Trial Outcomes & Findings for Evaluate Severe Hepatic Impairment on Dacomitinib PK (NCT NCT03865446)

NCT ID: NCT03865446

Last Updated: 2020-11-06

Results Overview

Cmax of Dacomitinib was analyzed.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 16 participants
• Primary outcome 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
• Results posted on: 2020-11-06

Participant Flow

Participant milestones

Measure	Severe Hepatic Impairment Participants with severe hepatic impairment received a single oral dose of dacomitinib 30 milligram (mg) tablet on Day 1 and were followed up to a maximum of 35 days for safety.	Normal Hepatic Function Participants with normal hepatic function received a single oral dose of dacomitinib 30 mg tablet on Day 1 and were followed up to a maximum of 35 days for safety.
Overall Study STARTED	8	8
Overall Study COMPLETED	8	8
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Evaluate Severe Hepatic Impairment on Dacomitinib PK

Baseline characteristics by cohort

Measure	Severe Hepatic Impairment n=8 Participants Participants with severe hepatic impairment received a single oral dose of dacomitinib 30 mg tablet on Day 1 and were followed up to a maximum of 35 days for safety.	Normal Hepatic Function n=8 Participants Participants with normal hepatic function received a single oral dose of dacomitinib 30 mg tablet on Day 1 and were followed up to a maximum of 35 days for safety.	Total n=16 Participants Total of all reporting groups
Age, Continuous	60.0 years STANDARD_DEVIATION 6.82 • n=5 Participants	59.0 years STANDARD_DEVIATION 5.37 • n=7 Participants	59.5 years STANDARD_DEVIATION 5.96 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	8 Participants n=7 Participants	16 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants	8 Participants n=7 Participants	15 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

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

Population: Pharmacokinetic (PK) population included all participants who took one dose of dacomitinib and had at least one dacomitinib plasma PK parameters of primary interest.

Cmax of Dacomitinib was analyzed.

Outcome measures

Measure	Severe Hepatic Impairment n=8 Participants Participants with severe hepatic impairment received a single oral dose of dacomitinib 30 mg tablet on Day 1 and were followed up to a maximum of 35 days for safety.	Normal Hepatic Function n=8 Participants Participants with normal hepatic function received a single oral dose of dacomitinib 30 mg tablet on Day 1 and were followed up to a maximum of 35 days for safety.
Maximum Observed Plasma Concentration (Cmax) of Dacomitinib	9.673 nanogram per milliliter Geometric Coefficient of Variation 35	7.389 nanogram per milliliter Geometric Coefficient of Variation 63

PRIMARY outcome

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

Population: PK population included all participants who took one dose of dacomitinib and had at least one dacomitinib plasma PK parameters of primary interest. Here, 'Overall Number of Participants Analyzed' = participants evaluable for this outcome measure.

AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf).

Outcome measures

Measure	Severe Hepatic Impairment n=8 Participants Participants with severe hepatic impairment received a single oral dose of dacomitinib 30 mg tablet on Day 1 and were followed up to a maximum of 35 days for safety.	Normal Hepatic Function n=7 Participants Participants with normal hepatic function received a single oral dose of dacomitinib 30 mg tablet on Day 1 and were followed up to a maximum of 35 days for safety.
Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) of Dacomitinib	735.0 nanogram*hour per milliliter Geometric Coefficient of Variation 37	703.9 nanogram*hour per milliliter Geometric Coefficient of Variation 48

SECONDARY outcome

Timeframe: Baseline up to Day 7

Population: Safety population included all participants assigned to dacomitinib and who took one dose of dacomitinib.

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.

Outcome measures

Measure	Severe Hepatic Impairment n=8 Participants Participants with severe hepatic impairment received a single oral dose of dacomitinib 30 mg tablet on Day 1 and were followed up to a maximum of 35 days for safety.	Normal Hepatic Function n=8 Participants Participants with normal hepatic function received a single oral dose of dacomitinib 30 mg tablet on Day 1 and were followed up to a maximum of 35 days for safety.
Number of Participants With Laboratory Abnormalities	8 Participants	5 Participants

SECONDARY outcome

Timeframe: Baseline up to Day 7

Population: Safety population included all participants assigned to dacomitinib and who took one dose of dacomitinib.

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

Outcome measures

Measure	Severe Hepatic Impairment n=8 Participants Participants with severe hepatic impairment received a single oral dose of dacomitinib 30 mg tablet on Day 1 and were followed up to a maximum of 35 days for safety.	Normal Hepatic Function n=8 Participants Participants with normal hepatic function received a single oral dose of dacomitinib 30 mg tablet on Day 1 and were followed up to a maximum of 35 days for safety.
Number of Participants With Physical Examination Abnormalities	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline up to Day 7

Population: Safety population included all participants assigned to dacomitinib and who took one dose of dacomitinib.

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.

Outcome measures

Measure	Severe Hepatic Impairment n=8 Participants Participants with severe hepatic impairment received a single oral dose of dacomitinib 30 mg tablet on Day 1 and were followed up to a maximum of 35 days for safety.	Normal Hepatic Function n=8 Participants Participants with normal hepatic function received a single oral dose of dacomitinib 30 mg tablet on Day 1 and were followed up to a maximum of 35 days for safety.
Number of Participants With Vital Sign Parameters Meeting Criteria of Potential Clinical Concern Increase in diastolic blood pressure	0 Participants	1 Participants
Number of Participants With Vital Sign Parameters Meeting Criteria of Potential Clinical Concern Increase in systolic blood pressure	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline up to Day 7

Population: Safety population included all participants assigned to dacomitinib and who took one dose of dacomitinib.

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.

Outcome measures

Measure	Severe Hepatic Impairment n=8 Participants Participants with severe hepatic impairment received a single oral dose of dacomitinib 30 mg tablet on Day 1 and were followed up to a maximum of 35 days for safety.	Normal Hepatic Function n=8 Participants Participants with normal hepatic function received a single oral dose of dacomitinib 30 mg tablet on Day 1 and were followed up to a maximum of 35 days for safety.
Number of Participants With ECG Parameters Meeting Criteria of Potential Clinical Concern	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline up to Day 35

Population: Safety population included all participants assigned to dacomitinib and who took one dose of dacomitinib.

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.

Outcome measures

Measure	Severe Hepatic Impairment n=8 Participants Participants with severe hepatic impairment received a single oral dose of dacomitinib 30 mg tablet on Day 1 and were followed up to a maximum of 35 days for safety.	Normal Hepatic Function n=8 Participants Participants with normal hepatic function received a single oral dose of dacomitinib 30 mg tablet on Day 1 and were followed up to a maximum of 35 days for safety.
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	0 Participants	0 Participants
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	0 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to Day 35

Population: Safety population included all participants assigned to dacomitinib and who took one dose of dacomitinib.

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.

Outcome measures

Measure	Severe Hepatic Impairment n=8 Participants Participants with severe hepatic impairment received a single oral dose of dacomitinib 30 mg tablet on Day 1 and were followed up to a maximum of 35 days for safety.	Normal Hepatic Function n=8 Participants Participants with normal hepatic function received a single oral dose of dacomitinib 30 mg tablet on Day 1 and were followed up to a maximum of 35 days for safety.
Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs)	0 Participants	0 Participants

Adverse Events

Severe Hepatic Impairment

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Normal Hepatic Function

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer Inc.

Phone: 1800-718-1021

Email: ClinicalTrials.gov_Inquiries@pfizer.com

Results disclosure agreements

• Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
• Publication restrictions are in place

Restriction type: OTHER