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This is a phase 1 study to describe the plasma pharmacokinetics of a single oral 75mg dose of palbociclib administered to healthy volunteers, and subjects with mild, moderate, and severely impaired hepatic function.
This is a 4-cohort single period study. The four cohorts will consist of healthy volunteers, and subjects with mild, moderate, and severely impaired hepatic function. Each cohort will receive the same treatment consisting of a single oral 75mg dose of palbociclib administered with food. Serial PK samples will be drawn up to 120 hours post dose for the cohort consisting of healthy volunteers, and will continue until up to 192 hours post-dose for the cohorts of hepatic impairment subjects.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Healthy Volunteers | Experimental | Cohort of Healthy Volunteers |
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| Mild Hepatic Impairment | Experimental | Cohort of mild hepatic impairment subjects meeting the criteria for Child-Pugh Class A |
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| Moderate Hepatic Impairment | Experimental | Cohort of moderate hepatic impairment subjects meeting the criteria for Child-Pugh Class B |
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| Severe Hepatic Impairment | Experimental | Cohort of severe hepatic impairment subjects meeting the criteria for Child-Pugh Class C |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Palbociclib 75 mg Capsule | Drug | Single oral 75 mg dose of palbociclib followed by serial PK sampling up to 192 hours post-dose (up to 120 hours post-dose for the healthy volunteer cohort). |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinite Time (AUCinf) | AUCinf is area under the plasma concentration time curve from time 0 extrapolated infinite time. It is calculated as AUClast + (Clast/kel), where AUClast is area under the concentration-time curve from time 0 to the time of the last quantifiable concentration, Clast is the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. | Pre-dose and 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose for all participants. Additional pharmacokinetics samples were collected from participants in hepatic impairment cohorts (Cohorts 2, 3 and 4) at 144, 168, and 192 hours post-dose. |
| Maximum Plasma Concentration (Cmax) | Cmax is maximum plasma concentration. It is observed directly from data. | Pre-dose and 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose for for all participants. Additional pharmacokinetics samples were collected from participants in hepatic impairment cohorts (Cohorts 2, 3 and 4) at 144, 168, and 192 hours post-dose. |
| Measure | Description | Time Frame |
|---|---|---|
| Unbound AUCinf (AUCinf,u) | AUCinf,u is unbound AUCinf, where AUCinf is area under the concentration-time curve from time 0 extrapolated to infinite time. It is obtained by fu*AUCinf, where fu is the fraction of unbound drug in plasma. | Pre-dose and 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose for for all participants. Additional pharmacokinetics samples were collected from participants in hepatic impairment cohorts (Cohorts 2, 3 and 4) at 144, 168, and 192 hours post-dose. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Orlando Clinical Research Center | Orlando | Florida | 32809 | United States | ||
| Weston Diagnostics (Ultrasound Facility) |
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| Label | URL |
|---|---|
| To obtain contact information for a study center near you, click here. | View source |
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A total of 28 participants were assigned to and received the study treatment (7 participants in each cohort).
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| ID | Title | Description |
|---|---|---|
| FG000 | Palbociclib 75 mg (Normal Hepatic Function, Cohort 1) | Participants with normal hepatic function were enrolled in this cohort. Participants received single oral dose of palbociclib 75 mg approximately 10 minutes after completion of the moderate fat standard calorie breakfast, with approximately 240 mL of ambient temperature water. |
| FG001 | Palbociclib 75 mg (Mild Hepatic Impairment, Cohort 2) | Participants with Child-Pugh scores of 5 to 6 points were enrolled in this cohort. Participants received single oral dose of palbociclib 75 mg approximately 10 minutes after completion of the moderate fat standard calorie breakfast, with approximately 240 mL of ambient temperature water. |
| FG002 | Palbociclib 75 mg (Moderate Hepatic Impairment, Cohort 3) | Participants with Child-Pugh scores of 7 to 9 points were enrolled in this cohort. Participants received single oral dose of palbociclib 75 mg approximately 10 minutes after completion of the moderate fat standard calorie breakfast, with approximately 240 mL of ambient temperature water. |
| FG003 | Palbociclib 75 mg (Severe Hepatic Impairment, Cohort 4) | Participants with Child-Pugh scores of 10 to 15 points were enrolled in this cohort. Participants received single oral dose of palbociclib 75 mg approximately 10 minutes after completion of the moderate fat standard calorie breakfast, with approximately 240 mL of ambient temperature water. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Palbociclib 75 mg (Normal Hepatic Function, Cohort 1) | Participants with normal hepatic function were enrolled in this cohort. Participants received single oral dose of palbociclib 75 mg approximately 10 minutes after completion of the moderate fat standard calorie breakfast, with approximately 240 mL of ambient temperature water. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
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| 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 | Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinite Time (AUCinf) | AUCinf is area under the plasma concentration time curve from time 0 extrapolated infinite time. It is calculated as AUClast + (Clast/kel), where AUClast is area under the concentration-time curve from time 0 to the time of the last quantifiable concentration, Clast is the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. | The pharmacokinetics parameter analysis population was defined as all participants enrolled and treated who had at least 1 of the palbociclib pharmacokinetics parameters of primary interest. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram*hour/milliliter (ng*hr/mL) | Pre-dose and 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose for all participants. Additional pharmacokinetics samples were collected from participants in hepatic impairment cohorts (Cohorts 2, 3 and 4) at 144, 168, and 192 hours post-dose. |
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For adverse event, from the time participant took at least 1 dose of palbociclib through the last visit. For serious adverse event, from the participant provided informed consent through 28 calendar days post last administration of palbociclib.
The listing of Other Adverse Events does not include events already captured in the Serious Adverse Event listing. An adverse event of diarrhea was reported in the moderate hepatic impairment cohort after database lock and release. It was therefore not recorded in the clinical database, but was added here for completeness and transparency.
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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 | Palbociclib 75 mg (Normal Hepatic Function, Cohort 1) | Participants with normal hepatic function were enrolled in this cohort. Participants received single oral dose of palbociclib 75 mg approximately 10 minutes after completion of the moderate fat standard calorie breakfast, with approximately 240 mL of ambient temperature water. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | MedDRA 19.0 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA 19.0 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pfizer ClinicalTrail.gov Call Center | Pfizer Inc. | 1-800-718-1021 | ClinicalTrials.gov_Inquiries@pfizer.com |
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| ID | Term |
|---|---|
| D048550 | Hepatic Insufficiency |
| ID | Term |
|---|---|
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| C500026 | palbociclib |
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| Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) | AUClast is area under the plasma concentration time curve from time 0 to time of last quantifiable concentration. It is obtained from linear/log trapezoidal method. | Pre-dose and 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose for for all participants. Additional pharmacokinetics samples were collected from participants in hepatic impairment cohorts (Cohorts 2, 3 and 4) at 144, 168, and 192 hours post-dose. |
| Unbound AUClast (AUClast,u) | AUClast,u is unbound AUClast, where AUClast is area under the concentration-time curve from time 0 to the time of the last quantifiable concentration. It is obtained by fu*AUClast, where fu is the fraction of unbound drug in plasma. | Pre-dose and 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose for for all participants. Additional pharmacokinetics samples were collected from participants in hepatic impairment cohorts (Cohorts 2, 3 and 4) at 144, 168, and 192 hours post-dose. |
| Apparent Clearance After Oral Dose(CL/F) | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance is obtained by dose/AUCinf, where AUCinf is the area under the concentration-time curve from time 0 extrapolated to infinite time. | Pre-dose and 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose for for all participants. Additional pharmacokinetics samples were collected from participants in hepatic impairment cohorts (Cohorts 2, 3 and 4) at 144, 168, and 192 hours post-dose. |
| Unbound CL/F (CLu/F) | CLu/F is unbound CL/F, where CL/F is apparent clearance after oral dose. It is obtained by dose/AUCinf,u, where AUCinf,u is unbound AUCinf (area under the concentration-time curve from time 0 extrapolated to infinite time). | Pre-dose and 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose for for all participants. Additional pharmacokinetics samples were collected from participants in hepatic impairment cohorts (Cohorts 2, 3 and 4) at 144, 168, and 192 hours post-dose. |
| Unbound Cmax (Cmax,u) | Cmax,u is unbound Cmax, where Cmax is maximum plasma concentration. It is obtained by fu*Cmax, where fu is fraction of unbound drug in plasma. | Pre-dose and 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose for for all participants. Additional pharmacokinetics samples were collected from participants in hepatic impairment cohorts (Cohorts 2, 3 and 4) at 144, 168, and 192 hours post-dose. |
| Fraction of Unbound Drug in Plasma (fu) | Fu is the fraction of unbound drug in plasma. It is obtained from measurement of protein binding. | Eight (8) hours post-dose. |
| Terminal Half-Life (t1/2) | T1/2 is terminal half-life. It is obtained by loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. | Pre-dose and 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose for for all participants. Additional pharmacokinetics samples were collected from participants in hepatic impairment cohorts (Cohorts 2, 3 and 4) at 144, 168, and 192 hours post-dose. |
| Time for Cmax (Tmax) | Tmax is time for maximum plasma concentration. It is observed directly from data as time of first occurrence of maximum plasma concentration. | Pre-dose and 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose for for all participants. Additional pharmacokinetics samples were collected from participants in hepatic impairment cohorts (Cohorts 2, 3 and 4) at 144, 168, and 192 hours post-dose. |
| Apparent Volunm of Distribution After Oral Dose (Vz/F) | Vz/F is the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. It is influenced by the fraction absorbed. It is obtained by dose/(AUCinf•kel), where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve, and AUCinf is the area under the concentration-time curve from time 0 extrapolated to infinite time. | pre-dose and 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose for for all participants. Additional pharmacokinetics samples were collected from participants in hepatic impairment cohorts (Cohorts 2, 3 and 4) at 144, 168, and 192 hours post-dose. |
| Unbound Vz/F (Vz,u/F) | Vz,u/F is unbound Vz/F, where Vz/F is apparent volume of distribution after oral dose. It is obtained by dose/(AUCinf,u*kel), where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve, and AUCinf,u is unbound AUCinf (area under the concentration-time curve from time 0 extrapolated to infinite time). | Pre-dose and 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose for for all participants. Additional pharmacokinetics samples were collected from participants in hepatic impairment cohorts (Cohorts 2, 3 and 4) at 144, 168, and 192 hours post-dose. |
| Number of Participants With Treatment Emergent Adverse Events | An adverse event is any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. Any events occurring following start of treatment or increasing in severity are counted as treatment emergent. Relatedness to palbociclib is assessed by the investigator (Yes/No). Participants with multiple occurrences of an adverse event within a category are counted once within the category. | Adverse events were recorded on the Case Report Form from the time the participant had taken at least 1 dose of palbociclib through the participant's last visit. |
| Number of Participants With Treatment Emergent Serious Adverse Events | A serious adverse event is any untoward medical occurrence at any dose that resulted in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; or results in congenital anomaly/birth defect. Any events occurring following start of treatment or increasing in severity are counted as treatment emergent. Relatedness to palbociclib is assessed by the investigator (Yes/No). | The active reporting period for serious adverse events began from the time that the participant provided informed consent through and including 28 calendar days after the last administration of palbociclib. |
| Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Laboratory tests included tests that were performed under the categories of hematology, chemistry, urinalysis, other, and additional tests needed for Hy's law. | Baseline up to Day 6 for Cohort 1 and to Day 9 for Cohorts 2, 3, and 4, inclusive of baseline values. |
| Number of Participants With Physical Examination Test Abnormalities (Change From Prior Visit) | A full physical examination included head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. The limited or abbreviated physical examination was focused on general appearance, the respiratory and cardiovascular systems, as well as towards participant reported symptoms. | Baseline up to Day 6 for Cohort 1 and to Day 9 for Cohorts 2, 3, and 4. |
| Number of Participants With Post Baseline Vital Signs Values Meeting Categorical Summarization Criteria | The number of participants with post baseline vital signs values meeting the following criteria was reported: A. absolute value of supine systolic blood pressure less than (<) 90 mmHg; B. absolute value of diastolic blood pressure <50 mmHg; C. absolute value of supine pulse rate <40 bmp; D. absolute value of supine pulse rate larger than (>) 120 bmp; E. maximum increase from baseline in supine systolic blood pressure larger than and equal to (>=) 30 mmHg; F. maximum increase from baseline in supine diastolic blood pressure >=20 mmHg; G. maximum decrease from baseline in supine systolic blood pressure >=30 mmHg; and H. maximum decrease from baseline in supine diastolic blood pressure >=20 mmHg. | Baseline up to Day 6 for Cohort 1 and to Day 9 for Cohorts 2, 3, and 4, not including baseline values. |
| Number of Participants With Post Baseline Electrocardiogram Values Meeting Categorical Summarization Criteria (Maximum Absolute Values) | Maximum absolute values of post baseline electrocardiogram were summarized for PR interval, QRS complex, QT interval, QTcB (QT interval calculated using Bazett's correction factor), and QTcF (QT interval calculated using Fridericia's correction factor). The number of participants with maximum absolute values of post baseline electrocardiogram meeting the following criteria was reported: (1) PR interval >=300 msec; (2) QRS complex >=140 msec; (3) QT interval 450 to <480 msec; (4) QT interval 480 to <500 msec; (5) QT interval >= 500 msec; (6) QTcB 450 to <480 msec; (7) QTcB 480 to <500 msec; (8) QTcB >= 500 msec; (9) QTcF 450 to <480 msec; (10) QTcF 480 to <500 msec; and (11) QTcF >=500 msec. Seven (7) participants in each cohort were evaluated for electrocardiogram tests except that 6 participants in the moderate hepatic impairment cohort (Cohort 3) were evaluated for PR interval. | Baseline up to Day 6 for Cohort 1 and to Day 9 for Cohorts 2, 3, and 4, not including baseline values. |
| Number of Participants With Post Baseline Electrocardiogram Values Meeting Categorical Summarization Criteria (Maximum Increase From Baseline) | Maximum increases from baseline for post baseline electrocardiogram values were summarized for PR interval, QRS complex, QT interval, QTcB (QT interval calculated using Bazett's correction factor), and QTcF (QT interval calculated using Fridericia's correction factor). The number of participants with maximum increase from baseline for post baseline electrocardiogram values meeting the following criteria was reported: (1) percent change of PR interval >=25/50%; (2) percent change of QRS complex >=50%; (3) QT interval 30 to <60 msec; (4) QT interval >= 60 msec; (5) QTcB 30 to <60 msec; (6) QTcB >= 60 msec; (7) QTcF 30 to <60 msec; and (8) QTcF >= 60 msec. Seven (7) participants in each cohort were evaluated for electrocardiogram tests except that 6 participants in the moderate hepatic impairment cohort (Cohort 3) were evaluated for PR interval. | Baseline up to Day 6 for Cohort 1 and to Day 9 for Cohorts 2, 3, and 4, not including baseline values. |
| Number of Participants With Concomitant Medications | Treatments taken after the first dose of study treatment were documented as concomitant treatments. | From screening through and including Day 6 for Cohort 1, and from screening through and including Day 9 for Cohorts 2, 3, and 4. |
| Orlando |
| Florida |
| 32825 |
| United States |
| Palbociclib 75 mg (Mild Hepatic Impairment, Cohort 2) |
Participants with Child-Pugh scores of 5 to 6 points were enrolled in this cohort. Participants received single oral dose of palbociclib 75 mg approximately 10 minutes after completion of the moderate fat standard calorie breakfast, with approximately 240 mL of ambient temperature water. |
| BG002 | Palbociclib 75 mg (Moderate Hepatic Impairment, Cohort 3) | Participants with Child-Pugh scores of 7 to 9 points were enrolled in this cohort. Participants received single oral dose of palbociclib 75 mg approximately 10 minutes after completion of the moderate fat standard calorie breakfast, with approximately 240 mL of ambient temperature water. |
| BG003 | Palbociclib 75 mg (Severe Hepatic Impairment, Cohort 4) | Participants with Child-Pugh scores of 10 to 15 points were enrolled in this cohort. Participants received single oral dose of palbociclib 75 mg approximately 10 minutes after completion of the moderate fat standard calorie breakfast, with approximately 240 mL of ambient temperature water. |
| BG004 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
|
| Description |
|---|
| OG000 | Palbociclib 75 mg (Normal Hepatic Function, Cohort 1) | Participants with normal hepatic function were enrolled in this cohort. Participants received single oral dose of palbociclib 75 mg approximately 10 minutes after completion of the moderate fat standard calorie breakfast, with approximately 240 mL of ambient temperature water. |
| OG001 | Palbociclib 75 mg (Mild Hepatic Impairment, Cohort 2) | Participants with Child-Pugh scores of 5 to 6 points were enrolled in this cohort. Participants received single oral dose of palbociclib 75 mg approximately 10 minutes after completion of the moderate fat standard calorie breakfast, with approximately 240 mL of ambient temperature water. |
| OG002 | Palbociclib 75 mg (Moderate Hepatic Impairment, Cohort 3) | Participants with Child-Pugh scores of 7 to 9 points were enrolled in this cohort. Participants received single oral dose of palbociclib 75 mg approximately 10 minutes after completion of the moderate fat standard calorie breakfast, with approximately 240 mL of ambient temperature water. |
| OG003 | Palbociclib 75 mg (Severe Hepatic Impairment, Cohort 4) | Participants with Child-Pugh scores of 10 to 15 points were enrolled in this cohort. Participants received single oral dose of palbociclib 75 mg approximately 10 minutes after completion of the moderate fat standard calorie breakfast, with approximately 240 mL of ambient temperature water. |
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| Primary | Maximum Plasma Concentration (Cmax) | Cmax is maximum plasma concentration. It is observed directly from data. | The pharmacokinetics concentration population was defined as all participants enrolled and treated who had at least 1 palbociclib concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram/milliliter (ng/mL) | Pre-dose and 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose for for all participants. Additional pharmacokinetics samples were collected from participants in hepatic impairment cohorts (Cohorts 2, 3 and 4) at 144, 168, and 192 hours post-dose. |
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| Secondary | Unbound AUCinf (AUCinf,u) | AUCinf,u is unbound AUCinf, where AUCinf is area under the concentration-time curve from time 0 extrapolated to infinite time. It is obtained by fu*AUCinf, where fu is the fraction of unbound drug in plasma. | The pharmacokinetics parameter analysis population was defined as all participants enrolled and treated who had at least 1 of the palbociclib pharmacokinetics parameters of primary interest. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | Pre-dose and 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose for for all participants. Additional pharmacokinetics samples were collected from participants in hepatic impairment cohorts (Cohorts 2, 3 and 4) at 144, 168, and 192 hours post-dose. |
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| Secondary | Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) | AUClast is area under the plasma concentration time curve from time 0 to time of last quantifiable concentration. It is obtained from linear/log trapezoidal method. | The pharmacokinetics parameter analysis population was defined as all participants enrolled and treated who had at least 1 of the palbociclib pharmacokinetics parameters of primary interest. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | Pre-dose and 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose for for all participants. Additional pharmacokinetics samples were collected from participants in hepatic impairment cohorts (Cohorts 2, 3 and 4) at 144, 168, and 192 hours post-dose. |
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| Secondary | Unbound AUClast (AUClast,u) | AUClast,u is unbound AUClast, where AUClast is area under the concentration-time curve from time 0 to the time of the last quantifiable concentration. It is obtained by fu*AUClast, where fu is the fraction of unbound drug in plasma. | The pharmacokinetics parameter analysis population was defined as all participants enrolled and treated who had at least 1 of the palbociclib pharmacokinetics parameters of primary interest. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | Pre-dose and 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose for for all participants. Additional pharmacokinetics samples were collected from participants in hepatic impairment cohorts (Cohorts 2, 3 and 4) at 144, 168, and 192 hours post-dose. |
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| Secondary | Apparent Clearance After Oral Dose(CL/F) | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance is obtained by dose/AUCinf, where AUCinf is the area under the concentration-time curve from time 0 extrapolated to infinite time. | The pharmacokinetics parameter analysis population was defined as all participants enrolled and treated who had at least 1 of the palbociclib pharmacokinetics parameters of primary interest. | Posted | Geometric Mean | Geometric Coefficient of Variation | liter/hour (L/hr) | Pre-dose and 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose for for all participants. Additional pharmacokinetics samples were collected from participants in hepatic impairment cohorts (Cohorts 2, 3 and 4) at 144, 168, and 192 hours post-dose. |
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| Secondary | Unbound CL/F (CLu/F) | CLu/F is unbound CL/F, where CL/F is apparent clearance after oral dose. It is obtained by dose/AUCinf,u, where AUCinf,u is unbound AUCinf (area under the concentration-time curve from time 0 extrapolated to infinite time). | The pharmacokinetics parameter analysis population was defined as all participants enrolled and treated who had at least 1 of the palbociclib pharmacokinetics parameters of primary interest. | Posted | Geometric Mean | Geometric Coefficient of Variation | L/hr | Pre-dose and 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose for for all participants. Additional pharmacokinetics samples were collected from participants in hepatic impairment cohorts (Cohorts 2, 3 and 4) at 144, 168, and 192 hours post-dose. |
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| Secondary | Unbound Cmax (Cmax,u) | Cmax,u is unbound Cmax, where Cmax is maximum plasma concentration. It is obtained by fu*Cmax, where fu is fraction of unbound drug in plasma. | The pharmacokinetics parameter analysis population was defined as all participants enrolled and treated who had at least 1 of the palbociclib pharmacokinetics parameters of primary interest. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Pre-dose and 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose for for all participants. Additional pharmacokinetics samples were collected from participants in hepatic impairment cohorts (Cohorts 2, 3 and 4) at 144, 168, and 192 hours post-dose. |
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| Secondary | Fraction of Unbound Drug in Plasma (fu) | Fu is the fraction of unbound drug in plasma. It is obtained from measurement of protein binding. | The pharmacokinetics parameter analysis population was defined as all participants enrolled and treated who had at least 1 of the palbociclib pharmacokinetics parameters of primary interest. | Posted | Mean | Standard Deviation | ratio | Eight (8) hours post-dose. |
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| Secondary | Terminal Half-Life (t1/2) | T1/2 is terminal half-life. It is obtained by loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. | The pharmacokinetics parameter analysis population was defined as all participants enrolled and treated who had at least 1 of the palbociclib pharmacokinetics parameters of primary interest. | Posted | Mean | Standard Deviation | hour (hr) | Pre-dose and 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose for for all participants. Additional pharmacokinetics samples were collected from participants in hepatic impairment cohorts (Cohorts 2, 3 and 4) at 144, 168, and 192 hours post-dose. |
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| Secondary | Time for Cmax (Tmax) | Tmax is time for maximum plasma concentration. It is observed directly from data as time of first occurrence of maximum plasma concentration. | The pharmacokinetics concentration population was defined as all participants enrolled and treated who had at least 1 palbociclib concentration | Posted | Median | Full Range | hr | Pre-dose and 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose for for all participants. Additional pharmacokinetics samples were collected from participants in hepatic impairment cohorts (Cohorts 2, 3 and 4) at 144, 168, and 192 hours post-dose. |
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| Secondary | Apparent Volunm of Distribution After Oral Dose (Vz/F) | Vz/F is the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. It is influenced by the fraction absorbed. It is obtained by dose/(AUCinf•kel), where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve, and AUCinf is the area under the concentration-time curve from time 0 extrapolated to infinite time. | The pharmacokinetics parameter analysis population was defined as all participants enrolled and treated who had at least 1 of the palbociclib pharmacokinetics parameters of primary interest. | Posted | Geometric Mean | Geometric Coefficient of Variation | liter (L) | pre-dose and 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose for for all participants. Additional pharmacokinetics samples were collected from participants in hepatic impairment cohorts (Cohorts 2, 3 and 4) at 144, 168, and 192 hours post-dose. |
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| Secondary | Unbound Vz/F (Vz,u/F) | Vz,u/F is unbound Vz/F, where Vz/F is apparent volume of distribution after oral dose. It is obtained by dose/(AUCinf,u*kel), where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve, and AUCinf,u is unbound AUCinf (area under the concentration-time curve from time 0 extrapolated to infinite time). | The pharmacokinetics parameter analysis population was defined as all participants enrolled and treated who had at least 1 of the palbociclib pharmacokinetics parameters of primary interest. | Posted | Geometric Mean | Geometric Coefficient of Variation | L | Pre-dose and 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose for for all participants. Additional pharmacokinetics samples were collected from participants in hepatic impairment cohorts (Cohorts 2, 3 and 4) at 144, 168, and 192 hours post-dose. |
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| Secondary | Number of Participants With Treatment Emergent Adverse Events | An adverse event is any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. Any events occurring following start of treatment or increasing in severity are counted as treatment emergent. Relatedness to palbociclib is assessed by the investigator (Yes/No). Participants with multiple occurrences of an adverse event within a category are counted once within the category. | All participants who received at least 1 dose of study medication were included in the safety analyses and listings. | Posted | Number | participant | Adverse events were recorded on the Case Report Form from the time the participant had taken at least 1 dose of palbociclib through the participant's last visit. |
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| Secondary | Number of Participants With Treatment Emergent Serious Adverse Events | A serious adverse event is any untoward medical occurrence at any dose that resulted in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; or results in congenital anomaly/birth defect. Any events occurring following start of treatment or increasing in severity are counted as treatment emergent. Relatedness to palbociclib is assessed by the investigator (Yes/No). | All participants who received at least 1 dose of study medication were included in the safety analyses and listings. | Posted | Number | participant | The active reporting period for serious adverse events began from the time that the participant provided informed consent through and including 28 calendar days after the last administration of palbociclib. |
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| Secondary | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Laboratory tests included tests that were performed under the categories of hematology, chemistry, urinalysis, other, and additional tests needed for Hy's law. | All participants who received at least 1 dose of study medication were included in the safety analyses and listings. | Posted | Number | participants | Baseline up to Day 6 for Cohort 1 and to Day 9 for Cohorts 2, 3, and 4, inclusive of baseline values. |
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| Secondary | Number of Participants With Physical Examination Test Abnormalities (Change From Prior Visit) | A full physical examination included head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. The limited or abbreviated physical examination was focused on general appearance, the respiratory and cardiovascular systems, as well as towards participant reported symptoms. | All participants who received at least 1 dose of study medication were included in the safety analyses and listings. | Posted | Number | participant | Baseline up to Day 6 for Cohort 1 and to Day 9 for Cohorts 2, 3, and 4. |
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| Secondary | Number of Participants With Post Baseline Vital Signs Values Meeting Categorical Summarization Criteria | The number of participants with post baseline vital signs values meeting the following criteria was reported: A. absolute value of supine systolic blood pressure less than (<) 90 mmHg; B. absolute value of diastolic blood pressure <50 mmHg; C. absolute value of supine pulse rate <40 bmp; D. absolute value of supine pulse rate larger than (>) 120 bmp; E. maximum increase from baseline in supine systolic blood pressure larger than and equal to (>=) 30 mmHg; F. maximum increase from baseline in supine diastolic blood pressure >=20 mmHg; G. maximum decrease from baseline in supine systolic blood pressure >=30 mmHg; and H. maximum decrease from baseline in supine diastolic blood pressure >=20 mmHg. | All participants who received at least 1 dose of study medication were included in the safety analyses and listings. | Posted | Number | participant | Baseline up to Day 6 for Cohort 1 and to Day 9 for Cohorts 2, 3, and 4, not including baseline values. |
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| Secondary | Number of Participants With Post Baseline Electrocardiogram Values Meeting Categorical Summarization Criteria (Maximum Absolute Values) | Maximum absolute values of post baseline electrocardiogram were summarized for PR interval, QRS complex, QT interval, QTcB (QT interval calculated using Bazett's correction factor), and QTcF (QT interval calculated using Fridericia's correction factor). The number of participants with maximum absolute values of post baseline electrocardiogram meeting the following criteria was reported: (1) PR interval >=300 msec; (2) QRS complex >=140 msec; (3) QT interval 450 to <480 msec; (4) QT interval 480 to <500 msec; (5) QT interval >= 500 msec; (6) QTcB 450 to <480 msec; (7) QTcB 480 to <500 msec; (8) QTcB >= 500 msec; (9) QTcF 450 to <480 msec; (10) QTcF 480 to <500 msec; and (11) QTcF >=500 msec. Seven (7) participants in each cohort were evaluated for electrocardiogram tests except that 6 participants in the moderate hepatic impairment cohort (Cohort 3) were evaluated for PR interval. | All participants who received at least 1 dose of study medication were included in the safety analyses and listings. Seven (7) participants in each cohort were evaluated for electrocardiogram tests except that 6 participants in the moderate hepatic impairment cohort (Cohort 3) were evaluated for PR interval. | Posted | Number | participant | Baseline up to Day 6 for Cohort 1 and to Day 9 for Cohorts 2, 3, and 4, not including baseline values. |
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| Secondary | Number of Participants With Post Baseline Electrocardiogram Values Meeting Categorical Summarization Criteria (Maximum Increase From Baseline) | Maximum increases from baseline for post baseline electrocardiogram values were summarized for PR interval, QRS complex, QT interval, QTcB (QT interval calculated using Bazett's correction factor), and QTcF (QT interval calculated using Fridericia's correction factor). The number of participants with maximum increase from baseline for post baseline electrocardiogram values meeting the following criteria was reported: (1) percent change of PR interval >=25/50%; (2) percent change of QRS complex >=50%; (3) QT interval 30 to <60 msec; (4) QT interval >= 60 msec; (5) QTcB 30 to <60 msec; (6) QTcB >= 60 msec; (7) QTcF 30 to <60 msec; and (8) QTcF >= 60 msec. Seven (7) participants in each cohort were evaluated for electrocardiogram tests except that 6 participants in the moderate hepatic impairment cohort (Cohort 3) were evaluated for PR interval. | All participants who received at least 1 dose of study medication were included in the safety analyses and listings. Seven (7) participants in each cohort were evaluated for electrocardiogram tests except that 6 participants in the moderate hepatic impairment cohort (Cohort 3) were evaluated for PR interval. | Posted | Number | paticipant | Baseline up to Day 6 for Cohort 1 and to Day 9 for Cohorts 2, 3, and 4, not including baseline values. |
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| Secondary | Number of Participants With Concomitant Medications | Treatments taken after the first dose of study treatment were documented as concomitant treatments. | All participants who received at least 1 dose of study medication were included in the safety analyses and listings. | Posted | Number | participant | From screening through and including Day 6 for Cohort 1, and from screening through and including Day 9 for Cohorts 2, 3, and 4. |
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| 0 |
| 7 |
| 2 |
| 7 |
| EG001 | Palbociclib 75 mg (Mild Hepatic Impairment, Cohort 2) | Participants with Child-Pugh scores of 5 to 6 points were enrolled in this cohort. Participants received single oral dose of palbociclib 75 mg approximately 10 minutes after completion of the moderate fat standard calorie breakfast, with approximately 240 mL of ambient temperature water. | 0 | 7 | 0 | 7 |
| EG002 | Palbociclib 75 mg (Moderate Hepatic Impairment, Cohort 3) | Participants with Child-Pugh scores of 7 to 9 points were enrolled in this cohort. Participants received single oral dose of palbociclib 75 mg approximately 10 minutes after completion of the moderate fat standard calorie breakfast, with approximately 240 mL of ambient temperature water. | 1 | 7 | 2 | 7 |
| EG003 | Palbociclib 75 mg (Severe Hepatic Impairment, Cohort 4) | Participants with Child-Pugh scores of 10 to 15 points were enrolled in this cohort. Participants received single oral dose of palbociclib 75 mg approximately 10 minutes after completion of the moderate fat standard calorie breakfast, with approximately 240 mL of ambient temperature water. | 0 | 7 | 1 | 7 |
| Vomiting | Gastrointestinal disorders | MedDRA 19.0 | Non-systematic Assessment |
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| Infusion site bruising | General disorders | MedDRA 19.0 | Non-systematic Assessment |
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| Infusion site reaction | General disorders | MedDRA 19.0 | Non-systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 19.0 | Non-systematic Assessment |
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| Radial nerve compression | Nervous system disorders | MedDRA 19.0 | Non-systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | MedDRA 19.0 | Non-systematic Assessment |
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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.
| ratio of adjusted geometric mean |
| 117.75 |
| 2-Sided |
| 90 |
| 86.69 |
| 159.95 |
| Superiority or Other |
| ratio of adjusted geometric mean | 129.89 | 2-Sided | 90 | 95.63 | 176.43 | Superiority or Other |
| ratio of adjusted geometric mean |
| 134.28 |
| 2-Sided |
| 90 |
| 105.73 |
| 170.53 |
| Superiority or Other |
| ratio of adjusted geometric mean | 176.88 | 2-Sided | 90 | 139.28 | 224.63 | Superiority or Other |
| ratio of adjusted geometric mean |
| 115.57 |
| 2-Sided |
| 90 |
| 89.58 |
| 149.11 |
| Superiority or Other |
| ratio of adjusted geometric mean | 134.66 | 2-Sided | 90 | 104.38 | 173.73 | Superiority or Other |
| ratio of adjusted geometric mean |
| 134.90 |
| 2-Sided |
| 90 |
| 104.82 |
| 173.60 |
| Superiority or Other |
| ratio of adjusted geometric mean | 178.39 | 2-Sided | 90 | 138.62 | 229.57 | Superiority or Other |
| ratio of adjusted geometric mean |
| 137.50 |
| 2-Sided |
| 90 |
| 99.96 |
| 189.12 |
| Superiority or Other |
| ratio of adjusted geometric mean | 172.27 | 2-Sided | 90 | 125.25 | 236.96 | Superiority or Other |
| criterion B |
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| criterion C |
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| criterion D |
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| criterion E |
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| criterion F |
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| criterion G |
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| criterion H |
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| QRS complex >=140 msec |
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| QT interval 450 to <480 msec |
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| QT interval 480 to <500 msec |
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| QT interval >= 500 msec |
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| QTcB 450 to <480 msec |
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| QTcB 480 to <500 msec |
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| QTcB >= 500 msec |
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| QTcF 450 to <480 msec |
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| QTcF 480 to <500 msec |
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| QTcF >=500 msec |
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| percent change of QRS complex >=50% |
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| QT interval 30 to <60 msec |
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| QT interval >= 60 msec |
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| QTcB 30 to <60 msec |
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| QTcB >= 60 msec |
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| QTcF 30 to <60 msec |
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| QTcF >= 60 msec |
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