PF-06826647

The PASI quantifies the severity of a participant's psoriasis based on both lesion severity and the percentage of body surface area (BSA) affected. PASI is a composite scoring by the investigator of degree of erythema, induration, and scaling (each scored separately) for each of 4 body regions (head and neck, upper limbs, trunk \[including axillae and groin\], and lower limbs \[including buttocks\]), with adjustment for the percent of BSA involved for each body region and for the proportion of the body region to the whole body. The PASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores representing greater severity of psoriasis. PASI 90 response was defined as at least a 90% reduction in PASI relative to baseline. The statistical analysis was for the data at Week 16.

An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious AE (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. In this outcome measure, an AE was considered treatment-emergent if the event started on or after the first dosing day and time/start time but before the last dose plus the lag time.

Treatment-related adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug. Serious AE (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. In this outcome measure, an AE was considered treatment-emergent if the event started on or after the first dosing day and time/start time but before the last dose plus the lag time. Relatedness to investigational product (PF-06826647 or placebo) was assessed by the investigator (Yes/No). Participants with multiple occurrences of an AE within a category were counted once within the category.

Following hematology parameters were analyzed for laboratory examination: hemoglobin (HGB), hematocrit, erythrocytes (Ery.), reticulocytes, Ery. mean corpuscular volume, Ery. mean corpuscular HGB, Ery. mean corpuscular HGB concentration, platelets, reticulocytes/erythrocytes, leukocytes, lymphocytes/leukocytes, neutrophils/leukocytes, basophils, basophils/leukocytes, eosinophils, eosinophils/leukocytes, monocytes, monocytes/leukocytes, activated partial thromboplastin time, prothrombin time, prothrombin international (Intl.) normalized ratio, neutrophils total count, and lymphocytes total count. LLN=lower limit of normal; ULN=upper limit of normal.

Following clinical chemistry parameters were analyzed for laboratory examination: bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, alkaline phosphatase, protein, albumin, blood urea nitrogen, urea, creatinine, urate, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, sodium, potassium, chloride, calcium, bicarbonate, glucose, creatine kinase, and cholesterol.

Following urinalysis parameters were analyzed for laboratory examination: urine pH, urine glucose, urine ketones, urine protein, urine hemoglobin, urine urobilinogen, urine bilirubin, urine nitrite, urine leukocyte esterase, urine erythrocytes, urine leukocytes, urine hyaline, and urine bacteria.

Criteria for ECG abnormalities: maximum increase PR interval increase from baseline (IFB): percent change (Pctchg) \>=25 percent (%) for baseline value of \>200 milliseconds (msec) and Pctchg\>=50% for baseline value of \<=200 msec for PR interval, a maximum IFB: Pctchg\>=50%, maximum QTcF interval (Fridericia's Correction) of 450 msec to \<=480 msec, 480 msec to \<=500 msec and a maximum change of \<30 change =\<60 or \>60 msec from baseline.

The vital signs were obtained with participant in the seated position, after having sat calmly for at least 5 minutes. Criteria for vital signs abnormalities: sitting diastolic blood pressure (BP) \< 50 millimeter of mercury (mmHg), sitting diastolic BP change \>= 20 mmHg increase, sitting diastolic BP change \>= 20 mmHg decrease, sitting systolic BP \< 90 mmHg, sitting systolic BP change \>= 30 mmHg increase, and sitting systolic BP change \>= 30 mmHg decrease.

Area under the plasma concentration time profile from time 0 to end of dosing interval (AUCtau), where dosing interval is 24 hours.

Area under the plasma concentration time profile from time 0 to end of dosing interval (AUCtau), where dosing interval is 24 hours.

AUCinf is calculated by AUClast + (Clast\*/kel), where AUClast is the area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration, Clast\* is the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.

Cmax will be observed directly from data.

Maximum absolute values and changes from baseline for vital signs (for supine systolic/diastolic blood pressure \[BP\] and supine pulse rate \[PR\]) were summarized descriptively by treatment. Numbers of participants meeting the categorical criteria were provided. Number of participants in PBO SAD cohorts = number of participants in \[PBO SAD (3mg, 10mg)\] cohorts + number of participants in \[PBO SAD -\> PBO QD MAD\] cohorts.

Maximum absolute values and changes from baseline for vital signs (for supine systolic/diastolic blood pressure and supine pulse rate) were summarized descriptively by treatment. Numbers of participants meeting the categorical criteria were provided.

Maximum absolute values and changes from baseline for vital signs (for supine systolic/diastolic blood pressure and supine pulse rate) were summarized descriptively by treatment. Numbers of participants meeting the categorical criteria were provided.

Physical examinations were conducted by a physician, trained physician assistant, or nurse practitioner as acceptable according to local regulation. A full physical examination included head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. The examination assessed the participants for any potential changes in general appearance, the respiratory and cardiovascular systems, as well as towards participant reported symptoms. Findings were considered to be clinically significant based on investigator's decision. Number of participants in PBO SAD cohorts = number of participants in \[PBO SAD (3mg, 10mg)\] cohorts + number of participants in \[PBO SAD -\> PBO QD MAD\] cohorts.

Physical examinations were conducted by a physician, trained physician assistant, or nurse practitioner as acceptable according to local regulation. A full physical examination included head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. The examination assessed the participants for any potential changes in general appearance, the respiratory and cardiovascular systems, as well as towards participant reported symptoms. Findings were considered to be clinically significant based on investigator's decision.

Physical examinations were conducted by a physician, trained physician assistant, or nurse practitioner as acceptable according to local regulation. A full physical examination included head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. The examination assessed the participants for any potential changes in general appearance, the respiratory and cardiovascular systems, as well as towards participant reported symptoms. Findings were considered to be clinically significant based on investigator's decision.

ECG endpoints and changes from baseline (QTcF, PR and QRS) were summarized descriptively by cohort and treatment using pre-defined categories. Numbers of participants meeting the categorical criteria were provided. All planned and unplanned post-dose time points were counted in these categorical summaries. Categorical summarization criteria for ECG were as follows: 1) QTcF maximum absolute value ≥450 and \<480 millisecond (msec), ≥480 and \<500 msec. ≥500 msec; 2) QTcF maximum increase ≥30 and \<60 msec, ≥60 msec; 3) PR maximum absolute value ≥300 msec; 4) PR maximum increases from baseline ≥25% if baseline \>200 msec, ≥50% if baseline ≤200 msec; 5) QRS maximum absolute value ≥140 msec; 6) QRS maximum increase from baseline ≥50%. Number of participants in PBO SAD cohorts = number of participants in \[PBO SAD (3mg, 10mg)\] cohorts + number of participants in \[PBO SAD -\> PBO QD MAD\] cohorts.

ECG endpoints and changes from baseline (QTcF, PR and QRS) were summarized descriptively by cohort and treatment using pre-defined categories. Numbers of participants meeting the categorical criteria were provided. All planned and unplanned post-dose time points were counted in these categorical summaries. Categorical summarization criteria for ECG were as follows: 1) QTcF maximum absolute value ≥450 and \<480 millisecond (msec), ≥480 and \<500 msec. ≥500 msec; 2) QTcF maximum increase ≥30 and \<60 msec, ≥60 msec; 3) PR maximum absolute value ≥300 msec; 4) PR maximum increases from baseline ≥25% if baseline \>200 msec, ≥50% if baseline ≤200 msec; 5) QRS maximum absolute value ≥140 msec; 6) QRS maximum increase from baseline ≥50%.

ECG endpoints and changes from baseline (QTcF, PR and QRS) were summarized descriptively by cohort and treatment using pre-defined categories. Numbers of participants meeting the categorical criteria were provided. All planned and unplanned post-dose time points were counted in these categorical summaries. Categorical summarization criteria for ECG were as follows: 1) QTcF maximum absolute value ≥450 and \<480 millisecond (msec), ≥480 and \<500 msec. ≥500 msec; 2) QTcF maximum increase ≥30 and \<60 msec, ≥60 msec; 3) PR maximum absolute value ≥300 msec; 4) PR maximum increases from baseline ≥25% if baseline \>200 msec, ≥50% if baseline ≤200 msec; 5) QRS maximum absolute value ≥140 msec; 6) QRS maximum increase from baseline ≥50%.

An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening (immediate risk of death); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. All events occurring following start of the treatment or increasing in severity were counted as treatment emergent. Events that occurred in a non-treatment period (eg, washout or follow-up) were counted as treatment emergent and attributed to the previous treatment taken. For each event, the investigator pursued and obtained adequate information both to determine the outcome and to assess whether it meets the criteria for classification as an SAE. PBO SAD cohorts = \[PBO SAD (3mg, 10mg)\] cohorts + \[PBO SAD -\> PBO QD MAD\] cohorts.

An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening (immediate risk of death); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. All events occurring following start of the treatment or increasing in severity were counted as treatment emergent. Events that occurred in a non-treatment period (eg, washout or follow-up) were counted as treatment emergent and attributed to the previous treatment taken. For each event, the investigator pursued and obtained adequate information both to determine the outcome and to assess whether it meets the criteria for classification as an SAE.

An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening (immediate risk of death); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. All events occurring following start of the treatment or increasing in severity were counted as treatment emergent. Events that occurred in a non-treatment period (eg, washout or follow-up) were counted as treatment emergent and attributed to the previous treatment taken. For each event, the investigator pursued and obtained adequate information both to determine the outcome and to assess whether it meets the criteria for classification as an SAE.

Laboratory data were listed and summarized by treatment in accordance with the sponsor reporting standards. Parameters for laboratory abnormalities evaluation included: erythrocyte mean corpuscular volume (Ery. MCV), erythrocyte mean corpuscular hemoglobin (Ery. MCH), reticulocytes/erythrocytes (%), limphocytes, eosinophils, bilirubin, aspartate aminotransferase (AST), urate, high-density lipoproteins (HDL) cholesterol, low-density lipoproteins (LDL) cholesterol, triglycerides, cholesterol, ketones, nitrite, leukocyte esterase, epithelial cells, urinalysis-bacteria. Number of participants in PBO SAD cohorts = number of participants in \[PBO SAD (3mg, 10mg)\] cohorts + number of participants in \[PBO SAD -\> PBO QD MAD\] cohorts.

Laboratory data were listed and summarized by treatment in accordance with the sponsor reporting standards. Parameters and corresponding primary criteria for laboratory abnormalities evaluation included: Ery. MCV \<0.9 × LLN, Ery. Mean corpuscular hemoglobin (Ery. MCH) \<0.9 × LLN or \>1.1 ULN, reticulocytes/erythrocytes (%) \>1.5 × ULN, lymphocytes \<0.8 × LLN or \>1.2 × ULN, neutrophils \<0.8 × LLN, eosinophils \>1.2 × ULN, bilirubin \>1.5 × ULN, urate \>1.2 × ULN, HDL cholesterol \<0.8 × LLN, LDL cholesterol \>1.2 × ULN, triglycerides \>1.3 × ULN, bicarbonate \>1.1 × ULN, cholesterol \>1.3 × ULN, urine glucose ≥1, urine hemoglobin ≥1, nitrite ≥1, leukocyte esterase ≥1, epithelial cells ≥6/LPF, urinalysis-casts \>1/LPF, urinalysis-bacteria \>20/HPF, urine 24 hours creatinine \>1.1 × ULN.

Laboratory data were listed and summarized by treatment in accordance with the sponsor reporting standards. Parameters and corresponding primary criteria for laboratory abnormalities evaluation included: reticulocytes/erythrocytes (%) \>1.5 × ULN, lymphocytes \<0.8 × LLN, neutrophils \<0.8 × LLN or \>1.2 × ULN, eosinophils \>1.2 × ULN, bilirubin \>1.5 × ULN, alanine aminotransferase (ALT) \>3.0 × ULN, creatinine \>1.3 × ULN, urate \>1.2 × ULN, HDL cholesterol \<0.8 × LLN, LDL cholesterol \>1.2 × ULN, triglycerides \>1.3 × ULN, potassium \>1.1 × ULN, bicarbonate \>1.1 × ULN, glucose \<0.6 × LLN or \>1.5 × ULN, Creatine Kinase (CK) \>2.0 × ULN, cholesterol \>1.3 × ULN, urine glucose ≥1, ketones ≥1, urine hemoglobin ≥1, urine bilirubin ≥1, leukocyte esterase ≥1, epithelial cells ≥6/LPF, urinalysis-bacteria/HPF.

Change in 24-hour creatinine clearance at Day 10 from Day -1 (baseline) during the MAD was presented by treatment group.