Evaluate Severe Hepatic Impairment on Dacomitinib PK

Phase 1

Completed

• Conditions: Severe Hepatic Impairment
• Interventions: Drug: Dacomitinib

• Registration Number: NCT03865446
• Lead Sponsor: Pfizer

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 Timeline

• Study First Submitted: 2019-02-07
• Study First Submitted QC: 2019-03-05
• Study First Posted: 2019-03-06
• Study Start: 2019-04-05
• Primary Completion: 2019-10-24
• Study Completion: 2019-10-24
• Status Verified: 2020-10
• Results First Submitted: 2020-10-13
• Results First Submitted QC: 2020-10-13
• Last Update Submitted: 2020-10-13
• Results First Posted: 2020-11-06
• Last Update Posted: 2020-11-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

Not provided

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 1 (Dacomitinib)	Dacomitinib	severe hepatic impairment group
Cohort 2 (Dacomitinib)	Dacomitinib	normal hepatic function

Primary Outcome Measures

Name	Time	Method
Maximum Observed Plasma Concentration (Cmax) of Dacomitinib	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	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 Outcome Measures

Name	Time	Method
Number of Participants With Laboratory Abnormalities	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.
Number of Participants With Vital Sign Parameters Meeting Criteria of Potential Clinical Concern	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.
Number of Participants With ECG Parameters Meeting Criteria of Potential Clinical Concern	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.
Number of Participants With Physical Examination Abnormalities	Baseline up to Day 7	Height and weight were measured to calculate body mass index abnormality.
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	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.

Trial Locations

Locations (3)

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

University of Miami Division of Clinical Pharmacology; 🇺🇸 Miami, Florida, United States

Orlando Clinical Research Center; 🇺🇸 Orlando, Florida, United States