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

NCT01652885 | Completed Phase 1 Results

• 2 other identifiers: AN2728-AD-203A3191007
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 6

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.

Conditions

Dermatitis, Atopic

Keywords

atopic dermatitis

Outcome Measures

Primary Outcomes (20)

• 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 Outcomes (2)

• Number of Participants Who Achieved Treatment Success Based on Investigator's Static Global Assessment (ISGA)

  Baseline up to Day 29

• Change From Baseline in Signs and Symptoms of Atopic Dermatitis at Day 8, 15, 22 and 29

  Baseline, Day 8, 15, 22, 29

Study Arms (1)

AN2728 Topical Ointment, 2%

EXPERIMENTAL

AN2728 Topical Ointment, 2%, applied twice daily for up to 28 days

Drug: AN2728 Topical Ointment, 2%

Interventions

AN2728 Topical Ointment, 2% DRUG

AN2728 Topical Ointment, 2%

AN2728 Topical Ointment, 2%

Eligibility Criteria

• Age: 12 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Pfizer: lead

Study Sites (6)

Anacor Investigational Site

Fremont, California, 94538, United States

Location

Anacor Investigational Site

San Diego, California, 92123, United States

Location

Anacor Investigational Site

Indianapolis, Indiana, 46256, United States

Location

Anacor Investigational Site

High Point, North Carolina, 27262, United States

Location

Anacor Investigational Site

Winston-Salem, North Carolina, 27104, United States

Location

Anacor Investigational Site

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Dermatitis, Atopic

Condition Hierarchy (Ancestors)

Skin Diseases, Genetic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Eczematous; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2012
• First Posted: July 30, 2012
• Study Start: July 1, 2012
• Primary Completion: October 1, 2012
• Study Completion: November 1, 2012
• Last Updated: April 24, 2017
• Results First Posted: April 24, 2017

Record last verified: 2017-03

Locations

US (6)