Back to resultsEvaluate Severe Hepatic Impairment on Dacomitinib PK
Primary Purpose
Severe Hepatic Impairment
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Dacomitinib
Sponsored by
About this trial
This is an interventional other trial for Severe Hepatic Impairment focused on measuring Pharmacokinetics, Dacomitinib, Hepatic Impairment
Eligibility Criteria
Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
- Male and/or female participants of non childbearing potential must be 18 to 75 years of age, inclusive, at the time of signing the informed consent document (ICD).
Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
Weight:
- Body mass index (BMI) of 17.5 to 40 kg/m2; and a total body weight >50 kg (110 lb).
- Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol.
Exclusion Criteria:
Participants are excluded from the study if any of the following criteria apply:
- Any condition possibly affecting drug absorption (eg, gastrectomy).
- Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or IP administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.
- History of or current positive results for human immunodeficiency virus (HIV).
- Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half lives preceding the first dose of IP used in this study (whichever is longer).
- Hypersensitivity to dacomitinib or its excipients.
- A positive urine drug test. Participants with severe hepatic impairment (Cohort 1) will be eligible to participate if their urine drug test is positive with a drug for a prescribed condition that is not expected to interfere with the PK of dacomitinib.
- Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing.
- History of sensitivity to heparin or heparin induced thrombocytopenia.
- Unwilling or unable to comply with the criteria in the Lifestyle Considerations section of this protocol.
- Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or Sponsor employees, including their family members, directly involved in the conduct of the study.
Sites / Locations
- Investigational Drug Services (IDS) University of Miami Hospitals and Clinics, Research Pharmacy
- University of Miami Division of Clinical Pharmacology
- Orlando Clinical Research Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Cohort 1 (Dacomitinib)
Cohort 2 (Dacomitinib)
Arm Description
severe hepatic impairment group
normal hepatic function
Outcomes
Primary Outcome Measures
Maximum Observed Plasma Concentration (Cmax) of Dacomitinib
Cmax of Dacomitinib was analyzed.
Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) of Dacomitinib
AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf).
Secondary Outcome Measures
Number of Participants With Laboratory Abnormalities
Laboratory abnormalities included hematology- Erythrocyte mean corpuscular hemoglobin: less than (<) 0.9 *lower limit of normal (LLN), platelets: < 0.5* LLN, leukocytes: < 0.6* LLN, lymphocytes: < 0.8* LLN, eosinophils: greater than (>) 1.2* lower limit of normal (ULN), partial thromboplastin time (PTT): > 1.1* ULN, prothrombin time: > 1.1* ULN, Prothrombin Intl. normalized ratio: > 1.1* ULN, clinical chemistry- bilirubin: > 1.5* ULN, protein: < 0.8* LLN, albumin: < 0.8* LLN, urinalysis- urine protein: greater than or equal to (>=) 1, urine hemoglobin: >= 1, urobilinogen: >= 1, urine erythrocytes: >= 20.
Number of Participants With Physical Examination Abnormalities
Height and weight were measured to calculate body mass index abnormality.
Number of Participants With Vital Sign Parameters Meeting Criteria of Potential Clinical Concern
Systolic blood pressure, diastolic blood pressure and pulse rate were evaluated for examination of vital signs. Criteria for potential concern in absolute values of vital sign: pulse rate: <40 beats per minute (bpm), >120 beats per minute; supine diastolic blood pressure: <50 millimeter of mercury (mm Hg); supine systolic blood pressure: <90 mm Hg. Criteria for potential concern in change from baseline in vital sign values: supine diastolic blood pressure: greater than or equal to >= 30 mm Hg increase or decrease from baseline; supine diastolic blood pressure: >=20 mm Hg increase or decrease from baseline. Only participants with vital sign parameters meeting criteria of potential clinical concern are reported.
Number of Participants With ECG Parameters Meeting Criteria of Potential Clinical Concern
ECG parameters RR interval, PR interval, QRS interval, QT interval, QTC interval, QTCB, QTCF and heart rate were measured. Criteria of potential concern for absolute values: PR interval: >=300 milliseconds; QRS interval >=140 milliseconds; QT interval: >=500 milliseconds; QTCF (Fridericia's correction formula) : >= 450 to < 480 milliseconds, >=480 to <500 milliseconds, >=500 milliseconds. Criteria of potential concern for change from baseline values: PR interval: when baseline is >200 millisecond- change >=25%, when baseline <200 milliseconds- change >=50%; QRS interval: change >= 50%; QTCF: change >=30 to <60, change >=60. In this outcome measure, participants meeting the criteria of potential concern for any of the ECG parameters are reported.
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; medically important events. A treatment emergent AE was defined as an event that emerged during the treatment period (Up to Day 35) that was absent before treatment, or worsened during the treatment period relative to the pretreatment state.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03865446
Brief Title
Evaluate Severe Hepatic Impairment on Dacomitinib PK
Official Title
A PHASE 1, OPEN-LABEL, SINGLE-DOSE, PARALLEL-GROUP STUDY TO EVALUATE THE PLASMA PHARMACOKINETICS AND SAFETY OF DACOMITINIB IN PARTICIPANTS WITH SEVERELY IMPAIRED HEPATIC FUNCTION RELATIVE TO PARTICIPANTS WITH NORMAL HEPATIC FUNCTION
Study Type
Interventional
2. Study Status
Record Verification Date
October 2020
Overall Recruitment Status
Completed
Study Start Date
April 5, 2019 (Actual)
Primary Completion Date
October 24, 2019 (Actual)
Study Completion Date
October 24, 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 is a post approval requirement to study the effect of severe hepatic impairment on the pharmacokinetics of dacomitinib.
Detailed Description
This is a Phase 1, open label, parallel group study to investigate the effect of severe hepatic impairment on the plasma PK, safety and tolerability after a single oral 30 mg dose of dacomitinib under fasted conditions.
Approximately 18 participants will be enrolled into the study to ensure at least 6 PK evaluable (having data for estimating primary PK parameters for dacomitinib) participants in each cohort.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Severe Hepatic Impairment
Keywords
Pharmacokinetics, Dacomitinib, Hepatic Impairment
7. Study Design
Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
16 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1 (Dacomitinib)
Arm Type
Experimental
Arm Description
severe hepatic impairment group
Arm Title
Cohort 2 (Dacomitinib)
Arm Type
Experimental
Arm Description
normal hepatic function
Intervention Type
Drug
Intervention Name(s)
Dacomitinib
Other Intervention Name(s)
PF-00299804; VIZIMPRO
Intervention Description
anti-cancer agent
Primary Outcome Measure Information:
Title
Maximum Observed Plasma Concentration (Cmax) of Dacomitinib
Description
Cmax of Dacomitinib was analyzed.
Time Frame
Pre-dose and 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 and 264 hours post dose on Day 1
Title
Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) of Dacomitinib
Description
AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf).
Time Frame
Pre-dose and 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 and 264 hours post dose on Day 1
Secondary Outcome Measure Information:
Title
Number of Participants With Laboratory Abnormalities
Description
Laboratory abnormalities included hematology- Erythrocyte mean corpuscular hemoglobin: less than (<) 0.9 *lower limit of normal (LLN), platelets: < 0.5* LLN, leukocytes: < 0.6* LLN, lymphocytes: < 0.8* LLN, eosinophils: greater than (>) 1.2* lower limit of normal (ULN), partial thromboplastin time (PTT): > 1.1* ULN, prothrombin time: > 1.1* ULN, Prothrombin Intl. normalized ratio: > 1.1* ULN, clinical chemistry- bilirubin: > 1.5* ULN, protein: < 0.8* LLN, albumin: < 0.8* LLN, urinalysis- urine protein: greater than or equal to (>=) 1, urine hemoglobin: >= 1, urobilinogen: >= 1, urine erythrocytes: >= 20.
Time Frame
Baseline up to Day 7
Title
Number of Participants With Physical Examination Abnormalities
Description
Height and weight were measured to calculate body mass index abnormality.
Time Frame
Baseline up to Day 7
Title
Number of Participants With Vital Sign Parameters Meeting Criteria of Potential Clinical Concern
Description
Systolic blood pressure, diastolic blood pressure and pulse rate were evaluated for examination of vital signs. Criteria for potential concern in absolute values of vital sign: pulse rate: <40 beats per minute (bpm), >120 beats per minute; supine diastolic blood pressure: <50 millimeter of mercury (mm Hg); supine systolic blood pressure: <90 mm Hg. Criteria for potential concern in change from baseline in vital sign values: supine diastolic blood pressure: greater than or equal to >= 30 mm Hg increase or decrease from baseline; supine diastolic blood pressure: >=20 mm Hg increase or decrease from baseline. Only participants with vital sign parameters meeting criteria of potential clinical concern are reported.
Time Frame
Baseline up to Day 7
Title
Number of Participants With ECG Parameters Meeting Criteria of Potential Clinical Concern
Description
ECG parameters RR interval, PR interval, QRS interval, QT interval, QTC interval, QTCB, QTCF and heart rate were measured. Criteria of potential concern for absolute values: PR interval: >=300 milliseconds; QRS interval >=140 milliseconds; QT interval: >=500 milliseconds; QTCF (Fridericia's correction formula) : >= 450 to < 480 milliseconds, >=480 to <500 milliseconds, >=500 milliseconds. Criteria of potential concern for change from baseline values: PR interval: when baseline is >200 millisecond- change >=25%, when baseline <200 milliseconds- change >=50%; QRS interval: change >= 50%; QTCF: change >=30 to <60, change >=60. In this outcome measure, participants meeting the criteria of potential concern for any of the ECG parameters are reported.
Time Frame
Baseline up to Day 7
Title
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; medically important events. A treatment emergent AE was defined as an event that emerged during the treatment period (Up to Day 35) that was absent before treatment, or worsened during the treatment period relative to the pretreatment state.
Time Frame
Baseline up to Day 35
Other Pre-specified Outcome Measures:
Title
Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs)
Description
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 first dose that were absent before treatment or that worsened relative to pretreatment state. Relatedness to Dacomitinib was assessed by the investigator.
Time Frame
Baseline up to Day 35
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
Participants are eligible to be included in the study only if all of the following criteria apply:
Male and/or female participants of non childbearing potential must be 18 to 75 years of age, inclusive, at the time of signing the informed consent document (ICD).
Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
Weight:
Body mass index (BMI) of 17.5 to 40 kg/m2; and a total body weight >50 kg (110 lb).
Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol.
Exclusion Criteria:
Participants are excluded from the study if any of the following criteria apply:
Any condition possibly affecting drug absorption (eg, gastrectomy).
Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or IP administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.
History of or current positive results for human immunodeficiency virus (HIV).
Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half lives preceding the first dose of IP used in this study (whichever is longer).
Hypersensitivity to dacomitinib or its excipients.
A positive urine drug test. Participants with severe hepatic impairment (Cohort 1) will be eligible to participate if their urine drug test is positive with a drug for a prescribed condition that is not expected to interfere with the PK of dacomitinib.
Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing.
History of sensitivity to heparin or heparin induced thrombocytopenia.
Unwilling or unable to comply with the criteria in the Lifestyle Considerations section of this protocol.
Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or Sponsor employees, including their family members, directly involved in the conduct of the study.
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
Investigational Drug Services (IDS) University of Miami Hospitals and Clinics, Research Pharmacy
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
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.
Citations:
PubMed Identifier
35195881
Citation
Piscitelli J, Chen J, LaBadie RR, Salageanu J, Chung CH, Tan W. The Effect of Hepatic Impairment on the Pharmacokinetics of Dacomitinib. Clin Drug Investig. 2022 Mar;42(3):221-235. doi: 10.1007/s40261-022-01125-x. Epub 2022 Feb 23.
Results Reference
derived
Links:
URL
https://pmiform.com/clinical-trial-info-request?StudyID=A7471058
Description
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Evaluate Severe Hepatic Impairment on Dacomitinib PK
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