This study will assess the effect of multi-dose administration of itraconazole on the single-dose pharmacokinetics (PK) of alisertib.
The drug being tested in this study is called alisertib. Alisertib is being tested in adult participants with advanced solid tumors or relapsed refactory lymphoma. The study will look at the effect of the pharmacokinetics (how the drug moves through the body) of alisertib in the presence and absence of itraconazole. This is an open label study. Participants will receive: * Alisertib tablets 30 mg in Part A and 50 mg in Part B * Itraconazole oral solution 200 mg in Part A Participation in Part A is approximately 25 days. Part B participation is repeating 21-day cycles. The maximum duration of treatment with alisertib will be 12 months (approximately 16 cycles) unless it is determined by the investigator, with agreement by the sponsor, that a participant would derive clinical benefit from continued treatment beyond 12 months. This multi-center study will take place in the United States.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
24
Alisertib tablets
Itraconazole oral solution
Unnamed facility
St Louis, Missouri, United States
Unnamed facility
Oklahoma City, Oklahoma, United States
Unnamed facility
Germantown, Tennessee, United States
Unnamed facility
Dallas, Texas, United States
Cmax: Maximum Observed Concentration of Alisertib in Presence and Absence of Itraconazole in Part A
Time frame: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm
AUC(Last): Area Under the Plasma Concentration Curve From Time 0 to the Time of the Last Quantifiable Concentration of Alisertib in Presence and Absence of Itraconazole in Part A
Time frame: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm
AUC∞: Area Under the Plasma Concentration Curve From Time 0 to Infinity of Alisertib in Presence and Absence of Itraconazole in Part A
Time frame: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm
CL/F: Oral Clearance of Alisertib in Presence and Absence of Itraconazole in Part A
Time frame: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm
Tmax: Time to Reach Maximum Plasma Concentration of Alisertib in Presence and Absence of Itraconazole in Part A
Time frame: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm
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Terminal Phase Elimination Half-Life of Alisertib in Presence and Absence of Itraconazole in Part A
Time frame: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm
Cmax: Maximum Observed Plasma Concentration for Alisertib Metabolites M1 and M2 in Presence and Absence of Itraconazole in Part A
Time frame: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Alisertib Metabolites M1 and M2 in Presence and Absence of Itraconazole in Part A
Time frame: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm
AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Alisertib Metabolites M1 and M2 in Presence and Absence of Itraconazole in Part A
Time frame: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
An AE is considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events. A SAE is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
Time frame: First dose of study drug to 30 days after the last dose of study drug (up to 12 months)
Number of Participants With Abnormal Laboratory Values Reported as AEs
Standard safety laboratory tests included Chemistry and Hematology. Abnormal laboratory values that led to discontinuation or delay in treatment, dose modification, therapeutic intervention, or were considered by the investigator to be a clinically significant change from baseline were reported as AEs.
Time frame: First dose of study drug to 30 days after the last dose of study drug (up to 12 months)
Number of Participants With Clinically Significant Change in Weight Reported as AEs
Change relative to baseline in participant's weight measured throughout study.
Time frame: First dose of study drug to 30 days after the last dose of study drug (up to 12 months)
Number of Participants With Clinically Significant Change in Vital Sign Reported as AEs
Vital signs will include body temperature (oral), sitting blood pressure (after the participant has rested for at least 5 minutes), and pulse (bpm).
Time frame: First dose of study drug to 30 days after the last dose of study drug (up to 12 months)