Safety, Tolerability And Efficacy Study Of Topical PF-06763809 In Subjects With Mild To Moderate Chronic Plaque Psoriasis

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03469336
• Collaborator: (none)
• Enrollment: 18
• Locations: 2
• Arm: 1
• Actual Duration (Months): 10.8
• Patients Per Site: 9
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

The study is a randomized, double blinded, vehicle and active comparator controlled, multiple dose study in subjects with chronic plaque psoriasis. The study will have approximately 15 completers. Each subjects will receive three different topical doses of PF 06763809, PF 06763809 vehicle, and two active comparators. These will be applied to six different treatment fields for 18 days. The total duration of participation in the study will be approximately 7 weeks (minimum) to approximately 11 weeks (maximum), including the interval from Screening to the Follow up phone call visit.

Condition or Disease	Intervention/Treatment	Phase
Psoriasis	Drug: PF-06763809; Other: Vehicle; Drug: Calcipotriene/calcipotriol; Drug: Betamethasone	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Masking Description: This study is a single arm multi-intervention study. The interventions are masked to participant, investigator, providers and assessors.
• Primary Purpose: Treatment
• Official Title: A PHASE 1, RANDOMIZED, DOUBLE-BLIND, VEHICLE AND ACTIVE COMPARATOR-CONTROLLED, PSORIASIS PLAQUE TEST STUDY TO ASSESS SAFETY, TOLERABILITY, AND PSORIATIC SKIN INFILTRATE THICKNESS FOLLOWING REPEATED, TOPICAL DOSES OF PF-06763809 SOLUTION IN SUBJECTS WITH MILD TO MODERATE CHRONIC PLAQUE PSORIASIS
• Actual Study Start Date: Apr 24, 2018
• Actual Primary Completion Date: Mar 20, 2019
• Actual Study Completion Date: Mar 20, 2019

Arms and Interventions

Arm	Intervention/Treatment
Other: All subjects All subjects will receive all six interventions/treatments applied to six different treatment fields.	Drug: PF-06763809; Three different concentrations will be administered to three different treatment fields: 2.3%, 0.8% and 0.23%; Other: Vehicle; Vehicle matching PF-06763809.; Drug: Calcipotriene/calcipotriol; Calcipotriene/calcipotriol 50 ug/mL solution; Drug: Betamethasone; Betamethasone 1 mg/g solution

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Psoriatic Skin Infiltrate Thickness [Baseline, Days 7, 13 and 19]

   Baseline was defined to be the measurement on Day 1. MMRM analysis of changes in psoriatic skin in psoriatic skin infiltrate thickness/echo poor band (EPB) in response to PF-06763809 2.3%, 0.8% and 0.23% applied topically for 18 consecutive days as compared to the vehicle control. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.

2. Number of Participants With Treatment-emergent Adverse Events (AEs) [Day 1 to Day 49]

   Baseline was defined to be the measurement on Day 1. An AE was any untoward medical occurrence in a clinical investigation patient administered a product or medical device. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of investigational product.

3. Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) [Day 1 to Day 49]

   Baseline was defined to be the measurement on Day 1. The safety laboratory tests including Hematology, Clinical Chemistry and Urinalysis were performed. Hematology evaluation included: hemoglobin (HGB) (gram per decilitre=g/dL), hematocrit, erythrocytes (Ery.), Ery. Mean Corpuscular Volume, Ery. Mean Corpuscular Hemoglobin, Ery. Mean Corpuscular HGB Concentration (picograms per cell=pg/cell), platelets, leukocytes, lymphocytes, and neutrophils. Clinical chemistry evaluation included: bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, protein, albumin, urea nitrogen, urea, creatinine, urate, sodium, potassium, chloride, calcium, bicarbonate, creatine kinase, and glucose. Urinalysis evaluation included: pH, urine glucose, ketones, urine protein, urine hemoglobin, urobilinogen, urine bilirubin, nitrite, and leukocyte esterase. LLN=lower limit of normal, ULN=upper limit of normal.

4. Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria [Day 1 to Day 49]

   Baseline was defined to be the measurement on Day 1. ECG categorical summarization criteria: 1) PR interval (Value>=300 milliseconds [msec], %Change [Chg]>=25/50%); 2) QRS interval (Value>=140 msec, >=50% change from baseline; 2) PR interval (the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization): >=300 msec, >=25% change when baseline is > 200 msec or >=50% change when baseline is less than or equal to (<=) 200 msec; 3) QT interval (time from ECG Q wave to the end of the T wave corresponding to electrical systole): absolute value of >=500 msec; 4) QTc interval (QT corrected for heart rate): absolute value of 450 to <480 msec, 480 to <500 msec, >=500 msec; a change from baseline of 30 to <60 msec or >=60 msec. The corrected QT interval by Fredericia=QTcF Interval.

5. Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria [Day 1 to Day 49]

   Baseline was defined to be the measurement on Day 1. Vital Signs including diastolic blood pressure (DBP), pulse rate, and systolic blood pressure (SBP) were measured.

Secondary Outcome Measures

1. Area Under the Curve of the Psoriatic Skin Infiltrate Thickness [Day 1 to Day 19]

   Baseline was defined to be the measurement on Day 1. To evaluate the Area Under the Curve (AUC) of psoriatic skin infiltrate thickness/EPB for PF 06763809 compared to vehicle by mixed model analysis. The AUC of the psoriatic skin infiltrate thickness/EPB from Day 1 to Day 19 was determined using the linear trapezoidal rule. The log AUC was performed by the natural logarithm of the AUC of the psoriatic skin infiltrate thickness/EPB. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.

2. Change From Baseline in Skin Infiltrate Thickness in Response to PF-06763809 Compared to Calcipotriene/Calcipotriol Solution. [Baseline, Days 7, 13 and 19]

   The effect of PF-06763809 compared to calcipotriene/calcipotriol solution in the change of psoriatic skin infiltrate thickness/EPB both within and following 18 days of treatment. Baseline was defined to be the measurement on Day 1. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.

3. Change From Baseline in Skin Infiltrate Thickness in Response to PF-06763809 Compared to Betamethasone Solution. [Baseline, Days 7, 13 and 19]

   The effect of PF-06763809 compared to betamethasone solution in the change of psoriatic skin infiltrate thickness/EPB both within and following 18 days of treatment. Baseline was defined to be the measurement on Day 1. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Psoriasis vulgaris in a chronic stable phase and with a plaque area of mild to moderate severity sufficient for six treatment fields located in up to three plaque areas

• Target lesion(s) should be on the trunk or extremities (excluding palms/soles).

Exclusion Criteria:

• History of skin sensitivity to topical prescription or non prescription products such as creams, lotions and cosmetics

• Psoriasis guttata, psoriasis punctata, psoriasis erythrodermatica, and pustular psoriasis

• Treatment with any biologics within 3 months prior to Day 1 of the study and during the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rothaar Studien GmbH	Berlin		Germany	10783
2	bioskin GmbH	Hamburg		Germany	20095

Sponsors and Collaborators

• Pfizer

Investigators

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

Study Documents (Full-Text)

• Statistical Analysis Plan - Apr 3, 2018
• Study Protocol - Feb 8, 2018

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT03469336
• Other Study ID Numbers: C3561001; 2017-002684-18
• First Posted: Mar 19, 2018
• Last Update Posted: Jun 25, 2020
• Last Verified: Jun 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Pfizer: Psoriasis; Topical
• Additional relevant MeSH terms: Psoriasis; Betamethasone; Calcipotriene

Study Results

Participant Flow

Pre-assignment Detail	Of 26 participants screened for entry into the study, 4 participants failed at Screening and 4 participants were eligible at Screening but were not randomized in the study, and the remaining 18 participants were assigned to the study treatment.

Arm/Group Title	PF-06763809+Vehicle+Calcipotriene+Betamethasone
Arm/Group Description	All participants with at least 6 test fields received blinded topical doses (2.3%, 0.8% and 0.23%) of PF-06763809, PF-06763809 vehicle, Calcipotriene (50 g/mL) and betamethasone 1 mg/g solution at the six test fields respectively. The dosing volume for all study treatments was 180 µL (164 µL/cm^2), applied topically once daily to 1.1 cm^2 skin surface area of each test field during an 18-day treatment period.
Period Title: Overall Study
STARTED	18
COMPLETED	17
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	PF-06763809+Vehicle+Calcipotriene+Betamethasone
Arm/Group Description	All participants with at least 6 test fields received blinded topical doses (2.3%, 0.8% and 0.23%) of PF-06763809, PF-06763809 vehicle, Calcipotriene (50 g/mL) and betamethasone 1 mg/g solution at the six test fields respectively. The dosing volume for all study treatments was 180 µL (164 µL/cm^2), applied topically once daily to 1.1 cm^2 skin surface area of each test field during an 18-day treatment period.
Overall Participants	18
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	15 83.3%
>=65 years	3 16.7%
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	18 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	6 33.3%
Unknown or Not Reported	12 66.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	18 100%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Psoriatic Skin Infiltrate Thickness
Description	Baseline was defined to be the measurement on Day 1. MMRM analysis of changes in psoriatic skin in psoriatic skin infiltrate thickness/echo poor band (EPB) in response to PF-06763809 2.3%, 0.8% and 0.23% applied topically for 18 consecutive days as compared to the vehicle control. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
Time Frame	Baseline, Days 7, 13 and 19

Outcome Measure Data

Analysis Population Description

Analysis population included all participants who had at least one application of the investigational products and had at least one post-baseline assessment of the primary efficacy variable, were included in the Full Analysis Set (FAS).

Arm/Group Title	A: PF-06763809 2.3% Solution	B: PF-06763809 0.8% Solution	C: PF-06763809 0.23% Solution	D: PF-06763809 Vehicle
Arm/Group Description	Participants were exposed to 2.3% PF-06763809 solution once daily during an 18-day treatment period. Daily dosage: approximately 4.1 mg PF-06763809. Total dosage: approximately 75 mg PF-06763809	Participants were exposed to 0.8% PF-06763809 solution once daily during an 18-day treatment period. Daily dosage: approximately 1.4 mg PF-06763809. Total dosage: approximately 26 mg PF-06763809	Participants were exposed to 0.23% PF-06763809 solution once daily during an 18-day treatment period. Daily dosage: approximately 0.41 mg PF-06763809. Total dosage: approximately 7.5 mg PF-06763809.	Participants were exposed to active ingredient-free vehicle to PF-06763809 treatments once daily during an 18-day treatment period.
Measure Participants	18	18	18	18
Day 7	0.89 (0.073)	0.92 (0.073)	0.97 (0.073)	0.93 (0.073)
Day 13	0.74 (0.458)	0.76 (0.458)	0.87 (0.458)	0.80 (0.458)
Day 19	0.71 (0.526)	0.70 (0.526)	0.80 (0.526)	0.70 (0.526)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A: PF-06763809 2.3% Solution, D: PF-06763809 Vehicle
	Comments	The efficacy assessment of PF-06763809 was performed for the change from baseline in log of the psoriatic skin infiltrate thickness/EPB on Day 19 using a longitudinal analysis of covariance model, with treatment, visit, treatment by visit interaction as main effects and the log of the psoriatic skin infiltrate thickness/EPB at baseline as covariate.
	Type of Statistical Test	Other
	Comments	Ratio
Statistical Test of Hypothesis	p-Value	0.9883
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Ratio (Test/Reference)
	Estimated Value	1.0109
	Confidence Interval	(2-Sided) 95%; 0.2364 to 4.3226
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.732
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	B: PF-06763809 0.8% Solution, D: PF-06763809 Vehicle
	Comments	The efficacy assessment of PF-06763809 was performed for the change from baseline in log of the psoriatic skin infiltrate thickness/EPB on Day 19 using a longitudinal analysis of covariance model, with treatment, visit, treatment by visit interaction as main effects and the log of the psoriatic skin infiltrate thickness/EPB at baseline as covariate.
	Type of Statistical Test	Other
	Comments	Ratio
Statistical Test of Hypothesis	p-Value	0.9977
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Ratio (Test/Reference)
	Estimated Value	0.9979
	Confidence Interval	(2-Sided) 95%; 0.2334 to 4.2671
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.732
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	C: PF-06763809 0.23% Solution, D: PF-06763809 Vehicle
	Comments	The efficacy assessment of PF-06763809 was performed for the change from baseline in log of the psoriatic skin infiltrate thickness/EPB on Day 19 using a longitudinal analysis of covariance model, with treatment, visit, treatment by visit interaction as main effects and the log of the psoriatic skin infiltrate thickness/EPB at baseline as covariate.
	Type of Statistical Test	Other
	Comments	Ratio
Statistical Test of Hypothesis	p-Value	0.8600
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Ratio (Test/Reference)
	Estimated Value	1.1382
	Confidence Interval	(2-Sided) 95%; 0.2662 to 4.8670
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.732
	Estimation Comments

2. Primary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events (AEs)
Description	Baseline was defined to be the measurement on Day 1. An AE was any untoward medical occurrence in a clinical investigation patient administered a product or medical device. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of investigational product.
Time Frame	Day 1 to Day 49

Outcome Measure Data

Analysis Population Description

Analysis population included all participants who received at least one application of the investigational products and had at least one post-baseline efficacy assessment value.

Arm/Group Title	PF-06763809+Vehicle+Calcipotriene+Betamethasone
Arm/Group Description	All participants with at least 6 test fields received blinded topical doses (2.3%, 0.8% and 0.23%) of PF-06763809, PF-06763809 vehicle, Calcipotriene (50 g/mL) and betamethasone 1 mg/g solution at the six test fields respectively. The dosing volume for all study treatments was 180 µL (164 µL/cm^2), applied topically once daily to 1.1 cm^2 skin surface area of each test field during an 18-day treatment period.
Measure Participants	18
Count of Participants [Participants]	6 33.3%

3. Primary Outcome

Title	Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)
Description	Baseline was defined to be the measurement on Day 1. The safety laboratory tests including Hematology, Clinical Chemistry and Urinalysis were performed. Hematology evaluation included: hemoglobin (HGB) (gram per decilitre=g/dL), hematocrit, erythrocytes (Ery.), Ery. Mean Corpuscular Volume, Ery. Mean Corpuscular Hemoglobin, Ery. Mean Corpuscular HGB Concentration (picograms per cell=pg/cell), platelets, leukocytes, lymphocytes, and neutrophils. Clinical chemistry evaluation included: bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, protein, albumin, urea nitrogen, urea, creatinine, urate, sodium, potassium, chloride, calcium, bicarbonate, creatine kinase, and glucose. Urinalysis evaluation included: pH, urine glucose, ketones, urine protein, urine hemoglobin, urobilinogen, urine bilirubin, nitrite, and leukocyte esterase. LLN=lower limit of normal, ULN=upper limit of normal.
Time Frame	Day 1 to Day 49

Outcome Measure Data

Analysis Population Description

Analysis population included all participants who received at least one application of the investigational products and had at least one post-baseline efficacy assessment value.

Arm/Group Title	PF-06763809+Vehicle+Calcipotriene+Betamethasone
Arm/Group Description	All participants with at least 6 test fields received blinded topical doses (2.3%, 0.8% and 0.23%) of PF-06763809, PF-06763809 vehicle, Calcipotriene (50 g/mL) and betamethasone 1 mg/g solution at the six test fields respectively. The dosing volume for all study treatments was 180 µL (164 µL/cm^2), applied topically once daily to 1.1 cm^2 skin surface area of each test field during an 18-day treatment period.
Measure Participants	18
Hemoglobin (HGB) (g/dL) <0.8xLLN	0 0%
Hematocrit (%) <0.8xLLN	0 0%
Erythrocytes (10^6/mm^3) <0.8xLLN	0 0%
Ery. Mean Corpuscular Volume (μm^3) <0.9xLLN	0 0%
Ery. Mean Corpuscular Volume (μm^3) >1.1xULN	1 5.6%
Ery. Mean Corpuscular HGB (pg/cell) <0.9xLLN	0 0%
Ery. Mean Corpuscular HGB (pg/cell) >1.1xULN	0 0%
Ery. Mean Corpuscular HGB Conc. (g/dL) <0.9xLLN	1 5.6%
Ery. Mean Corpuscular HGB Conc. (g/dL) >1.1xULN	0 0%
Platelets (10^3/mm^3) <0.5xLLN	0 0%
Platelets (10^3/mm^3) >1.75xULN	0 0%
Leukocytes (10^3/mm^3) <0.6xLLN	0 0%
Leukocytes (10^3/mm^3) >1.5xULN	0 0%
Lymphocytes (10^3/mm^3) <0.8xLLN	2 11.1%
Lymphocytes (10^3/mm^3) >1.2xULN	0 0%
Neutrophils (10^3/mm^3) <0.8xLLN	0 0%
Neutrophils (10^3/mm^3) >1.2xULN	0 0%
Basophils (10^3/mm^3) >1.2xULN	0 0%
Eosinophils (10^3/mm^3) >1.2xULN	0 0%
Monocytes (10^3/mm^3) >1.2xULN	1 5.6%
Bilirubin (mg/dL) >1.5xULN	0 0%
Aspartate Aminotransferase (U/L) >3.0xULN	0 0%
Alanine Aminotransferase (U/L) >3.0xULN	0 0%
Alkaline Phosphatase (U/L) >3.0xULN	0 0%
Protein (g/dL) <0.8xLLN	0 0%
Protein (g/dL) >1.2xULN	0 0%
Albumin (g/dL) <0.8x LLN	0 0%
Albumin (g/dL) >1.2xULN	0 0%
Urea Nitrogen (mg/dL) >1.3xULN	0 0%
Urea (mmol/L) >1.3xULN	0 0%
Creatinine (mg/dL) >1.3xULN	0 0%
Urate (mg/dL) >1.2xULN	0 0%
Sodium (mEq/L) <0.95xLLN	0 0%
Sodium (mEq/L) >1.05xULN	0 0%
Potassium (mEq/L) <0.9x LLN	0 0%
Potassium (mEq/L) >1.1xULN	0 0%
Chloride (mEq/L) <0.9xLLN	0 0%
Chloride (mEq/L) >1.1xULN	0 0%
Calcium (mg/dL) <0.9x LLN	0 0%
Calcium (mg/dL) >1.1xULN	0 0%
Bicarbonate (mEq/L) <0.9x LLN	0 0%
Bicarbonate (mEq/L) >1.1xULN	0 0%
Glucose (mg/dL) <0.6xLLN	0 0%
Glucose (mg/dL) >1.5xULN	0 0%
pH (Scalar) <4.5	0 0%
pH (Scalar) >8	0 0%
URINE Glucose (Scalar) >=1	0 0%
Ketones (Scalar) >=1	0 0%
URINE Protein (Scalar) >=1	0 0%
URINE Hemoglobin (Scalar) >=1	0 0%
Urobilinogen (Scalar) >=1	0 0%
URINE Bilirubin (Scalar) >=1	0 0%
Nitrite (Scalar) >=1	0 0%
Leukocyte Esterase (Scalar) >=1	0 0%

4. Primary Outcome

Title	Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria
Description	Baseline was defined to be the measurement on Day 1. ECG categorical summarization criteria: 1) PR interval (Value>=300 milliseconds [msec], %Change [Chg]>=25/50%); 2) QRS interval (Value>=140 msec, >=50% change from baseline; 2) PR interval (the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization): >=300 msec, >=25% change when baseline is > 200 msec or >=50% change when baseline is less than or equal to (<=) 200 msec; 3) QT interval (time from ECG Q wave to the end of the T wave corresponding to electrical systole): absolute value of >=500 msec; 4) QTc interval (QT corrected for heart rate): absolute value of 450 to <480 msec, 480 to <500 msec, >=500 msec; a change from baseline of 30 to <60 msec or >=60 msec. The corrected QT interval by Fredericia=QTcF Interval.
Time Frame	Day 1 to Day 49

Outcome Measure Data

Analysis Population Description

Analysis population included all participants who received at least one application of the investigational products and had at least one post-baseline efficacy assessment value. All scheduled ECGs were performed after the participant had rested quietly for 10 minutes in a supine position.

Arm/Group Title	PF-06763809+Vehicle+Calcipotriene+Betamethasone
Arm/Group Description	All participants with at least 6 test fields received blinded topical doses (2.3%, 0.8% and 0.23%) of PF-06763809, PF-06763809 vehicle, Calcipotriene (50 g/mL) and betamethasone 1 mg/g solution at the six test fields respectively. The dosing volume for all study treatments was 180 µL (164 µL/cm^2), applied topically once daily to 1.1 cm^2 skin surface area of each test field during an 18-day treatment period.
Measure Participants	18
Value>=300 msec (PR Interval)	0 0%
%Change (Chg)>=25/50% (PR Interval)	0 0%
Value>=140 msec (QRS Interval)	0 0%
%Chg>=50% (QRS Interval)	0 0%
Value>=500 msec (QT Interval)	0 0%
450<=Value<480 msec (QTc Interval)	2 11.1%
480<=Value<500 msec (QTc Interval)	0 0%
Value>=500 msec (QTc Interval)	0 0%
30<=Chg<60 msec (QTc Interval)	2 11.1%
Chg>=60 msec (QTc Interval)	1 5.6%
450<=Value<480 msec (QTcF Interval)	0 0%
480<=Value<500 msec (QTcF Interval)	0 0%
Value>=500 msec (QTcF Interval)	0 0%
30<=Chg<60 msec (QTcF Interval)	0 0%
Chg>=60 msec (QTcF Interval)	0 0%

5. Primary Outcome

Title	Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria
Description	Baseline was defined to be the measurement on Day 1. Vital Signs including diastolic blood pressure (DBP), pulse rate, and systolic blood pressure (SBP) were measured.
Time Frame	Day 1 to Day 49

Outcome Measure Data

Analysis Population Description

Analysis population included all participants who received at least one application of the investigational products and had at least one post-baseline efficacy assessment value.

Arm/Group Title	PF-06763809+Vehicle+Calcipotriene+Betamethasone
Arm/Group Description	All participants with at least 6 test fields received blinded topical doses (2.3%, 0.8% and 0.23%) of PF-06763809, PF-06763809 vehicle, Calcipotriene (50 g/mL) and betamethasone 1 mg/g solution at the six test fields respectively. The dosing volume for all study treatments was 180 µL (164 µL/cm^2), applied topically once daily to 1.1 cm^2 skin surface area of each test field during an 18-day treatment period.
Measure Participants	18
DBP Value <50 mmHg	0 0%
DBP Chg >= 20 mmHg increase	0 0%
DBP Chg >= 20 mmHg decrease	0 0%
Pulse Rate Value <40 beats per minute (bpm)	0 0%
Pulse Rate Value >120 bpm	0 0%
SBP Value <90 mmHg	0 0%
SBP Chg >= 30 mmHg increase	0 0%
SBP Chg >= 30 mmHg decrease	0 0%

6. Secondary Outcome

Title	Area Under the Curve of the Psoriatic Skin Infiltrate Thickness
Description	Baseline was defined to be the measurement on Day 1. To evaluate the Area Under the Curve (AUC) of psoriatic skin infiltrate thickness/EPB for PF 06763809 compared to vehicle by mixed model analysis. The AUC of the psoriatic skin infiltrate thickness/EPB from Day 1 to Day 19 was determined using the linear trapezoidal rule. The log AUC was performed by the natural logarithm of the AUC of the psoriatic skin infiltrate thickness/EPB. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
Time Frame	Day 1 to Day 19

Outcome Measure Data

Analysis Population Description

Analysis population included all participants who had at least one application of the investigational products and had at least one post-baseline assessment of the primary efficacy variable, were included in the Full Analysis Set (FAS).

Arm/Group Title	A: PF-06763809 2.3% Solution	B: PF-06763809 0.8% Solution	C: PF-06763809 0.23% Solution	D: PF-06763809 Vehicle
Arm/Group Description	Participants were exposed to 2.3% PF-06763809 solution once daily during an 18-day treatment period. Daily dosage: approximately 4.1 mg PF-06763809. Total dosage: approximately 75 mg PF-06763809	Participants were exposed to 0.8% PF-06763809 solution once daily during an 18-day treatment period. Daily dosage: approximately 1.4 mg PF-06763809. Total dosage: approximately 26 mg PF-06763809	Participants were exposed to 0.23% PF-06763809 solution once daily during an 18-day treatment period. Daily dosage: approximately 0.41 mg PF-06763809. Total dosage: approximately 7.5 mg PF-06763809.	Participants were exposed to active ingredient-free vehicle to PF-06763809 treatments once daily during an 18-day treatment period.
Measure Participants	18	18	18	18
Geometric Mean (Standard Error) [nanograms*hour per milliliter (ng*h/mL)]	6191.52 (0.124)	5996.26 (0.115)	6921.58 (0.107)	6204.82 (0.094)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A: PF-06763809 2.3% Solution, D: PF-06763809 Vehicle
	Comments	To evaluate the AUC of psoriatic skin infiltrate thickness/EPB for PF-06763809 compared to vehicle.
	Type of Statistical Test	Other
	Comments	Ratio
Statistical Test of Hypothesis	p-Value	0.9763
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Ratio (Test/Reference)
	Estimated Value	0.9979
	Confidence Interval	(2-Sided) 95%; 0.8588 to 1.1594
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.071
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	B: PF-06763809 0.8% Solution, D: PF-06763809 Vehicle
	Comments	To evaluate the AUC of psoriatic skin infiltrate thickness/EPB for PF-06763809 compared to vehicle.
	Type of Statistical Test	Other
	Comments	Ratio
Statistical Test of Hypothesis	p-Value	0.5081
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Ratio (Test/Reference)
	Estimated Value	0.9664
	Confidence Interval	(2-Sided) 95%; 0.8686 to 1.0752
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.051
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	C: PF-06763809 0.23% Solution, D: PF-06763809 Vehicle
	Comments	To evaluate the AUC of psoriatic skin infiltrate thickness/EPB for PF-06763809 compared to vehicle.
	Type of Statistical Test	Other
	Comments	Ratio
Statistical Test of Hypothesis	p-Value	0.0249
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Ratio (Test/Reference)
	Estimated Value	1.1155
	Confidence Interval	(2-Sided) 95%; 1.0157 to 1.2252
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.044
	Estimation Comments

7. Secondary Outcome

Title	Change From Baseline in Skin Infiltrate Thickness in Response to PF-06763809 Compared to Calcipotriene/Calcipotriol Solution.
Description	The effect of PF-06763809 compared to calcipotriene/calcipotriol solution in the change of psoriatic skin infiltrate thickness/EPB both within and following 18 days of treatment. Baseline was defined to be the measurement on Day 1. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
Time Frame	Baseline, Days 7, 13 and 19

Outcome Measure Data

Analysis Population Description

Analysis population included all participants who had at least one application of the investigational products and had at least one post-baseline assessment of the primary efficacy variable, were included in the Full Analysis Set (FAS).

Arm/Group Title	A: PF-06763809 2.3% Solution	B: PF-06763809 0.8% Solution	C: PF-06763809 0.23% Solution	E: Calcipotriene/Calcipotriol Solution
Arm/Group Description	Participants were exposed to 2.3% PF-06763809 solution once daily during an 18-day treatment period. Daily dosage: approximately 4.1 mg PF-06763809. Total dosage: approximately 75 mg PF-06763809	Participants were exposed to 0.8% PF-06763809 solution once daily during an 18-day treatment period. Daily dosage: approximately 1.4 mg PF-06763809. Total dosage: approximately 26 mg PF-06763809	Participants were exposed to 0.23% PF-06763809 solution once daily during an 18-day treatment period. Daily dosage: approximately 0.41 mg PF-06763809. Total dosage: approximately 7.5 mg PF-06763809.	Participants were exposed to Calcipotriene/ calcipotriol (50 g/mL) once daily during an 18-day treatment period. Daily dosage of calcipotriol: approximately 0.01 mg. Total dosage: approximately 0.18 mg.
Measure Participants	18	18	18	18
Day 7	0.89 (0.073)	0.92 (0.073)	0.97 (0.073)	0.77 (0.073)
Day 13	0.74 (0.458)	0.76 (0.458)	0.87 (0.458)	0.86 (0.458)
Day 19	0.71 (0.526)	0.70 (0.526)	0.80 (0.526)	0.90 (0.526)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A: PF-06763809 2.3% Solution, D: PF-06763809 Vehicle
	Comments	The effect of PF-06763809 compared to calcipotriene/calcipotriol solution in the change of psoriatic skin infiltrate thickness/EPB on Day 19.
	Type of Statistical Test	Other
	Comments	Ratio
Statistical Test of Hypothesis	p-Value	0.7540
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Ratio (Test/Reference)
	Estimated Value	0.7946
	Confidence Interval	(2-Sided) 95%; 0.1858 to 3.3977
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.732
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	B: PF-06763809 0.8% Solution, D: PF-06763809 Vehicle
	Comments	The effect of PF-06763809 compared to calcipotriene/calcipotriol solution in the change of psoriatic skin infiltrate thickness/EPB on Day 19.
	Type of Statistical Test	Other
	Comments	Ratio
Statistical Test of Hypothesis	p-Value	0.7407
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Ratio (Test/Reference)
	Estimated Value	0.7844
	Confidence Interval	(2-Sided) 95%; 0.1834 to 3.3540
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.732
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	C: PF-06763809 0.23% Solution, D: PF-06763809 Vehicle
	Comments	The effect of PF-06763809 compared to calcipotriene/calcipotriol solution in the change of psoriatic skin infiltrate thickness/EPB on Day 19.
	Type of Statistical Test	Other
	Comments	Ratio
Statistical Test of Hypothesis	p-Value	0.8793
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Ratio (Test/Reference)
	Estimated Value	0.8946
	Confidence Interval	(2-Sided) 95%; 0.2092 to 3.8256
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.732
	Estimation Comments

8. Secondary Outcome

Title	Change From Baseline in Skin Infiltrate Thickness in Response to PF-06763809 Compared to Betamethasone Solution.
Description	The effect of PF-06763809 compared to betamethasone solution in the change of psoriatic skin infiltrate thickness/EPB both within and following 18 days of treatment. Baseline was defined to be the measurement on Day 1. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
Time Frame	Baseline, Days 7, 13 and 19

Outcome Measure Data

Analysis Population Description

Analysis population included all participants who had at least one application of the investigational products and had at least one post-baseline assessment of the primary efficacy variable, were included in the Full Analysis Set (FAS).

Arm/Group Title	A: PF-06763809 2.3% Solution	B: PF-06763809 0.8% Solution	C: PF-06763809 0.23% Solution	F: Betamethasone Solution.
Arm/Group Description	Participants were exposed to 2.3% PF-06763809 solution once daily during an 18-day treatment period. Daily dosage: approximately 4.1 mg PF-06763809. Total dosage: approximately 75 mg PF-06763809	Participants were exposed to 0.8% PF-06763809 solution once daily during an 18-day treatment period. Daily dosage: approximately 1.4 mg PF-06763809. Total dosage: approximately 26 mg PF-06763809	Participants were exposed to 0.23% PF-06763809 solution once daily during an 18-day treatment period. Daily dosage: approximately 0.41 mg PF-06763809. Total dosage: approximately 7.5 mg PF-06763809.	Participants were exposed to Betamethasone (1 mg/g) once daily during an 18-day treatment period. Daily dosage of approximately 0.18 mg. Total dosage: approximately 3.2 mg.
Measure Participants	18	18	18	18
Day 7	0.89 (0.073)	0.92 (0.073)	0.97 (0.073)	0.43 (0.073)
Day 13	0.74 (0.458)	0.76 (0.458)	0.87 (0.458)	0.03 (0.458)
Day 19	0.71 (0.526)	0.70 (0.526)	0.80 (0.526)	0.01 (0.526)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A: PF-06763809 2.3% Solution, D: PF-06763809 Vehicle
	Comments	The effect of PF-06763809 compared to betamethasone solution in the change of psoriatic skin infiltrate thickness/EPB on Day 19.
	Type of Statistical Test	Other
	Comments	Ratio
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Ratio (Test/Reference)
	Estimated Value	1.081321
	Confidence Interval	(2-Sided) 95%; 0.25287 to 4.623941
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.732
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	B: PF-06763809 0.8% Solution, D: PF-06763809 Vehicle
	Comments	The effect of PF-06763809 compared to betamethasone solution in the change of psoriatic skin infiltrate thickness/EPB on Day 19.
	Type of Statistical Test	Other
	Comments	Ratio
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Ratio (Test/Reference)
	Estimated Value	1.067453
	Confidence Interval	(2-Sided) 95%; 0.249631 to 4.564555
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.732
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	C: PF-06763809 0.23% Solution, D: PF-06763809 Vehicle
	Comments	The effect of PF-06763809 compared to betamethasone solution in the change of psoriatic skin infiltrate thickness/EPB on Day 19.
	Type of Statistical Test	Other
	Comments	Ratio
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Ratio (Test/Reference)
	Estimated Value	1.217483
	Confidence Interval	(2-Sided) 95%; 0.284708 to 5.206258
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.732
	Estimation Comments

Adverse Events

Time Frame	Day 1 to Day 49
Adverse Event Reporting Description	All Participants with a treatment area sufficient for 6 treatment fields received topical doses (2.3%, 0.8% and 0.23%) of PF-06763809, vehicle, Calcipotriene (50 g/mL) and betamethasone 1 mg/g solution at 6 test areas, respectively. Therefore, although treatment-emergent skin-related AEs could tell which treatment caused the AE, other treatment-emergent AEs not related to a specific treatment area could not be assigned to a treatment and were reported for the entire participant population.
Arm/Group Title	PF-06763809+Vehicle+Calcipotriene+Betamethasone
Arm/Group Description	All participants with at least 6 test fields received blinded topical doses (2.3%, 0.8% and 0.23%) of PF-06763809, PF-06763809 vehicle, Calcipotriene (50 g/mL) and betamethasone 1 mg/g solution at the six test fields respectively. The dosing volume for all study treatments was 180 µL (164 µL/cm^2), applied topically once daily to 1.1 cm^2 skin surface area of each test field during an 18-day treatment period.
All Cause Mortality
	PF-06763809+Vehicle+Calcipotriene+Betamethasone
	Affected / at Risk (%)	# Events
Total	0/18 (0%)
Serious Adverse Events
	PF-06763809+Vehicle+Calcipotriene+Betamethasone
	Affected / at Risk (%)	# Events
Total	0/18 (0%)
Other (Not Including Serious) Adverse Events
	PF-06763809+Vehicle+Calcipotriene+Betamethasone
	Affected / at Risk (%)	# Events
Total	6/18 (33.3%)
Eye disorders
Blepharitis	1/18 (5.6%)	1
Infections and infestations
Nasopharyngitis	1/18 (5.6%)	1
Skin and subcutaneous tissue disorders
Psoriasis	1/18 (5.6%)	1
Dermatitis contact	4/18 (22.2%)	4
Pruritus	1/18 (5.6%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.