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

Study Overview
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Brief Summary
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The purpose of this study is to investigate the safety, tolerability, and systemic exposure of AN2728 Topical Ointment, 2%, in subjects with atopic dermatitis.

Official Title
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An Open-Label Study to Determine the Safety, Tolerability, and Pharmacokinetic Profile of AN2728 Ointment in Adolescents With Atopic Dermatitis

Conditions
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Dermatitis, Atopic

Intervention / Treatment
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* Drug: AN2728 Topical Ointment, 2%


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female 12 to 17 years of age, inclusive Clinical diagnosis of atopic dermatitis (according to the criteria of Hanifin and Rajka) AD in treatable areas (excludes the scalp and venous access areas) involving ≥10% and ≤35% of the total body surface area(BSA) Investigator's Static Global Assessment (ISGA) score of 2 or 3 Normal or not clinically significant screening laboratory results Have adequate venous access to permit repeated PK sampling on Days 1 - 9 through uninfected skin that has not been treated with study drug; each untreated venous access area should provide a margin of at least 5 cm radius around the venipuncture site Willing and able to comply with study instructions and commit to attending all visits Females must use a highly effective method of birth control. Parent/guardian has the ability to understand, agree to and sign the study Informed Consent Form (ICF) prior to initiation of any protocol-related procedures; subject has the ability to give assent Exclusion Criteria: Significant confounding conditions as assessed by study doctor Unstable or actively infected AD Active or potentially recurrent dermatologic condition other than atopic dermatitis that may confound evaluation History or evidence of allergies requiring acute or chronic treatment (except seasonal allergic rhinitis) Concurrent or recent use of certain topical or systemic medications or phototherapy without a sufficient washout period Treatment for any type of cancer (except squamous cell carcinoma, basal cell carcinoma, or carcinoma in situ of the skin, curatively treated with cryosurgery or surgical excision only) within the last 5 years Current pregnancy or lactation, or intent to become pregnant during the study Known sensitivity to any of the components of the study drug Participated in any other trial of an investigational drug or device within 30 days or participation in a research study concurrent with this study Participated in a previous AN2728 clinical study

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AN2728 Topical Ointment, 2%<br>AN2728 Topical Ointment, 2%, applied twice daily for up to 28 days | Drug: AN2728 Topical Ointment, 2%<br>* AN2728 Topical Ointment, 2%<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Local Tolerability Symptoms According to Severity on Baseline | 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. | Baseline | 
| Number of Participants With Local Tolerability Symptoms According to Severity on Day 2 | 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. | Day 2 | 
| Number of Participants With Local Tolerability Symptoms According to Severity on Day 4 | 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. | Day 4 | 
| Number of Participants With Local Tolerability Symptoms According to Severity on Day 6 | 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. | Day 6 | 
| Number of Participants With Local Tolerability Symptoms According to Severity on Day 8 | 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. | Day 8 | 
| Number of Participants With Local Tolerability Symptoms According to Severity on Day 9 | 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. | Day 9 | 
| Number of Participants With Local Tolerability Symptoms According to Severity on Day 15 | 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. | Day 15 | 
| Number of Participants With Local Tolerability Symptoms According to Severity on Day 22 | 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. | Day 22 | 
| Number of Participants With Local Tolerability Symptoms According to Severity on Day 29 | 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. | Day 29 | 
| Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | 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. | Baseline (Day 1) up to Day 29 | 
| Number of Participants With Clinically Significant Vital Signs Abnormalities | 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. | Baseline (Day 1) up to Day 29 | 
| Number of Participants With Clinically Significant Laboratory Test Abnormalities | 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. | Baseline (Day 1) up to Day 29 | 
| Maximum Observed Plasma Concentration (Cmax) of AN2728 and Major Oxidative Metabolites of AN2728: Day 1 | Maximum observed plasma concentration of AN2728 and its two identified oxidative metabolites, AN7602 and AN8323 on Day 1 was reported in the outcome measure. | Pre-dose (0 hour), 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 1 | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of AN2728 and Major Oxidative Metabolites of AN2728: Day 1 | 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. | Pre-dose (0 hour), 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 1 | 
| 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 | 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. | Pre-dose (0 hour), 1, 2, 4, 6, 8 and 12 hours post-dose on Day 1 | 
| Apparent Terminal Half-Life of AN2728 and Major Oxidative Metabolites of AN2728: Day 1 | 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. | Pre-dose (0 hour), 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 1 | 
| Maximum Observed Plasma Concentration (Cmax) of AN2728 and Major Oxidative Metabolites of AN2728: Day 8 | Maximum observed plasma concentration of AN2728 and its two identified oxidative metabolites, AN7602 and AN8323 on Day 8 was reported in the outcome measure. | Pre-dose (0 hour), 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 8 | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of AN2728 and Major Oxidative Metabolites of AN2728: Day 8 | 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. | Pre-dose (0 hour), 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 8 | 
| 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 | 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. | Pre-dose (0 hour), 1, 2, 4, 6, 8 and 12 hours post-dose on Day 8 | 
| Apparent Terminal Half-Life of AN2728 and Major Oxidative Metabolites of AN2728: Day 8 | 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. | Pre-dose (0 hour), 1, 2, 4, 6, 8, 12 and 24 hours post-dose on Day 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Achieved Treatment Success Based on Investigator's Static Global Assessment (ISGA) | 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. | Baseline up to Day 29 | 
| Change From Baseline in Signs and Symptoms of Atopic Dermatitis at Day 8, 15, 22 and 29 | 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. | Baseline, Day 8, 15, 22, 29 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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atopic dermatitis