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Completed

NCT Number: NCT03865446

Evaluate Severe Hepatic Impairment on Dacomitinib PK

This is a post approval requirement to study the effect of severe hepatic impairment on the pharmacokinetics of dacomitinib.

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Key information

Conditions

Severe Hepatic Impairment

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Investigational Drug Services (IDS) University of Miami Hospitals and Clinics, Research Pharmacy, Miami, Florida, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

dacomitinib

Drug

anti-cancer agent

Other names: PF-00299804; VIZIMPRO

Primary outcomes

  1. 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.

  2. 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

  1. Number of Participants With Laboratory Abnormalities

    Time frame: Baseline up to Day 7

    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.

  2. Number of Participants With Physical Examination Abnormalities

    Time frame: Baseline up to Day 7

    Height and weight were measured to calculate body mass index abnormality.

  3. Number of Participants With Vital Sign Parameters Meeting Criteria of Potential Clinical Concern

    Time frame: Baseline up to Day 7

    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.

  4. Number of Participants With ECG Parameters Meeting Criteria of Potential Clinical Concern

    Time frame: Baseline up to Day 7

    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.

  5. Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Time frame: Baseline up to Day 35

    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.

Other outcomes

  1. Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs)

    Time frame: Baseline up to Day 35

    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.

Sponsors and collaborators

Lead sponsor

Pfizer

Industry

Registry information

Official study 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

Important dates

Study start
2019
Primary completion
2019
Study completion
2019
First posted
Mar 6, 2019
Registry last updated
Nov 6, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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