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
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Pfizer
- Enrollment
- 16
- Locations
- 3
- Primary Endpoint
- Maximum Observed Plasma Concentration (Cmax) of Dacomitinib
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Other
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- Not provided
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.
Arms & Interventions
Cohort 1 (Dacomitinib)
severe hepatic impairment group
Intervention: Dacomitinib (Drug)
Cohort 2 (Dacomitinib)
normal hepatic function
Intervention: Dacomitinib (Drug)
Outcomes
Primary Outcomes
Maximum Observed Plasma Concentration (Cmax) of Dacomitinib
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
Cmax of Dacomitinib was analyzed.
Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) of Dacomitinib
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
AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf).
Secondary Outcomes
- Number of Participants With Laboratory Abnormalities(Baseline up to Day 7)
- Number of Participants With Vital Sign Parameters Meeting Criteria of Potential Clinical Concern(Baseline up to Day 7)
- Number of Participants With ECG Parameters Meeting Criteria of Potential Clinical Concern(Baseline up to Day 7)
- Number of Participants With Physical Examination Abnormalities(Baseline up to Day 7)
- Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)(Baseline up to Day 35)