Back to resultsA Study of Crisaborole Ointment 2% in Adult Japanese Healthy Subjects and Adult Japanese Subjects With Mild To Moderate Atopic Dermatitis
Primary Purpose
Healthy, Atopic Dermatitis
Status
Completed
Phase
Phase 1
Locations
Japan
Study Type
Interventional
Intervention
Crisaborole ointment 2%
Vehicle
Sponsored by
About this trial
This is an interventional basic science trial for Healthy
Eligibility Criteria
Inclusion Criteria:
Cohort 1
- Healthy male Japanese subjects who, at the time of screening, are between the ages of 20 and 55 years, inclusive.
- Healthy skin on which reddening can be easily recognized in the area of the test fields.
Cohort 2
- 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.
- Diagnosis of AD based on the criteria of Hanifin and Rajka (1980).
- Has at least 25% Treatable %BSA on Day 1 (excluding the scalp and designated venous access areas).
- Has an Investigator's static global assessment (ISGA) score of Mild (2) or Moderate (3) on Day 1.
Exclusion Criteria:
Cohort 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.
- Subjects who have psoriasis and/or active AD/eczema.
- Subjects who have a history of AD.
- 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.
- Known sensitivity to any of the components of the investigational products.
- History of the rash to the adhesive plaster, contact dermatitis to metal, or cosmetic and household articles.
Cohort 2
- 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.
- Has unstable AD or a consistent requirement for strong to strongest potency topical corticosteroids to manage AD signs and symptoms.
- Has a significant active systemic or localized infection, including known actively infected AD.
- Has a history or evidence of clinically significant or severe allergies (eg, seasonal, pet dander, environmental, food) requiring acute or chronic treatment.
- Has recent or anticipated concomitant use of topical or systemic therapies that might alter the course of AD.
- 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]).
- Has a known sensitivity to any of the components of crisaborole ointment 2%.
- 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.
Sites / Locations
- Medical Corporation Heishinkai OPHAC Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Crisaborole ointment 2%
Vehicle
Arm Description
Outcomes
Primary Outcome Measures
Cohort 1: Skin Irritation Index
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)
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
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
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
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.
Secondary Outcome Measures
Cohort 1: 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. 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
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
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
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)
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
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
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
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03260595
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
September 13, 2017 (Actual)
Primary Completion Date
November 27, 2017 (Actual)
Study Completion Date
November 27, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Healthy, Atopic Dermatitis
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
32 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Crisaborole ointment 2%
Arm Type
Experimental
Arm Title
Vehicle
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Crisaborole ointment 2%
Intervention Description
Crisaborole ointment 2%
Intervention Type
Drug
Intervention Name(s)
Vehicle
Intervention Description
Vehicle
Primary Outcome Measure Information:
Title
Cohort 1: Skin Irritation Index
Description
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.
Time Frame
Day 3 to 4
Title
Cohort 2: Number of Participants With Treatment-Emergent Adverse Events (AEs) And Serious Adverse Events (SAEs)
Description
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.
Time Frame
Baseline up to Day 36
Title
Cohort 2: Number of Participants With Clinically Significant Vital Signs Abnormalities
Description
Vital signs included pulse rate and blood pressure. Clinical significance of vital signs was determined at the investigator's discretion.
Time Frame
Baseline up to end of treatment (Day 8)
Title
Cohort 2: Number of Participants With Laboratory Tests Abnormalities
Description
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).
Time Frame
Baseline up to end of treatment (Day 8)
Title
Cohort 2: Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities
Description
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.
Time Frame
Baseline up to end of treatment (Day 8)
Secondary Outcome Measure Information:
Title
Cohort 1: Number of Participants With Treatment-Emergent Adverse Events (AEs) And Serious Adverse Events (SAEs)
Description
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.
Time Frame
Baseline up to Day 29
Title
Cohort 2: Maximum Observed Plasma Concentration (Cmax) of Crisaborole and Its Identified Main Oxidative Metabolites
Description
AN7602 and AN8323 were the main identified oxidative metabolites of Crisaborole.
Time Frame
Pre-dose, 3, 12 and 24 hours post-dose on Day 1 and Day 8
Title
Cohort 2: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Crisaborole and Its Metabolites
Description
AN7602 and AN8323 were the main identified oxidative metabolites of Crisaborole.
Time Frame
Pre-dose, 3, 12 and 24 hours post-dose on Day 1 and Day 8
Title
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
Description
AN7602 and AN8323 were the main identified oxidative metabolites of Crisaborole.
Time Frame
Pre-dose, 3, 12 and 24 hours post-dose on Day 1 and Day 8
Title
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)
Description
AN7602 and AN8323 were the main identified oxidative metabolites of Crisaborole.
Time Frame
Pre-dose, 3, 12 and 24 hours post-dose on Day 1 and Day 8
Title
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
Description
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.
Time Frame
Pre-dose, 3, 12 and 24 hours post-dose on Day 1 and Day 8
Title
Cohort 2: Accumulation Ratio for Cmax (Rac [Cmax]) of Crisaborole and Its Identified Main Oxidative Metabolites
Description
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.
Time Frame
Pre-dose, 3, 12 and 24 hours post-dose on Day 1 and 8
Title
Cohort 2: Accumulation Ratio for AUCtau (Rac [AUCtau]) of Crisaborole and Its Identified Main Oxidative Metabolites
Description
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.
Time Frame
Pre-dose, 3, 12 and 24 hours post-dose on Day 1 and 8
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Cohort 1
Healthy male Japanese subjects who, at the time of screening, are between the ages of 20 and 55 years, inclusive.
Healthy skin on which reddening can be easily recognized in the area of the test fields.
Cohort 2
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.
Diagnosis of AD based on the criteria of Hanifin and Rajka (1980).
Has at least 25% Treatable %BSA on Day 1 (excluding the scalp and designated venous access areas).
Has an Investigator's static global assessment (ISGA) score of Mild (2) or Moderate (3) on Day 1.
Exclusion Criteria:
Cohort 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.
Subjects who have psoriasis and/or active AD/eczema.
Subjects who have a history of AD.
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.
Known sensitivity to any of the components of the investigational products.
History of the rash to the adhesive plaster, contact dermatitis to metal, or cosmetic and household articles.
Cohort 2
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.
Has unstable AD or a consistent requirement for strong to strongest potency topical corticosteroids to manage AD signs and symptoms.
Has a significant active systemic or localized infection, including known actively infected AD.
Has a history or evidence of clinically significant or severe allergies (eg, seasonal, pet dander, environmental, food) requiring acute or chronic treatment.
Has recent or anticipated concomitant use of topical or systemic therapies that might alter the course of AD.
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]).
Has a known sensitivity to any of the components of crisaborole ointment 2%.
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Medical Corporation Heishinkai OPHAC Hospital
City
Osaka-shi
State/Province
Osaka
ZIP/Postal Code
532-0003
Country
Japan
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing 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
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=C3291029&StudyName=A+Phase+1%2C+Single-center%2C+Randomized%2C+Vehicle-controlled%2C+Parallel-cohort+Study+Of+Crisaborole+Ointment+2%25+To+Evaluate+The+Skin+Irritation+Potential+In+Adult+Japanese+Healthy+Subjects%2C+And+To+Evaluate+The+Safety%2C+Tolerability+And+Pharmacokinetics+In+Adult+Japanese+Subjects+With+Mild+To+Moderate+Atopic+Dermatitis
Description
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A Study of Crisaborole Ointment 2% in Adult Japanese Healthy Subjects and Adult Japanese Subjects With Mild To Moderate Atopic Dermatitis
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