A Study of Crisaborole Ointment 2% in Adult Japanese Healthy Subjects and Adult Japanese Subjects With Mild To Moderate Atopic Dermatitis

• ClinicalTrials.gov Identifier: NCT03260595
• Recruitment Status: Completed
• First Posted: August 24, 2017
• Results First Posted: March 1, 2019
• Last Update Posted: March 1, 2019
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: August 9, 2017
• First Posted Date: August 24, 2017
• Results First Submitted Date: October 26, 2018
• Results First Posted Date: March 1, 2019
• Last Update Posted Date: March 1, 2019
• Actual Study Start Date: September 13, 2017
• Actual Primary Completion Date: November 27, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 26, 2018)

• Cohort 1: Skin Irritation Index [ Time Frame: Day 3 to 4 ]
  The skin irritation index is a common measure of skin irritation potential (safety criteria) of investigational product and derived using skin irritation scores. Individual skin irritation score ranges from 0-4, where 0 = no reaction, 0.5 = mild erythema, 1 = erythema, 2 = erythema with edema and papula, 3 = erythema with edema, papula and small water blister, 4 = large water blister, higher score indicates more skin irritation. For each investigational product, the skin irritation index was calculated as the sum of the maximum individual skin irritation scores divided by the number of evaluable participants and multiplied by 100, which ranged from 0 to 400; where, lower score indicated less skin irritation and higher score indicated more skin irritation.
• Cohort 2: Number of Participants With Treatment-Emergent Adverse Events (AEs) And Serious Adverse Events (SAEs) [ Time Frame: Baseline up to Day 36 ]
  An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. 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 28 days after last dose of study drug (up to Day 36) that were absent before treatment or that worsened relative to pre-treatment state. AEs included both SAEs and non-serious AEs.
• Cohort 2: Number of Participants With Clinically Significant Vital Signs Abnormalities [ Time Frame: Baseline up to end of treatment (Day 8) ]
  Vital signs included pulse rate and blood pressure. Clinical significance of vital signs was determined at the investigator's discretion.
• Cohort 2: Number of Participants With Laboratory Tests Abnormalities [ Time Frame: Baseline up to end of treatment (Day 8) ]
  Laboratory tests abnormalities included: hematology (haemoglobin[Hb], haematocrit and erythrocytes<0.8*lower limit of normal[LLN]; erythrocyte mean corpuscular volume, erythrocyte mean corpuscular Hb and erythrocyte mean corpuscular Hb concentration <0.9*LLN and >1.1*upper limit of normal[ULN]; platelets <0.5*LLN and >1.75*ULN; leukocytes <0.6*LLN and >1.5*ULN; lymphocytes/leukocytes[%], neutrophils/leukocytes[%] <0.8*LLN and >1.2*ULN; basophils/leukocytes[%], eosinophils/leukocytes[%], monocytes/leukocytes[% ]>1.2*ULN); clinical chemistry(bilirubin>1.5*ULN; aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase>3.0*ULN; protein and albumin<0.8*LLN and >1.2*ULN; urea nitrogen and creatinine >1.3*ULN; urate>1.2*ULN; sodium <0.95*LLN and >1.05*ULN; potassium, chloride and calcium <0.9*LLN and >1.1*ULN; fasting glucose <0.6*LLN and >1.5*ULN); and urinalysis (pH <4.5 and >8; glucose, ketones, protein, Hb, urobilinogen, bilirubin, nitrite and leukocyte esterase >=1).
• Cohort 2: Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities [ Time Frame: Baseline up to end of treatment (Day 8) ]
  Criteria for clinically significant ECG abnormalities included: QT interval >=500 milliseconds (msec); QT interval corrected using the Fridericia's formula (QTcF) >=450 msec to <480 msec, >=480 msec and >=500 msec; increase from baseline in QTcF interval >=30 msec to <60 msec and >=60 msec.

• Original Primary Outcome Measures (submitted: August 23, 2017): Skin irritation index for Cohort 1 [ Time Frame: Day 4 ]

Current Secondary Outcome Measures (submitted: October 26, 2018)

• Cohort 1: Number of Participants With Treatment-Emergent Adverse Events (AEs) And Serious Adverse Events (SAEs) [ Time Frame: Baseline 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. 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 28 days after last dose of study drug (up to Day 29) that were absent before treatment or that worsened relative to pre-treatment state. AEs included both SAEs and non-serious AEs.
• Cohort 2: Maximum Observed Plasma Concentration (Cmax) of Crisaborole and Its Identified Main Oxidative Metabolites [ Time Frame: Pre-dose, 3, 12 and 24 hours post-dose on Day 1 and Day 8 ]
  AN7602 and AN8323 were the main identified oxidative metabolites of Crisaborole.
• Cohort 2: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Crisaborole and Its Metabolites [ Time Frame: Pre-dose, 3, 12 and 24 hours post-dose on Day 1 and Day 8 ]
  AN7602 and AN8323 were the main identified oxidative metabolites of Crisaborole.
• 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 [ Time Frame: Pre-dose, 3, 12 and 24 hours post-dose on Day 1 and Day 8 ]
  AN7602 and AN8323 were the main identified oxidative metabolites of Crisaborole.
• 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) [ Time Frame: Pre-dose, 3, 12 and 24 hours post-dose on Day 1 and Day 8 ]
  AN7602 and AN8323 were the main identified oxidative metabolites of Crisaborole.
• 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 [ Time Frame: Pre-dose, 3, 12 and 24 hours post-dose on Day 1 and Day 8 ]
  AN7602 and AN8323 were the main identified oxidative metabolites of Crisaborole. AUC tau was defined as area under the plasma concentration-time curve from time 0 to time tau, the dosing interval, where tau =12 hours.
• Cohort 2: Accumulation Ratio for Cmax (Rac [Cmax]) of Crisaborole and Its Identified Main Oxidative Metabolites [ Time Frame: Pre-dose, 3, 12 and 24 hours post-dose on Day 1 and 8 ]
  AN7602 and AN8323 were the main identified oxidative metabolites of Crisaborole. Accumulation ratio for Cmax (Rac, Cmax) was calculated as Cmax on Day 8 divided by Cmax on Day 1. Cmax was the maximum plasma concentration of Crisaborole and its identified main oxidative metabolites.
• Cohort 2: Accumulation Ratio for AUCtau (Rac [AUCtau]) of Crisaborole and Its Identified Main Oxidative Metabolites [ Time Frame: Pre-dose, 3, 12 and 24 hours post-dose on Day 1 and 8 ]
  AN7602 and AN8323 were the main identified oxidative metabolites of Crisaborole. Accumulation ratio for AUCtau (Rac) was calculated as area under the curve from time zero to end of dosing interval (AUCtau) on Day 8 divided by AUCtau on Day 1. Dosing interval = 12 hours.

Original Secondary Outcome Measures (submitted: August 23, 2017)

• Maximum observed plasma concentration (Cmax) [ Time Frame: Day 1 and 8 ]
• Time to reach maximum observed plasma concentration (Tmax) [ Time Frame: Day 1 and 8 ]
• Area under the plasma concentration-time curve from zero time until (AUClast) [ Time Frame: Day 1 and 8 ]
• Area under the plasma concentration-time curve from time zero to the 24 hours (AUC24) [ Time Frame: Day 1 and 8 ]
• Area under the plasma concentration-time curve from time zero to time tau (AUCt) [ Time Frame: Day 1 and 8 ]
• Accumulation ratio for Cmax [ Time Frame: Day 8 ]
• Accumulation ratio for AUCt [ Time Frame: Day 8 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Basic Science

Condition

• Healthy
• Atopic Dermatitis

Intervention

• Drug: Crisaborole ointment 2%
  Crisaborole ointment 2%
• Drug: Vehicle
  Vehicle

Study Arms

• Experimental: Crisaborole ointment 2%
  Intervention: Drug: Crisaborole ointment 2%
• Placebo Comparator: Vehicle
  Intervention: Drug: Vehicle

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 23, 2017): 32
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: November 27, 2017
• Actual Primary Completion Date: November 27, 2017 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan

Administrative Information

• NCT Number: NCT03260595
• Other Study ID Numbers: C3291029
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: Information relating to our policy on data sharing and the process for requesting data can be found at the following link: http://www.pfizer.com/research/clinical_trials/trial_data_and_results/data_requests

• Current Responsible Party: Pfizer
• Original Responsible Party: Same as current
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: October 2018