Atopic Dermatitis, Chronic Rhinosinusitis With Nasal Polyps, Healthy
Conditions
Keywords
FIH, Pharmacokinetics, Pharmacodynamics, Safety, Tolerability, Atopic Dermatitis, Chronic Rhinosinusitis, Nasal Polyps
Brief summary
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
Detailed description
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
Interventions
BIOLOGICALPF-06817024
Subjects will be given one dose of PF-06817024 intravenously
OTHERPlacebo for PF-06817024
Subjects will be given one dose of placebo for PF-06817024 intravenously
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male subjects, healthy female subjects of non-childbearing potential, 18-55 years of age (Part 1) * Male subjects, female subjects of non-childbearing potential, female subjects of childbearing potential with documented bilateral tubal ligation (tubes tied) or bilateral salpingectomy (tubes removed), 18-65 years of age, and 2 of the following symptoms: nasal congestion/obstruction, nasal discharge, face pain/pressure,or reduction/loss of smell (Part 2) * Male or female subjects between the ages of 18 and 75 years, inclusive with moderate-to-severe Atopic Dermatitis, agree to avoid prolonged exposure to the sun and not to use tanning booths, sun lamps, or other ultraviolet light sources during the study (Part 3)
Exclusion criteria
* Clinically significant diseases (cardiac, psychiatric, autoimmune, renal, etc.), positive urine drug test, fever within 7 days of dosing, active infections within 28 days of dosing (Part 1 and 2 and 3) * History of allergic reaction to topical lidocaine, nasal surgery within 6 months (Part 2) * Exposure to live or attenuated vaccines, have skin conditions other than Atopic Dermatitis, use of JAK inhibitors and biologics (Part 3)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With All-causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) in Part 1 | 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). | 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. |
| Number of Participants With Treatment-Related TEAEs and SAEs in Part 1 | 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). | 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. |
| Number of All-Causality TEAEs According to Severity in Part 1 | 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). | 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. |
| Number of Participants With Permanent Discontinuation Due to TEAEs in Part 1 | 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). | 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. |
| Number of Participants With All-Causality TEAEs and SAEs in Part 2 | From Study Day 1 (baseline) up to Day 691. | 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. |
| Number of Participants With Treatment-Related TEAEs and SAEs in Part 2 | From Study Day 1 (baseline) up to Day 691. | 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. |
| Number of All-Causality TEAEs According to Severity in Part 2 | From Study Day 1 (baseline) up to Day 691. | 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. |
| Number of Participants With Permanent Discontinuation Due to TEAEs in Part 2 | From Study Day 1 (baseline) up to Day 691. | 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. |
| Number of Participants With All-Causality TEAEs and SAEs in Part 3 | From Study Day 1 (baseline) up to Day 1105. | 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. |
| Number of Participants With Treatment-Related TEAEs and SAEs in Part 3 | From Study Day 1 (baseline) up to Day 1105. | 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. |
| Number of All-Causality TEAEs According to Severity in Part 3 | From Study Day 1 (baseline) up to Day 1105. | 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. |
| Number of Participants With Permanent Discontinuation Due to TEAEs in Part 3 | From Study Day 1 (baseline) up to Day 1105. | 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. |
| Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis in Part 1 | 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. | 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. |
| Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis in Part 2 | Part 2: from Study Day 1 (baseline) up to Day 211. | 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. |
| Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis in Part 3 | Part 3: from Study Day 1 (baseline) up to Day 966. | 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. |
| Number of Participants With Vital Sign Abnormalities in Part 1 | 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). | 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. |
| Number of Participants With Vital Sign Abnormalities in Part 2 | Study Day 1 (baseline) up to end of study (Study Day 211). | 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. |
| Number of Participants With Vital Sign Abnormalities in Part 3 | Study Day 1 (baseline) up to end of study (Study Day 337). | 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. |
| Number of Participants With Electrocardiogram (ECG) Abnormalities in Part 1 | 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). | 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. |
| Number of Participants With ECG Abnormalities in Part 2 | Study Day 1 (baseline) up to end of study (Study Day 211). | 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. |
| Number of Participants With ECG Abnormalities in Part 3 | Study Day 1 (baseline) up to end of study (Study Day 337). | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| t1/2 of PF-06817024 Following Multiple Doses in Part 1 | 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 following multiple doses in Part 1; t1/2 was defined as terminal elimination half life. |
| t1/2 of PF-06817024 in Part 2 | 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 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. |
| t1/2 of PF-06817024 in Part 3 | 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). | 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. |
| Apparent Volume of Distribution (Vz/F) of PF-06817024 for the Subcutaneous Cohort in Part 1 | 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 volume of distribution (Vz/F) of PF-06817024 for the subcutaneous cohort in Part 1; Vz/F was defined as apparent volume of distribution. |
| Apparent Clearance (CL/F) of PF-06817024 for the Subcutaneous Cohort in Part 1 | 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; CL/F was defined as apparent clearance. |
| Volume of Distribution at Steady State (Vss) of PF-06817024 Following Single Intravenous Dose in Part 1 and Part 2 | 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. | 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. |
| Clearance (CL) of PF-06817024 Following Single Intravenous Dose in Part 1 and Part 2 | 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. | CL was defined as Clearance, calculated by Dose/AUCinf. AUCinf was defined as area under the curve from time zero to infinity concentration. |
| Trough Serum Concentration (Cmin) of PF-06817024 Post Second Dose Following Multiple Doses in Part 1 | At pre-dose on Day 31 or Day 46. | Trough serum concentration (Cmin) of PF-06817024 post second dose following multiple doses in Part 1; Cmin was defined as the trough serum concentration. |
| Cmin of PF-06817024 Post Last Dose Following Multiple Doses in Part 3 | At pre dose (0 hour) on Day 85. | Cmin of PF-06817024 post last dose following multiple doses in Part 3; Cmin was defined as the trough serum concentration. |
| Accumulation Ratio for Cmax (Rac, Cmax) of PF-06817024 Post Second Dose Following Multiple Doses in Part 1 | 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 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. |
| Rac, Cmax of PF-06817024 Post Last Dose Following Multiple Doses in Part 3 | 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). | 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. |
| Accumulation Ratio for AUCtau (Rac) of PF-06817024 Post Second Dose Following Multiple Doses in Part 1 | 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 was defined as accumulation ratio for AUCtau. AUCtau was defined as area under the curve within dosing interval. The dosing interval was 720 hours. |
| Rac of PF-06817024 Post Last Dose Following Multiple Doses in Part 3 | 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). | 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. |
| Number of Participants With Treatment-Induced Anti-Drug Antibody (ADA) Against PF-06817024 in Part 1, 2, and 3 | 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. | 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. |
| Maximum Observed Serum Concentration (Cmax) of PF-06817024 Following Single Dose in Part 1 | 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). | Maximum observed serum concentration (Cmax) of PF-06817024 following single dose in Part 1; Cmax was defined as the maximum observed serum concentration. |
| Number of Participants With Treatment-Induced Neutralizing Antibodies (NAbs) Against PF-06817024 in Part 1, 2, and 3 | 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. | 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. |
| Cmax of PF-06817024 Following Multiple Doses in Part 1 | 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 was defined as the maximum observed serum concentration. |
| Cmax of PF-06817024 in Part 2 | 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 was defined as the maximum observed serum concentration. |
| Cmax of PF-06817024 in Part 3 | 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). | Cmax was defined as the maximum observed serum concentration. |
| Dose Normalized Maximum Observed Serum Concentration (Cmax[dn]) of PF-06817024 Following Single Dose in Part 1 | 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) was defined as the dose normalized maximum observed serum concentration, and calculated by Cmax/Dose. Cmax was defined as the maximum observed serum concentration. |
| Cmax(dn) of PF-06817024 Following Multiple Doses in Part 1 | 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) was defined as dose normalized maximum observed serum concentration, and calculated by Cmax/Dose. Cmax was defined as the maximum observed serum concentration. |
| Cmax(dn) of PF-06817024 in Part 2 | 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) was defined as the dose normalized maximum observed serum concentration, and calculated by Cmax/Dose. Cmax was defined as the maximum observed serum concentration. |
| Cmax(dn) of PF-06817024 in Part 3 | 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). | 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 to Reach Maximum Observed Serum Concentration (Tmax) of PF-06817024 Following Single Dose in Part 1 | 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). | 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. |
| Tmax of PF-06817024 Following Multiple Doses in Part 1 | 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 was defined as time to reach maximum observed serum concentration. |
| Tmax of PF-06817024 in Part 2 | 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 was defined as time to reach maximum observed serum concentration. |
| Tmax of PF-06817024 in Part 3 | 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). | Tmax was defined as time to reach maximum observed serum concentration. |
| Area Under the Curve From Time Zero to Infinity Concentration (AUCinf) of PF-06817024 Following Single Dose in Part 1 and 2 | 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 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. |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-06817024 Following Single Dose in Part 1 and 2 | 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; AUClast was defined as area under the curve from time zero to last quantifiable concentration. |
| Area Under the Curve Within Dosing Interval (AUCtau) of PF-06817024 Following Multiple Doses in Part 1 | 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). | 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. |
| AUCtau of PF-06817024 in Part 3 | 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). | AUCtau was defined as area under the curve within dosing interval. The dosing interval was 672 hours. |
| Dose Normalized Area Under the Curve Within Dosing Interval (AUCtau[dn]) of PF-06817024 Following Multiple Doses in Part 1 | 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). | 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. |
| AUCtau(dn) of PF-06817024 Following Multiple Doses in Part 3 | 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). | AUCtau(dn) was defined as dose normalized area under the curve within dosing interval. The dosing interval was 672 hours. |
| Average Concentration Over Dosing Interval (Cav) of PF-06817024 Following Multiple Doses in Part 1 | 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). | 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. |
| Cav of PF-06817024 Following Multiple Doses in Part 3 | 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). | Cav was defined as average concentration over dosing interval. The dosing interval was 672 hours. |
| Terminal Elimination Half Life (t1/2) of PF-06817024 Following Single Dose in Part 1 | 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 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. |
Countries
United States
Participant flow
Pre-assignment details
A total of 97 participants were assigned and treated in this study, with 49, 20, and 28 participants in Part 1, 2, and 3, respectively.
Participants by arm
| Arm | Count |
|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD Healthy participants who might be mildly atopic received PF-06817024 10 mg IV for a SD on Study Day 1. | 6 |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD Healthy participants who might be mildly atopic received PF-06817024 30 mg IV for a SD on Study Day 1. | 6 |
| Part 1 Cohort 7: PF-06817024 30 mg SC SD Healthy participants who might be mildly atopic received PF-06817024 30 mg SC for a SD on Study Day 1. | 6 |
| Part 1 Cohort 3: PF-06817024 100 mg IV SD Healthy participants who might be mildly atopic received PF-06817024 100 mg IV for a SD on Study Day 1. | 3 |
| Part 1 Cohort 3: PF-06817024 100 mg IV MD Healthy participants who might be mildly atopic received PF-06817024 100 mg IV for MD (2 doses, on Study Days 1 and 31/46). | 4 |
| Part 1 Cohort 4: PF-06817024 300 mg IV SD Healthy participants who might be mildly atopic received PF-06817024 300 mg IV for a SD on Study Day 1. | 6 |
| Part 1 Cohort 5: PF-06817024 1000 mg IV SD Healthy participants who might be mildly atopic received PF-06817024 1000 mg IV for a SD on Study Day 1. | 6 |
| Part 1: Placebo IV SD Healthy participants who might be mildly atopic received the matching placebo of PF-06817024 IV for a SD on Study Day 1. | 8 |
| Part 1 Cohort 3: Placebo IV MD Healthy participants who might be mildly atopic received the matching placebo of PF-06817024 IV for MD (2 doses, on Study Days 1 and 46/47). | 2 |
| Part 1 Cohort 7: Placebo SC SD Healthy participants who might be mildly atopic received the matching placebo of PF-06817024 SC for a SD on Study Day 1. | 2 |
| Part 2 Cohort 8: PF-06817024 300 mg IV CRSwNP Participants with CRSwNP received PF-06817024 300 mg IV for a SD on Study Day 1. | 11 |
| Part 2 Cohort 8: Placebo IV CRSwNP Participants with CRSwNP received the matching placebo of PF-06817024 IV for a SD on Study Day 1. | 9 |
| Part 3 Cohort 13: PF-06817024 600 mg => 300 mg IV AD Participants with moderate to severe AD received PF-06817024 600 mg loading dose IV on Study Day 1 followed by 3 doses of PF-06817024 300 mg IV on Study Days 29, 57, and 85. | 20 |
| Part 3 Cohort 13: Placebo IV AD Participants with moderate to severe AD received the matching placebo of PF-06817024 IV on Study Days 1, 29, 57, and 85. | 8 |
| Total | 97 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 2 | 0 | 0 |
| Overall Study | Other | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 1 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 12 | 6 |
Baseline characteristics
| Characteristic | Part 1 Cohort 1: PF-06817024 10 mg IV SD | Part 1 Cohort 2: PF-06817024 30 mg IV SD | Part 1 Cohort 7: PF-06817024 30 mg SC SD | Part 1 Cohort 3: PF-06817024 100 mg IV SD | Part 1 Cohort 3: PF-06817024 100 mg IV MD | Part 1 Cohort 4: PF-06817024 300 mg IV SD | Part 1 Cohort 5: PF-06817024 1000 mg IV SD | Part 1: Placebo IV SD | Part 1 Cohort 3: Placebo IV MD | Part 1 Cohort 7: Placebo SC SD | Part 2 Cohort 8: PF-06817024 300 mg IV CRSwNP | Part 2 Cohort 8: Placebo IV CRSwNP | Part 3 Cohort 13: PF-06817024 600 mg => 300 mg IV AD | Part 3 Cohort 13: Placebo IV AD | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 34.0 years STANDARD_DEVIATION 4.9 | 37.0 years STANDARD_DEVIATION 10.7 | 43.2 years STANDARD_DEVIATION 8.7 | 27.0 years STANDARD_DEVIATION 6.1 | 26.5 years STANDARD_DEVIATION 6.8 | 36.3 years STANDARD_DEVIATION 7.7 | 39.8 years STANDARD_DEVIATION 8.7 | 33.3 years STANDARD_DEVIATION 12 | 23.5 years STANDARD_DEVIATION 0.7 | 34.5 years STANDARD_DEVIATION 4.9 | 54.4 years STANDARD_DEVIATION 6.2 | 42.8 years STANDARD_DEVIATION 10.7 | 38.9 years STANDARD_DEVIATION 13.8 | 41.0 years STANDARD_DEVIATION 17.4 | 49.2 years STANDARD_DEVIATION 10.2 |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized Black | 4 Participants | 2 Participants | 2 Participants | 2 Participants | 1 Participants | 4 Participants | 3 Participants | 3 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 9 Participants | 3 Participants | 37 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants | 12 Participants |
| Race/Ethnicity, Customized White | 1 Participants | 3 Participants | 3 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 3 Participants | 0 Participants | 1 Participants | 11 Participants | 7 Participants | 8 Participants | 3 Participants | 44 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants | 4 Participants | 12 Participants | 7 Participants | 29 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 4 Participants | 3 Participants | 4 Participants | 6 Participants | 6 Participants | 7 Participants | 2 Participants | 2 Participants | 8 Participants | 5 Participants | 8 Participants | 1 Participants | 68 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 3 | 0 / 4 | 0 / 6 | 0 / 6 | 0 / 8 | 0 / 2 | 0 / 2 | 0 / 11 | 0 / 9 | 0 / 20 | 0 / 8 |
| other Total, other adverse events | 6 / 6 | 4 / 6 | 5 / 6 | 3 / 3 | 1 / 4 | 6 / 6 | 4 / 6 | 8 / 8 | 2 / 2 | 2 / 2 | 10 / 11 | 8 / 9 | 8 / 20 | 5 / 8 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 3 | 0 / 4 | 0 / 6 | 1 / 6 | 0 / 8 | 0 / 2 | 0 / 2 | 0 / 11 | 1 / 9 | 3 / 20 | 1 / 8 |
Outcome results
Primary
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.
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).
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of All-Causality TEAEs According to Severity in Part 1 | Severe | 0 Events |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of All-Causality TEAEs According to Severity in Part 1 | Mild | 14 Events |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of All-Causality TEAEs According to Severity in Part 1 | Moderate | 2 Events |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of All-Causality TEAEs According to Severity in Part 1 | Moderate | 2 Events |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of All-Causality TEAEs According to Severity in Part 1 | Mild | 10 Events |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of All-Causality TEAEs According to Severity in Part 1 | Severe | 0 Events |
| Part 1 Cohort 3: PF-06817024 30 mg SC SD | Number of All-Causality TEAEs According to Severity in Part 1 | Severe | 0 Events |
| Part 1 Cohort 3: PF-06817024 30 mg SC SD | Number of All-Causality TEAEs According to Severity in Part 1 | Moderate | 1 Events |
| Part 1 Cohort 3: PF-06817024 30 mg SC SD | Number of All-Causality TEAEs According to Severity in Part 1 | Mild | 20 Events |
| Part 1 Cohort 3: PF-06817024 100 mg IV SD | Number of All-Causality TEAEs According to Severity in Part 1 | Severe | 0 Events |
| Part 1 Cohort 3: PF-06817024 100 mg IV SD | Number of All-Causality TEAEs According to Severity in Part 1 | Moderate | 0 Events |
| Part 1 Cohort 3: PF-06817024 100 mg IV SD | Number of All-Causality TEAEs According to Severity in Part 1 | Mild | 11 Events |
| Part 1 Cohort 3: PF-06817024 100 mg IV MD | Number of All-Causality TEAEs According to Severity in Part 1 | Moderate | 0 Events |
| Part 1 Cohort 3: PF-06817024 100 mg IV MD | Number of All-Causality TEAEs According to Severity in Part 1 | Mild | 4 Events |
| Part 1 Cohort 3: PF-06817024 100 mg IV MD | Number of All-Causality TEAEs According to Severity in Part 1 | Severe | 0 Events |
| Part 1 Cohort 4: PF-06817024 300 mg IV SD | Number of All-Causality TEAEs According to Severity in Part 1 | Mild | 15 Events |
| Part 1 Cohort 4: PF-06817024 300 mg IV SD | Number of All-Causality TEAEs According to Severity in Part 1 | Severe | 0 Events |
| Part 1 Cohort 4: PF-06817024 300 mg IV SD | Number of All-Causality TEAEs According to Severity in Part 1 | Moderate | 2 Events |
| Part 1 Cohort 5: PF-06817024 1000 mg IV SD | Number of All-Causality TEAEs According to Severity in Part 1 | Severe | 0 Events |
| Part 1 Cohort 5: PF-06817024 1000 mg IV SD | Number of All-Causality TEAEs According to Severity in Part 1 | Mild | 10 Events |
| Part 1 Cohort 5: PF-06817024 1000 mg IV SD | Number of All-Causality TEAEs According to Severity in Part 1 | Moderate | 1 Events |
| Part 1: Placebo IV SD | Number of All-Causality TEAEs According to Severity in Part 1 | Moderate | 2 Events |
| Part 1: Placebo IV SD | Number of All-Causality TEAEs According to Severity in Part 1 | Severe | 0 Events |
| Part 1: Placebo IV SD | Number of All-Causality TEAEs According to Severity in Part 1 | Mild | 30 Events |
| Part 1 Cohort 3: Placebo IV MD | Number of All-Causality TEAEs According to Severity in Part 1 | Mild | 3 Events |
| Part 1 Cohort 3: Placebo IV MD | Number of All-Causality TEAEs According to Severity in Part 1 | Moderate | 0 Events |
| Part 1 Cohort 3: Placebo IV MD | Number of All-Causality TEAEs According to Severity in Part 1 | Severe | 0 Events |
| Part 1 Cohort 7: Placebo SC SD | Number of All-Causality TEAEs According to Severity in Part 1 | Moderate | 0 Events |
| Part 1 Cohort 7: Placebo SC SD | Number of All-Causality TEAEs According to Severity in Part 1 | Mild | 4 Events |
| Part 1 Cohort 7: Placebo SC SD | Number of All-Causality TEAEs According to Severity in Part 1 | Severe | 0 Events |
Primary
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.
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of All-Causality TEAEs According to Severity in Part 2 | Mild | 44 Events |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of All-Causality TEAEs According to Severity in Part 2 | Moderate | 14 Events |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of All-Causality TEAEs According to Severity in Part 2 | Severe | 0 Events |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of All-Causality TEAEs According to Severity in Part 2 | Mild | 24 Events |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of All-Causality TEAEs According to Severity in Part 2 | Moderate | 9 Events |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of All-Causality TEAEs According to Severity in Part 2 | Severe | 3 Events |
Primary
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.
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of All-Causality TEAEs According to Severity in Part 3 | Mild | 12 TEAEs |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of All-Causality TEAEs According to Severity in Part 3 | Moderate | 15 TEAEs |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of All-Causality TEAEs According to Severity in Part 3 | Severe | 13 TEAEs |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of All-Causality TEAEs According to Severity in Part 3 | Mild | 2 TEAEs |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of All-Causality TEAEs According to Severity in Part 3 | Severe | 1 TEAEs |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of All-Causality TEAEs According to Severity in Part 3 | Moderate | 5 TEAEs |
Primary
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.
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of Participants With All-Causality TEAEs and SAEs in Part 2 | Number of Participants With All-Causality TEAEs | 10 Participants |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of Participants With All-Causality TEAEs and SAEs in Part 2 | Number of Participants With All-Causality SAEs | 0 Participants |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of Participants With All-Causality TEAEs and SAEs in Part 2 | Number of Participants With All-Causality TEAEs | 8 Participants |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of Participants With All-Causality TEAEs and SAEs in Part 2 | Number of Participants With All-Causality SAEs | 1 Participants |
Primary
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.
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of Participants With All-Causality TEAEs and SAEs in Part 3 | Number of Participants With All-Causality TEAEs | 12 Participants |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of Participants With All-Causality TEAEs and SAEs in Part 3 | Number of Participants With All-Causality SAEs | 3 Participants |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of Participants With All-Causality TEAEs and SAEs in Part 3 | Number of Participants With All-Causality TEAEs | 5 Participants |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of Participants With All-Causality TEAEs and SAEs in Part 3 | Number of Participants With All-Causality SAEs | 1 Participants |
Primary
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).
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of Participants With All-causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) in Part 1 | Number of Participants With All-Causality TEAEs | 6 Participants |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of Participants With All-causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) in Part 1 | Number of Participants With All-Causality SAEs | 0 Participants |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of Participants With All-causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) in Part 1 | Number of Participants With All-Causality TEAEs | 4 Participants |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of Participants With All-causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) in Part 1 | Number of Participants With All-Causality SAEs | 0 Participants |
| Part 1 Cohort 3: PF-06817024 30 mg SC SD | Number of Participants With All-causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) in Part 1 | Number of Participants With All-Causality TEAEs | 5 Participants |
| Part 1 Cohort 3: PF-06817024 30 mg SC SD | Number of Participants With All-causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) in Part 1 | Number of Participants With All-Causality SAEs | 0 Participants |
| Part 1 Cohort 3: PF-06817024 100 mg IV SD | Number of Participants With All-causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) in Part 1 | Number of Participants With All-Causality TEAEs | 3 Participants |
| Part 1 Cohort 3: PF-06817024 100 mg IV SD | Number of Participants With All-causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) in Part 1 | Number of Participants With All-Causality SAEs | 0 Participants |
| Part 1 Cohort 3: PF-06817024 100 mg IV MD | Number of Participants With All-causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) in Part 1 | Number of Participants With All-Causality SAEs | 0 Participants |
| Part 1 Cohort 3: PF-06817024 100 mg IV MD | Number of Participants With All-causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) in Part 1 | Number of Participants With All-Causality TEAEs | 1 Participants |
| Part 1 Cohort 4: PF-06817024 300 mg IV SD | Number of Participants With All-causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) in Part 1 | Number of Participants With All-Causality SAEs | 0 Participants |
| Part 1 Cohort 4: PF-06817024 300 mg IV SD | Number of Participants With All-causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) in Part 1 | Number of Participants With All-Causality TEAEs | 6 Participants |
| Part 1 Cohort 5: PF-06817024 1000 mg IV SD | Number of Participants With All-causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) in Part 1 | Number of Participants With All-Causality SAEs | 1 Participants |
| Part 1 Cohort 5: PF-06817024 1000 mg IV SD | Number of Participants With All-causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) in Part 1 | Number of Participants With All-Causality TEAEs | 4 Participants |
| Part 1: Placebo IV SD | Number of Participants With All-causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) in Part 1 | Number of Participants With All-Causality TEAEs | 8 Participants |
| Part 1: Placebo IV SD | Number of Participants With All-causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) in Part 1 | Number of Participants With All-Causality SAEs | 0 Participants |
| Part 1 Cohort 3: Placebo IV MD | Number of Participants With All-causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) in Part 1 | Number of Participants With All-Causality TEAEs | 2 Participants |
| Part 1 Cohort 3: Placebo IV MD | Number of Participants With All-causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) in Part 1 | Number of Participants With All-Causality SAEs | 0 Participants |
| Part 1 Cohort 7: Placebo SC SD | Number of Participants With All-causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) in Part 1 | Number of Participants With All-Causality TEAEs | 2 Participants |
| Part 1 Cohort 7: Placebo SC SD | Number of Participants With All-causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) in Part 1 | Number of Participants With All-Causality SAEs | 0 Participants |
Primary
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.
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis in Part 1 | Blood creatine phosphokinase increased | 0 Participants |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis in Part 1 | Transaminases increased | 0 Participants |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis in Part 1 | Blood creatine phosphokinase increased | 0 Participants |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis in Part 1 | Transaminases increased | 0 Participants |
| Part 1 Cohort 3: PF-06817024 30 mg SC SD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis in Part 1 | Blood creatine phosphokinase increased | 0 Participants |
| Part 1 Cohort 3: PF-06817024 30 mg SC SD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis in Part 1 | Transaminases increased | 0 Participants |
| Part 1 Cohort 3: PF-06817024 100 mg IV SD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis in Part 1 | Blood creatine phosphokinase increased | 0 Participants |
| Part 1 Cohort 3: PF-06817024 100 mg IV SD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis in Part 1 | Transaminases increased | 0 Participants |
| Part 1 Cohort 3: PF-06817024 100 mg IV MD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis in Part 1 | Transaminases increased | 0 Participants |
| Part 1 Cohort 3: PF-06817024 100 mg IV MD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis in Part 1 | Blood creatine phosphokinase increased | 0 Participants |
| Part 1 Cohort 4: PF-06817024 300 mg IV SD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis in Part 1 | Transaminases increased | 0 Participants |
| Part 1 Cohort 4: PF-06817024 300 mg IV SD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis in Part 1 | Blood creatine phosphokinase increased | 0 Participants |
| Part 1 Cohort 5: PF-06817024 1000 mg IV SD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis in Part 1 | Transaminases increased | 0 Participants |
| Part 1 Cohort 5: PF-06817024 1000 mg IV SD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis in Part 1 | Blood creatine phosphokinase increased | 0 Participants |
| Part 1: Placebo IV SD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis in Part 1 | Blood creatine phosphokinase increased | 0 Participants |
| Part 1: Placebo IV SD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis in Part 1 | Transaminases increased | 0 Participants |
| Part 1 Cohort 3: Placebo IV MD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis in Part 1 | Blood creatine phosphokinase increased | 1 Participants |
| Part 1 Cohort 3: Placebo IV MD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis in Part 1 | Transaminases increased | 1 Participants |
| Part 1 Cohort 7: Placebo SC SD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis in Part 1 | Blood creatine phosphokinase increased | 0 Participants |
| Part 1 Cohort 7: Placebo SC SD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis in Part 1 | Transaminases increased | 0 Participants |
Primary
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.
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis in Part 2 | Blood creatine phosphokinase increased | 0 Participants |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis in Part 2 | Transaminases increased | 0 Participants |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis in Part 2 | Blood creatine phosphokinase increased | 0 Participants |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis in Part 2 | Transaminases increased | 0 Participants |
Primary
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.
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis in Part 3 | Blood creatine phosphokinase increased | 0 Participants |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis in Part 3 | Transaminases increased | 1 Participants |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis in Part 3 | Blood creatine phosphokinase increased | 0 Participants |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis in Part 3 | Transaminases increased | 0 Participants |
Primary
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).
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of Participants With ECG Abnormalities in Part 2 | 450 <= maximum QTcF interval (msec) <480 | 1 Participants |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of Participants With ECG Abnormalities in Part 2 | 30 <= maximum QTcF interval increase from baseline (msec) <60 | 1 Participants |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of Participants With ECG Abnormalities in Part 2 | 450 <= maximum QTcF interval (msec) <480 | 2 Participants |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of Participants With ECG Abnormalities in Part 2 | 30 <= maximum QTcF interval increase from baseline (msec) <60 | 1 Participants |
Primary
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).
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of Participants With ECG Abnormalities in Part 3 | 450 <= maximum QTcF interval (msec) <480 | 2 Participants |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of Participants With ECG Abnormalities in Part 3 | 30 <= maximum QTcF interval increase from baseline (msec) <60 | 5 Participants |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of Participants With ECG Abnormalities in Part 3 | Maximum QTcF interval increase from baseline (msec) >=60 | 1 Participants |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of Participants With ECG Abnormalities in Part 3 | Maximum QTcF interval (msec) >=500 | 0 Participants |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of Participants With ECG Abnormalities in Part 3 | Maximum QTcF interval (msec) >=500 | 1 Participants |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of Participants With ECG Abnormalities in Part 3 | 450 <= maximum QTcF interval (msec) <480 | 2 Participants |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of Participants With ECG Abnormalities in Part 3 | Maximum QTcF interval increase from baseline (msec) >=60 | 0 Participants |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of Participants With ECG Abnormalities in Part 3 | 30 <= maximum QTcF interval increase from baseline (msec) <60 | 2 Participants |
Primary
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).
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of Participants With Electrocardiogram (ECG) Abnormalities in Part 1 | 450 <= maximum QTcF interval (msec) <480 | 1 Participants |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of Participants With Electrocardiogram (ECG) Abnormalities in Part 1 | 30 <= maximum QTcF interval increase from baseline (msec) <60 | 0 Participants |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of Participants With Electrocardiogram (ECG) Abnormalities in Part 1 | 450 <= maximum QTcF interval (msec) <480 | 0 Participants |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of Participants With Electrocardiogram (ECG) Abnormalities in Part 1 | 30 <= maximum QTcF interval increase from baseline (msec) <60 | 0 Participants |
| Part 1 Cohort 3: PF-06817024 30 mg SC SD | Number of Participants With Electrocardiogram (ECG) Abnormalities in Part 1 | 450 <= maximum QTcF interval (msec) <480 | 0 Participants |
| Part 1 Cohort 3: PF-06817024 30 mg SC SD | Number of Participants With Electrocardiogram (ECG) Abnormalities in Part 1 | 30 <= maximum QTcF interval increase from baseline (msec) <60 | 0 Participants |
| Part 1 Cohort 3: PF-06817024 100 mg IV SD | Number of Participants With Electrocardiogram (ECG) Abnormalities in Part 1 | 450 <= maximum QTcF interval (msec) <480 | 0 Participants |
| Part 1 Cohort 3: PF-06817024 100 mg IV SD | Number of Participants With Electrocardiogram (ECG) Abnormalities in Part 1 | 30 <= maximum QTcF interval increase from baseline (msec) <60 | 0 Participants |
| Part 1 Cohort 3: PF-06817024 100 mg IV MD | Number of Participants With Electrocardiogram (ECG) Abnormalities in Part 1 | 30 <= maximum QTcF interval increase from baseline (msec) <60 | 0 Participants |
| Part 1 Cohort 3: PF-06817024 100 mg IV MD | Number of Participants With Electrocardiogram (ECG) Abnormalities in Part 1 | 450 <= maximum QTcF interval (msec) <480 | 0 Participants |
| Part 1 Cohort 4: PF-06817024 300 mg IV SD | Number of Participants With Electrocardiogram (ECG) Abnormalities in Part 1 | 30 <= maximum QTcF interval increase from baseline (msec) <60 | 0 Participants |
| Part 1 Cohort 4: PF-06817024 300 mg IV SD | Number of Participants With Electrocardiogram (ECG) Abnormalities in Part 1 | 450 <= maximum QTcF interval (msec) <480 | 0 Participants |
| Part 1 Cohort 5: PF-06817024 1000 mg IV SD | Number of Participants With Electrocardiogram (ECG) Abnormalities in Part 1 | 30 <= maximum QTcF interval increase from baseline (msec) <60 | 0 Participants |
| Part 1 Cohort 5: PF-06817024 1000 mg IV SD | Number of Participants With Electrocardiogram (ECG) Abnormalities in Part 1 | 450 <= maximum QTcF interval (msec) <480 | 0 Participants |
| Part 1: Placebo IV SD | Number of Participants With Electrocardiogram (ECG) Abnormalities in Part 1 | 450 <= maximum QTcF interval (msec) <480 | 2 Participants |
| Part 1: Placebo IV SD | Number of Participants With Electrocardiogram (ECG) Abnormalities in Part 1 | 30 <= maximum QTcF interval increase from baseline (msec) <60 | 2 Participants |
| Part 1 Cohort 3: Placebo IV MD | Number of Participants With Electrocardiogram (ECG) Abnormalities in Part 1 | 450 <= maximum QTcF interval (msec) <480 | 0 Participants |
| Part 1 Cohort 3: Placebo IV MD | Number of Participants With Electrocardiogram (ECG) Abnormalities in Part 1 | 30 <= maximum QTcF interval increase from baseline (msec) <60 | 1 Participants |
| Part 1 Cohort 7: Placebo SC SD | Number of Participants With Electrocardiogram (ECG) Abnormalities in Part 1 | 450 <= maximum QTcF interval (msec) <480 | 0 Participants |
| Part 1 Cohort 7: Placebo SC SD | Number of Participants With Electrocardiogram (ECG) Abnormalities in Part 1 | 30 <= maximum QTcF interval increase from baseline (msec) <60 | 0 Participants |
Primary
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).
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of Participants With Permanent Discontinuation Due to TEAEs in Part 1 | 1 Participants |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of Participants With Permanent Discontinuation Due to TEAEs in Part 1 | 0 Participants |
| Part 1 Cohort 3: PF-06817024 30 mg SC SD | Number of Participants With Permanent Discontinuation Due to TEAEs in Part 1 | 0 Participants |
| Part 1 Cohort 3: PF-06817024 100 mg IV SD | Number of Participants With Permanent Discontinuation Due to TEAEs in Part 1 | 0 Participants |
| Part 1 Cohort 3: PF-06817024 100 mg IV MD | Number of Participants With Permanent Discontinuation Due to TEAEs in Part 1 | 0 Participants |
| Part 1 Cohort 4: PF-06817024 300 mg IV SD | Number of Participants With Permanent Discontinuation Due to TEAEs in Part 1 | 0 Participants |
| Part 1 Cohort 5: PF-06817024 1000 mg IV SD | Number of Participants With Permanent Discontinuation Due to TEAEs in Part 1 | 0 Participants |
| Part 1: Placebo IV SD | Number of Participants With Permanent Discontinuation Due to TEAEs in Part 1 | 0 Participants |
| Part 1 Cohort 3: Placebo IV MD | Number of Participants With Permanent Discontinuation Due to TEAEs in Part 1 | 0 Participants |
| Part 1 Cohort 7: Placebo SC SD | Number of Participants With Permanent Discontinuation Due to TEAEs in Part 1 | 0 Participants |
Primary
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.
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of Participants With Permanent Discontinuation Due to TEAEs in Part 2 | 0 Participants |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of Participants With Permanent Discontinuation Due to TEAEs in Part 2 | 0 Participants |
Primary
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.
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of Participants With Permanent Discontinuation Due to TEAEs in Part 3 | 0 Participants |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of Participants With Permanent Discontinuation Due to TEAEs in Part 3 | 0 Participants |
Primary
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).
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of Participants With Treatment-Related TEAEs and SAEs in Part 1 | Number of Participants With Treatment-Related TEAEs | 2 Participants |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of Participants With Treatment-Related TEAEs and SAEs in Part 1 | Number of Participants With Treatment-Related SAEs | 0 Participants |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of Participants With Treatment-Related TEAEs and SAEs in Part 1 | Number of Participants With Treatment-Related TEAEs | 2 Participants |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of Participants With Treatment-Related TEAEs and SAEs in Part 1 | Number of Participants With Treatment-Related SAEs | 0 Participants |
| Part 1 Cohort 3: PF-06817024 30 mg SC SD | Number of Participants With Treatment-Related TEAEs and SAEs in Part 1 | Number of Participants With Treatment-Related TEAEs | 2 Participants |
| Part 1 Cohort 3: PF-06817024 30 mg SC SD | Number of Participants With Treatment-Related TEAEs and SAEs in Part 1 | Number of Participants With Treatment-Related SAEs | 0 Participants |
| Part 1 Cohort 3: PF-06817024 100 mg IV SD | Number of Participants With Treatment-Related TEAEs and SAEs in Part 1 | Number of Participants With Treatment-Related TEAEs | 2 Participants |
| Part 1 Cohort 3: PF-06817024 100 mg IV SD | Number of Participants With Treatment-Related TEAEs and SAEs in Part 1 | Number of Participants With Treatment-Related SAEs | 0 Participants |
| Part 1 Cohort 3: PF-06817024 100 mg IV MD | Number of Participants With Treatment-Related TEAEs and SAEs in Part 1 | Number of Participants With Treatment-Related SAEs | 0 Participants |
| Part 1 Cohort 3: PF-06817024 100 mg IV MD | Number of Participants With Treatment-Related TEAEs and SAEs in Part 1 | Number of Participants With Treatment-Related TEAEs | 1 Participants |
| Part 1 Cohort 4: PF-06817024 300 mg IV SD | Number of Participants With Treatment-Related TEAEs and SAEs in Part 1 | Number of Participants With Treatment-Related SAEs | 0 Participants |
| Part 1 Cohort 4: PF-06817024 300 mg IV SD | Number of Participants With Treatment-Related TEAEs and SAEs in Part 1 | Number of Participants With Treatment-Related TEAEs | 3 Participants |
| Part 1 Cohort 5: PF-06817024 1000 mg IV SD | Number of Participants With Treatment-Related TEAEs and SAEs in Part 1 | Number of Participants With Treatment-Related SAEs | 0 Participants |
| Part 1 Cohort 5: PF-06817024 1000 mg IV SD | Number of Participants With Treatment-Related TEAEs and SAEs in Part 1 | Number of Participants With Treatment-Related TEAEs | 1 Participants |
| Part 1: Placebo IV SD | Number of Participants With Treatment-Related TEAEs and SAEs in Part 1 | Number of Participants With Treatment-Related TEAEs | 1 Participants |
| Part 1: Placebo IV SD | Number of Participants With Treatment-Related TEAEs and SAEs in Part 1 | Number of Participants With Treatment-Related SAEs | 0 Participants |
| Part 1 Cohort 3: Placebo IV MD | Number of Participants With Treatment-Related TEAEs and SAEs in Part 1 | Number of Participants With Treatment-Related TEAEs | 0 Participants |
| Part 1 Cohort 3: Placebo IV MD | Number of Participants With Treatment-Related TEAEs and SAEs in Part 1 | Number of Participants With Treatment-Related SAEs | 0 Participants |
| Part 1 Cohort 7: Placebo SC SD | Number of Participants With Treatment-Related TEAEs and SAEs in Part 1 | Number of Participants With Treatment-Related TEAEs | 1 Participants |
| Part 1 Cohort 7: Placebo SC SD | Number of Participants With Treatment-Related TEAEs and SAEs in Part 1 | Number of Participants With Treatment-Related SAEs | 0 Participants |
Primary
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.
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of Participants With Treatment-Related TEAEs and SAEs in Part 2 | Number of Participants With Treatment-Related TEAEs | 5 Participants |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of Participants With Treatment-Related TEAEs and SAEs in Part 2 | Number of Participants With Treatment-Related SAEs | 0 Participants |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of Participants With Treatment-Related TEAEs and SAEs in Part 2 | Number of Participants With Treatment-Related TEAEs | 3 Participants |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of Participants With Treatment-Related TEAEs and SAEs in Part 2 | Number of Participants With Treatment-Related SAEs | 0 Participants |
Primary
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.
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of Participants With Treatment-Related TEAEs and SAEs in Part 3 | Number of Participants With Treatment-Related TEAEs | 5 Participants |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of Participants With Treatment-Related TEAEs and SAEs in Part 3 | Number of Participants With Treatment-Related SAEs | 1 Participants |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of Participants With Treatment-Related TEAEs and SAEs in Part 3 | Number of Participants With Treatment-Related TEAEs | 0 Participants |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of Participants With Treatment-Related TEAEs and SAEs in Part 3 | Number of Participants With Treatment-Related SAEs | 0 Participants |
Primary
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).
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Supine SBP <90 mmHg | 0 Participants |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Maximum Decrease from Baseline in Supine SBP >= 30 mmHg | 0 Participants |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Supine DBP <50 mmHg | 0 Participants |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Maximum Increase from Baseline in Supine SBP >= 30 mmHg | 1 Participants |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Maximum Increase from Baseline in Supine DBP >= 20 mmHg | 0 Participants |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Maximum Decrease from Baseline in Supine DBP >= 20 mmHg | 0 Participants |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Supine SBP <90 mmHg | 0 Participants |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Maximum Increase from Baseline in Supine SBP >= 30 mmHg | 0 Participants |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Maximum Decrease from Baseline in Supine DBP >= 20 mmHg | 0 Participants |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Maximum Decrease from Baseline in Supine SBP >= 30 mmHg | 0 Participants |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Supine DBP <50 mmHg | 0 Participants |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Maximum Increase from Baseline in Supine DBP >= 20 mmHg | 0 Participants |
| Part 1 Cohort 3: PF-06817024 30 mg SC SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Maximum Decrease from Baseline in Supine DBP >= 20 mmHg | 0 Participants |
| Part 1 Cohort 3: PF-06817024 30 mg SC SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Maximum Increase from Baseline in Supine SBP >= 30 mmHg | 1 Participants |
| Part 1 Cohort 3: PF-06817024 30 mg SC SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Supine SBP <90 mmHg | 0 Participants |
| Part 1 Cohort 3: PF-06817024 30 mg SC SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Maximum Increase from Baseline in Supine DBP >= 20 mmHg | 1 Participants |
| Part 1 Cohort 3: PF-06817024 30 mg SC SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Maximum Decrease from Baseline in Supine SBP >= 30 mmHg | 0 Participants |
| Part 1 Cohort 3: PF-06817024 30 mg SC SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Supine DBP <50 mmHg | 0 Participants |
| Part 1 Cohort 3: PF-06817024 100 mg IV SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Maximum Decrease from Baseline in Supine SBP >= 30 mmHg | 0 Participants |
| Part 1 Cohort 3: PF-06817024 100 mg IV SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Supine DBP <50 mmHg | 0 Participants |
| Part 1 Cohort 3: PF-06817024 100 mg IV SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Maximum Increase from Baseline in Supine DBP >= 20 mmHg | 0 Participants |
| Part 1 Cohort 3: PF-06817024 100 mg IV SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Supine SBP <90 mmHg | 0 Participants |
| Part 1 Cohort 3: PF-06817024 100 mg IV SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Maximum Decrease from Baseline in Supine DBP >= 20 mmHg | 0 Participants |
| Part 1 Cohort 3: PF-06817024 100 mg IV SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Maximum Increase from Baseline in Supine SBP >= 30 mmHg | 0 Participants |
| Part 1 Cohort 3: PF-06817024 100 mg IV MD | Number of Participants With Vital Sign Abnormalities in Part 1 | Supine SBP <90 mmHg | 0 Participants |
| Part 1 Cohort 3: PF-06817024 100 mg IV MD | Number of Participants With Vital Sign Abnormalities in Part 1 | Maximum Increase from Baseline in Supine SBP >= 30 mmHg | 0 Participants |
| Part 1 Cohort 3: PF-06817024 100 mg IV MD | Number of Participants With Vital Sign Abnormalities in Part 1 | Maximum Increase from Baseline in Supine DBP >= 20 mmHg | 0 Participants |
| Part 1 Cohort 3: PF-06817024 100 mg IV MD | Number of Participants With Vital Sign Abnormalities in Part 1 | Maximum Decrease from Baseline in Supine SBP >= 30 mmHg | 0 Participants |
| Part 1 Cohort 3: PF-06817024 100 mg IV MD | Number of Participants With Vital Sign Abnormalities in Part 1 | Maximum Decrease from Baseline in Supine DBP >= 20 mmHg | 0 Participants |
| Part 1 Cohort 3: PF-06817024 100 mg IV MD | Number of Participants With Vital Sign Abnormalities in Part 1 | Supine DBP <50 mmHg | 0 Participants |
| Part 1 Cohort 4: PF-06817024 300 mg IV SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Maximum Increase from Baseline in Supine SBP >= 30 mmHg | 0 Participants |
| Part 1 Cohort 4: PF-06817024 300 mg IV SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Supine DBP <50 mmHg | 0 Participants |
| Part 1 Cohort 4: PF-06817024 300 mg IV SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Maximum Decrease from Baseline in Supine SBP >= 30 mmHg | 0 Participants |
| Part 1 Cohort 4: PF-06817024 300 mg IV SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Supine SBP <90 mmHg | 0 Participants |
| Part 1 Cohort 4: PF-06817024 300 mg IV SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Maximum Increase from Baseline in Supine DBP >= 20 mmHg | 0 Participants |
| Part 1 Cohort 4: PF-06817024 300 mg IV SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Maximum Decrease from Baseline in Supine DBP >= 20 mmHg | 0 Participants |
| Part 1 Cohort 5: PF-06817024 1000 mg IV SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Maximum Decrease from Baseline in Supine DBP >= 20 mmHg | 0 Participants |
| Part 1 Cohort 5: PF-06817024 1000 mg IV SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Maximum Increase from Baseline in Supine DBP >= 20 mmHg | 1 Participants |
| Part 1 Cohort 5: PF-06817024 1000 mg IV SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Maximum Increase from Baseline in Supine SBP >= 30 mmHg | 0 Participants |
| Part 1 Cohort 5: PF-06817024 1000 mg IV SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Maximum Decrease from Baseline in Supine SBP >= 30 mmHg | 0 Participants |
| Part 1 Cohort 5: PF-06817024 1000 mg IV SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Supine SBP <90 mmHg | 1 Participants |
| Part 1 Cohort 5: PF-06817024 1000 mg IV SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Supine DBP <50 mmHg | 0 Participants |
| Part 1: Placebo IV SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Maximum Increase from Baseline in Supine SBP >= 30 mmHg | 2 Participants |
| Part 1: Placebo IV SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Maximum Decrease from Baseline in Supine SBP >= 30 mmHg | 1 Participants |
| Part 1: Placebo IV SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Supine DBP <50 mmHg | 1 Participants |
| Part 1: Placebo IV SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Supine SBP <90 mmHg | 1 Participants |
| Part 1: Placebo IV SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Maximum Decrease from Baseline in Supine DBP >= 20 mmHg | 0 Participants |
| Part 1: Placebo IV SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Maximum Increase from Baseline in Supine DBP >= 20 mmHg | 1 Participants |
| Part 1 Cohort 3: Placebo IV MD | Number of Participants With Vital Sign Abnormalities in Part 1 | Supine SBP <90 mmHg | 0 Participants |
| Part 1 Cohort 3: Placebo IV MD | Number of Participants With Vital Sign Abnormalities in Part 1 | Supine DBP <50 mmHg | 0 Participants |
| Part 1 Cohort 3: Placebo IV MD | Number of Participants With Vital Sign Abnormalities in Part 1 | Maximum Increase from Baseline in Supine DBP >= 20 mmHg | 0 Participants |
| Part 1 Cohort 3: Placebo IV MD | Number of Participants With Vital Sign Abnormalities in Part 1 | Maximum Decrease from Baseline in Supine DBP >= 20 mmHg | 1 Participants |
| Part 1 Cohort 3: Placebo IV MD | Number of Participants With Vital Sign Abnormalities in Part 1 | Maximum Decrease from Baseline in Supine SBP >= 30 mmHg | 0 Participants |
| Part 1 Cohort 3: Placebo IV MD | Number of Participants With Vital Sign Abnormalities in Part 1 | Maximum Increase from Baseline in Supine SBP >= 30 mmHg | 0 Participants |
| Part 1 Cohort 7: Placebo SC SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Maximum Decrease from Baseline in Supine SBP >= 30 mmHg | 0 Participants |
| Part 1 Cohort 7: Placebo SC SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Maximum Increase from Baseline in Supine DBP >= 20 mmHg | 0 Participants |
| Part 1 Cohort 7: Placebo SC SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Maximum Decrease from Baseline in Supine DBP >= 20 mmHg | 1 Participants |
| Part 1 Cohort 7: Placebo SC SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Maximum Increase from Baseline in Supine SBP >= 30 mmHg | 0 Participants |
| Part 1 Cohort 7: Placebo SC SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Supine SBP <90 mmHg | 1 Participants |
| Part 1 Cohort 7: Placebo SC SD | Number of Participants With Vital Sign Abnormalities in Part 1 | Supine DBP <50 mmHg | 1 Participants |
Primary
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).
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of Participants With Vital Sign Abnormalities in Part 2 | Maximum Increase from Baseline in Supine SBP >= 30 mmHg | 1 Participants |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of Participants With Vital Sign Abnormalities in Part 2 | Maximum Decrease from Baseline in Supine SBP >= 30 mmHg | 2 Participants |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of Participants With Vital Sign Abnormalities in Part 2 | Supine SBP <90 mmHg | 1 Participants |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of Participants With Vital Sign Abnormalities in Part 2 | Maximum Increase from Baseline in Supine SBP >= 30 mmHg | 0 Participants |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of Participants With Vital Sign Abnormalities in Part 2 | Maximum Decrease from Baseline in Supine SBP >= 30 mmHg | 0 Participants |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of Participants With Vital Sign Abnormalities in Part 2 | Supine SBP <90 mmHg | 0 Participants |
Primary
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).
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of Participants With Vital Sign Abnormalities in Part 3 | Maximum Increase from Baseline in Supine SBP >= 30 mmHg | 1 Participants |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of Participants With Vital Sign Abnormalities in Part 3 | Maximum Increase from Baseline in Supine DBP >= 20 mmHg | 3 Participants |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of Participants With Vital Sign Abnormalities in Part 3 | Maximum Decrease from Baseline in Supine DBP >= 20 mmHg | 2 Participants |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of Participants With Vital Sign Abnormalities in Part 3 | Supine DBP <50 mmHg | 1 Participants |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of Participants With Vital Sign Abnormalities in Part 3 | Supine DBP <50 mmHg | 0 Participants |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of Participants With Vital Sign Abnormalities in Part 3 | Maximum Increase from Baseline in Supine SBP >= 30 mmHg | 0 Participants |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of Participants With Vital Sign Abnormalities in Part 3 | Maximum Decrease from Baseline in Supine DBP >= 20 mmHg | 0 Participants |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of Participants With Vital Sign Abnormalities in Part 3 | Maximum Increase from Baseline in Supine DBP >= 20 mmHg | 0 Participants |
Secondary
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).
Population: All enrolled participants treated who had at least 1 of the PK parameters of interest measured.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Accumulation Ratio for AUCtau (Rac) of PF-06817024 Post Second Dose Following Multiple Doses in Part 1 | Day 31 | NA Ratio | — |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Accumulation Ratio for AUCtau (Rac) of PF-06817024 Post Second Dose Following Multiple Doses in Part 1 | Day 46 | 1.499 Ratio | Geometric Coefficient of Variation 10 |
Secondary
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).
Population: All enrolled participants treated who had at least 1 of the PK parameters of interest measured.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Accumulation Ratio for Cmax (Rac, Cmax) of PF-06817024 Post Second Dose Following Multiple Doses in Part 1 | Day 31 | NA Ratio | — |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Accumulation Ratio for Cmax (Rac, Cmax) of PF-06817024 Post Second Dose Following Multiple Doses in Part 1 | Day 46 | 1.106 Ratio | Geometric Coefficient of Variation 3 |
Secondary
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).
Population: All enrolled participants treated who had at least 1 of the PK parameters of interest measured.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Apparent Clearance (CL/F) of PF-06817024 for the Subcutaneous Cohort in Part 1 | 0.003470 L/hr | Geometric Coefficient of Variation 38 |
Secondary
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).
Population: All enrolled participants treated who had at least 1 of the PK parameters of interest measured.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Apparent Volume of Distribution (Vz/F) of PF-06817024 for the Subcutaneous Cohort in Part 1 | 11.60 L | Geometric Coefficient of Variation 37 |
Secondary
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.
Population: All enrolled participants treated who had at least 1 of the PK parameters of interest measured.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Area Under the Curve From Time Zero to Infinity Concentration (AUCinf) of PF-06817024 Following Single Dose in Part 1 and 2 | 4384 ug*hr/mL | Geometric Coefficient of Variation 28 |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Area Under the Curve From Time Zero to Infinity Concentration (AUCinf) of PF-06817024 Following Single Dose in Part 1 and 2 | 14640 ug*hr/mL | Geometric Coefficient of Variation 28 |
| Part 1 Cohort 3: PF-06817024 30 mg SC SD | Area Under the Curve From Time Zero to Infinity Concentration (AUCinf) of PF-06817024 Following Single Dose in Part 1 and 2 | 8646 ug*hr/mL | Geometric Coefficient of Variation 38 |
| Part 1 Cohort 3: PF-06817024 100 mg IV SD | Area Under the Curve From Time Zero to Infinity Concentration (AUCinf) of PF-06817024 Following Single Dose in Part 1 and 2 | 44460 ug*hr/mL | Geometric Coefficient of Variation 22 |
| Part 1 Cohort 3: PF-06817024 100 mg IV MD | Area Under the Curve From Time Zero to Infinity Concentration (AUCinf) of PF-06817024 Following Single Dose in Part 1 and 2 | 116700 ug*hr/mL | Geometric Coefficient of Variation 23 |
| Part 1 Cohort 4: PF-06817024 300 mg IV SD | Area Under the Curve From Time Zero to Infinity Concentration (AUCinf) of PF-06817024 Following Single Dose in Part 1 and 2 | 427100 ug*hr/mL | Geometric Coefficient of Variation 10 |
| Part 1 Cohort 5: PF-06817024 1000 mg IV SD | Area Under the Curve From Time Zero to Infinity Concentration (AUCinf) of PF-06817024 Following Single Dose in Part 1 and 2 | 146200 ug*hr/mL | Geometric Coefficient of Variation 19 |
Secondary
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.
Population: All enrolled participants treated who had at least 1 of the PK parameters of interest measured.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-06817024 Following Single Dose in Part 1 and 2 | 4075 ug*hr/mL | Geometric Coefficient of Variation 29 |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-06817024 Following Single Dose in Part 1 and 2 | 14070 ug*hr/mL | Geometric Coefficient of Variation 26 |
| Part 1 Cohort 3: PF-06817024 30 mg SC SD | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-06817024 Following Single Dose in Part 1 and 2 | 8333 ug*hr/mL | Geometric Coefficient of Variation 39 |
| Part 1 Cohort 3: PF-06817024 100 mg IV SD | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-06817024 Following Single Dose in Part 1 and 2 | 43510 ug*hr/mL | Geometric Coefficient of Variation 22 |
| Part 1 Cohort 3: PF-06817024 100 mg IV MD | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-06817024 Following Single Dose in Part 1 and 2 | 116000 ug*hr/mL | Geometric Coefficient of Variation 22 |
| Part 1 Cohort 4: PF-06817024 300 mg IV SD | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-06817024 Following Single Dose in Part 1 and 2 | 425700 ug*hr/mL | Geometric Coefficient of Variation 10 |
| Part 1 Cohort 5: PF-06817024 1000 mg IV SD | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-06817024 Following Single Dose in Part 1 and 2 | 143300 ug*hr/mL | Geometric Coefficient of Variation 23 |
Secondary
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).
Population: All enrolled participants treated who had at least 1 of the PK parameters of interest measured.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Area Under the Curve Within Dosing Interval (AUCtau) of PF-06817024 Following Multiple Doses in Part 1 | Day 1 | 10580 ug*hr/mL | Geometric Coefficient of Variation 11 |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Area Under the Curve Within Dosing Interval (AUCtau) of PF-06817024 Following Multiple Doses in Part 1 | Day 31 | NA ug*hr/mL | — |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Area Under the Curve Within Dosing Interval (AUCtau) of PF-06817024 Following Multiple Doses in Part 1 | Day 46 | 16210 ug*hr/mL | Geometric Coefficient of Variation 15 |
Secondary
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).
Population: All enrolled participants treated who had at least 1 of the PK parameters of interest measured.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | AUCtau(dn) of PF-06817024 Following Multiple Doses in Part 3 | Day 1 | 97.98 ug*hr/mL/mg | Geometric Coefficient of Variation 30 |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | AUCtau(dn) of PF-06817024 Following Multiple Doses in Part 3 | Day 29 | 259.1 ug*hr/mL/mg | Geometric Coefficient of Variation 38 |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | AUCtau(dn) of PF-06817024 Following Multiple Doses in Part 3 | Day 57 | 301.1 ug*hr/mL/mg | Geometric Coefficient of Variation 42 |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | AUCtau(dn) of PF-06817024 Following Multiple Doses in Part 3 | Day 85 | 307.3 ug*hr/mL/mg | Geometric Coefficient of Variation 42 |
Secondary
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).
Population: All enrolled participants treated who had at least 1 of the PK parameters of interest measured.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | AUCtau of PF-06817024 in Part 3 | Day 57 | 90340 ug*hr/mL | Geometric Coefficient of Variation 42 |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | AUCtau of PF-06817024 in Part 3 | Day 1 | 58350 ug*hr/mL | Geometric Coefficient of Variation 31 |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | AUCtau of PF-06817024 in Part 3 | Day 29 | 77550 ug*hr/mL | Geometric Coefficient of Variation 38 |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | AUCtau of PF-06817024 in Part 3 | Day 85 | 92230 ug*hr/mL | Geometric Coefficient of Variation 42 |
Secondary
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).
Population: All enrolled participants treated who had at least 1 of the PK parameters of interest measured.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Average Concentration Over Dosing Interval (Cav) of PF-06817024 Following Multiple Doses in Part 1 | Day 1 | 14.70 ug/mL | Geometric Coefficient of Variation 12 |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Average Concentration Over Dosing Interval (Cav) of PF-06817024 Following Multiple Doses in Part 1 | Day 31 | NA ug/mL | — |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Average Concentration Over Dosing Interval (Cav) of PF-06817024 Following Multiple Doses in Part 1 | Day 46 | 22.55 ug/mL | Geometric Coefficient of Variation 16 |
Secondary
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).
Population: All enrolled participants treated who had at least 1 of the PK parameters of interest measured.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Cav of PF-06817024 Following Multiple Doses in Part 3 | Day 1 | 86.78 ug/mL | Geometric Coefficient of Variation 30 |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Cav of PF-06817024 Following Multiple Doses in Part 3 | Day 29 | 115.4 ug/mL | Geometric Coefficient of Variation 38 |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Cav of PF-06817024 Following Multiple Doses in Part 3 | Day 57 | 134.4 ug/mL | Geometric Coefficient of Variation 42 |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Cav of PF-06817024 Following Multiple Doses in Part 3 | Day 85 | 137.2 ug/mL | Geometric Coefficient of Variation 42 |
Secondary
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.
Population: All enrolled participants treated who had at least 1 of the PK parameters of interest measured.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Clearance (CL) of PF-06817024 Following Single Intravenous Dose in Part 1 and Part 2 | 0.00228 L/hr | Geometric Coefficient of Variation 28 |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Clearance (CL) of PF-06817024 Following Single Intravenous Dose in Part 1 and Part 2 | 0.00205 L/hr | Geometric Coefficient of Variation 28 |
| Part 1 Cohort 3: PF-06817024 30 mg SC SD | Clearance (CL) of PF-06817024 Following Single Intravenous Dose in Part 1 and Part 2 | 0.002249 L/hr | Geometric Coefficient of Variation 22 |
| Part 1 Cohort 3: PF-06817024 100 mg IV SD | Clearance (CL) of PF-06817024 Following Single Intravenous Dose in Part 1 and Part 2 | 0.002574 L/hr | Geometric Coefficient of Variation 23 |
| Part 1 Cohort 3: PF-06817024 100 mg IV MD | Clearance (CL) of PF-06817024 Following Single Intravenous Dose in Part 1 and Part 2 | 0.002341 L/hr | Geometric Coefficient of Variation 10 |
| Part 1 Cohort 4: PF-06817024 300 mg IV SD | Clearance (CL) of PF-06817024 Following Single Intravenous Dose in Part 1 and Part 2 | 0.002053 L/hr | Geometric Coefficient of Variation 19 |
Secondary
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).
Population: All enrolled participants treated who had at least 1 of the PK parameters of interest measured.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Cmax(dn) of PF-06817024 Following Multiple Doses in Part 1 | Day 1 | 0.3535 ug/mL/mg | Geometric Coefficient of Variation 15 |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Cmax(dn) of PF-06817024 Following Multiple Doses in Part 1 | Day 31 | NA ug/mL/mg | — |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Cmax(dn) of PF-06817024 Following Multiple Doses in Part 1 | Day 46 | 0.4132 ug/mL/mg | Geometric Coefficient of Variation 11 |
Secondary
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).
Population: All enrolled participants treated who had at least 1 of the PK parameters of interest measured.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Cmax(dn) of PF-06817024 in Part 2 | 0.3569 ug/mL/mg | Geometric Coefficient of Variation 15 |
Secondary
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).
Population: All enrolled participants treated who had at least 1 of the PK parameters of interest measured.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Cmax(dn) of PF-06817024 in Part 3 | Day 1 | 0.3306 ug/mL/mg | Geometric Coefficient of Variation 36 |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Cmax(dn) of PF-06817024 in Part 3 | Day 29 | 0.5544 ug/mL/mg | Geometric Coefficient of Variation 36 |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Cmax(dn) of PF-06817024 in Part 3 | Day 57 | 0.6361 ug/mL/mg | Geometric Coefficient of Variation 39 |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Cmax(dn) of PF-06817024 in Part 3 | Day 85 | 0.6663 ug/mL/mg | Geometric Coefficient of Variation 37 |
Secondary
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).
Population: All enrolled participants treated who had at least 1 of the PK parameters of interest measured.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Cmax of PF-06817024 Following Multiple Doses in Part 1 | Day 1 | 35.35 ug/mL | Geometric Coefficient of Variation 15 |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Cmax of PF-06817024 Following Multiple Doses in Part 1 | Day 31 | NA ug/mL | — |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Cmax of PF-06817024 Following Multiple Doses in Part 1 | Day 46 | 41.32 ug/mL | Geometric Coefficient of Variation 11 |
Secondary
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).
Population: All enrolled participants treated who had at least 1 of the PK parameters of interest measured.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Cmax of PF-06817024 in Part 2 | 107.1 ug/mL | Geometric Coefficient of Variation 15 |
Secondary
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).
Population: All enrolled participants treated who had at least 1 of the PK parameters of interest measured.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Cmax of PF-06817024 in Part 3 | Day 1 | 197.3 ug/mL | Geometric Coefficient of Variation 36 |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Cmax of PF-06817024 in Part 3 | Day 29 | 165.9 ug/mL | Geometric Coefficient of Variation 36 |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Cmax of PF-06817024 in Part 3 | Day 57 | 190.7 ug/mL | Geometric Coefficient of Variation 39 |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Cmax of PF-06817024 in Part 3 | Day 85 | 199.8 ug/mL | Geometric Coefficient of Variation 37 |
Secondary
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.
Population: All enrolled participants treated who had at least 1 of the PK parameters of interest measured.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Cmin of PF-06817024 Post Last Dose Following Multiple Doses in Part 3 | 81.1 ug/mL | Geometric Coefficient of Variation 51 |
Secondary
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).
Population: All enrolled participants treated who had at least 1 of the PK parameters of interest measured.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Dose Normalized Area Under the Curve Within Dosing Interval (AUCtau[dn]) of PF-06817024 Following Multiple Doses in Part 1 | Day 1 | 105.8 ug*hr/mL/mg | Geometric Coefficient of Variation 11 |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Dose Normalized Area Under the Curve Within Dosing Interval (AUCtau[dn]) of PF-06817024 Following Multiple Doses in Part 1 | Day 31 | NA ug*hr/mL/mg | — |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Dose Normalized Area Under the Curve Within Dosing Interval (AUCtau[dn]) of PF-06817024 Following Multiple Doses in Part 1 | Day 46 | 162.1 ug*hr/mL/mg | Geometric Coefficient of Variation 15 |
Secondary
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).
Population: All enrolled participants treated who had at least 1 of the PK parameters of interest measured.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Dose Normalized Maximum Observed Serum Concentration (Cmax[dn]) of PF-06817024 Following Single Dose in Part 1 | 0.2879 ug/mL/mg | Geometric Coefficient of Variation 19 |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Dose Normalized Maximum Observed Serum Concentration (Cmax[dn]) of PF-06817024 Following Single Dose in Part 1 | 0.4091 ug/mL/mg | Geometric Coefficient of Variation 20 |
| Part 1 Cohort 3: PF-06817024 30 mg SC SD | Dose Normalized Maximum Observed Serum Concentration (Cmax[dn]) of PF-06817024 Following Single Dose in Part 1 | 0.08230 ug/mL/mg | Geometric Coefficient of Variation 43 |
| Part 1 Cohort 3: PF-06817024 100 mg IV SD | Dose Normalized Maximum Observed Serum Concentration (Cmax[dn]) of PF-06817024 Following Single Dose in Part 1 | 0.3556 ug/mL/mg | Geometric Coefficient of Variation 11 |
| Part 1 Cohort 3: PF-06817024 100 mg IV MD | Dose Normalized Maximum Observed Serum Concentration (Cmax[dn]) of PF-06817024 Following Single Dose in Part 1 | 0.3249 ug/mL/mg | Geometric Coefficient of Variation 7 |
| Part 1 Cohort 4: PF-06817024 300 mg IV SD | Dose Normalized Maximum Observed Serum Concentration (Cmax[dn]) of PF-06817024 Following Single Dose in Part 1 | 0.3132 ug/mL/mg | Geometric Coefficient of Variation 17 |
Secondary
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).
Population: All enrolled participants treated who had at least 1 of the pharmacokinetic (PK) parameters of interest measured.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Maximum Observed Serum Concentration (Cmax) of PF-06817024 Following Single Dose in Part 1 | 2.879 ug/mL | Geometric Coefficient of Variation 19 |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Maximum Observed Serum Concentration (Cmax) of PF-06817024 Following Single Dose in Part 1 | 12.26 ug/mL | Geometric Coefficient of Variation 20 |
| Part 1 Cohort 3: PF-06817024 30 mg SC SD | Maximum Observed Serum Concentration (Cmax) of PF-06817024 Following Single Dose in Part 1 | 2.471 ug/mL | Geometric Coefficient of Variation 43 |
| Part 1 Cohort 3: PF-06817024 100 mg IV SD | Maximum Observed Serum Concentration (Cmax) of PF-06817024 Following Single Dose in Part 1 | 35.56 ug/mL | Geometric Coefficient of Variation 11 |
| Part 1 Cohort 3: PF-06817024 100 mg IV MD | Maximum Observed Serum Concentration (Cmax) of PF-06817024 Following Single Dose in Part 1 | 97.49 ug/mL | Geometric Coefficient of Variation 7 |
| Part 1 Cohort 4: PF-06817024 300 mg IV SD | Maximum Observed Serum Concentration (Cmax) of PF-06817024 Following Single Dose in Part 1 | 313.2 ug/mL | Geometric Coefficient of Variation 17 |
Secondary
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.
Population: All enrolled participants who received at least 1 dose of investigational product and had at least 1 post-treatment measurement of immunogenicity parameters of interest.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of Participants With Treatment-Induced Anti-Drug Antibody (ADA) Against PF-06817024 in Part 1, 2, and 3 | 0 Participants |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of Participants With Treatment-Induced Anti-Drug Antibody (ADA) Against PF-06817024 in Part 1, 2, and 3 | 0 Participants |
| Part 1 Cohort 3: PF-06817024 30 mg SC SD | Number of Participants With Treatment-Induced Anti-Drug Antibody (ADA) Against PF-06817024 in Part 1, 2, and 3 | 1 Participants |
| Part 1 Cohort 3: PF-06817024 100 mg IV SD | Number of Participants With Treatment-Induced Anti-Drug Antibody (ADA) Against PF-06817024 in Part 1, 2, and 3 | 0 Participants |
| Part 1 Cohort 3: PF-06817024 100 mg IV MD | Number of Participants With Treatment-Induced Anti-Drug Antibody (ADA) Against PF-06817024 in Part 1, 2, and 3 | 2 Participants |
| Part 1 Cohort 4: PF-06817024 300 mg IV SD | Number of Participants With Treatment-Induced Anti-Drug Antibody (ADA) Against PF-06817024 in Part 1, 2, and 3 | 0 Participants |
| Part 1 Cohort 5: PF-06817024 1000 mg IV SD | Number of Participants With Treatment-Induced Anti-Drug Antibody (ADA) Against PF-06817024 in Part 1, 2, and 3 | 1 Participants |
| Part 1: Placebo IV SD | Number of Participants With Treatment-Induced Anti-Drug Antibody (ADA) Against PF-06817024 in Part 1, 2, and 3 | 1 Participants |
| Part 1 Cohort 3: Placebo IV MD | Number of Participants With Treatment-Induced Anti-Drug Antibody (ADA) Against PF-06817024 in Part 1, 2, and 3 | 1 Participants |
Secondary
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.
Population: All enrolled participants who received at least 1 dose of investigational product and had at least 1 post-treatment measurement of immunogenicity parameters of interest.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Number of Participants With Treatment-Induced Neutralizing Antibodies (NAbs) Against PF-06817024 in Part 1, 2, and 3 | 0 Participants |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Number of Participants With Treatment-Induced Neutralizing Antibodies (NAbs) Against PF-06817024 in Part 1, 2, and 3 | 0 Participants |
| Part 1 Cohort 3: PF-06817024 30 mg SC SD | Number of Participants With Treatment-Induced Neutralizing Antibodies (NAbs) Against PF-06817024 in Part 1, 2, and 3 | 0 Participants |
| Part 1 Cohort 3: PF-06817024 100 mg IV SD | Number of Participants With Treatment-Induced Neutralizing Antibodies (NAbs) Against PF-06817024 in Part 1, 2, and 3 | 0 Participants |
| Part 1 Cohort 3: PF-06817024 100 mg IV MD | Number of Participants With Treatment-Induced Neutralizing Antibodies (NAbs) Against PF-06817024 in Part 1, 2, and 3 | 0 Participants |
| Part 1 Cohort 4: PF-06817024 300 mg IV SD | Number of Participants With Treatment-Induced Neutralizing Antibodies (NAbs) Against PF-06817024 in Part 1, 2, and 3 | 0 Participants |
| Part 1 Cohort 5: PF-06817024 1000 mg IV SD | Number of Participants With Treatment-Induced Neutralizing Antibodies (NAbs) Against PF-06817024 in Part 1, 2, and 3 | 1 Participants |
| Part 1: Placebo IV SD | Number of Participants With Treatment-Induced Neutralizing Antibodies (NAbs) Against PF-06817024 in Part 1, 2, and 3 | 0 Participants |
| Part 1 Cohort 3: Placebo IV MD | Number of Participants With Treatment-Induced Neutralizing Antibodies (NAbs) Against PF-06817024 in Part 1, 2, and 3 | 0 Participants |
Secondary
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).
Population: All enrolled participants treated who had at least 1 of the PK parameters of interest measured.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Rac, Cmax of PF-06817024 Post Last Dose Following Multiple Doses in Part 3 | 2.005 Ratio | Geometric Coefficient of Variation 24 |
Secondary
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).
Population: All enrolled participants treated who had at least 1 of the PK parameters of interest measured.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Rac of PF-06817024 Post Last Dose Following Multiple Doses in Part 3 | 3.163 Ratio | Geometric Coefficient of Variation 20 |
Secondary
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).
Population: All enrolled participants treated who had at least 1 of the PK parameters of interest measured.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | t1/2 of PF-06817024 Following Multiple Doses in Part 1 | Day 31 | NA Day | — |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | t1/2 of PF-06817024 Following Multiple Doses in Part 1 | Day 46 | 98.87 Day | Standard Deviation 5.6083 |
Secondary
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).
Population: All enrolled participants treated who had at least 1 of the PK parameters of interest measured.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | t1/2 of PF-06817024 in Part 2 | 85.68 Days | Standard Deviation 11.447 |
Secondary
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).
Population: All enrolled participants treated who had at least 1 of the PK parameters of interest measured.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | t1/2 of PF-06817024 in Part 3 | 75.98 Days | Standard Deviation 15.996 |
Secondary
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).
Population: All enrolled participants treated who had at least 1 of the PK parameters of interest measured.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Terminal Elimination Half Life (t1/2) of PF-06817024 Following Single Dose in Part 1 | 91.34 Days | Standard Deviation 14.499 |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Terminal Elimination Half Life (t1/2) of PF-06817024 Following Single Dose in Part 1 | 88.88 Days | Standard Deviation 15.358 |
| Part 1 Cohort 3: PF-06817024 30 mg SC SD | Terminal Elimination Half Life (t1/2) of PF-06817024 Following Single Dose in Part 1 | 97.17 Days | Standard Deviation 11.189 |
| Part 1 Cohort 3: PF-06817024 100 mg IV SD | Terminal Elimination Half Life (t1/2) of PF-06817024 Following Single Dose in Part 1 | 83.70 Days | Standard Deviation 32.608 |
| Part 1 Cohort 3: PF-06817024 100 mg IV MD | Terminal Elimination Half Life (t1/2) of PF-06817024 Following Single Dose in Part 1 | 83.33 Days | Standard Deviation 20.016 |
| Part 1 Cohort 4: PF-06817024 300 mg IV SD | Terminal Elimination Half Life (t1/2) of PF-06817024 Following Single Dose in Part 1 | 93.90 Days | Standard Deviation 5.4749 |
Secondary
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).
Population: All enrolled participants treated who had at least 1 of the PK parameters of interest measured.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Time to Reach Maximum Observed Serum Concentration (Tmax) of PF-06817024 Following Single Dose in Part 1 | 4.00 Hours |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Time to Reach Maximum Observed Serum Concentration (Tmax) of PF-06817024 Following Single Dose in Part 1 | 1.76 Hours |
| Part 1 Cohort 3: PF-06817024 30 mg SC SD | Time to Reach Maximum Observed Serum Concentration (Tmax) of PF-06817024 Following Single Dose in Part 1 | 338 Hours |
| Part 1 Cohort 3: PF-06817024 100 mg IV SD | Time to Reach Maximum Observed Serum Concentration (Tmax) of PF-06817024 Following Single Dose in Part 1 | 1.07 Hours |
| Part 1 Cohort 3: PF-06817024 100 mg IV MD | Time to Reach Maximum Observed Serum Concentration (Tmax) of PF-06817024 Following Single Dose in Part 1 | 2.00 Hours |
| Part 1 Cohort 4: PF-06817024 300 mg IV SD | Time to Reach Maximum Observed Serum Concentration (Tmax) of PF-06817024 Following Single Dose in Part 1 | 1.775 Hours |
Secondary
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).
Population: All enrolled participants treated who had at least 1 of the PK parameters of interest measured.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Tmax of PF-06817024 Following Multiple Doses in Part 1 | Day 46 | 1.550 hour |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Tmax of PF-06817024 Following Multiple Doses in Part 1 | Day 1 | 2.010 hour |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Tmax of PF-06817024 Following Multiple Doses in Part 1 | Day 31 | NA hour |
Secondary
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).
Population: All enrolled participants treated who had at least 1 of the PK parameters of interest measured.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Tmax of PF-06817024 in Part 2 | 2.00 Hours |
Secondary
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).
Population: All enrolled participants treated who had at least 1 of the PK parameters of interest measured.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Tmax of PF-06817024 in Part 3 | Day 1 | 2.03 Hours |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Tmax of PF-06817024 in Part 3 | Day 29 | 1.70 Hours |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Tmax of PF-06817024 in Part 3 | Day 57 | 1.75 Hours |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Tmax of PF-06817024 in Part 3 | Day 85 | 1.76 Hours |
Secondary
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.
Population: All enrolled participants treated who had at least 1 of the PK parameters of interest measured.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Trough Serum Concentration (Cmin) of PF-06817024 Post Second Dose Following Multiple Doses in Part 1 | Day 31 | NA ug/mL | — |
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Trough Serum Concentration (Cmin) of PF-06817024 Post Second Dose Following Multiple Doses in Part 1 | Day 46 | 9.851 ug/mL | Geometric Coefficient of Variation 20 |
Secondary
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.
Population: All enrolled participants treated who had at least 1 of the PK parameters of interest measured.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 Cohort 1: PF-06817024 10 mg IV SD | Volume of Distribution at Steady State (Vss) of PF-06817024 Following Single Intravenous Dose in Part 1 and Part 2 | 6.949 L | Geometric Coefficient of Variation 15 |
| Part 1 Cohort 2: PF-06817024 30 mg IV SD | Volume of Distribution at Steady State (Vss) of PF-06817024 Following Single Intravenous Dose in Part 1 and Part 2 | 5.929 L | Geometric Coefficient of Variation 22 |
| Part 1 Cohort 3: PF-06817024 30 mg SC SD | Volume of Distribution at Steady State (Vss) of PF-06817024 Following Single Intravenous Dose in Part 1 and Part 2 | 6.449 L | Geometric Coefficient of Variation 19 |
| Part 1 Cohort 3: PF-06817024 100 mg IV SD | Volume of Distribution at Steady State (Vss) of PF-06817024 Following Single Intravenous Dose in Part 1 and Part 2 | 6.863 L | Geometric Coefficient of Variation 16 |
| Part 1 Cohort 3: PF-06817024 100 mg IV MD | Volume of Distribution at Steady State (Vss) of PF-06817024 Following Single Intravenous Dose in Part 1 and Part 2 | 7.260 L | Geometric Coefficient of Variation 12 |
| Part 1 Cohort 4: PF-06817024 300 mg IV SD | Volume of Distribution at Steady State (Vss) of PF-06817024 Following Single Intravenous Dose in Part 1 and Part 2 | 6.250 L | Geometric Coefficient of Variation 17 |