Study to Evaluate Safety and Tolerability of PF-07242813 in Healthy Participants and Participants With Atopic Dermatitis

An adverse event (AE) was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE was defined as any untoward medical occurrence that, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or other important medical events. An AE was considered as treatment emergent if the event started during the effective duration of treatment. All events that started on or after the first dosing day up to the last dose plus the lag time were considered as TEAEs.

An AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE was defined as any untoward medical occurrence that, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or other important medical events. An AE was considered as treatment emergent if the event started during the effective duration of treatment. All events that started on or after the first dosing day up to the last dose plus the lag time were considered as TEAEs.

An AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE was defined as any untoward medical occurrence that, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or other important medical events. An AE was considered as treatment emergent if the event started during the effective duration of treatment. All events that started on or after the first dosing day up to the last dose plus the lag time were considered as TEAEs.

Vital signs included blood pressure, pulse rate, respiratory rate and temperature. Temperature was measured by oral, tympanic, or temporal artery method. Blood pressure and respiratory rate were measured with the participant in a supine position after 5 minutes of rest for the participant. Clinically significant findings were determined by the investigator.

Vital signs included blood pressure, pulse rate, respiratory rate and temperature. Temperature was measured by oral, tympanic, or temporal artery method. Blood pressure and respiratory rate were measured with the participant in a supine position after 5 minutes of rest for the participant. Clinically significant findings were determined by the investigator.

Vital signs included blood pressure, pulse rate, respiratory rate and temperature. Temperature was measured by oral, tympanic, or temporal artery method. Blood pressure and respiratory rate were measured with the participant in a supine position after 5 minutes of rest for the participant. Clinically significant findings were determined by the investigator.

Pre-defined criteria for laboratory parameters were hemoglobin (HGB) (<0.8* Lower limit normal (LLN)), Erythrocyte (Ery). Mean Corpuscular (MC) Volume (<0.9* LLN), Ery MC Hemoglobin (<0.9* LLN), Ery. MC HGB Concentration (<0.9* LLN), Leukocytes (<0.6* LLN), Neutrophils (<0.8* LLN), Bilirubin (>1.5* Upper limit normal (ULN)), Aspartate Aminotransferase (>3.0* ULN), Urea Nitrogen (>1.3* ULN), Creatinine (>1.3* ULN), Urate (>1.2* ULN). Number of participants with any laboratory test abnormalities meeting pre-defined criteria was reported in this outcome measure.

Pre-defined criteria for laboratory parameters were HGB (<0.8* LLN), Ery MCV (<0.9* LLN), Ery MC Hemoglobin (<0.9* LLN), Ery. MC HGB Concentration (<0.9* LLN), Leukocytes (<0.6* LLN), Neutrophils (<0.8* LLN), Bilirubin (>1.5* ULN), Aspartate Aminotransferase (>3.0* ULN), Urea Nitrogen (>1.3* ULN), Creatinine (>1.3* ULN), Urate (>1.2* ULN). Number of participants with any laboratory test abnormalities meeting pre-defined criteria was reported in this outcome measure.

Pre-defined criteria for laboratory parameters were HGB (<0.8* LLN), Ery MCV (<0.9* LLN), Ery MC Hemoglobin (<0.9* LLN), Ery. MC HGB Concentration (<0.9* LLN), Leukocytes (<0.6* LLN), Neutrophils (<0.8* LLN), Bilirubin (>1.5* ULN), Aspartate Aminotransferase (>3.0* ULN), Urea Nitrogen (>1.3* ULN), Creatinine (>1.3* ULN), Urate (>1.2* ULN). Number of participants with any laboratory test abnormalities meeting pre-defined criteria was reported in this outcome measure.

Cardiac telemetry was collected in Part 1 SAD cohorts only. Number of participants with any cardiac telemetry abnormalities were reported in this outcome measure.

Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR interval, QT interval, corrected QT (QTc) intervals and QRS complex. ECGs were performed after the participant had rested quietly for at least 10 minutes in a supine position. Clinically significant findings were determined by the investigator.

Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR interval, QT interval, QTc intervals and QRS complex. ECGs were performed after the participant had rested quietly for at least 10 minutes in a supine position. Clinically significant findings were determined by the investigator.

Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR interval, QT interval, QTc intervals and QRS complex. ECGs were performed after the participant had rested quietly for at least 10 minutes in a supine position. Clinically significant findings were determined by the investigator.

AUClast was calculated using the linear/log trapezoidal method.

AUCinf was determined as AUClast + (Clast divided by kel), where Clast = predicted serum concentration at the last quantifiable time point estimated from the log-linear regression analysis and kel= terminal phase rate constant.

t1/2 was determined by "Loge(2)/kel", where kel was the terminal phase rate constant calculated by a linear regression of the loglinear -concentration time- curve.

Area under the serum concentration time- profile over the dosing interval tau where tau=2 weeks (336 hours).

t1/2 was determined by "Loge(2) per kel", where kel was the terminal phase rate constant calculated by a linear regression of the log/linear -concentration time- curve.

EASI quantifies severity of AD based on severity of lesion clinical signs and percentage (%) of body surface area (BSA) affected. Severity of clinical signs of AD lesions (erythema, induration/papulation, excoriation and lichenification) were scored separately for each of 4 body regions (head and neck, upper limbs, trunk [including axillae and groin)] and lower limbs [including buttocks]) on a 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based on % BSA with AD in body region: 0 (0%), 1 (>0 to <10%), 2 (10 to <30%), 3 (30 to <50%), 4 (50 to <70%), 5 (70 to <90%) and 6 (90 to 100%). Total EASI score =0.1*Ah*(Eh+Ih+Exh+Lh) + 0.2*Au*(Eu+Iu+ExU+Lu) + 0.3*At*(Et+It+Ext+Lt) + 0.4*Al*(El+Il+Exl+Ll); A = EASI area score; E = erythema; I = induration/papulation; Ex = excoriation; L = lichenification; h = head and neck; u = upper limbs; t = trunk; l = lower limbs. Total EASI score ranged from 0.0 to 72.0, with higher scores indicating greater severity of AD.