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This is a post approval requirement to study the effect of severe hepatic impairment on the pharmacokinetics of dacomitinib.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 (Dacomitinib) | Experimental | severe hepatic impairment group |
|
| Cohort 2 (Dacomitinib) | Experimental | normal hepatic function |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dacomitinib | Drug | anti-cancer agent |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of Dacomitinib | Cmax of Dacomitinib was analyzed. | 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 |
| Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) of Dacomitinib | AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). | 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 | Description | Time Frame |
|---|---|---|
| Number of Participants With Laboratory Abnormalities | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) | 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. |
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:
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| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Investigational Drug Services (IDS) University of Miami Hospitals and Clinics, Research Pharmacy | Miami | Florida | 33136 | United States | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35195881 | Derived | 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. |
| Label | URL |
|---|---|
| To obtain contact information for a study center near you, click here. | View source |
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Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Safety analysis set included all participants assigned to dacomitinib and who take 1 dose of dacomitinib.
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| ID | Title | Description |
|---|---|---|
| BG000 | Severe Hepatic Impairment | 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. |
| BG001 | Normal Hepatic Function |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Maximum Observed Plasma Concentration (Cmax) of Dacomitinib | Cmax of Dacomitinib was analyzed. | Pharmacokinetic (PK) population included all participants who took one dose of dacomitinib and had at least one dacomitinib plasma PK parameters of primary interest. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram per milliliter | 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 |
|
Baseline up to Day 35
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Severe Hepatic Impairment | 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. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pfizer ClinicalTrials.gov Call Center | Pfizer Inc. | 1800-718-1021 | ClinicalTrials.gov_Inquiries@pfizer.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Nov 14, 2018 | Oct 13, 2020 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 11, 2019 | Oct 13, 2020 | SAP_001.pdf |
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| ID | Term |
|---|---|
| C525726 | dacomitinib |
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| Baseline up to Day 7 |
| Number of Participants With Physical Examination Abnormalities | Height and weight were measured to calculate body mass index abnormality. | Baseline up to Day 7 |
| Number of Participants With Vital Sign Parameters Meeting Criteria of Potential Clinical Concern | 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. | Baseline up to Day 7 |
| Number of Participants With ECG Parameters Meeting Criteria of Potential Clinical Concern | 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. | Baseline up to Day 7 |
| Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | 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. | Baseline up to Day 35 |
| Baseline up to Day 35 |
| University of Miami Division of Clinical Pharmacology |
| Miami |
| Florida |
| 33136 |
| United States |
| Orlando Clinical Research Center | Orlando | Florida | 32809 | United States |
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.
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | 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. |
|
|
|
| Primary | Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUCinf) of Dacomitinib | AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram*hour per milliliter | 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 | Number of Participants With Laboratory Abnormalities | 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. | Safety population included all participants assigned to dacomitinib and who took one dose of dacomitinib. | Posted | Count of Participants | Participants | Baseline up to Day 7 |
|
|
|
| Secondary | Number of Participants With Physical Examination Abnormalities | Height and weight were measured to calculate body mass index abnormality. | Safety population included all participants assigned to dacomitinib and who took one dose of dacomitinib. | Posted | Count of Participants | Participants | Baseline up to Day 7 |
|
|
|
| Secondary | Number of Participants With Vital Sign Parameters Meeting Criteria of Potential Clinical Concern | 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. | Safety population included all participants assigned to dacomitinib and who took one dose of dacomitinib. | Posted | Count of Participants | Participants | Baseline up to Day 7 |
|
|
|
| Secondary | Number of Participants With ECG Parameters Meeting Criteria of Potential Clinical Concern | 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. | Safety population included all participants assigned to dacomitinib and who took one dose of dacomitinib. | Posted | Count of Participants | Participants | Baseline up to Day 7 |
|
|
|
| Secondary | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | 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. | Safety population included all participants assigned to dacomitinib and who took one dose of dacomitinib. | Posted | Count of Participants | Participants | Baseline up to Day 35 |
|
|
|
| Other Pre-specified | Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) | 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. | Safety population included all participants assigned to dacomitinib and who took one dose of dacomitinib. | Posted | Count of Participants | Participants | Baseline up to Day 35 |
|
|
|
| 0 |
| 8 |
| 0 |
| 8 |
| 0 |
| 8 |
| EG001 | 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. | 0 | 8 | 0 | 8 | 0 | 8 |
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.