Dermatitis, Atopic
Conditions
Keywords
atopic dermatitis
Brief summary
The purpose of this study is to investigate the safety, tolerability, and systemic exposure of AN2728 Topical Ointment, 2%, in subjects with atopic dermatitis.
Interventions
AN2728 Topical Ointment, 2%
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 17 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Apparent Terminal Half-Life of AN2728 and Major Oxidative Metabolites of AN2728: Day 8 | Pre-dose (0 hour), 1, 2, 4, 6, 8, 12 and 24 hours post-dose on 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. |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of AN2728 and Major Oxidative Metabolites of AN2728: Day 8 | Pre-dose (0 hour), 1, 2, 4, 6, 8, 12 and 24 hours post-dose on 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. |
| 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 | Pre-dose (0 hour), 1, 2, 4, 6, 8 and 12 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 its two identified oxidative metabolites, AN7602 and AN8323 on Day 8 was reported in the outcome measure. |
| Number of Participants With Local Tolerability Symptoms According to Severity on Baseline | 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. |
| Number of Participants With Local Tolerability Symptoms According to Severity on Day 2 | 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. |
| Number of Participants With Local Tolerability Symptoms According to Severity on Day 4 | 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. |
| Number of Participants With Local Tolerability Symptoms According to Severity on Day 6 | 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. |
| Number of Participants With Local Tolerability Symptoms According to Severity on Day 8 | 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. |
| Number of Participants With Local Tolerability Symptoms According to Severity on Day 9 | 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. |
| Number of Participants With Local Tolerability Symptoms According to Severity on Day 15 | 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. |
| Number of Participants With Local Tolerability Symptoms According to Severity on Day 22 | 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. |
| Number of Participants With Local Tolerability Symptoms According to Severity on Day 29 | 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. |
| Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Baseline (Day 1) up to Day 29 | 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. |
| Number of Participants With Clinically Significant Vital Signs Abnormalities | Baseline (Day 1) up to Day 29 | 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. |
| Number of Participants With Clinically Significant Laboratory Test Abnormalities | Baseline (Day 1) up to Day 29 | 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. |
| Maximum Observed Plasma Concentration (Cmax) of AN2728 and Major Oxidative Metabolites of AN2728: Day 1 | Pre-dose (0 hour), 1, 2, 4, 6, 8, 12 and 24 hours post-dose on 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. |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of AN2728 and Major Oxidative Metabolites of AN2728: Day 1 | Pre-dose (0 hour), 1, 2, 4, 6, 8, 12 and 24 hours post-dose on 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. |
| 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 | Pre-dose (0 hour), 1, 2, 4, 6, 8 and 12 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 its two identified oxidative metabolites, AN7602 and AN8323 on Day 1 was reported in the outcome measure. |
| Apparent Terminal Half-Life of AN2728 and Major Oxidative Metabolites of AN2728: Day 1 | Pre-dose (0 hour), 1, 2, 4, 6, 8, 12 and 24 hours post-dose on 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. |
| Maximum Observed Plasma Concentration (Cmax) of AN2728 and Major Oxidative Metabolites of AN2728: Day 8 | Pre-dose (0 hour), 1, 2, 4, 6, 8, 12 and 24 hours post-dose on 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Signs and Symptoms of Atopic Dermatitis at Day 8, 15, 22 and 29 | Baseline, Day 8, 15, 22, 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. |
| Number of Participants Who Achieved Treatment Success Based on Investigator's Static Global Assessment (ISGA) | Baseline up to Day 29 | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AN2728 Topical Ointment 2 Percent 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. | 23 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | AN2728 Topical Ointment 2 Percent |
|---|---|
| Age, Continuous | 15.0 years STANDARD_DEVIATION 1.55 |
| Sex: Female, Male Female | 19 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 10 / 23 |
| serious Total, serious adverse events | 0 / 23 |
Outcome results
Primary
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AN2728 Topical Ointment 2 Percent | Apparent Terminal Half-Life of AN2728 and Major Oxidative Metabolites of AN2728: Day 1 | AN2728 (n =16) | 7.17 hour | Standard Deviation 2.3 |
| AN2728 Topical Ointment 2 Percent | Apparent Terminal Half-Life of AN2728 and Major Oxidative Metabolites of AN2728: Day 1 | AN7602 (n =18) | 8.19 hour | Standard Deviation 5.13 |
| AN2728 Topical Ointment 2 Percent | 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
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AN2728 Topical Ointment 2 Percent | Apparent Terminal Half-Life of AN2728 and Major Oxidative Metabolites of AN2728: Day 8 | AN7602 (n =16) | 10.5 hour | Standard Deviation 6.38 |
| AN2728 Topical Ointment 2 Percent | Apparent Terminal Half-Life of AN2728 and Major Oxidative Metabolites of AN2728: Day 8 | AN8323 (n =6) | 33.5 hour | Standard Deviation 10.1 |
| AN2728 Topical Ointment 2 Percent | Apparent Terminal Half-Life of AN2728 and Major Oxidative Metabolites of AN2728: Day 8 | AN2728 (n =17) | 11.9 hour | Standard Deviation 8.28 |
Primary
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AN2728 Topical Ointment 2 Percent | 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 |
| AN2728 Topical Ointment 2 Percent | 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 |
| AN2728 Topical Ointment 2 Percent | 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
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AN2728 Topical Ointment 2 Percent | 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 |
| AN2728 Topical Ointment 2 Percent | 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 |
| AN2728 Topical Ointment 2 Percent | 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
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AN2728 Topical Ointment 2 Percent | Maximum Observed Plasma Concentration (Cmax) of AN2728 and Major Oxidative Metabolites of AN2728: Day 1 | AN2728 | 105 nanogram per milliliter | Standard Deviation 160 |
| AN2728 Topical Ointment 2 Percent | Maximum Observed Plasma Concentration (Cmax) of AN2728 and Major Oxidative Metabolites of AN2728: Day 1 | AN7602 | 28.2 nanogram per milliliter | Standard Deviation 37 |
| AN2728 Topical Ointment 2 Percent | Maximum Observed Plasma Concentration (Cmax) of AN2728 and Major Oxidative Metabolites of AN2728: Day 1 | AN8323 | 998 nanogram per milliliter | Standard Deviation 1220 |
Primary
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AN2728 Topical Ointment 2 Percent | Maximum Observed Plasma Concentration (Cmax) of AN2728 and Major Oxidative Metabolites of AN2728: Day 8 | AN2728 | 94.6 nanogram per milliliter | Standard Deviation 189 |
| AN2728 Topical Ointment 2 Percent | 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 |
| AN2728 Topical Ointment 2 Percent | Maximum Observed Plasma Concentration (Cmax) of AN2728 and Major Oxidative Metabolites of AN2728: Day 8 | AN8323 | 1850 nanogram per milliliter | Standard Deviation 1830 |
Primary
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AN2728 Topical Ointment 2 Percent | Number of Participants With Clinically Significant Laboratory Test Abnormalities | 0 participants |
Primary
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AN2728 Topical Ointment 2 Percent | Number of Participants With Clinically Significant Vital Signs Abnormalities | 0 participants |
Primary
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.
Time frame: Baseline
Population: Safety population included all participants who were enrolled and had received any amount of the study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AN2728 Topical Ointment 2 Percent | Number of Participants With Local Tolerability Symptoms According to Severity on Baseline | None | 10 participants |
| AN2728 Topical Ointment 2 Percent | Number of Participants With Local Tolerability Symptoms According to Severity on Baseline | Mild | 7 participants |
| AN2728 Topical Ointment 2 Percent | Number of Participants With Local Tolerability Symptoms According to Severity on Baseline | Moderate | 6 participants |
| AN2728 Topical Ointment 2 Percent | Number of Participants With Local Tolerability Symptoms According to Severity on Baseline | Severe | 0 participants |
Primary
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.
Time frame: Day 15
Population: Safety population included all participants who were enrolled and had received any amount of the study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AN2728 Topical Ointment 2 Percent | Number of Participants With Local Tolerability Symptoms According to Severity on Day 15 | None | 19 participants |
| AN2728 Topical Ointment 2 Percent | Number of Participants With Local Tolerability Symptoms According to Severity on Day 15 | Mild | 4 participants |
| AN2728 Topical Ointment 2 Percent | Number of Participants With Local Tolerability Symptoms According to Severity on Day 15 | Moderate | 0 participants |
| AN2728 Topical Ointment 2 Percent | Number of Participants With Local Tolerability Symptoms According to Severity on Day 15 | Severe | 0 participants |
Primary
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.
Time frame: Day 2
Population: Safety population included all participants who were enrolled and had received any amount of the study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AN2728 Topical Ointment 2 Percent | Number of Participants With Local Tolerability Symptoms According to Severity on Day 2 | None | 17 participants |
| AN2728 Topical Ointment 2 Percent | Number of Participants With Local Tolerability Symptoms According to Severity on Day 2 | Mild | 5 participants |
| AN2728 Topical Ointment 2 Percent | Number of Participants With Local Tolerability Symptoms According to Severity on Day 2 | Moderate | 1 participants |
| AN2728 Topical Ointment 2 Percent | Number of Participants With Local Tolerability Symptoms According to Severity on Day 2 | Severe | 0 participants |
Primary
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.
Time frame: Day 22
Population: Safety population included all participants who were enrolled and had received any amount of the study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AN2728 Topical Ointment 2 Percent | Number of Participants With Local Tolerability Symptoms According to Severity on Day 22 | Moderate | 0 participants |
| AN2728 Topical Ointment 2 Percent | Number of Participants With Local Tolerability Symptoms According to Severity on Day 22 | Severe | 0 participants |
| AN2728 Topical Ointment 2 Percent | Number of Participants With Local Tolerability Symptoms According to Severity on Day 22 | None | 21 participants |
| AN2728 Topical Ointment 2 Percent | Number of Participants With Local Tolerability Symptoms According to Severity on Day 22 | Mild | 2 participants |
Primary
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.
Time frame: Day 29
Population: Safety population included all participants who were enrolled and had received any amount of the study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AN2728 Topical Ointment 2 Percent | Number of Participants With Local Tolerability Symptoms According to Severity on Day 29 | Mild | 2 participants |
| AN2728 Topical Ointment 2 Percent | Number of Participants With Local Tolerability Symptoms According to Severity on Day 29 | Moderate | 0 participants |
| AN2728 Topical Ointment 2 Percent | Number of Participants With Local Tolerability Symptoms According to Severity on Day 29 | Severe | 1 participants |
| AN2728 Topical Ointment 2 Percent | Number of Participants With Local Tolerability Symptoms According to Severity on Day 29 | None | 20 participants |
Primary
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.
Time frame: Day 4
Population: Safety population included all participants who were enrolled and had received any amount of the study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AN2728 Topical Ointment 2 Percent | Number of Participants With Local Tolerability Symptoms According to Severity on Day 4 | Moderate | 2 participants |
| AN2728 Topical Ointment 2 Percent | Number of Participants With Local Tolerability Symptoms According to Severity on Day 4 | Severe | 0 participants |
| AN2728 Topical Ointment 2 Percent | Number of Participants With Local Tolerability Symptoms According to Severity on Day 4 | None | 18 participants |
| AN2728 Topical Ointment 2 Percent | Number of Participants With Local Tolerability Symptoms According to Severity on Day 4 | Mild | 3 participants |
Primary
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.
Time frame: Day 6
Population: Safety population included all participants who were enrolled and had received any amount of the study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AN2728 Topical Ointment 2 Percent | Number of Participants With Local Tolerability Symptoms According to Severity on Day 6 | Mild | 4 participants |
| AN2728 Topical Ointment 2 Percent | Number of Participants With Local Tolerability Symptoms According to Severity on Day 6 | None | 18 participants |
| AN2728 Topical Ointment 2 Percent | Number of Participants With Local Tolerability Symptoms According to Severity on Day 6 | Moderate | 1 participants |
| AN2728 Topical Ointment 2 Percent | Number of Participants With Local Tolerability Symptoms According to Severity on Day 6 | Severe | 0 participants |
Primary
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.
Time frame: Day 8
Population: Safety population included all participants who were enrolled and had received any amount of the study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AN2728 Topical Ointment 2 Percent | Number of Participants With Local Tolerability Symptoms According to Severity on Day 8 | None | 20 participants |
| AN2728 Topical Ointment 2 Percent | Number of Participants With Local Tolerability Symptoms According to Severity on Day 8 | Mild | 3 participants |
| AN2728 Topical Ointment 2 Percent | Number of Participants With Local Tolerability Symptoms According to Severity on Day 8 | Moderate | 0 participants |
| AN2728 Topical Ointment 2 Percent | Number of Participants With Local Tolerability Symptoms According to Severity on Day 8 | Severe | 0 participants |
Primary
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.
Time frame: Day 9
Population: Safety population included all participants who were enrolled and had received any amount of the study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AN2728 Topical Ointment 2 Percent | Number of Participants With Local Tolerability Symptoms According to Severity on Day 9 | None | 18 participants |
| AN2728 Topical Ointment 2 Percent | Number of Participants With Local Tolerability Symptoms According to Severity on Day 9 | Mild | 4 participants |
| AN2728 Topical Ointment 2 Percent | Number of Participants With Local Tolerability Symptoms According to Severity on Day 9 | Moderate | 1 participants |
| AN2728 Topical Ointment 2 Percent | Number of Participants With Local Tolerability Symptoms According to Severity on Day 9 | Severe | 0 participants |
Primary
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AN2728 Topical Ointment 2 Percent | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 10 participants |
| AN2728 Topical Ointment 2 Percent | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 participants |
Primary
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| AN2728 Topical Ointment 2 Percent | Time to Reach Maximum Observed Plasma Concentration (Tmax) of AN2728 and Major Oxidative Metabolites of AN2728: Day 1 | AN2728 | 2.37 hour |
| AN2728 Topical Ointment 2 Percent | Time to Reach Maximum Observed Plasma Concentration (Tmax) of AN2728 and Major Oxidative Metabolites of AN2728: Day 1 | AN7602 | 2.08 hour |
| AN2728 Topical Ointment 2 Percent | Time to Reach Maximum Observed Plasma Concentration (Tmax) of AN2728 and Major Oxidative Metabolites of AN2728: Day 1 | AN8323 | 6.25 hour |
Primary
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| AN2728 Topical Ointment 2 Percent | Time to Reach Maximum Observed Plasma Concentration (Tmax) of AN2728 and Major Oxidative Metabolites of AN2728: Day 8 | AN2728 | 2.17 hour |
| AN2728 Topical Ointment 2 Percent | Time to Reach Maximum Observed Plasma Concentration (Tmax) of AN2728 and Major Oxidative Metabolites of AN2728: Day 8 | AN7602 | 3.94 hour |
| AN2728 Topical Ointment 2 Percent | Time to Reach Maximum Observed Plasma Concentration (Tmax) of AN2728 and Major Oxidative Metabolites of AN2728: Day 8 | AN8323 | 6.00 hour |
Secondary
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.
Time frame: Baseline, Day 8, 15, 22, 29
Population: Safety population included all participants who were enrolled and had received any amount of the study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AN2728 Topical Ointment 2 Percent | 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 |
| AN2728 Topical Ointment 2 Percent | 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 |
| AN2728 Topical Ointment 2 Percent | 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 |
| AN2728 Topical Ointment 2 Percent | 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 |
| AN2728 Topical Ointment 2 Percent | 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 |
| AN2728 Topical Ointment 2 Percent | 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 |
| AN2728 Topical Ointment 2 Percent | 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 |
| AN2728 Topical Ointment 2 Percent | 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 |
| AN2728 Topical Ointment 2 Percent | 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 |
| AN2728 Topical Ointment 2 Percent | 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 0.52 |
| AN2728 Topical Ointment 2 Percent | 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 |
| AN2728 Topical Ointment 2 Percent | 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 |
| AN2728 Topical Ointment 2 Percent | 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 |
| AN2728 Topical Ointment 2 Percent | 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 |
| AN2728 Topical Ointment 2 Percent | 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 |
| AN2728 Topical Ointment 2 Percent | 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 |
| AN2728 Topical Ointment 2 Percent | 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 |
| AN2728 Topical Ointment 2 Percent | 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 |
| AN2728 Topical Ointment 2 Percent | 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 |
| AN2728 Topical Ointment 2 Percent | 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 |
| AN2728 Topical Ointment 2 Percent | 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 |
| AN2728 Topical Ointment 2 Percent | 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 |
| AN2728 Topical Ointment 2 Percent | 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 |
| AN2728 Topical Ointment 2 Percent | 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 |
| AN2728 Topical Ointment 2 Percent | 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 |
Secondary
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.
Time frame: Baseline up to Day 29
Population: Safety population included all participants who were enrolled and had received any amount of the study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AN2728 Topical Ointment 2 Percent | Number of Participants Who Achieved Treatment Success Based on Investigator's Static Global Assessment (ISGA) | 9 Participants |