Study Of PF-06817024 In Healthy Subjects, In Patients With Chronic Rhinosinusitis With Nasal Polyps And in Patients With Atopic Dermatitis
- Conditions
- Atopic DermatitisChronic Rhinosinusitis With Nasal PolypsHealthy
- Interventions
- Biological: PF-06817024Other: Placebo for PF-06817024
- Registration Number
- NCT02743871
- Lead Sponsor
- Pfizer
- 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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 97
Not provided
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort 1 PF-06817024 10 mg of PF-06817024 or placebo Cohort 2 Placebo for PF-06817024 30 mg of PF-06817024 or placebo Cohort 3 Placebo for PF-06817024 100 mg of PF-06817024 or placebo Cohort 7 PF-06817024 30 mg subcutaneous dose of PF-06817024 or placebo Cohort 10 PF-06817024 PF-06817024 or placebo Cohort 11 Placebo for PF-06817024 PF-06817024 or placebo Cohort 1 Placebo for PF-06817024 10 mg of PF-06817024 or placebo Cohort 4 Placebo for PF-06817024 300 mg of PF-06817024 or placebo Cohort 5 PF-06817024 1000 mg of PF-06817024 or placebo Cohort 5 Placebo for PF-06817024 1000 mg of PF-06817024 or placebo Cohort 8 PF-06817024 300 mg of PF-06817024 or placebo Cohort 9 PF-06817024 IV dose to be determined of PF-06817024 or placebo Cohort 12 PF-06817024 PF-06817024 or placebo Cohort 2 PF-06817024 30 mg of PF-06817024 or placebo Cohort 3 PF-06817024 100 mg of PF-06817024 or placebo Cohort 4 PF-06817024 300 mg of PF-06817024 or placebo Cohort 6 PF-06817024 2000 mg of PF-06817024 or placebo Cohort 6 Placebo for PF-06817024 2000 mg of PF-06817024 or placebo Cohort 7 Placebo for PF-06817024 30 mg subcutaneous dose of PF-06817024 or placebo Cohort 8 Placebo for PF-06817024 300 mg of PF-06817024 or placebo Cohort 10 Placebo for PF-06817024 PF-06817024 or placebo Cohort 9 Placebo for PF-06817024 IV dose to be determined of PF-06817024 or placebo Cohort 11 PF-06817024 PF-06817024 or placebo Cohort 13 PF-06817024 PF-06817024 or placebo Cohort 12 Placebo for PF-06817024 PF-06817024 or placebo Cohort 13 Placebo for PF-06817024 PF-06817024 or placebo
- Primary Outcome Measures
Name Time Method 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 Outcome Measures
Name Time Method 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 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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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 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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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 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.
Trial Locations
- Locations (20)
UC Davis Dermatology
🇺🇸Sacramento, California, United States
UC Davis CTSC Clinical Research Center
🇺🇸Sacramento, California, United States
New Haven Clinical Research Unit
🇺🇸New Haven, Connecticut, United States
UC Davis Health
🇺🇸Sacramento, California, United States
ForCare Clinical Research
🇺🇸Tampa, Florida, United States
Dawes Fretzin Clinical Research Group, LLC
🇺🇸Indianapolis, Indiana, United States
Dermatology Physicians of Connecticut
🇺🇸Shelton, Connecticut, United States
Dawes Fretzin Dermatology Group, LLC
🇺🇸Indianapolis, Indiana, United States
The Indiana Clinical Trials Center
🇺🇸Plainfield, Indiana, United States
Clinical Research Institute, Inc.
🇺🇸Minneapolis, Minnesota, United States
Hassman Research Institute
🇺🇸Berlin, New Jersey, United States
Ear, Nose & Throat Specialty Care of Minnesota, P.A.
🇺🇸Minneapolis, Minnesota, United States
Academic Dermatology
🇺🇸Edina, Minnesota, United States
Carolina Phase 1 Research, LLC
🇺🇸Raleigh, North Carolina, United States
Vital Prospects Clinical Research Institute, PC
🇺🇸Tulsa, Oklahoma, United States
Lee Medical Associates, PA
🇺🇸San Antonio, Texas, United States
Progressive Clinical Research, PA
🇺🇸San Antonio, Texas, United States
Virginia Clinical Research, Inc.
🇺🇸Norfolk, Virginia, United States
Health Concepts
🇺🇸Rapid City, South Dakota, United States
Prism Research, LLC
🇺🇸Saint Paul, Minnesota, United States