Clinical trial NCT02334800: A Study To Describe The Effect Of Impaired Hepatic Function Of The Pharmacokinetics Of Palbociclib
Official title: A Phase 1, Open-label, Single Dose, Parallel-cohort Study To Evaluate The Pharmacokinetics Of Palbociclib (Pd-0332991) In Subjects With Impaired Hepatic Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy, Hepatic Insufficiency
Keywords: Palbociclib, PD-0332991, Hepatic Impairment
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2015-01-08
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Body Mass Index (BMI) of 18 to 40 kg/m2; and a total body weight \>50 kg (110 lbs)
* Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study
* Subjects who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures

Exclusion Criteria:

* Any condition possibly affecting drug absorption (eg, gastrectomy)
* A positive urine drug screen
* Pregnant female subjects; breastfeeding female subjects; female subjects of childbearing potential; male subjects with partners currently pregnant; male subjects of childbearing potential who are unwilling or unable to use a highly effective method of contraception for the duration of the study and for 90 days after the last dose of investigational product
* History of sensitivity to heparin or heparin-induced thrombocytopenia
* Blood donation of approximately 1 pint (500 mL) or more within 56 days prior to dosing
* Unwilling or unable to comply with the Lifestyle Guidelines described in this protocol
* Use of tobacco or nicotine products in excess of 5 cigarettes per day (or equivalent)
* History of sensitivity to palbociclib

Primary outcomes:
measure: Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinite Time (AUCinf)
timeFrame: 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.
measure: Maximum Plasma Concentration (Cmax)
timeFrame: 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.
Secondary outcomes:
measure: Unbound AUCinf (AUCinf,u)
timeFrame: 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: Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast)
timeFrame: 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: Unbound AUClast (AUClast,u)
timeFrame: 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: Apparent Clearance After Oral Dose(CL/F)
timeFrame: 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: Unbound CL/F (CLu/F)
timeFrame: 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: Unbound Cmax (Cmax,u)
timeFrame: 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: Fraction of Unbound Drug in Plasma (fu)
timeFrame: Eight (8) hours post-dose.
measure: Terminal Half-Life (t1/2)
timeFrame: 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: Time for Cmax (Tmax)
timeFrame: 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: Apparent Volunm of Distribution After Oral Dose (Vz/F)
timeFrame: 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: Unbound Vz/F (Vz,u/F)
timeFrame: 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: Number of Participants With Treatment Emergent Adverse Events
timeFrame: 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.
measure: Number of Participants With Treatment Emergent Serious Adverse Events
timeFrame: 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.
measure: Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)
timeFrame: Baseline up to Day 6 for Cohort 1 and to Day 9 for Cohorts 2, 3, and 4, inclusive of baseline values.
measure: Number of Participants With Physical Examination Test Abnormalities (Change From Prior Visit)
timeFrame: Baseline up to Day 6 for Cohort 1 and to Day 9 for Cohorts 2, 3, and 4.
measure: Number of Participants With Post Baseline Vital Signs Values Meeting Categorical Summarization Criteria
timeFrame: Baseline up to Day 6 for Cohort 1 and to Day 9 for Cohorts 2, 3, and 4, not including baseline values.
measure: Number of Participants With Post Baseline Electrocardiogram Values Meeting Categorical Summarization Criteria (Maximum Absolute Values)
timeFrame: Baseline up to Day 6 for Cohort 1 and to Day 9 for Cohorts 2, 3, and 4, not including baseline values.
measure: Number of Participants With Post Baseline Electrocardiogram Values Meeting Categorical Summarization Criteria (Maximum Increase From Baseline)
timeFrame: Baseline up to Day 6 for Cohort 1 and to Day 9 for Cohorts 2, 3, and 4, not including baseline values.
measure: Number of Participants With Concomitant Medications
timeFrame: From screening through and including Day 6 for Cohort 1, and from screening through and including Day 9 for Cohorts 2, 3, and 4.
Other outcomes:
Locations:
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
city: Orlando
country: United States
facility: Weston Diagnostics (Ultrasound Facility)
state: Florida
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: