The purpose of this study is to evaluate the effect of moderate or severe hepatic impairment on the single-dose pharmacokinetics of alisertib in adult participants with cancer.
The drug being tested in this study is called alisertib. Alisertib was tested to assess how it was processed by the body in participants with advanced solid tumors or relapsed/refractory lymphoma with varying degrees of liver function. This study also assessed laboratory results and safety. The study enrolled 36 participants. Participants were assigned to 1 of the 3 treatment groups based on the status of their liver function: Normal hepatic function (Total bilirubin ≤ upper limit of the normal range \[ULN\] and alanine aminotransferase \[ALT\] level ≤ ULN), moderate hepatic impairment (Total bilirubin \> 1.5-3 x ULN and ALT level = Any), or severe hepatic impairment (Total bilirubin \> 3 x ULN and ALT level = Any). All participants were administered one 50 mg dose of alisertib on Day 1, Cycle 1. Alisertib was administered again on Days 8 through 14 of Cycle 1, followed by a 14-day rest period. Doses administered on Days 8-14 were 50, 30, or 20 mg of alisertib, depending on hepatic function. Alisertib was then continued at the same dose as in Cycle 1, Days 8-14 in 21-day cycles (7 days of alisertib followed by a 14-day rest period) for up to 1 year (approximately 16 cycles). This multicenter trial was conducted in USA only. The overall time to participate in this study was up to 312 Days. Participants made multiple visits to the clinic including an end-of-study visit 30 days after the last dose of study drug for a follow-up assessment.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
36
Alisertib will be supplied as enteric coated tablets.
Unnamed facility
Miami, Florida, United States
Unnamed facility
Chicago, Illinois, United States
Unnamed facility
Ann Arbor, Michigan, United States
Unnamed facility
St Louis, Missouri, United States
Unbound Cmax: Maximum Observed Plasma Concentration for Alisertib
Time frame: Cycle 1 Day 1 Pre-dose and, and at multiple timepoints (up to 168 hours) post-dose
Unbound AUClast: Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Alisertib
Time frame: Cycle 1 Day 1 Pre-dose and, and at multiple timepoints (up to 168 hours) post-dose
Unbound AUC0-∞: Area Under the Concentration-Time Curve From Time 0 to Infinity for Alisertib
Time frame: Cycle 1 Day 1 Pre-dose and, and at multiple timepoints (up to 168 hours) post-dose
Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event
An adverse event is any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event is defined as an adverse event with an onset that occurs after receiving study drug.
Time frame: Baseline to 30 days after last dose (Up to 312 Days)
Percentage of Participants Who Experienced at Least 1 Serious Adverse Event
A serious adverse event is any untoward medical occurrence or effect that at any dose of a drug results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is medically important due to other reasons than the above mentioned criteria.
Time frame: Baseline to 30 days after last dose (Up to 312 Days)
Percentage of Participants With Clinically Significant Laboratory Values
Laboratory assessments include serum chemistry and hematology. An abnormal laboratory value was assessed as an AE if that value led to discontinuation or delay in treatment, dose modification, therapeutic intervention, or was considered by the investigator to be a clinically significant change from baseline.
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Unnamed facility
Dallas, Texas, United States
Unnamed facility
Houston, Texas, United States
Unnamed facility
San Antonio, Texas, United States
Time frame: Baseline to the end of the study (Up to 312 Days)
Percentage of Participants With Clinically Significant Vital Signs
Vital signs include measurements of sitting diastolic and systolic blood pressure, heart rate, and temperature. Any vital signs determined by the investigator to be clinically significant were recorded as AEs.
Time frame: Baseline to the end of the study (Up to 312 days)
Cmax: Maximum Observed Plasma Concentration for Alisertib Metabolites M1 and M2
Time frame: Cycle 1 Day 1 Pre-dose and, and at multiple timepoints (up to 168 hours) post-dose
Tmax: Time of First Occurrence of Cmax for Alisertib Metabolites M1 and M2
Time frame: Cycle 1 Day 1 Pre-dose and, and at multiple timepoints (up to 168 hours) post-dose
AUClast: Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Alisertib Metabolites M1 and M2
The area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration (AUC0-last) of the alisertib metabolites M1 and M2 was determined from the concentration-time curve of each participant using non-compartmental methods.
Time frame: Cycle 1 Day 1 Pre-dose and, and at multiple timepoints (up to 168 hours) post-dose
Dose-normalized Trough Concentration of Alisertib on Cycle 1 Day 14
A single blood sample will be collected pre-dose on Cycle 1 Day 14. The concentration of alisertib was determined in the plasma sample and dose-normalized.
Time frame: Pre-dose on Day 14 of Cycle 1