The purpose of this study is to evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics of PF-06817024 in healthy volunteers, in participants with chronic rhinosinusitis, with nasal polyps and in participants with moderate-to-severe Atopic Dermatitis
The purpose of the study for Part 1 is to evaluate the safety and tolerability of PF-06817024 in healthy subjects. The purpose of the study for Part 2 is to evaluate the safety and tolerability of PF-06817024 in patients with chronic rhinosinusitis with nasal polyps. The purpose of the study for Part 3 is to evaluate the safety and tolerability of PF-06817024 in patients with moderate-to-severe Atopic Dermatitis
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
97
Subjects will be given one dose of PF-06817024 intravenously
Subjects will be given one dose of placebo for PF-06817024 intravenously
Subjects will be given one dose of PF-06817024 subcutaneously
UC Davis Dermatology
Sacramento, California, United States
Number of Participants With All-causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) in Part 1
An adverse event (AE) was any untoward medical occurrence in a clinical investigation where participants administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. TEAEs were events between first dose of study drug and up to discharge from study that were absent before treatment or that worsened relative to pretreatment state. An SAE was any untoward medical occurrence at any dose that: results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or results in congenital anomaly/birth defect.
Time frame: From Study Day 1 (baseline) up to Day 421 (Cohort 1 and 2), Day 601 (Cohort 3), Day 691 (Cohort 4), Day 781 (Cohort 5), and Day 511 (Cohort 7).
Number of Participants With Treatment-Related TEAEs and SAEs in Part 1
An AE was any untoward medical occurrence in a clinical investigation where participants administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. TEAEs were events between first dose of study drug and up to discharge from study that were absent before treatment or that worsened relative to pretreatment state. An SAE was any untoward medical occurrence at any dose that: results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or results in congenital anomaly/birth defect. The causality of TEAEs and SAEs was determined by the investigator.
Time frame: From Study Day 1 (baseline) up to Day 421 (Cohort 1 and 2), Day 601 (Cohort 3), Day 691 (Cohort 4), Day 781 (Cohort 5), and Day 511 (Cohort 7).
Number of All-Causality TEAEs According to Severity in Part 1
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were events between first dose of study drug and up to discharge from study that were absent before treatment or that worsened relative to pretreatment state. TEAE was assessed by the investigator according to severity; Mild: did not interfere with participant's usual function; moderate: interfered to some extent with participant's usual function; severe: interfered significantly with participant's usual function.
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Subjects will be given one dose of placebo for PF-06817024 subcutaneously
Subjects will be given two doses of PF-06817024 intravenously
Subjects will be given two doses of PF-06817024 intravenously
Subjects will be given 2 doses intravenously
Subjects will be given 2 doses intravenously
Subjects will be given doses of PF-06817024 intravenously
Subjects will be given doses of Placebo intravenously
UC Davis CTSC Clinical Research Center
Sacramento, California, United States
UC Davis Health
Sacramento, California, United States
New Haven Clinical Research Unit
New Haven, Connecticut, United States
Dermatology Physicians of Connecticut
Shelton, Connecticut, United States
ForCare Clinical Research
Tampa, Florida, United States
Dawes Fretzin Clinical Research Group, LLC
Indianapolis, Indiana, United States
Dawes Fretzin Dermatology Group, LLC
Indianapolis, Indiana, United States
The Indiana Clinical Trials Center
Plainfield, Indiana, United States
Academic Dermatology
Edina, Minnesota, United States
...and 10 more locations
Time frame: From Study Day 1 (baseline) up to Day 421 (Cohort 1 and 2), Day 601 (Cohort 3), Day 691 (Cohort 4), Day 781 (Cohort 5), and Day 511 (Cohort 7).
Number of Participants With Permanent Discontinuation Due to TEAEs in Part 1
An AE was any untoward medical occurrence in a clinical investigation where participants administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. TEAEs were events between first dose of study drug and up to discharge from study that were absent before treatment or that worsened relative to pretreatment state.
Time frame: From Study Day 1 (baseline) up to Day 421 (Cohort 1 and 2), Day 601 (Cohort 3), Day 691 (Cohort 4), Day 781 (Cohort 5), and Day 511 (Cohort 7).
Number of Participants With All-Causality TEAEs and SAEs in Part 2
An AE was any untoward medical occurrence in a clinical investigation where participants administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. TEAEs were events between first dose of study drug and up to discharge from study that were absent before treatment or that worsened relative to pretreatment state. An SAE was any untoward medical occurrence at any dose that: results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or results in congenital anomaly/birth defect.
Time frame: From Study Day 1 (baseline) up to Day 691.
Number of Participants With Treatment-Related TEAEs and SAEs in Part 2
An AE was any untoward medical occurrence in a clinical investigation where participants administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. TEAEs were events between first dose of study drug and up to discharge from study that were absent before treatment or that worsened relative to pretreatment state. An SAE was any untoward medical occurrence at any dose that: results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or results in congenital anomaly/birth defect. The causality of TEAEs and SAEs was determined by the investigator.
Time frame: From Study Day 1 (baseline) up to Day 691.
Number of All-Causality TEAEs According to Severity in Part 2
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were events between first dose of study drug and up to discharge from study that were absent before treatment or that worsened relative to pretreatment state. TEAE was assessed by the investigator according to severity; Mild: did not interfere with participant's usual function; moderate: interfered to some extent with participant's usual function; severe: interfered significantly with participant's usual function.
Time frame: From Study Day 1 (baseline) up to Day 691.
Number of Participants With Permanent Discontinuation Due to TEAEs in Part 2
An AE was any untoward medical occurrence in a clinical investigation where participants administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. TEAEs were events between first dose of study drug and up to discharge from study that were absent before treatment or that worsened relative to pretreatment state.
Time frame: From Study Day 1 (baseline) up to Day 691.
Number of Participants With All-Causality TEAEs and SAEs in Part 3
An AE was any untoward medical occurrence in a clinical investigation where participants administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. TEAEs were events between first dose of study drug and up to discharge from study that were absent before treatment or that worsened relative to pretreatment state. An SAE was any untoward medical occurrence at any dose that: results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or results in congenital anomaly/birth defect.
Time frame: From Study Day 1 (baseline) up to Day 1105.
Number of Participants With Treatment-Related TEAEs and SAEs in Part 3
An AE was any untoward medical occurrence in a clinical investigation where participants administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. TEAEs were events between first dose of study drug and up to discharge from study that were absent before treatment or that worsened relative to pretreatment state. An SAE was any untoward medical occurrence at any dose that: results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or results in congenital anomaly/birth defect. The causality of TEAEs and SAEs was determined by the investigator.
Time frame: From Study Day 1 (baseline) up to Day 1105.
Number of All-Causality TEAEs According to Severity in Part 3
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were events between first dose of study drug and up to discharge from study that were absent before treatment or that worsened relative to pretreatment state. TEAE was assessed by the investigator according to severity; Mild: did not interfere with participant's usual function; moderate: interfered to some extent with participant's usual function; severe: interfered significantly with participant's usual function.
Time frame: From Study Day 1 (baseline) up to Day 1105.
Number of Participants With Permanent Discontinuation Due to TEAEs in Part 3
An AE was any untoward medical occurrence in a clinical investigation participants administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. TEAEs were events between first dose of study drug and up to discharge from study that were absent before treatment or that worsened relative to pretreatment state.
Time frame: From Study Day 1 (baseline) up to Day 1105.
Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis in Part 1
Hematology parameters included hemoglobin, hematocrit, red blood cell, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet and white blood cell count, total neutrophils, eosinophils, monocytes, basophils and lymphocytes. Chemistry parameters included blood urea nitrogen, glucose (fasting), calcium, sodium, potassium, chloride, bicarbonate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid, albumin, total protein. Urine parameters included pH, glucose, protein, blood, ketones, nitrites, leukocyte esterase, urobilinogen, urine bilirubin, microscopy. Clinical significance was judged by the investigator and those met the criteria of AE are listed here. Clinically significant laboratory abnormalities reported for at least 1 participant in the whole study are presented here.
Time frame: Part 1 single-dose cohorts: from Study Day 1 (baseline) up to Day 211. Part 1 multiple-dose cohorts: from Study Day 1 (baseline) up to Day 241.
Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis in Part 2
Hematology parameters included hemoglobin, hematocrit, red blood cell, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet and white blood cell count, total neutrophils, eosinophils, monocytes, basophils and lymphocytes. Chemistry parameters included blood urea nitrogen, glucose (fasting), calcium, sodium, potassium, chloride, bicarbonate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid, albumin, total protein. Urine parameters included pH, glucose, protein, blood, ketones, nitrites, leukocyte esterase, urobilinogen, urine bilirubin, microscopy. Clinical significance was judged by the investigator and those met the criteria of AE are listed here. Clinically significant laboratory abnormalities reported for at least 1 participant in the whole study are presented here.
Time frame: Part 2: from Study Day 1 (baseline) up to Day 211.
Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis in Part 3
Hematology parameters included hemoglobin, hematocrit, red blood cell, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet and white blood cell count, total neutrophils, eosinophils, monocytes, basophils and lymphocytes. Chemistry parameters included blood urea nitrogen, glucose (fasting), calcium, sodium, potassium, chloride, bicarbonate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid, albumin, total protein. Urine parameters included pH, glucose, protein, blood, ketones, nitrites, leukocyte esterase, urobilinogen, urine bilirubin, microscopy. Clinical significance was judged by the investigator and those met the criteria of AE are listed here. Clinically significant laboratory abnormalities reported for at least 1 participant in the whole study are presented here.
Time frame: Part 3: from Study Day 1 (baseline) up to Day 966.
Number of Participants With Vital Sign Abnormalities in Part 1
Criteria for abnormality in vital signs: supine pulse rate \<40 beats per minute (bpm) or \>120 bpm; supine diastolic blood pressure (DBP) \<50 mmHg, maximum increase or decrease from baseline of \>=20 mmHg; supine systolic blood pressure (SBP) \<90 mmHg, maximum increase or decrease from baseline of \>=30 mmHg. Baseline was defined as the last measurement prior to the first dosing. Vital sign abnormalities reported for at least 1 participant are presented here.
Time frame: Study Day 1 (baseline) up to end of study (Study Day 211 for Part 1 SD cohorts, and Study Day 241 for Part 1 MD cohorts).
Number of Participants With Vital Sign Abnormalities in Part 2
Criteria for abnormality in vital signs: supine pulse rate \<40 bpm or \>120 bpm; supine DBP \<50 mmHg, maximum increase or decrease from baseline of \>=20 mmHg; supine SBP \<90 mmHg, maximum increase or decrease from baseline of \>=30 mmHg. Baseline was defined as the last measurement prior to the first dosing. Vital sign abnormalities reported for at least 1 participant are presented here.
Time frame: Study Day 1 (baseline) up to end of study (Study Day 211).
Number of Participants With Vital Sign Abnormalities in Part 3
Criteria for abnormality in vital signs: supine pulse rate \<40 bpm or \>120 bpm; supine DBP \<50 mmHg, maximum increase or decrease from baseline of \>=20 mmHg; supine SBP \<90 mmHg, maximum increase or decrease from baseline of \>=30 mmHg. Baseline was defined as the last measurement prior to the first dosing. Vital sign abnormalities reported for at least 1 participant are presented here.
Time frame: Study Day 1 (baseline) up to end of study (Study Day 337).
Number of Participants With Electrocardiogram (ECG) Abnormalities in Part 1
ECG abnormalities criteria included: 1) maximum QTc interval adjusted according Fridericia formula (QTcF) (msec): 450\<= QTcF \<480, 480\<= QTcF \<500, and QTcF \>=500; QTcF maximum increase from baseline(msec): 30\<= change \<60, and change \>=60; 2) maximum PR interval (msec): \>=300; PR increase from baseline (msec): baseline \>200 with 25% increase at maximum, baseline \<=200 with 50% increase at maximum; 3) maximum QRS (msec): \>=140; QRS increase from baseline (msec) \>=50%. Baseline was defined as the average of the last triplicate measurement prior to the first dosing. ECG abnormalities reported for at least 1 participant are presented here.
Time frame: Study Day 1 (baseline) up to end of study (Study Day 211 for Part 1 SD cohorts, and Study Day 241 for Part 1 MD cohorts).
Number of Participants With ECG Abnormalities in Part 2
ECG abnormalities criteria included: 1) maximum QTc interval adjusted according Fridericia formula (QTcF) (msec): 450\<= QTcF \<480, 480\<= QTcF \<500, and QTcF \>=500; QTcF maximum increase from baseline(msec): 30\<= change \<60, and change \>=60; 2) maximum PR interval (msec): \>=300; PR increase from baseline (msec): baseline \>200 with 25% increase at maximum, baseline \<=200 with 50% increase at maximum; 3) maximum QRS (msec): \>=140; QRS increase from baseline (msec) \>=50%. Baseline was defined as the average of the last triplicate measurement prior to the first dosing. ECG abnormalities reported for at least 1 participant are presented here.
Time frame: Study Day 1 (baseline) up to end of study (Study Day 211).
Number of Participants With ECG Abnormalities in Part 3
ECG abnormalities criteria included: 1) maximum QTc interval adjusted according Fridericia formula (QTcF) (msec): 450\<= QTcF \<480, 480\<= QTcF \<500, and QTcF \>=500; QTcF maximum increase from baseline(msec): 30\<= change \<60, and change \>=60; 2) maximum PR interval (msec): \>=300; PR increase from baseline (msec): baseline \>200 with 25% increase at maximum, baseline \<=200 with 50% increase at maximum; 3) maximum QRS (msec): \>=140; QRS increase from baseline (msec) \>=50%. Baseline was defined as the average of the last triplicate measurement prior to the first dosing. ECG abnormalities reported for at least 1 participant are presented here.
Time frame: Study Day 1 (baseline) up to end of study (Study Day 337).
Maximum Observed Serum Concentration (Cmax) of PF-06817024 Following Single Dose in Part 1
Maximum observed serum concentration (Cmax) of PF-06817024 following single dose in Part 1; Cmax was defined as the maximum observed serum concentration.
Time frame: Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, 96 hours post dose on Day 1, and on Follow-up Days 8, 15, 32, 46, 61, 91, 121, 151, 181, 211, and at Extended Follow-Up visits (up to a maximum of 780 days/18720 hours post dose).
Cmax of PF-06817024 Following Multiple Doses in Part 1
Cmax was defined as the maximum observed serum concentration.
Time frame: Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hr post dose on Day 1, Days 8 and 15, Day 31/46 (at pre-dose, 1, 2, 4, 8, 12, 24, 48 hr), Days 61, 91, 121, 151, 181, 211, 241, at Extended Follow-Up visits (up to a maximum of 645 days/15480 hr post dose).
Cmax of PF-06817024 in Part 2
Cmax was defined as the maximum observed serum concentration.
Time frame: Pre-dose, 1, 2, 4, 8, 12, 24, and 96 hour post dose on Day 1, and Days 8, 15, 32, 61, 91, 121, 181, 211, and at Extended Follow-Up visits (up to a maximum of 690 days/16560 hours post dose).
Cmax of PF-06817024 in Part 3
Cmax was defined as the maximum observed serum concentration.
Time frame: On Day 1 (at pre-dose, 1.5, 4, and 168 hours post dose), and Days 29, 57, and 85 (at pre-dose, 1.5 and 4 hours post dose), and on Days 113, 253, 337, and Extended Follow-Up visits (up to a maximum of 882 days/21168 hours post dose on Day 85).
Dose Normalized Maximum Observed Serum Concentration (Cmax[dn]) of PF-06817024 Following Single Dose in Part 1
Cmax(dn) was defined as the dose normalized maximum observed serum concentration, and calculated by Cmax/Dose. Cmax was defined as the maximum observed serum concentration.
Time frame: Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, 96 hours post dose on Day 1, and on Follow-up Days 8, 15, 32, 46, 61, 91, 121, 151, 181, 211, and at Extended Follow-Up visits (up to a maximum of 780 days/18720 hours post dose).
Cmax(dn) of PF-06817024 Following Multiple Doses in Part 1
Cmax(dn) was defined as dose normalized maximum observed serum concentration, and calculated by Cmax/Dose. Cmax was defined as the maximum observed serum concentration.
Time frame: Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hr post dose on Day 1, Days 8 and 15, Day 31/46 (at pre-dose, 1, 2, 4, 8, 12, 24, 48 hr), Days 61, 91, 121, 151, 181, 211, 241, at Extended Follow-Up visits (up to a maximum of 645 days/15480 hr post dose).
Cmax(dn) of PF-06817024 in Part 2
Cmax(dn) was defined as the dose normalized maximum observed serum concentration, and calculated by Cmax/Dose. Cmax was defined as the maximum observed serum concentration.
Time frame: Pre-dose, 1, 2, 4, 8, 12, 24, and 96 hour post dose on Day 1, and Days 8, 15, 32, 61, 91, 121, 181, 211, and at Extended Follow-Up visits (up to a maximum of 690 days/16560 hours post dose).
Cmax(dn) of PF-06817024 in Part 3
Cmax(dn) was defined as the dose normalized maximum observed serum concentration, and calculated by Cmax/Dose. Cmax was defined as the maximum observed serum concentration.
Time frame: On Day 1 (at pre-dose, 1.5, 4, and 168 hours post dose), and Days 29, 57, and 85 (at pre-dose, 1.5 and 4 hours post dose), and on Days 113, 253, 337, and Extended Follow-Up visits (up to a maximum of 882 days/21168 hours post dose on Day 85).
Time to Reach Maximum Observed Serum Concentration (Tmax) of PF-06817024 Following Single Dose in Part 1
Time to reach maximum observed serum concentration (Tmax) of PF-06817024 in Part 1; Tmax was defined as time to reach maximum observed serum concentration.
Time frame: Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, 96 hours post dose on Day 1, and on Follow-up Days 8, 15, 32, 46, 61, 91, 121, 151, 181, 211, and at Extended Follow-Up visits (up to a maximum of 780 days/18720 hours post dose).
Tmax of PF-06817024 Following Multiple Doses in Part 1
Tmax was defined as time to reach maximum observed serum concentration.
Time frame: Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hr post dose on Day 1, Days 8 and 15, Day 31/46 (at pre-dose, 1, 2, 4, 8, 12, 24, 48 hr), Days 61, 91, 121, 151, 181, 211, 241, at Extended Follow-Up visits (up to a maximum of 645 days/15480 hr post dose).
Tmax of PF-06817024 in Part 2
Tmax was defined as time to reach maximum observed serum concentration.
Time frame: Pre-dose, 1, 2, 4, 8, 12, 24, and 96 hour post dose on Day 1, and Days 8, 15, 32, 61, 91, 121, 181, 211, and at Extended Follow-Up visits (up to a maximum of 690 days/16560 hours post dose).
Tmax of PF-06817024 in Part 3
Tmax was defined as time to reach maximum observed serum concentration.
Time frame: On Day 1 (at pre-dose, 1.5, 4, and 168 hours post dose), and Days 29, 57, and 85 (at pre-dose, 1.5 and 4 hours post dose), and on Days 113, 253, 337, and Extended Follow-Up visits (up to a maximum of 882 days/21168 hours post dose on Day 85).
Area Under the Curve From Time Zero to Infinity Concentration (AUCinf) of PF-06817024 Following Single Dose in Part 1 and 2
Area under the curve from time zero to infinity concentration (AUCinf) of PF-06817024 following single dose in Part 1 and 2; AUCinf was defined as area under the curve from time zero to infinity concentration.
Time frame: Pre-dose, 1, 2, 4, 8, 12, 24, and 96 hour post dose on Day 1, and Days 8, 15, 32, 61, 91, 121, 181, 211, and at Extended Follow-Up visits (up to 780 days for Part 1 and 690 days for Part 2). For Part 1 only: at post-dose 48 and 72 hour, Days 46 and 151.
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-06817024 Following Single Dose in Part 1 and 2
Area under the curve from time zero to last quantifiable concentration (AUClast) of PF-06817024 following single dose in Part 1 and 2; AUClast was defined as area under the curve from time zero to last quantifiable concentration.
Time frame: Pre-dose, 1, 2, 4, 8, 12, 24, and 96 hour post dose on Day 1, and Days 8, 15, 32, 61, 91, 121, 181, 211, and at Extended Follow-Up visits (up to 780 days for Part 1 and 690 days for Part 2). For Part 1 only: at post-dose 48 and 72 hour, Days 46 and 151.
Area Under the Curve Within Dosing Interval (AUCtau) of PF-06817024 Following Multiple Doses in Part 1
Area under the curve within dosing interval (AUCtau) of PF-06817024 following multiple doses in Part 1; AUCtau was defined as area under the curve within dosing interval. The dosing interval was 720 hours.
Time frame: Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hr post dose on Day 1, Days 8 and 15, Day 31/46 (at pre-dose, 1, 2, 4, 8, 12, 24, 48 hr), Days 61, 91, 121, 151, 181, 211, 241, at Extended Follow-Up visits (up to a maximum of 645 days/15480 hr post dose).
AUCtau of PF-06817024 in Part 3
AUCtau was defined as area under the curve within dosing interval. The dosing interval was 672 hours.
Time frame: On Day 1 (at pre-dose, 1.5, 4, and 168 hours post dose), and Days 29, 57, and 85 (at pre-dose, 1.5 and 4 hours post dose), and on Days 113, 253, 337, and Extended Follow-Up visits (up to a maximum of 882 days/21168 hours post dose on Day 85).
Dose Normalized Area Under the Curve Within Dosing Interval (AUCtau[dn]) of PF-06817024 Following Multiple Doses in Part 1
Dose normalized area under the curve within dosing interval (AUCtau\[dn\]) of PF-06817024 following multiple doses in Part 1; AUCtau(dn) was defined as dose normalized area under the curve within dosing interval. The dosing interval was 720 hours.
Time frame: Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hr post dose on Day 1, Days 8 and 15, Day 31/46 (at pre-dose, 1, 2, 4, 8, 12, 24, 48 hr), Days 61, 91, 121, 151, 181, 211, 241, at Extended Follow-Up visits (up to a maximum of 645 days/15480 hr post dose).
AUCtau(dn) of PF-06817024 Following Multiple Doses in Part 3
AUCtau(dn) was defined as dose normalized area under the curve within dosing interval. The dosing interval was 672 hours.
Time frame: On Day 1 (at pre-dose, 1.5, 4, and 168 hours post dose), and Days 29, 57, and 85 (at pre-dose, 1.5 and 4 hours post dose), and on Days 113, 253, 337, and Extended Follow-Up visits (up to a maximum of 882 days/21168 hours post dose on Day 85).
Average Concentration Over Dosing Interval (Cav) of PF-06817024 Following Multiple Doses in Part 1
Average concentration over dosing interval (Cav) of PF-06817024 following multiple doses in Part 1; Cav was defined as average concentration over dosing interval. The dosing interval was 720 hours.
Time frame: Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hr post dose on Day 1, Days 8 and 15, Day 31/46 (at pre-dose, 1, 2, 4, 8, 12, 24, 48 hr), Days 61, 91, 121, 151, 181, 211, 241, at Extended Follow-Up visits (up to a maximum of 645 days/15480 hr post dose).
Cav of PF-06817024 Following Multiple Doses in Part 3
Cav was defined as average concentration over dosing interval. The dosing interval was 672 hours.
Time frame: On Day 1 (at pre-dose, 1.5, 4, and 168 hours post dose), and Days 29, 57, and 85 (at pre-dose, 1.5 and 4 hours post dose), and on Days 113, 253, 337, and Extended Follow-Up visits (up to a maximum of 882 days/21168 hours post dose on Day 85).
Terminal Elimination Half Life (t1/2) of PF-06817024 Following Single Dose in Part 1
t1/2 was defined as terminal elimination half life, and was calculated by Loge(2)/kel, where kel was the terminal elimination phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Time frame: Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, 96 hours post dose on Day 1, and on Follow-up Days 8, 15, 32, 46, 61, 91, 121, 151, 181, 211, and at Extended Follow-Up visits (up to a maximum of 780 days/18720 hours post dose).
t1/2 of PF-06817024 Following Multiple Doses in Part 1
T1/2 of PF-06817024 following multiple doses in Part 1; t1/2 was defined as terminal elimination half life.
Time frame: Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hr post dose on Day 1, Days 8 and 15, Day 31/46 (at pre-dose, 1, 2, 4, 8, 12, 24, 48 hr), Days 61, 91, 121, 151, 181, 211, 241, at Extended Follow-Up visits (up to a maximum of 645 days/15480 hr post dose).
t1/2 of PF-06817024 in Part 2
t1/2 was defined as terminal elimination half life, and was calculated by Loge(2)/kel, where kel was the terminal elimination phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Time frame: Pre-dose, 1, 2, 4, 8, 12, 24, and 96 hour post dose on Day 1, and Days 8, 15, 32, 61, 91, 121, 181, 211, and at Extended Follow-Up visits (up to a maximum of 690 days/16560 hours post dose).
t1/2 of PF-06817024 in Part 3
t1/2 was defined as terminal elimination half life, and was calculated by Loge(2)/kel, where kel was the terminal elimination phase rate constant calculated by a linear regression of the log-linear concentration-time curve. For Part 3 Cohort 13: PF-06817024 600 mg + 300 mg IV AD, t1/2 of the last dose on Day 85 was reported in the table.
Time frame: On Day 1 (at pre-dose, 1.5, 4, and 168 hours post dose), and Days 29, 57, and 85 (at pre-dose, 1.5 and 4 hours post dose), and on Days 113, 253, 337, and Extended Follow-Up visits (up to a maximum of 882 days/21168 hours post dose on Day 85).
Apparent Volume of Distribution (Vz/F) of PF-06817024 for the Subcutaneous Cohort in Part 1
Apparent volume of distribution (Vz/F) of PF-06817024 for the subcutaneous cohort in Part 1; Vz/F was defined as apparent volume of distribution.
Time frame: Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, 96 hours post dose on Day 1, and on Follow-up Days 8, 15, 32, 46, 61, 91, 121, 151, 181, 211, and at Extended Follow-Up visits (up to a maximum of 780 days/18720 hours post dose).
Apparent Clearance (CL/F) of PF-06817024 for the Subcutaneous Cohort in Part 1
Apparent clearance (CL/F) of PF-06817024 for the subcutaneous cohort in Part 1; CL/F was defined as apparent clearance.
Time frame: Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, 96 hours post dose on Day 1, and on Follow-up Days 8, 15, 32, 46, 61, 91, 121, 151, 181, 211, and at Extended Follow-Up visits (up to a maximum of 780 days/18720 hours post dose).
Volume of Distribution at Steady State (Vss) of PF-06817024 Following Single Intravenous Dose in Part 1 and Part 2
Volume of distribution at steady state (Vss) of PF-06817024 following a single dose in Part 1 and Part 2; Vss was defined as volume of distribution at steady state.
Time frame: Pre-dose, 1, 2, 4, 8, 12, 24, and 96 hour post dose on Day 1, and Days 8, 15, 32, 61, 91, 121, 181, 211, and at Extended Follow-Up visits (up to 780 days for Part 1 and 690 days for Part 2). For Part 1 only: at post-dose 48 and 72 hour, Days 46 and 151.
Clearance (CL) of PF-06817024 Following Single Intravenous Dose in Part 1 and Part 2
CL was defined as Clearance, calculated by Dose/AUCinf. AUCinf was defined as area under the curve from time zero to infinity concentration.
Time frame: On Day 1 at pre-dose, post-dose 1, 2, 4, 8, 12, 24, 96 hour, Day 8, 15, 32, 61, 91, 121,181, 211, 241, 331, and 421. For Part 1 only: at post-dose 48 and 72 hour, Day 46 and 151. For Part 2 only: on Day 511, 601, and 691.
Trough Serum Concentration (Cmin) of PF-06817024 Post Second Dose Following Multiple Doses in Part 1
Trough serum concentration (Cmin) of PF-06817024 post second dose following multiple doses in Part 1; Cmin was defined as the trough serum concentration.
Time frame: At pre-dose on Day 31 or Day 46.
Cmin of PF-06817024 Post Last Dose Following Multiple Doses in Part 3
Cmin of PF-06817024 post last dose following multiple doses in Part 3; Cmin was defined as the trough serum concentration.
Time frame: At pre dose (0 hour) on Day 85.
Accumulation Ratio for Cmax (Rac, Cmax) of PF-06817024 Post Second Dose Following Multiple Doses in Part 1
Rac, Cmax was defined as accumulation ratio for Cmax, and was calculated by (Cmax on Day 31 or Day 46) / Cmax on Day 1. Cmax was defined as the maximum observed serum concentration.
Time frame: Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hr post dose on Day 1, Days 8 and 15, Day 31/46 (at pre-dose, 1, 2, 4, 8, 12, 24, 48 hr), Days 61, 91, 121, 151, 181, 211, 241, at Extended Follow-Up visits (up to a maximum of 645 days/15480 hr post dose).
Rac, Cmax of PF-06817024 Post Last Dose Following Multiple Doses in Part 3
Rac, Cmax was defined as accumulation ratio for Cmax, and was calculated by (Cmax on Day 85) / (Cmax on Day 1). Cmax was defined as the maximum observed serum concentration.
Time frame: On Day 1 (at pre-dose, 1.5, 4, and 168 hours post dose), and Days 29, 57, and 85 (at pre-dose, 1.5 and 4 hours post dose), and on Days 113, 253, 337, and Extended Follow-Up visits (up to a maximum of 882 days/21168 hours post dose on Day 85).
Accumulation Ratio for AUCtau (Rac) of PF-06817024 Post Second Dose Following Multiple Doses in Part 1
Rac was defined as accumulation ratio for AUCtau. AUCtau was defined as area under the curve within dosing interval. The dosing interval was 720 hours.
Time frame: Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hr post dose on Day 1, Days 8 and 15, Day 31/46 (at pre-dose, 1, 2, 4, 8, 12, 24, 48 hr), Days 61, 91, 121, 151, 181, 211, 241, at Extended Follow-Up visits (up to a maximum of 645 days/15480 hr post dose).
Rac of PF-06817024 Post Last Dose Following Multiple Doses in Part 3
Rac was defined as accumulation ratio for AUCtau. AUCtau was defined as area under the curve within dosing interval. The dosing interval was 672 hours.
Time frame: On Day 1 (at pre-dose, 1.5, 4, and 168 hours post dose), and Days 29, 57, and 85 (at pre-dose, 1.5 and 4 hours post dose), and on Days 113, 253, 337, and Extended Follow-Up visits (up to a maximum of 882 days/21168 hours post dose on Day 85).
Number of Participants With Treatment-Induced Anti-Drug Antibody (ADA) Against PF-06817024 in Part 1, 2, and 3
ADA was an immunogenicity endpoint. A participant had treatment-induced ADA when baseline titer was missing or negative and the participant had \>=1 post-treatment positive titer.
Time frame: Part 1 SD cohorts: baseline up to Day 780; Part 1 MD cohort: baseline up to Day 693; Part 2: baseline up to Day 692, Part 3: baseline up to Day 964.
Number of Participants With Treatment-Induced Neutralizing Antibodies (NAbs) Against PF-06817024 in Part 1, 2, and 3
NAb was an immunogenicity endpoint. A participant had treatment-induced NAb when baseline titer was missing or negative and the participant had \>=1 post-treatment positive titer.
Time frame: Part 1 SD cohorts: baseline up to Day 780; Part 1 MD cohort: baseline up to Day 693; Part 2: baseline up to Day 692, Part 3: baseline up to Day 964.