Advanced Solid Tumors, Relapsed/Refractory Lymphoma
Conditions
Brief summary
This study will assess the effect of multi-dose administration of itraconazole on the single-dose pharmacokinetics (PK) of alisertib.
Detailed description
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.
Interventions
DRUGAlisertib
Alisertib tablets
DRUGItraconazole
Itraconazole oral solution
Sponsors
Millennium Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male and female participants 18 years of age or older. 2. Participants with histologic or cytologic diagnosis of advanced or metastatic solid tumors or lymphomas for which no curative or life-prolonging therapies exist. 3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Exclusion criteria
1. Systemic treatment with moderate or strong CYP3A inhibitors or inducers must be discontinued at least 14 days before the first dose of alisertib, and the use of these agents is not permitted during the study (except for the protocol-specified administration of itraconazole). 2. Known gastrointestinal (GI) abnormality (including recurrent nausea or vomiting) or GI procedure that could interfere with or modify the oral absorption or tolerance of alisertib. 3. Known hypersensitivity or intolerance to itraconazole or similar class agents.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cmax: Maximum Observed Concentration of Alisertib in Presence and Absence of Itraconazole in Part A | 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 | 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 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax: Maximum Observed Plasma Concentration for Alisertib Metabolites M1 and M2 in Presence and Absence of Itraconazole in Part A | 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 | 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 | 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 | 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 Abnormal Laboratory Values Reported as AEs | First dose of study drug to 30 days after the last dose of study drug (up to 12 months) | 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. |
| Number of Participants With Clinically Significant Change in Weight Reported as AEs | First dose of study drug to 30 days after the last dose of study drug (up to 12 months) | Change relative to baseline in participant's weight measured throughout study. |
| Number of Participants With Clinically Significant Change in Vital Sign Reported as AEs | First dose of study drug to 30 days after the last dose of study drug (up to 12 months) | Vital signs will include body temperature (oral), sitting blood pressure (after the participant has rested for at least 5 minutes), and pulse (bpm). |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | First dose of study drug to 30 days after the last dose of study drug (up to 12 months) | 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. |
| Tmax: Time to Reach Maximum Plasma Concentration of Alisertib in Presence and Absence of Itraconazole in Part A | 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 | — |
| Terminal Phase Elimination Half-Life of Alisertib in Presence and Absence of Itraconazole in Part A | 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 | — |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 4 investigative sites in the United States from 22 October 2014 to 21 October 2016. Data cutoff for the primary analysis was 27 March 2015.
Pre-assignment details
Participants with a diagnosis of advanced solid tumors or lymphomas were enrolled to receive alisertib 30 mg tablets, orally along with itraconazole 200 mg, oral solution in part A followed by alisertib 50 mg, tablets in part B.
Participants by arm
| Arm | Count |
|---|---|
| Part A: Alisertib 30 mg+Itraconazole; Part B: Alisertib 50 mg All participants were to complete Part A prior to Part B. Part A: Alisertib 30 mg, tablets, orally, on Days 1 and 10 plus itraconazole, 200 mg, oral solution, once daily on Days 5 to 13. Part A and B were separated by a washout period of at least 10 days (and up to 4 weeks). Part B: Alisertib 50 mg, tablets, orally, twice daily, for 7 days in 21-day cycles until disease progression or unacceptable toxicity (up to 16 cycles). | 24 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Didn't Completed Dosing; PK Assessment | 5 |
Baseline characteristics
| Characteristic | Part A: Alisertib 30 mg+Itraconazole; Part B: Alisertib 50 mg |
|---|---|
| Age, Continuous | 61.0 years STANDARD_DEVIATION 9.52 |
| Body Surface Area | 1.983 m^2 STANDARD_DEVIATION 0.3024 |
| Height | 168.3 cm STANDARD_DEVIATION 8.99 |
| Race/Ethnicity, Customized Asian | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 20 Participants |
| Race/Ethnicity, Customized Not Reported | 3 Participants |
| Race/Ethnicity, Customized Other | 1 Participants |
| Race/Ethnicity, Customized White | 20 Participants |
| Region of Enrollment United States | 24 Participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 11 Participants |
| Weight | 85.55 kg STANDARD_DEVIATION 25.641 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 24 |
| other Total, other adverse events | 24 / 24 |
| serious Total, serious adverse events | 12 / 24 |
Outcome results
Primary
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
Population: PK-Evaluable Population included participants who completed the protocol-specified dosing at Part A and had sufficient PK assessment to reliably estimate PK parameters. Here number of participants analyzed are the participants who were evaluable for this outcome measure at specified time points.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alisertib Without Itraconazole | AUC∞: Area Under the Plasma Concentration Curve From Time 0 to Infinity of Alisertib in Presence and Absence of Itraconazole in Part A | 16804.6 hr*nmol/L | Standard Deviation 9232.87 |
| Alisertib With Itraconazole | AUC∞: Area Under the Plasma Concentration Curve From Time 0 to Infinity of Alisertib in Presence and Absence of Itraconazole in Part A | 23488.7 hr*nmol/L | Standard Deviation 13262.31 |
90% CI: [0.99, 1.95]
Primary
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
Population: PK-Evaluable Population included participants who completed the protocol-specified dosing at Part A and had sufficient PK assessment to reliably estimate PK parameters.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alisertib Without Itraconazole | 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 | 15541.6 hr*nmol/L | Standard Deviation 9119.52 |
| Alisertib With Itraconazole | 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 | 20219.5 hr*nmol/L | Standard Deviation 9930.93 |
90% CI: [1.02, 1.79]
Primary
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
Population: Pharmacokinetic (PK) -Evaluable Population included participants who completed the protocol-specified dosing at Part A and had sufficient PK assessment to reliably estimate PK parameters.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alisertib Without Itraconazole | Cmax: Maximum Observed Concentration of Alisertib in Presence and Absence of Itraconazole in Part A | 1060.3 nmol/L | Standard Deviation 403.9 |
| Alisertib With Itraconazole | Cmax: Maximum Observed Concentration of Alisertib in Presence and Absence of Itraconazole in Part A | 1002.8 nmol/L | Standard Deviation 263.81 |
90% CI: [0.82, 1.19]
Secondary
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
Population: PK-Evaluable Population included participants who completed the protocol-specified dosing at Part A and had sufficient PK assessment to reliably estimate PK parameters. Here, number of participants analyzed are the total number of participants who were evaluable to this outcome measure at specified endpoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alisertib Without Itraconazole | 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 | Metabolite 1 (M1) | 10550.8 hr*nmol/L | Standard Deviation 17276.38 |
| Alisertib Without Itraconazole | 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 | Metabolite 2 (M2) | 5880.6 hr*nmol/L | Standard Deviation 3404.27 |
| Alisertib With Itraconazole | 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 | Metabolite 1 (M1) | 15776.1 hr*nmol/L | Standard Deviation 29461.34 |
| Alisertib With Itraconazole | 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 | Metabolite 2 (M2) | 5081.6 hr*nmol/L | Standard Deviation 3334.41 |
Secondary
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
Population: PK-Evaluable Population included participants who completed the protocol-specified dosing at Part A and had sufficient PK assessment to reliably estimate PK parameters. Here, number of participants analyzed are the total number of participants who were evaluable to this outcome measure at specified endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alisertib Without Itraconazole | CL/F: Oral Clearance of Alisertib in Presence and Absence of Itraconazole in Part A | 4.416 L/hr | Standard Deviation 2.4007 |
| Alisertib With Itraconazole | CL/F: Oral Clearance of Alisertib in Presence and Absence of Itraconazole in Part A | 3.177 L/hr | Standard Deviation 1.5765 |
Secondary
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
Population: PK-Evaluable Population included participants who completed the protocol-specified dosing at Part A and had sufficient PK assessment to reliably estimate PK parameters. Here, number of participants analyzed are the total number of participants who were evaluable to this outcome measure at specified endpoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alisertib Without Itraconazole | Cmax: Maximum Observed Plasma Concentration for Alisertib Metabolites M1 and M2 in Presence and Absence of Itraconazole in Part A | Metabolite 1 (M1) | 409.4 nmol/L | Standard Deviation 479.92 |
| Alisertib Without Itraconazole | Cmax: Maximum Observed Plasma Concentration for Alisertib Metabolites M1 and M2 in Presence and Absence of Itraconazole in Part A | Metabolite 2 (M2) | 114.0 nmol/L | Standard Deviation 52.71 |
| Alisertib With Itraconazole | Cmax: Maximum Observed Plasma Concentration for Alisertib Metabolites M1 and M2 in Presence and Absence of Itraconazole in Part A | Metabolite 1 (M1) | 450.0 nmol/L | Standard Deviation 664.65 |
| Alisertib With Itraconazole | Cmax: Maximum Observed Plasma Concentration for Alisertib Metabolites M1 and M2 in Presence and Absence of Itraconazole in Part A | Metabolite 2 (M2) | 103.5 nmol/L | Standard Deviation 99.28 |
Secondary
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)
Population: Safety Population is defined as all participants who received at least 1 dose of any study drug and were used for all safety analyses. Although there were 2 parts to the study, however, data for adverse events was not collected separately for each part.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Alisertib Without Itraconazole | Number of Participants With Abnormal Laboratory Values Reported as AEs | Hypokalemia | 3 Participants |
| Alisertib Without Itraconazole | Number of Participants With Abnormal Laboratory Values Reported as AEs | Elevated blood creatinine | 3 Participants |
| Alisertib Without Itraconazole | Number of Participants With Abnormal Laboratory Values Reported as AEs | Hypercalcemia | 1 Participants |
| Alisertib Without Itraconazole | Number of Participants With Abnormal Laboratory Values Reported as AEs | Increased international normalized ratio | 2 Participants |
| Alisertib Without Itraconazole | Number of Participants With Abnormal Laboratory Values Reported as AEs | Hypomagnesemia | 1 Participants |
| Alisertib Without Itraconazole | Number of Participants With Abnormal Laboratory Values Reported as AEs | Hypoalbuminemia | 1 Participants |
| Alisertib Without Itraconazole | Number of Participants With Abnormal Laboratory Values Reported as AEs | Decreased blood potassium | 1 Participants |
| Alisertib Without Itraconazole | Number of Participants With Abnormal Laboratory Values Reported as AEs | Decreased blood sodium | 1 Participants |
| Alisertib Without Itraconazole | Number of Participants With Abnormal Laboratory Values Reported as AEs | Elevated blood alkaline phosphatase | 1 Participants |
| Alisertib Without Itraconazole | Number of Participants With Abnormal Laboratory Values Reported as AEs | Anemia | 5 Participants |
| Alisertib Without Itraconazole | Number of Participants With Abnormal Laboratory Values Reported as AEs | Neutropenia | 4 Participants |
| Alisertib Without Itraconazole | Number of Participants With Abnormal Laboratory Values Reported as AEs | Leukopenia | 2 Participants |
| Alisertib Without Itraconazole | Number of Participants With Abnormal Laboratory Values Reported as AEs | Thrombocytopenia | 2 Participants |
| Alisertib Without Itraconazole | Number of Participants With Abnormal Laboratory Values Reported as AEs | Decreased lymphocyte count | 2 Participants |
| Alisertib Without Itraconazole | Number of Participants With Abnormal Laboratory Values Reported as AEs | Decreased white blood cell count | 1 Participants |
| Alisertib Without Itraconazole | Number of Participants With Abnormal Laboratory Values Reported as AEs | Decreased platelet count | 1 Participants |
Secondary
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)
Population: Safety Population is defined as all participants who received at least 1 dose of any study drug and were used for all safety analyses. Although there were 2 parts to the study, however, data for adverse events was not collected separately for each part.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Alisertib Without Itraconazole | Number of Participants With Clinically Significant Change in Vital Sign Reported as AEs | Pyrexia | 3 Participants |
| Alisertib Without Itraconazole | Number of Participants With Clinically Significant Change in Vital Sign Reported as AEs | Palpitations | 2 Participants |
| Alisertib Without Itraconazole | Number of Participants With Clinically Significant Change in Vital Sign Reported as AEs | Tachycardia | 1 Participants |
Secondary
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)
Population: Safety Population is defined as all participants who received at least 1 dose of any study drug and were used for all safety analyses. Although there were 2 parts to the study, however, data for adverse events was not collected separately for each part.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Alisertib Without Itraconazole | Number of Participants With Clinically Significant Change in Weight Reported as AEs | 2 Participants |
Secondary
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)
Population: Safety Population is defined as all participants who received at least 1 dose of any study drug and were used for all safety analyses. Although there were 2 parts to the study, however, data for adverse events was not collected separately for each part.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Alisertib Without Itraconazole | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | AEs | 24 Participants |
| Alisertib Without Itraconazole | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 12 Participants |
Secondary
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
Population: PK-Evaluable Population included participants who completed the protocol-specified dosing at Part A and had sufficient PK assessment to reliably estimate PK parameters. Here, number of participants analyzed are the total number of participants who were evaluable to this outcome measure at specified endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alisertib Without Itraconazole | Terminal Phase Elimination Half-Life of Alisertib in Presence and Absence of Itraconazole in Part A | 22.55 hr | Standard Deviation 10.316 |
| Alisertib With Itraconazole | Terminal Phase Elimination Half-Life of Alisertib in Presence and Absence of Itraconazole in Part A | 25.37 hr | Standard Deviation 9.215 |
Secondary
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
Population: PK-Evaluable Population included participants who completed the protocol-specified dosing at Part A and had sufficient PK assessment to reliably estimate PK parameters.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Alisertib Without Itraconazole | Tmax: Time to Reach Maximum Plasma Concentration of Alisertib in Presence and Absence of Itraconazole in Part A | 2.920 hr | Full Range 2.371 |
| Alisertib With Itraconazole | Tmax: Time to Reach Maximum Plasma Concentration of Alisertib in Presence and Absence of Itraconazole in Part A | 2.920 hr | Full Range 2.0244 |
Secondary
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
Population: PK-Evaluable Population included participants who completed the protocol-specified dosing at Part A and had sufficient PK assessment to reliably estimate PK parameters. Here, number of participants analyzed are the total number of participants who were evaluable to this outcome measure at specified endpoint.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Alisertib Without Itraconazole | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Alisertib Metabolites M1 and M2 in Presence and Absence of Itraconazole in Part A | Metabolite 1 (M1) | 3.090 hr |
| Alisertib Without Itraconazole | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Alisertib Metabolites M1 and M2 in Presence and Absence of Itraconazole in Part A | Metabolite 2 (M2) | 9.360 hr |
| Alisertib With Itraconazole | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Alisertib Metabolites M1 and M2 in Presence and Absence of Itraconazole in Part A | Metabolite 1 (M1) | 3.800 hr |
| Alisertib With Itraconazole | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Alisertib Metabolites M1 and M2 in Presence and Absence of Itraconazole in Part A | Metabolite 2 (M2) | 23.600 hr |