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Study Of PF-06817024 In Healthy Subjects, In Patients With Chronic Rhinosinusitis With Nasal Polyps And in Patients With Atopic Dermatitis

Primary Purpose

Healthy, Chronic Rhinosinusitis With Nasal Polyps, Atopic Dermatitis

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
PF-06817024
Placebo for PF-06817024
PF-06817024
Placebo for PF-06817024
PF-06817024
Placebo for PF-06817024
PF-06817024
Placebo for PF-06817024
PF-06817024
Placebo for PF-06817024
Sponsored by
Pfizer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Healthy focused on measuring FIH, Pharmacokinetics, Pharmacodynamics, Safety, Tolerability, Atopic Dermatitis, Chronic Rhinosinusitis, Nasal Polyps

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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)

Sites / Locations

  • UC Davis Dermatology
  • UC Davis CTSC Clinical Research Center
  • UC Davis Health
  • New Haven Clinical Research Unit
  • Dermatology Physicians of Connecticut
  • ForCare Clinical Research
  • Dawes Fretzin Clinical Research Group, LLC
  • Dawes Fretzin Dermatology Group, LLC
  • The Indiana Clinical Trials Center
  • Academic Dermatology
  • Clinical Research Institute, Inc.
  • Ear, Nose & Throat Specialty Care of Minnesota, P.A.
  • Prism Research, LLC
  • Hassman Research Institute
  • Carolina Phase 1 Research, LLC
  • Vital Prospects Clinical Research Institute, PC
  • Health Concepts
  • Lee Medical Associates, PA
  • Progressive Clinical Research, PA
  • Virginia Clinical Research, Inc.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm 13

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Cohort 1

Cohort 2

Cohort 3

Cohort 4

Cohort 5

Cohort 6

Cohort 7

Cohort 8

Cohort 9

Cohort 10

Cohort 11

Cohort 12

Cohort 13

Arm Description

10 mg of PF-06817024 or placebo

30 mg of PF-06817024 or placebo

100 mg of PF-06817024 or placebo

300 mg of PF-06817024 or placebo

1000 mg of PF-06817024 or placebo

2000 mg of PF-06817024 or placebo

30 mg subcutaneous dose of PF-06817024 or placebo

300 mg of PF-06817024 or placebo

IV dose to be determined of PF-06817024 or placebo

PF-06817024 or placebo

PF-06817024 or placebo

PF-06817024 or placebo

PF-06817024 or placebo

Outcomes

Primary Outcome Measures

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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.

Secondary Outcome Measures

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.
Cmax of PF-06817024 Following Multiple Doses in Part 1
Cmax was defined as the maximum observed serum concentration.
Cmax of PF-06817024 in Part 2
Cmax was defined as the maximum observed serum concentration.
Cmax of PF-06817024 in Part 3
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
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
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
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
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
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
Tmax was defined as time to reach maximum observed serum concentration.
Tmax of PF-06817024 in Part 2
Tmax was defined as time to reach maximum observed serum concentration.
Tmax of PF-06817024 in Part 3
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
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
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
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
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
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
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
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
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
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 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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.

Full Information

First Posted
April 15, 2016
Last Updated
February 28, 2022
Sponsor
Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT02743871
Brief Title
Study Of PF-06817024 In Healthy Subjects, In Patients With Chronic Rhinosinusitis With Nasal Polyps And in Patients With Atopic Dermatitis
Official Title
A PHASE 1, RANDOMIZED, DOUBLE-BLIND, THIRD-PARTY OPEN, PLACEBO-CONTROLLED, DOSE ESCALATING STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS AND PHARMACODYNAMICS OF SINGLE AND/OR MULTIPLE INTRAVENOUS AND/OR SUBCUTANEOUS DOSES OF PF-06817024 IN HEALTHY SUBJECTS WHO MAY BE MILDLY ATOPIC, SUBJECTS WITH CHRONIC RHINOSINUSITIS WITH NASAL POLYPS, AND SUBJECTS WITH MODERATE-SEVERE ATOPIC DERMATITIS
Study Type
Interventional

2. Study Status

Record Verification Date
February 2022
Overall Recruitment Status
Completed
Study Start Date
April 27, 2016 (Actual)
Primary Completion Date
March 9, 2021 (Actual)
Study Completion Date
March 9, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Healthy, Chronic Rhinosinusitis With Nasal Polyps, Atopic Dermatitis
Keywords
FIH, Pharmacokinetics, Pharmacodynamics, Safety, Tolerability, Atopic Dermatitis, Chronic Rhinosinusitis, Nasal Polyps

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
97 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
10 mg of PF-06817024 or placebo
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
30 mg of PF-06817024 or placebo
Arm Title
Cohort 3
Arm Type
Experimental
Arm Description
100 mg of PF-06817024 or placebo
Arm Title
Cohort 4
Arm Type
Experimental
Arm Description
300 mg of PF-06817024 or placebo
Arm Title
Cohort 5
Arm Type
Experimental
Arm Description
1000 mg of PF-06817024 or placebo
Arm Title
Cohort 6
Arm Type
Experimental
Arm Description
2000 mg of PF-06817024 or placebo
Arm Title
Cohort 7
Arm Type
Experimental
Arm Description
30 mg subcutaneous dose of PF-06817024 or placebo
Arm Title
Cohort 8
Arm Type
Experimental
Arm Description
300 mg of PF-06817024 or placebo
Arm Title
Cohort 9
Arm Type
Experimental
Arm Description
IV dose to be determined of PF-06817024 or placebo
Arm Title
Cohort 10
Arm Type
Experimental
Arm Description
PF-06817024 or placebo
Arm Title
Cohort 11
Arm Type
Experimental
Arm Description
PF-06817024 or placebo
Arm Title
Cohort 12
Arm Type
Experimental
Arm Description
PF-06817024 or placebo
Arm Title
Cohort 13
Arm Type
Experimental
Arm Description
PF-06817024 or placebo
Intervention Type
Biological
Intervention Name(s)
PF-06817024
Intervention Description
Subjects will be given one dose of PF-06817024 intravenously
Intervention Type
Other
Intervention Name(s)
Placebo for PF-06817024
Intervention Description
Subjects will be given one dose of placebo for PF-06817024 intravenously
Intervention Type
Biological
Intervention Name(s)
PF-06817024
Intervention Description
Subjects will be given one dose of PF-06817024 subcutaneously
Intervention Type
Other
Intervention Name(s)
Placebo for PF-06817024
Intervention Description
Subjects will be given one dose of placebo for PF-06817024 subcutaneously
Intervention Type
Biological
Intervention Name(s)
PF-06817024
Intervention Description
Subjects will be given two doses of PF-06817024 intravenously
Intervention Type
Other
Intervention Name(s)
Placebo for PF-06817024
Intervention Description
Subjects will be given two doses of PF-06817024 intravenously
Intervention Type
Biological
Intervention Name(s)
PF-06817024
Intervention Description
Subjects will be given 2 doses intravenously
Intervention Type
Other
Intervention Name(s)
Placebo for PF-06817024
Intervention Description
Subjects will be given 2 doses intravenously
Intervention Type
Biological
Intervention Name(s)
PF-06817024
Intervention Description
Subjects will be given doses of PF-06817024 intravenously
Intervention Type
Other
Intervention Name(s)
Placebo for PF-06817024
Intervention Description
Subjects will be given doses of Placebo intravenously
Primary Outcome Measure Information:
Title
Number of Participants With All-causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) in Part 1
Description
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).
Title
Number of Participants With Treatment-Related TEAEs and SAEs in Part 1
Description
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).
Title
Number of All-Causality TEAEs According to Severity in Part 1
Description
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).
Title
Number of Participants With Permanent Discontinuation Due to TEAEs in Part 1
Description
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).
Title
Number of Participants With All-Causality TEAEs and SAEs in Part 2
Description
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.
Title
Number of Participants With Treatment-Related TEAEs and SAEs in Part 2
Description
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.
Title
Number of All-Causality TEAEs According to Severity in Part 2
Description
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.
Title
Number of Participants With Permanent Discontinuation Due to TEAEs in Part 2
Description
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.
Title
Number of Participants With All-Causality TEAEs and SAEs in Part 3
Description
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.
Title
Number of Participants With Treatment-Related TEAEs and SAEs in Part 3
Description
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.
Title
Number of All-Causality TEAEs According to Severity in Part 3
Description
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.
Title
Number of Participants With Permanent Discontinuation Due to TEAEs in Part 3
Description
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.
Title
Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis in Part 1
Description
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.
Title
Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis in Part 2
Description
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.
Title
Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis in Part 3
Description
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.
Title
Number of Participants With Vital Sign Abnormalities in Part 1
Description
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).
Title
Number of Participants With Vital Sign Abnormalities in Part 2
Description
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).
Title
Number of Participants With Vital Sign Abnormalities in Part 3
Description
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).
Title
Number of Participants With Electrocardiogram (ECG) Abnormalities in Part 1
Description
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).
Title
Number of Participants With ECG Abnormalities in Part 2
Description
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).
Title
Number of Participants With ECG Abnormalities in Part 3
Description
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).
Secondary Outcome Measure Information:
Title
Maximum Observed Serum Concentration (Cmax) of PF-06817024 Following Single Dose in Part 1
Description
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).
Title
Cmax of PF-06817024 Following Multiple Doses in Part 1
Description
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).
Title
Cmax of PF-06817024 in Part 2
Description
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).
Title
Cmax of PF-06817024 in Part 3
Description
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).
Title
Dose Normalized Maximum Observed Serum Concentration (Cmax[dn]) of PF-06817024 Following Single Dose in Part 1
Description
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).
Title
Cmax(dn) of PF-06817024 Following Multiple Doses in Part 1
Description
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).
Title
Cmax(dn) of PF-06817024 in Part 2
Description
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).
Title
Cmax(dn) of PF-06817024 in Part 3
Description
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).
Title
Time to Reach Maximum Observed Serum Concentration (Tmax) of PF-06817024 Following Single Dose in Part 1
Description
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).
Title
Tmax of PF-06817024 Following Multiple Doses in Part 1
Description
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).
Title
Tmax of PF-06817024 in Part 2
Description
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).
Title
Tmax of PF-06817024 in Part 3
Description
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).
Title
Area Under the Curve From Time Zero to Infinity Concentration (AUCinf) of PF-06817024 Following Single Dose in Part 1 and 2
Description
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.
Title
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-06817024 Following Single Dose in Part 1 and 2
Description
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.
Title
Area Under the Curve Within Dosing Interval (AUCtau) of PF-06817024 Following Multiple Doses in Part 1
Description
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).
Title
AUCtau of PF-06817024 in Part 3
Description
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).
Title
Dose Normalized Area Under the Curve Within Dosing Interval (AUCtau[dn]) of PF-06817024 Following Multiple Doses in Part 1
Description
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).
Title
AUCtau(dn) of PF-06817024 Following Multiple Doses in Part 3
Description
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).
Title
Average Concentration Over Dosing Interval (Cav) of PF-06817024 Following Multiple Doses in Part 1
Description
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).
Title
Cav of PF-06817024 Following Multiple Doses in Part 3
Description
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).
Title
Terminal Elimination Half Life (t1/2) of PF-06817024 Following Single Dose in Part 1
Description
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).
Title
t1/2 of PF-06817024 Following Multiple Doses in Part 1
Description
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).
Title
t1/2 of PF-06817024 in Part 2
Description
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).
Title
t1/2 of PF-06817024 in Part 3
Description
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).
Title
Apparent Volume of Distribution (Vz/F) of PF-06817024 for the Subcutaneous Cohort in Part 1
Description
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).
Title
Apparent Clearance (CL/F) of PF-06817024 for the Subcutaneous Cohort in Part 1
Description
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).
Title
Volume of Distribution at Steady State (Vss) of PF-06817024 Following Single Intravenous Dose in Part 1 and Part 2
Description
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.
Title
Clearance (CL) of PF-06817024 Following Single Intravenous Dose in Part 1 and Part 2
Description
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.
Title
Trough Serum Concentration (Cmin) of PF-06817024 Post Second Dose Following Multiple Doses in Part 1
Description
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.
Title
Cmin of PF-06817024 Post Last Dose Following Multiple Doses in Part 3
Description
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.
Title
Accumulation Ratio for Cmax (Rac, Cmax) of PF-06817024 Post Second Dose Following Multiple Doses in Part 1
Description
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).
Title
Rac, Cmax of PF-06817024 Post Last Dose Following Multiple Doses in Part 3
Description
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).
Title
Accumulation Ratio for AUCtau (Rac) of PF-06817024 Post Second Dose Following Multiple Doses in Part 1
Description
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).
Title
Rac of PF-06817024 Post Last Dose Following Multiple Doses in Part 3
Description
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).
Title
Number of Participants With Treatment-Induced Anti-Drug Antibody (ADA) Against PF-06817024 in Part 1, 2, and 3
Description
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.
Title
Number of Participants With Treatment-Induced Neutralizing Antibodies (NAbs) Against PF-06817024 in Part 1, 2, and 3
Description
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.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
UC Davis Dermatology
City
Sacramento
State/Province
California
ZIP/Postal Code
95816
Country
United States
Facility Name
UC Davis CTSC Clinical Research Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
UC Davis Health
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
New Haven Clinical Research Unit
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06511
Country
United States
Facility Name
Dermatology Physicians of Connecticut
City
Shelton
State/Province
Connecticut
ZIP/Postal Code
06484
Country
United States
Facility Name
ForCare Clinical Research
City
Tampa
State/Province
Florida
ZIP/Postal Code
33613
Country
United States
Facility Name
Dawes Fretzin Clinical Research Group, LLC
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46256
Country
United States
Facility Name
Dawes Fretzin Dermatology Group, LLC
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46256
Country
United States
Facility Name
The Indiana Clinical Trials Center
City
Plainfield
State/Province
Indiana
ZIP/Postal Code
46168
Country
United States
Facility Name
Academic Dermatology
City
Edina
State/Province
Minnesota
ZIP/Postal Code
55435
Country
United States
Facility Name
Clinical Research Institute, Inc.
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55402
Country
United States
Facility Name
Ear, Nose & Throat Specialty Care of Minnesota, P.A.
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55404
Country
United States
Facility Name
Prism Research, LLC
City
Saint Paul
State/Province
Minnesota
ZIP/Postal Code
55114
Country
United States
Facility Name
Hassman Research Institute
City
Berlin
State/Province
New Jersey
ZIP/Postal Code
08009
Country
United States
Facility Name
Carolina Phase 1 Research, LLC
City
Raleigh
State/Province
North Carolina
ZIP/Postal Code
27612
Country
United States
Facility Name
Vital Prospects Clinical Research Institute, PC
City
Tulsa
State/Province
Oklahoma
ZIP/Postal Code
74136
Country
United States
Facility Name
Health Concepts
City
Rapid City
State/Province
South Dakota
ZIP/Postal Code
57702
Country
United States
Facility Name
Lee Medical Associates, PA
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78213
Country
United States
Facility Name
Progressive Clinical Research, PA
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78213
Country
United States
Facility Name
Virginia Clinical Research, Inc.
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23502
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
Links:
URL
https://pmiform.com/clinical-trial-info-request?StudyID=C0341001
Description
To obtain contact information for a study center near you, click here.

Learn more about this trial

Study Of PF-06817024 In Healthy Subjects, In Patients With Chronic Rhinosinusitis With Nasal Polyps And in Patients With Atopic Dermatitis

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