Back to resultsA Renal Impairment Study for PF-04965842
Primary Purpose
Renal Impairment
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
PF-04965842
Sponsored by
About this trial
This is an interventional basic science trial for Renal Impairment
Eligibility Criteria
Inclusion Criteria:
- Breath alcohol test at Screening and Day -1 must be negative.
- Body mass index (BMI) of ≥ 17.5 to ≤ 40.0 kg/m2; and a total body weight >50 kg (110 lb).
Additional inclusion criteria for subjects with renal impairment:
Meet the following eGFR criteria during the screening period based on the MDRD equation:
- Severe renal impairment: eGFR <30 mL/min, but not requiring hemodialysis.
- Moderate renal impairment (Part 2 only): eGFR ≥30 mL/min and <60 mL/min.
- Any form of renal impairment except acute nephritic syndrome (subjects with history of previous nephritic syndrome but in remission can be included).
- Stable concomitant drug regimen.
Exclusion Criteria:
- Renal transplant recipients.
- Urinary incontinence without catheterization.
- Subjects with clinically significant infections within the past 3 months (for example, those requiring hospitalization, or as judged by the Investigator), evidence of any infection (including influenza) within the past 7 days prior to baseline, history of disseminated herpes simplex infection or recurrent or disseminated herpes zoster.
- Subjects with a malignancy or with a history of malignancy, with the exception of adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ.
- History of or current positive results for human immunodeficiency virus, Hepatitis B, Hepatitis C.
Additional exclusion criteria for subjects with renal impairment:
- Subjects requiring hemodialysis and peritoneal dialysis.
- Screening BP ≥ 180 mm Hg (systolic) or ≥ 110 mm Hg (diastolic).
- Screening supine 12-lead ECG demonstrating QTcF >470 msec or a QRS interval >120 msec.
Sites / Locations
- University of Miami Division of Clinical Pharmacology
- University of Miami, Sylvester Comprehensive Cancer Center
- Orlando Clinical Research Center
- Brussels Clinical Research Unit
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
PF-04965842
Arm Description
PF 04965842 is an oral selevtive janus kinase (JAK) 1 inhibitor
Outcomes
Primary Outcome Measures
Maximum Observed Plasma Concentration (Cmax) for PF-04965842
Maximum observed plasma PF-04965842 concentration.
Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for PF-04965842
Area under the plasma PF-04965842 concentration-time profile from time 0 extrapolated to infinite time.
Maximum Observed Plasma Concentration (Cmax) for PF-06471658 (M1)
Maximum observed plasma concentration for active metabolite, PF-06471658 (M1).
Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for PF-06471658 (M1)
Area under the plasma concentration-time profile from time 0 extrapolated to infinite time for active metabolite, PF-06471658 (M1).
Maximum Observed Plasma Concentration (Cmax) for PF-07055087 (M2)
Maximum observed plasma concentration for active metabolite, PF-07055087 (M2).
Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for PF-07055087 (M2)
Area under the plasma concentration-time profile from time 0 extrapolated to infinite time for active metabolite, PF-07055087 (M2).
Secondary Outcome Measures
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Adverse events (AEs): any untoward medical occurrence in a clinical investigation subject administered a product or medical device, without regard to causality. Treatment-emergent AEs (TEAEs): AEs which occurred for the first time during the effective duration of treatment or AEs that increased in severity during treatment. Serious AEs (SAEs) were any untoward medical occurrence at any dose that resulted in death; was life-threatening; required inpatient hospitalization or caused prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduction normal life functions). AEs included SAEs and non-serious AEs. Treatment-related TEAEs were any untoward medical occurrence attributed to study treatment. Causality to study treatment was determined by the investigator.
Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)
Protocol-required safety laboratory assessments included chemistry, hematology, and urinalysis (and microscopy, if needed). Each parameter was evaluated against commonly used and widely accepted criteria.
Number of Participants With Clinically Significant Vital Sign Values
Vital sign data included blood pressure and pulse rate. Clinical significance was assessed by the investigator.
Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Values
Clinical significance of ECG data was assessed by the investigator.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03660241
Brief Title
A Renal Impairment Study for PF-04965842
Official Title
A PHASE 1, NON-RANDOMIZED, OPEN-LABEL, SINGLE-DOSE STUDY TO EVALUATE THE PHARMACOKINETICS, SAFETY AND TOLERABILITY OF PF-04965842 IN SUBJECTS WITH RENAL IMPAIRMENT AND IN HEALTHY SUBJECTS WITH NORMAL RENAL FUNCTION
Study Type
Interventional
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
October 5, 2018 (Actual)
Primary Completion Date
November 5, 2019 (Actual)
Study Completion Date
November 5, 2019 (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
This study is a phase 1 non-randomized, open-label, single-dose, parallel-group study of PF 04965842 in subjects with severe renal impairment and subjects without renal impairment (Part 1) and in subjects with moderate renal impairment (Part 2).
Detailed Description
This is a Phase 1 non randomized, open label, single dose, parallel cohort, multisite study to investigate the effect of renal impairment on the pharmacokinetics, safety and tolerability of PF-04965842 after a single 200 mg oral dose. Subjects will be selected and categorized into normal renal function or renal impairment groups based on their estimated glomerular filtration rate. Part 1: A total of approximately16 subjects will be enrolled; approximately 8 subjects with severe renal impairment and approximately 8 with normal renal function. After statistical evaluation of results from Part 1, Part 2 may be conducted and approximately 8 subjects with moderate renal impairment will be enrolled. The total duration of participation from the Screening Visit to Day 4 will be a maximum of 31 days and from the Screening Visit to Follow-up Contact/Visit will be a maximum of 67 days.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Renal Impairment
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Model Description
Part 1 will be conducted. The 8 subjects from the renal impaired group will be recruited before recruiting the 8 subjects without renal impairment function in Part 1. After statistical evaluation of results from Part 1, Part 2 may be conducted.
Masking
None (Open Label)
Allocation
N/A
Enrollment
23 (Actual)
8. Arms, Groups, and Interventions
Arm Title
PF-04965842
Arm Type
Experimental
Arm Description
PF 04965842 is an oral selevtive janus kinase (JAK) 1 inhibitor
Intervention Type
Drug
Intervention Name(s)
PF-04965842
Intervention Description
PF 04965842 is a janus kinase (JAK) 1 inhibitor that is currently being developed for the treatment of atopic dermatitis (AD).
Primary Outcome Measure Information:
Title
Maximum Observed Plasma Concentration (Cmax) for PF-04965842
Description
Maximum observed plasma PF-04965842 concentration.
Time Frame
0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose
Title
Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for PF-04965842
Description
Area under the plasma PF-04965842 concentration-time profile from time 0 extrapolated to infinite time.
Time Frame
0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose.
Title
Maximum Observed Plasma Concentration (Cmax) for PF-06471658 (M1)
Description
Maximum observed plasma concentration for active metabolite, PF-06471658 (M1).
Time Frame
0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose.
Title
Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for PF-06471658 (M1)
Description
Area under the plasma concentration-time profile from time 0 extrapolated to infinite time for active metabolite, PF-06471658 (M1).
Time Frame
0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose.
Title
Maximum Observed Plasma Concentration (Cmax) for PF-07055087 (M2)
Description
Maximum observed plasma concentration for active metabolite, PF-07055087 (M2).
Time Frame
0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose.
Title
Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for PF-07055087 (M2)
Description
Area under the plasma concentration-time profile from time 0 extrapolated to infinite time for active metabolite, PF-07055087 (M2).
Time Frame
0 (pre-dose), and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose.
Secondary Outcome Measure Information:
Title
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Description
Adverse events (AEs): any untoward medical occurrence in a clinical investigation subject administered a product or medical device, without regard to causality. Treatment-emergent AEs (TEAEs): AEs which occurred for the first time during the effective duration of treatment or AEs that increased in severity during treatment. Serious AEs (SAEs) were any untoward medical occurrence at any dose that resulted in death; was life-threatening; required inpatient hospitalization or caused prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduction normal life functions). AEs included SAEs and non-serious AEs. Treatment-related TEAEs were any untoward medical occurrence attributed to study treatment. Causality to study treatment was determined by the investigator.
Time Frame
Baseline up to Follow-Up (Day 36)
Title
Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)
Description
Protocol-required safety laboratory assessments included chemistry, hematology, and urinalysis (and microscopy, if needed). Each parameter was evaluated against commonly used and widely accepted criteria.
Time Frame
Baseline, post-dose on Day 1, Day 2 and Day 4.
Title
Number of Participants With Clinically Significant Vital Sign Values
Description
Vital sign data included blood pressure and pulse rate. Clinical significance was assessed by the investigator.
Time Frame
Day 1 (pre-dose) and Day 4
Title
Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Values
Description
Clinical significance of ECG data was assessed by the investigator.
Time Frame
Baseline, post-dose on Day 1 and on Day 4
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:
Breath alcohol test at Screening and Day -1 must be negative.
Body mass index (BMI) of ≥ 17.5 to ≤ 40.0 kg/m2; and a total body weight >50 kg (110 lb).
Additional inclusion criteria for subjects with renal impairment:
Meet the following eGFR criteria during the screening period based on the MDRD equation:
Severe renal impairment: eGFR <30 mL/min, but not requiring hemodialysis.
Moderate renal impairment (Part 2 only): eGFR ≥30 mL/min and <60 mL/min.
Any form of renal impairment except acute nephritic syndrome (subjects with history of previous nephritic syndrome but in remission can be included).
Stable concomitant drug regimen.
Exclusion Criteria:
Renal transplant recipients.
Urinary incontinence without catheterization.
Subjects with clinically significant infections within the past 3 months (for example, those requiring hospitalization, or as judged by the Investigator), evidence of any infection (including influenza) within the past 7 days prior to baseline, history of disseminated herpes simplex infection or recurrent or disseminated herpes zoster.
Subjects with a malignancy or with a history of malignancy, with the exception of adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ.
History of or current positive results for human immunodeficiency virus, Hepatitis B, Hepatitis C.
Additional exclusion criteria for subjects with renal impairment:
Subjects requiring hemodialysis and peritoneal dialysis.
Screening BP ≥ 180 mm Hg (systolic) or ≥ 110 mm Hg (diastolic).
Screening supine 12-lead ECG demonstrating QTcF >470 msec or a QRS interval >120 msec.
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
University of Miami Division of Clinical Pharmacology
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
University of Miami, Sylvester Comprehensive Cancer Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Orlando Clinical Research Center
City
Orlando
State/Province
Florida
ZIP/Postal Code
32809
Country
United States
Facility Name
Brussels Clinical Research Unit
City
Brussels
State/Province
Be-bru
ZIP/Postal Code
B-1070
Country
Belgium
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.
Citations:
PubMed Identifier
34637151
Citation
Wang EQ, Le V, Winton JA, Tripathy S, Raje S, Wang L, Dowty ME, Malhotra BK. Effects of Renal Impairment on the Pharmacokinetics of Abrocitinib and Its Metabolites. J Clin Pharmacol. 2022 Apr;62(4):505-519. doi: 10.1002/jcph.1980. Epub 2022 Feb 15.
Results Reference
derived
Links:
URL
https://pmiform.com/clinical-trial-info-request?StudyID=B7451021
Description
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