades for classification of severity: 0= clear (minor residual discoloration, no erythema or induration or papulation, no oozing or crusting), 1= almost clear (trace faint pink erythema, with barely perceptible induration or papulation and no oozing or crusting), 2= mild (faint pink erythema with mild induration or papulation and no oozing or crusting), 3= moderate (pink-red erythema with moderate induration or papulation with or without oozing or crusting) and 4= severe (deep or bright red erythema with severe induration or papulation and with oozing or crusting). Treatment success was defined as ISGA score of 0 or 1, and a minimum improvement of 2 grades in ISGA from Baseline to Day 29.

Outcome measures

Measure	AN2728 Topical Ointment 2 Percent n=23 Participants AN2728 ointment 2 percent was applied topically to treatment-targeted lesions in participant with mild to moderate AD, twice daily for up to 28 days, except on Day 1 and 8 applied once daily. Lesions were identified at Baseline (Day 1) by investigator.
Number of Participants Who Achieved Treatment Success Based on Investigator's Static Global Assessment (ISGA)	9 Participants

SECONDARY outcome

Timeframe: Baseline, Day 8, 15, 22, 29

Population: Safety population included all participants who were enrolled and had received any amount of the study drug.

5 signs and symptoms of atopic dermatitis were: 1) erythema, 2) pruritus, 3) exudation, 4) excoriation and 5) lichenification. The severity of each of these 5 signs and symptoms were assessed on a 4 point scale, ranging from 0 (none) to 3 (severe). Higher scores (for each of the 5 signs and symptoms) indicate higher degree of severity of atopic dermatitis.

Outcome measures

Measure	AN2728 Topical Ointment 2 Percent n=23 Participants AN2728 ointment 2 percent was applied topically to treatment-targeted lesions in participant with mild to moderate AD, twice daily for up to 28 days, except on Day 1 and 8 applied once daily. Lesions were identified at Baseline (Day 1) by investigator.
Change From Baseline in Signs and Symptoms of Atopic Dermatitis at Day 8, 15, 22 and 29 Change at Day 22: Excoriation	-0.52 units on a scale Standard Deviation 0.805
Change From Baseline in Signs and Symptoms of Atopic Dermatitis at Day 8, 15, 22 and 29 Change at Day 29: Excoriation	-0.61 units on a scale Standard Deviation 0.852
Change From Baseline in Signs and Symptoms of Atopic Dermatitis at Day 8, 15, 22 and 29 Baseline: Lichenification	1.67 units on a scale Standard Deviation 0.614
Change From Baseline in Signs and Symptoms of Atopic Dermatitis at Day 8, 15, 22 and 29 Change at Day 8: Lichenification	-0.54 units on a scale Standard Deviation 0.520
Change From Baseline in Signs and Symptoms of Atopic Dermatitis at Day 8, 15, 22 and 29 Change at Day 15: Lichenification	-0.59 units on a scale Standard Deviation 0.596
Change From Baseline in Signs and Symptoms of Atopic Dermatitis at Day 8, 15, 22 and 29 Change at Day 22: Lichenification	-0.85 units on a scale Standard Deviation 0.573
Change From Baseline in Signs and Symptoms of Atopic Dermatitis at Day 8, 15, 22 and 29 Change at Day 29: Lichenification	-0.78 units on a scale Standard Deviation 0.671
Change From Baseline in Signs and Symptoms of Atopic Dermatitis at Day 8, 15, 22 and 29 Baseline: Erythema	1.63 units on a scale Standard Deviation 0.607
Change From Baseline in Signs and Symptoms of Atopic Dermatitis at Day 8, 15, 22 and 29 Change at Day 8: Erythema	-0.63 units on a scale Standard Deviation 0.588
Change From Baseline in Signs and Symptoms of Atopic Dermatitis at Day 8, 15, 22 and 29 Change at Day 15: Erythema	-0.70 units on a scale Standard Deviation 0.617
Change From Baseline in Signs and Symptoms of Atopic Dermatitis at Day 8, 15, 22 and 29 Change at Day 22: Erythema	-0.87 units on a scale Standard Deviation 0.626
Change From Baseline in Signs and Symptoms of Atopic Dermatitis at Day 8, 15, 22 and 29 Change at Day 29: Erythema	-0.89 units on a scale Standard Deviation 0.673
Change From Baseline in Signs and Symptoms of Atopic Dermatitis at Day 8, 15, 22 and 29 Baseline: Pruritus	1.87 units on a scale Standard Deviation 0.815
Change From Baseline in Signs and Symptoms of Atopic Dermatitis at Day 8, 15, 22 and 29 Change at Day 8: Pruritus	-1.11 units on a scale Standard Deviation 0.916
Change From Baseline in Signs and Symptoms of Atopic Dermatitis at Day 8, 15, 22 and 29 Change at Day 15: Pruritus	-1.11 units on a scale Standard Deviation 0.825
Change From Baseline in Signs and Symptoms of Atopic Dermatitis at Day 8, 15, 22 and 29 Change at Day 22: Pruritus	-1.15 units on a scale Standard Deviation 0.804
Change From Baseline in Signs and Symptoms of Atopic Dermatitis at Day 8, 15, 22 and 29 Change at Day 29: Pruritus	-1.30 units on a scale Standard Deviation 0.735
Change From Baseline in Signs and Symptoms of Atopic Dermatitis at Day 8, 15, 22 and 29 Baseline: Exudation	0.33 units on a scale Standard Deviation 0.467
Change From Baseline in Signs and Symptoms of Atopic Dermatitis at Day 8, 15, 22 and 29 Change at Day 8: Exudation	-0.20 units on a scale Standard Deviation 0.328
Change From Baseline in Signs and Symptoms of Atopic Dermatitis at Day 8, 15, 22 and 29 Change at Day 15: Exudation	-0.20 units on a scale Standard Deviation 0.328
Change From Baseline in Signs and Symptoms of Atopic Dermatitis at Day 8, 15, 22 and 29 Change at Day 22: Exudation	-0.09 units on a scale Standard Deviation 0.492
Change From Baseline in Signs and Symptoms of Atopic Dermatitis at Day 8, 15, 22 and 29 Change at Day 29: Exudation	-0.07 units on a scale Standard Deviation 0.645
Change From Baseline in Signs and Symptoms of Atopic Dermatitis at Day 8, 15, 22 and 29 Baseline: Excoriation	1.04 units on a scale Standard Deviation 0.689
Change From Baseline in Signs and Symptoms of Atopic Dermatitis at Day 8, 15, 22 and 29 Change at Day 8: Excoriation	-0.50 units on a scale Standard Deviation 0.603
Change From Baseline in Signs and Symptoms of Atopic Dermatitis at Day 8, 15, 22 and 29 Change at Day 15: Excoriation	-0.57 units on a scale Standard Deviation 0.728

Adverse Events

AN2728 Topical Ointment 2 Percent

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	AN2728 Topical Ointment 2 Percent n=23 participants at risk AN2728 ointment 2 percent was applied topically to treatment-targeted lesions in participant with mild to moderate AD, twice daily for up to 28 days, except on Day 1 and 8 applied once daily. Lesions were identified at Baseline (Day 1) by investigator.
General disorders Application site dermatitis	4.3% 1/23
General disorders Application site discomfort	4.3% 1/23
General disorders Application site pain	13.0% 3/23
Infections and infestations Upper respiratory tract infection	4.3% 1/23
Injury, poisoning and procedural complications Arthropod bite	4.3% 1/23
Injury, poisoning and procedural complications Hand fracture	4.3% 1/23
Nervous system disorders Headache	4.3% 1/23
Nervous system disorders Migraine	4.3% 1/23
Reproductive system and breast disorders Dysmenorrhoea	5.3% 1/19
Respiratory, thoracic and mediastinal disorders Nasal congestion	4.3% 1/23
Respiratory, thoracic and mediastinal disorders Nasopharyngitis	13.0% 3/23
Respiratory, thoracic and mediastinal disorders Sinus congestion	4.3% 1/23
Skin and subcutaneous tissue disorders Milia	4.3% 1/23
Skin and subcutaneous tissue disorders Solar dermatitis	4.3% 1/23

Additional Information

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Phone: 1-800-718-1021

Email: ClinicalTrials.gov_Inquiries@pfizer.com

Results disclosure agreements

• Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
• Publication restrictions are in place

Restriction type: OTHER