Dose Ranging Study To Assess Efficacy, Safety and Tolerability Of PF-06700841 Topical Cream In Psoriasis

The Psoriasis Area and Severity Index (PASI) score (0-72, with higher score representing greater severity) is a measurement of the severity and extent of psoriasis. The four regions of the body parts are head (10%), arms (20%), trunk (30%) and legs (40%). In each region, the area is expressed as a score of 0 (nothing), 1 (1-9%), 2 (10-29%), 3 (30-49%), 4 (50-69%), 5 (70-89%) or 6 (90-100%). Within each area, the degree of severity for erythema, induration and scaling are estimated between 0 and 4, with 4 being the highest severity. The final score combines disease severity and effected body surface area (BSA) from for four regions using the formula PASI =0.1Ah(Eh + Ih + Sh) + 0.2Au(Eu + Iu + Su) + 0.3At(Et + It + St) + 0.4Al(El + Il + Sl) where A = Area Score; E = erythema; I =induration; S = scaling; h = head; u = upper limbs; t = trunk; l = lower limbs.

PGA of psoriasis was scored on a 5-point scale, reflecting a global consideration of the erythema, induration, and scaling across all psoriatic lesions. Average erythema, induration, and scaling were scored separately over the whole body according to a 5-point severity scale (0 [no symptom] to 4 [severe symptom]). The total score was calculated as average of the 3 severity scores and rounded to the nearest whole number score to determine the PGA score and category. Scale for PGA: 0= clear, 1= almost clear, 2= mild, 3= moderate and 4= severe. Higher scores indicate more severity.

The PASI score (0-72, with higher score representing greater severity) is a measurement of the severity and extent of psoriasis. The four regions of the body parts are head (10%), arms (20%), trunk (30%) and legs (40%). In each region, the area is expressed as a score of 0 (nothing), 1 (1-9%), 2 (10-29%), 3 (30-49%), 4 (50-69%), 5 (70-89%) or 6 (90-100%). Within each area, the degree of severity for erythema, induration and scaling are estimated between 0 and 4, with 4 being the highest severity. The final score combines disease severity and effected BSA from for four regions using the formula PASI =0.1Ah(Eh + Ih + Sh) + 0.2Au(Eu + Iu + Su) + 0.3At(Et + It + St) + 0.4Al(El + Il + Sl) where A = Area Score; E = erythema; I =induration; S = scaling; h = head; u = upper limbs; t = trunk; l = lower limbs.

The PASI score (0-72, with higher score representing greater severity) is a measurement of the severity and extent of psoriasis. The four regions of the body parts are head (10%), arms (20%), trunk (30%) and legs (40%). In each region, the area is expressed as a score of 0 (nothing), 1 (1-9%), 2 (10-29%), 3 (30-49%), 4 (50-69%), 5 (70-89%) or 6 (90-100%). Within each area, the degree of severity for erythema, induration and scaling are estimated between 0 and 4, with 4 being the highest severity. The final score combines disease severity and effected BSA from for four regions using the formula PASI =0.1Ah(Eh + Ih + Sh) + 0.2Au(Eu + Iu + Su) + 0.3At(Et + It + St) + 0.4Al(El + Il + Sl) where A = Area Score; E = erythema; I =induration; S = scaling; h = head; u = upper limbs; t = trunk; l = lower limbs.

The PASI score (0-72, with higher score representing greater severity) is a measurement of the severity and extent of psoriasis. The four regions of the body parts are head (10%), arms (20%), trunk (30%) and legs (40%). In each region, the area is expressed as a score of 0 (nothing), 1 (1-9%), 2 (10-29%), 3 (30-49%), 4 (50-69%), 5 (70-89%) or 6 (90-100%). Within each area, the degree of severity for erythema, induration and scaling are estimated between 0 and 4, with 4 being the highest severity. The final score combines disease severity and effected BSA from for four regions using the formula PASI =0.1Ah(Eh + Ih + Sh) + 0.2Au(Eu + Iu + Su) + 0.3At(Et + It + St) + 0.4Al(El + Il + Sl) where A = Area Score; E = erythema; I =induration; S = scaling; h = head; u = upper limbs; t = trunk; l = lower limbs.

The PASI score (0-72, with higher score representing greater severity) is a measurement of the severity and extent of psoriasis. The four regions of the body parts are head (10%), arms (20%), trunk (30%) and legs (40%). In each region, the area is expressed as a score of 0 (nothing), 1 (1-9%), 2 (10-29%), 3 (30-49%), 4 (50-69%), 5 (70-89%) or 6 (90-100%). Within each area, the degree of severity for erythema, induration and scaling are estimated between 0 and 4, with 4 being the highest severity. The final score combines disease severity and effected BSA from for four regions using the formula PASI =0.1Ah(Eh + Ih + Sh) + 0.2Au(Eu + Iu + Su) + 0.3At(Et + It + St) + 0.4Al(El + Il + Sl) where A = Area Score; E = erythema; I =induration; S = scaling; h = head; u = upper limbs; t = trunk; l = lower limbs.

The PASI score (0-72, with higher score representing greater severity) is a measurement of the severity and extent of psoriasis. The four regions of the body parts are head (10%), arms (20%), trunk (30%) and legs (40%). In each region, the area is expressed as a score of 0 (nothing), 1 (1-9%), 2 (10-29%), 3 (30-49%), 4 (50-69%), 5 (70-89%) or 6 (90-100%). Within each area, the degree of severity for erythema, induration and scaling are estimated between 0 and 4, with 4 being the highest severity. The final score combines disease severity and effected BSA from for four regions using the formula PASI =0.1Ah(Eh + Ih + Sh) + 0.2Au(Eu + Iu + Su) + 0.3At(Et + It + St) + 0.4Al(El + Il + Sl) where A = Area Score; E = erythema; I =induration; S = scaling; h = head; u = upper limbs; t = trunk; l = lower limbs.

Participants were asked to assess their itch intensity over the past 24 hours, on a scale from 0 (no itching) to 10 (worst possible itching). Higher scores indicated worse itch.

Participants were asked to assess their itch intensity over the past 24 hours, on a scale from 0 (no itching) to 10 (worst possible itching). Higher scores indicated worse itch.

Participants were asked to assess their itch intensity over the past 24 hours, on a scale from 0 (no itching) to 10 (worst possible itching). Higher scores indicated worse itch.

Participants were asked to assess their itch intensity over the past 24 hours, on a scale from 0 (no itching) to 10 (worst possible itching). Higher scores indicated worse itch.

PSI was a self-administered 8-item questionnaire that measured the severity of psoriasis symptoms over the past 24 hours and the past 7 days. PSI included following 8 items: itch, pain, burning, stinging, cracking, scaling, flaking, and redness. Each item was rated on a scale from 0 to 4, where 0= not at all severe, 1= mild, 2= moderate, 3= severe and 4= very severe. Scores from all items were summed to give PSI score range from 0 (no severity) to 32 (maximum severity), higher PSI score indicated greater severity.

PSI was a self-administered 8-item questionnaire that measured the severity of psoriasis symptoms over the past 24 hours and the past 7 days. PSI included following 8 items: itch, pain, burning, stinging, cracking, scaling, flaking, and redness. Each item was rated on a scale from 0 to 4, where 0= not at all severe, 1= mild, 2= moderate, 3= severe and 4= very severe. Scores from all items were summed to give PSI score range from 0 (no severity) to 32 (maximum severity), higher PSI score indicated greater severity.

PGA of psoriasis was scored on a 5-point scale, reflecting a global consideration of the erythema, induration, and scaling across all psoriatic lesions. Average erythema, induration, and scaling were scored separately over the whole body according to a 5-point severity scale (0 [no symptom] to 4 [severe symptom]). The total score was calculated as average of the 3 severity scores and rounded to the nearest whole number score to determine the PGA score and category. Scale for PGA: 0= clear, 1= almost clear, 2= mild, 3= moderate and 4= severe. Higher scores indicate more severity.

PSI was a self-administered 8-item questionnaire that measured the severity of psoriasis symptoms over the past 24 hours and the past 7 days. PSI included following 8 items: itch, pain, burning, stinging, cracking, scaling, flaking, and redness. Each item was rated on a scale from 0 to 4, where 0= not at all severe, 1= mild, 2= moderate, 3= severe and 4= very severe. Scores from all items were summed to give PSI score range from 0 (no severity) to 32 (maximum severity), higher PSI score indicated greater severity.

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. AEs included both SAEs and all non-SAEs. Treatment emergent AEs (TEAEs) were events that occurred between first dose of study drug and up to 4 weeks after last dose that were absent before treatment or that worsened relative to pretreatment state. A treatment-related AE was any untoward medical occurrence attributed to the study drug in a participant who received study drug. Relatedness to study drug was assessed by the investigator.

An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. AE was assessed according to severity; mild (not causing any significant problem, dose adjustment not required), moderate (caused problem that does not interfere significantly with usual activities or the clinical status, dose adjustment needed due to adverse event) and severe (caused problem that interfered significantly with usual activities or the clinical status, study drug stopped due to adverse event).

An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship.

Bilirubin: greater than (>) 1.5* upper limit normal (ULN); aspartate aminotransferase, alanine aminotransferase: >2.5*ULN; creatinine, cystatin C: >1.3*ULN; creatine kinase: >2.0*ULN; glomerular filtration rate (GFR) CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) Equat: less than (<) 60 milliliter (mL)/minute (min)/1.73 meter(m)^2, greater than or equal to (>=) 30% decrease from baseline; GFR: <60 mL/min/1.73m^2.

Following were ECG criteria used for categorical summary:1) PR interval: percentage change >=25/50%, QRS interval: value >140 msec, and QT interval corrected using the Fridericia's formula (QTcF): 450 msec < value less than equal to (<=) 480 and 30 < change <=60.

Following were the vital signs criteria: 1) Pulse rate: value <40 beats per min (bpm), value >120 bpm; 2) Sitting diastolic blood pressure (DBP): value <50 mmHg; change >=20 mmHg increase; change >=20 mmHg decrease; 3) Sitting systolic blood pressure (SBP): value <90 mmHg, change >=30 mmHg increase, change >=30 mmHg decrease; 4) Supine DBP: value <50 mmHg, change >=20 mmHg increase, change >=20 mmHg decrease; 5) Supine SBP: value <90 mmHg, change >=30 mmHg increase, change >=30 mmHg decrease.

At the site of study drug application, skin tolerability was assessed for non-lesional skin surrounding the plaques on a scale from 0 to 4. Grade 0= none (no evidence of local intolerance), Grade 1= mild (minimal erythema and/or edema, slight glazed appearance), Grade 2= moderate (definite erythema and/or oedema with peeling and/or cracking but needs no adaptation of posology), Grade 3= severe, reported as AE (erythema, oedema glazing with fissures, few vesicles or papules: consider removing topical agent [if still in place]), Grade 4= very severe, reported as AE (strong reaction spreading beyond the treated area, bullous reaction, erosions: removal of topical agent [if still in place]).