Clinical trial NCT03865446: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Severe Hepatic Impairment
Keywords: Pharmacokinetics
Dacomitinib
Hepatic Impairment
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2019-03-06
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

Eligibility criteria: Inclusion Criteria

Participants are eligible to be included in the study only if all of the following criteria apply:

1. 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).
2. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.

   Weight:
3. Body mass index (BMI) of 17.5 to 40 kg/m2; and a total body weight \>50 kg (110 lb).
4. 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:

1. Any condition possibly affecting drug absorption (eg, gastrectomy).
2. 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.
3. History of or current positive results for human immunodeficiency virus (HIV).
4. 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).
5. Hypersensitivity to dacomitinib or its excipients.
6. 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.
7. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing.
8. History of sensitivity to heparin or heparin induced thrombocytopenia.
9. Unwilling or unable to comply with the criteria in the Lifestyle Considerations section of this protocol.
10. 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.

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of Dacomitinib
timeFrame: 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
measure: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) of Dacomitinib
timeFrame: 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 outcomes:
measure: Number of Participants With Laboratory Abnormalities
timeFrame: Baseline up to Day 7
measure: Number of Participants With Physical Examination Abnormalities
timeFrame: Baseline up to Day 7
measure: Number of Participants With Vital Sign Parameters Meeting Criteria of Potential Clinical Concern
timeFrame: Baseline up to Day 7
measure: Number of Participants With ECG Parameters Meeting Criteria of Potential Clinical Concern
timeFrame: Baseline up to Day 7
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to Day 35
Other outcomes:
measure: Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs)
timeFrame: Baseline up to Day 35
Locations:
city: Miami
country: United States
facility: Investigational Drug Services (IDS) University of Miami Hospitals and Clinics, Research Pharmacy
state: Florida
city: Miami
country: United States
facility: University of Miami Division of Clinical Pharmacology
state: Florida
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
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.