Back to resultsA Study to Evaluate the Pharmacokinetics, Safety and Tolerability of PF-06651600 in Subjects With Hepatic Impairment and Healthy Volunteers
Primary Purpose
Hepatic Impairment, Healthy Participants
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
PF-06651600 30 mg
Sponsored by
About this trial
This is an interventional basic science trial for Hepatic Impairment focused on measuring PF-06651600, Pharmacokinetics, Hepatic impairment
Eligibility Criteria
Inclusion Criteria:
- Willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations and other study procedures
- Body mass index (BMI) of 17.5 to 40 kg/m2; and a total body weight >50 kg (110 lb)
Additional Inclusion Criteria for Participants with Normal Hepatic Function:
- Healthy male or female participants
- No known or suspected hepatic disease
Additional Inclusion Criteria for Participants with Impaired Hepatic Function:
- Stable hepatic impairment, defined as no clinically significant change in disease status within the last 30 days prior to the Screening visit
- No other ongoing clinically significant abnormalities based on medical history, physical examination, vital signs, 12-lead ECG, and clinical laboratory tests except for the abnormal findings that are related to the participant's hepatic impairment.
- Satisfy the criteria for Class A or Class B of the Child-Pugh classification (mild: Child-Pugh Scores 5-6 points, and moderate: Child Pugh Scores 7-9 points), within 28 days of investigational product administration.
Exclusion Criteria:
- Has active acute or chronic infection requiring treatment or history of systemic infection requiring hospitalization, incl. herpes zoster, herpes simplex, tuberculosis
- Infection with hepatitis B, hepatitis C or HIV
- Any condition affecting drug absorption, distribution, metabolism and excretion (eg, status post porta-caval shunt surgery, prior bariatric surgery, gastrectomy, ileal resection)
- Has malignancy, lymphoproliferative disorder, surgery or other condition not allowed per protocol
Additional Exclusion Criteria for Participants with Normal Hepatic Function:
- Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, gynecologic or allergic disease
Additional Exclusion Criteria for Participants with Impaired Hepatic Function:
- Has encephalopathy, severe ascites and/or pleural effusion, Child-Pugh score >9 or medical conditions (like hepatorenal syndrome, gastrointestinal hemorrhage, etc.) excluded per protocol
Sites / Locations
- University of Miami Division of Clinical Pharmacology
- Orlando Clinical Research Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
PF-06651600 Moderate Hepatic Impairment
PF-06651600 Healthy participants
PF-06651600 Mild Hepatic Impairment
Arm Description
This arm includes participants with moderate hepatic impairment who will receive oral doses of PF-06651600 30 mg on Day 1 through Day 10.
This arm includes healthy adult participants who will receive oral doses of PF-06651600 30 mg on Day 1 through Day 10.
This arm is in Part 2 which will be conducted if the decision criterion to proceed to Part 2 is met. The arm includes participants with mild hepatic impairment who will receive oral doses of PF-06651600 30 mg on Day 1 through Day 10.
Outcomes
Primary Outcome Measures
Area Under the Plasma Concentration-time Profile From Time 0 to 24 Hours (AUC24) for PF-06651600
AUC24 of PF-06651600 pre and post dose.
Maximum Plasma Concentration (Cmax) for PF-06651600
Cmax is maximum observed plasma concentration.
Secondary Outcome Measures
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) (All Causalities and Treatment-related)
AEs with all causalities were any untoward medical occurrences in a study participant administered a product which did not necessarily had causal relationship with the treatment or usage. An SAE was an AE resulting in any of the following endpoints or deemed significant for any other reason: death; life threatening (immediate risk of death); inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or considered to be an important medical event. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-emergent are events between first dose of study drug and up to 35 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)
Laboratory parameters included: hematology (hemoglobin, hematocrit, erythrocytes, leukocytes, neutrophils, prothrombin time, prothrombin intl. normalized ratio), chemistry (bilirubin, direct bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, albumin, sodium, potassium, calcium, bicarbonate and glucose), urinalysis (glucose, ketones, protein, hemoglobin, urobilinogen, bilirubin and nitrite). Each parameter was evaluated against commonly used and widely accepted criteria.
Number of Participants With Out of Range Vital Signs
Vital signs included supine blood pressure, pulse rate and temperature. The pre-specified out of range criterion for supine diastolic blood pressure was change from baseline equal to or over than (≥) 20 millimeter of mercury (mmHg). Clinical significance of vital signs and out of range criterion were determined at the investigator's discretion.
Number of Adverse Events Leading to Discontinuation
Adverse events result in participants discontinuations from the study drug.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04016077
Brief Title
A Study to Evaluate the Pharmacokinetics, Safety and Tolerability of PF-06651600 in Subjects With Hepatic Impairment and Healthy Volunteers
Official Title
A PHASE 1, NON-RANDOMIZED, OPEN LABEL, MULTIPLE DOSE STUDY TO EVALUATE THE PHARMACOKINETICS, SAFETY AND TOLERABILITY OF PF 06651600 IN SUBJECTS WITH HEPATIC IMPAIRMENT AND IN HEALTHY SUBJECTS WITH NORMAL HEPATIC FUNCTION
Study Type
Interventional
2. Study Status
Record Verification Date
April 2021
Overall Recruitment Status
Completed
Study Start Date
July 19, 2019 (Actual)
Primary Completion Date
March 5, 2020 (Actual)
Study Completion Date
March 5, 2020 (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 characterize the effect of hepatic impairment on the pharmacokinetic(s) (PK) of PF-06651600 following administration of multiple once daily doses of PF-06651600. The safety and tolerability of PF-06651600 will also be evaluated in this study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatic Impairment, Healthy Participants
Keywords
PF-06651600, Pharmacokinetics, Hepatic impairment
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
18 (Actual)
8. Arms, Groups, and Interventions
Arm Title
PF-06651600 Moderate Hepatic Impairment
Arm Type
Experimental
Arm Description
This arm includes participants with moderate hepatic impairment who will receive oral doses of PF-06651600 30 mg on Day 1 through Day 10.
Arm Title
PF-06651600 Healthy participants
Arm Type
Experimental
Arm Description
This arm includes healthy adult participants who will receive oral doses of PF-06651600 30 mg on Day 1 through Day 10.
Arm Title
PF-06651600 Mild Hepatic Impairment
Arm Type
Experimental
Arm Description
This arm is in Part 2 which will be conducted if the decision criterion to proceed to Part 2 is met.
The arm includes participants with mild hepatic impairment who will receive oral doses of PF-06651600 30 mg on Day 1 through Day 10.
Intervention Type
Drug
Intervention Name(s)
PF-06651600 30 mg
Intervention Description
PF-06651600 in 10 mg oral tablets will be administered on days 1 to 10.
Primary Outcome Measure Information:
Title
Area Under the Plasma Concentration-time Profile From Time 0 to 24 Hours (AUC24) for PF-06651600
Description
AUC24 of PF-06651600 pre and post dose.
Time Frame
Hour 0 (pre-dose) on Days 7, 8 and 9, and hour 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 14, 24 hours post-dose on Day 10
Title
Maximum Plasma Concentration (Cmax) for PF-06651600
Description
Cmax is maximum observed plasma concentration.
Time Frame
Hour 0 (pre-dose) on Days 7, 8 and 9, and hour 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 14, 24 hours post-dose on Day 10
Secondary Outcome Measure Information:
Title
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) (All Causalities and Treatment-related)
Description
AEs with all causalities were any untoward medical occurrences in a study participant administered a product which did not necessarily had causal relationship with the treatment or usage. An SAE was an AE resulting in any of the following endpoints or deemed significant for any other reason: death; life threatening (immediate risk of death); inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or considered to be an important medical event. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-emergent are events between first dose of study drug and up to 35 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
Time Frame
Baseline (Day 0) up to 28 days after last dose of study medication (Day 39)
Title
Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)
Description
Laboratory parameters included: hematology (hemoglobin, hematocrit, erythrocytes, leukocytes, neutrophils, prothrombin time, prothrombin intl. normalized ratio), chemistry (bilirubin, direct bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, albumin, sodium, potassium, calcium, bicarbonate and glucose), urinalysis (glucose, ketones, protein, hemoglobin, urobilinogen, bilirubin and nitrite). Each parameter was evaluated against commonly used and widely accepted criteria.
Time Frame
Baseline (Day 0) up to 28 days after last dose of study medication (Day 39)
Title
Number of Participants With Out of Range Vital Signs
Description
Vital signs included supine blood pressure, pulse rate and temperature. The pre-specified out of range criterion for supine diastolic blood pressure was change from baseline equal to or over than (≥) 20 millimeter of mercury (mmHg). Clinical significance of vital signs and out of range criterion were determined at the investigator's discretion.
Time Frame
Baseline (Day 0) up to 28 days after last dose of study medication (Day 39)
Title
Number of Adverse Events Leading to Discontinuation
Description
Adverse events result in participants discontinuations from the study drug.
Time Frame
Baseline (Day 0) up to 28 days after last dose of study medication (Day 39)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations and other study procedures
Body mass index (BMI) of 17.5 to 40 kg/m2; and a total body weight >50 kg (110 lb)
Additional Inclusion Criteria for Participants with Normal Hepatic Function:
Healthy male or female participants
No known or suspected hepatic disease
Additional Inclusion Criteria for Participants with Impaired Hepatic Function:
Stable hepatic impairment, defined as no clinically significant change in disease status within the last 30 days prior to the Screening visit
No other ongoing clinically significant abnormalities based on medical history, physical examination, vital signs, 12-lead ECG, and clinical laboratory tests except for the abnormal findings that are related to the participant's hepatic impairment.
Satisfy the criteria for Class A or Class B of the Child-Pugh classification (mild: Child-Pugh Scores 5-6 points, and moderate: Child Pugh Scores 7-9 points), within 28 days of investigational product administration.
Exclusion Criteria:
Has active acute or chronic infection requiring treatment or history of systemic infection requiring hospitalization, incl. herpes zoster, herpes simplex, tuberculosis
Infection with hepatitis B, hepatitis C or HIV
Any condition affecting drug absorption, distribution, metabolism and excretion (eg, status post porta-caval shunt surgery, prior bariatric surgery, gastrectomy, ileal resection)
Has malignancy, lymphoproliferative disorder, surgery or other condition not allowed per protocol
Additional Exclusion Criteria for Participants with Normal Hepatic Function:
- Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, gynecologic or allergic disease
Additional Exclusion Criteria for Participants with Impaired Hepatic Function:
- Has encephalopathy, severe ascites and/or pleural effusion, Child-Pugh score >9 or medical conditions (like hepatorenal syndrome, gastrointestinal hemorrhage, etc.) excluded per protocol
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
Orlando Clinical Research Center
City
Orlando
State/Province
Florida
ZIP/Postal Code
32809
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=B7981016
Description
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Learn more about this trial
A Study to Evaluate the Pharmacokinetics, Safety and Tolerability of PF-06651600 in Subjects With Hepatic Impairment and Healthy Volunteers
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