Clinical trial NCT03260595: A Study of Crisaborole Ointment 2% in Adult Japanese Healthy Subjects and Adult Japanese Subjects With Mild To Moderate Atopic Dermatitis
Official title: A Phase 1, Single-center, Randomized, Vehicle-controlled, Parallel-cohort Study Of Crisaborole Ointment 2% To Evaluate The Skin Irritation Potential In Adult Japanese Healthy Subjects, And To Evaluate The Safety, Tolerability And Pharmacokinetics In Adult Japanese Subjects With Mild To Moderate Atopic Dermatitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Atopic Dermatitis
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2017-08-24
Enrollment: 32
Sex: ALL
Minimum age (years): 20
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: This is a Phase 1 parallel-cohort study of crisaborole ointment 2% to evaluate the skin irritation potential in adult Japanese healthy subjects in Cohort 1, and to evaluate the safety, tolerability and PK in adult Japanese subjects with mild to moderate AD in Cohort 2.


Eligibility criteria: Inclusion Criteria:

Cohort 1

1. Healthy male Japanese subjects who, at the time of screening, are between the ages of 20 and 55 years, inclusive.
2. Healthy skin on which reddening can be easily recognized in the area of the test fields.

Cohort 2

1. Male or female Japanese subjects aged 20 years to 55 years (inclusive) at the time of screening, and in generally good health except for AD.
2. Diagnosis of AD based on the criteria of Hanifin and Rajka (1980).
3. Has at least 25% Treatable %BSA on Day 1 (excluding the scalp and designated venous access areas).
4. Has an Investigator's static global assessment (ISGA) score of Mild (2) or Moderate (3) on Day 1.

Exclusion Criteria:

Cohort 1

1. Subjects who have any visible skin disease at the application site which, in the opinion of the investigative personnel, will interfere with the evaluation of the test site reaction.
2. Subjects who have psoriasis and/or active AD/eczema.
3. Subjects who have a history of AD.
4. Subjects who have damaged skin in or around the test sites, including sunburn, excessively deep tans, uneven skin tones, tattoos, scars, excessive hair, numerous freckles, or other disfigurations of the test site.
5. Known sensitivity to any of the components of the investigational products.
6. History of the rash to the adhesive plaster, contact dermatitis to metal, or cosmetic and household articles.

Cohort 2

1. Has any clinically significant medical disorder, condition, disease (including active or potentially recurrent dermatological conditions other than AD), significant physical examination or laboratory findings that may interfere with study objectives, in the Investigator's opinion.
2. Has unstable AD or a consistent requirement for strong to strongest potency topical corticosteroids to manage AD signs and symptoms.
3. Has a significant active systemic or localized infection, including known actively infected AD.
4. Has a history or evidence of clinically significant or severe allergies (eg, seasonal, pet dander, environmental, food) requiring acute or chronic treatment.
5. Has recent or anticipated concomitant use of topical or systemic therapies that might alter the course of AD.
6. Has a history of recent (within 4 weeks of Day 1) sunbathing, tanning bed use, or ultraviolet (UV) light B therapy (UVB) or psoralen plus UVA \[PUVA\]).
7. Has a known sensitivity to any of the components of crisaborole ointment 2%.
8. Pregnant female subjects; breastfeeding female subjects; female subjects of childbearing potential who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 28 days after the last dose of investigational product.

Primary outcomes:
measure: Cohort 1: Skin Irritation Index
timeFrame: Day 3 to 4
measure: Cohort 2: Number of Participants With Treatment-Emergent Adverse Events (AEs) And Serious Adverse Events (SAEs)
timeFrame: Baseline up to Day 36
measure: Cohort 2: Number of Participants With Clinically Significant Vital Signs Abnormalities
timeFrame: Baseline up to end of treatment (Day 8)
measure: Cohort 2: Number of Participants With Laboratory Tests Abnormalities
timeFrame: Baseline up to end of treatment (Day 8)
measure: Cohort 2: Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities
timeFrame: Baseline up to end of treatment (Day 8)
Secondary outcomes:
measure: Cohort 1: Number of Participants With Treatment-Emergent Adverse Events (AEs) And Serious Adverse Events (SAEs)
timeFrame: Baseline up to Day 29
measure: Cohort 2: Maximum Observed Plasma Concentration (Cmax) of Crisaborole and Its Identified Main Oxidative Metabolites
timeFrame: Pre-dose, 3, 12 and 24 hours post-dose on Day 1 and Day 8
measure: Cohort 2: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Crisaborole and Its Metabolites
timeFrame: Pre-dose, 3, 12 and 24 hours post-dose on Day 1 and Day 8
measure: Cohort 2: Area Under the Plasma Concentration-Time Curve From Time Zero Until the Last Measurable Concentration (AUClast) of Crisaborole and Its Identified Main Oxidative Metabolites
timeFrame: Pre-dose, 3, 12 and 24 hours post-dose on Day 1 and Day 8
measure: Cohort 2: Area Under the Plasma Concentration-Time Curve From Time Zero to the 24 Hours Post-Dose (AUC24) of Crisaborole and Its Identified Main Oxidative Metabolites (AN7602 and AN8323)
timeFrame: Pre-dose, 3, 12 and 24 hours post-dose on Day 1 and Day 8
measure: Cohort 2: Area Under the Plasma Concentration-Time Curve From Time Zero to Tau (12 Hours Dosing Interval) (AUCtau) of Crisaborole and Its Identified Main Oxidative Metabolites
timeFrame: Pre-dose, 3, 12 and 24 hours post-dose on Day 1 and Day 8
measure: Cohort 2: Accumulation Ratio for Cmax (Rac [Cmax]) of Crisaborole and Its Identified Main Oxidative Metabolites
timeFrame: Pre-dose, 3, 12 and 24 hours post-dose on Day 1 and 8
measure: Cohort 2: Accumulation Ratio for AUCtau (Rac [AUCtau]) of Crisaborole and Its Identified Main Oxidative Metabolites
timeFrame: Pre-dose, 3, 12 and 24 hours post-dose on Day 1 and 8
Other outcomes:
Locations:
city: Osaka-shi
country: Japan
facility: Medical Corporation Heishinkai OPHAC Hospital
state: Osaka
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: