Lymphoma, Solid Tumors
Conditions
Brief summary
The purpose of this study is to assess the drug-drug interaction (DDI) of either esomeprazole or rifampin on the single-dose PK of alisertib, and to complete an intensive QT study of single and multiple-dose alisertib.
Detailed description
The drug tested in this study is called alisertib. Alisertib is being tested to assess the effect of a proton pump inhibitor and strong metabolic inducer on the PK of a single 50 mg dose of alisertib administered as enteric-coated tablets (ECTs). The study enrolled 55 patients. Participants received either: * Esomeprazole 40 mg and Alisertib 50 mg * Rifampin 600 mg and Alisertib 50 mg All participants were asked to take one tablet of alisertib either once or twice daily in all cycles. In Cycle 2, participants were asked to take alisertib plus either esomeprazole or rifampin. This trial was conducted the United States. The overall time to participate in this study was 10 months. Participants made multiple visits to the clinic plus a final visit, 30 days after receiving their last dose of study drug for a follow-up assessment.
Interventions
DRUGAlisertib
Alisertib tablets
DRUGEsomeprazole
Esomeprazole capsules
DRUGRifampin
Rifampin capsules
Sponsors
Millennium Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female participants 18 years or older * Histologically or cytologically confirmed metastatic and/or advanced solid tumors or lymphomas * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 * Expected survival longer than 3 months from enrollment in the study * Female participants who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or agree to abstain from heterosexual intercourse * Male participants who agree to practice effective barrier contraception or agree to abstain from heterosexual intercourse
Exclusion criteria
* Treatment with any anticancer therapy or any investigational agents within 4 weeks before the first dose of alisertib \- Known hypersensitivity or intolerance to rifampin (for participants considered for the rifampin drug-drug interaction \[DDI\] group) or to esomeprazole (for participants considered for the esomeprazole DDI group) * Recurrent nausea and/or vomiting within 14 days before the first dose of alisertib, and known gastrointestinal (GI) abnormality or GI procedure that could interfere with or modify the oral absorption or tolerance of alisertib * Participants requiring treatment with clinically significant enzyme inducers within 14 days before the first dose of alisertib and/or requiring the use of these medications during the study * A medical condition requiring use of pancreatic enzymes; or daily, chronic, or regular use of proton pump inhibitors (PPI); or histamine (H2) receptor antagonists * Participants requiring systemic anticoagulation (excluding low-dose aspirin, or low-dose anticoagulation to maintain patency of venous access devices). * Any cardiovascular condition * Female participants who are lactating or have a positive serum pregnancy test * Major surgery within the 14 days preceding the first dose of alisertib \- Life-threatening or uncontrolled medical illness unrelated to cancer * Newly diagnosed or uncontrolled cancer-related central nervous system (CNS) disease * Autologous stem cell transplant within 3 months * Prior allogeneic bone marrow or other organ transplantation \- Other severe acute or chronic medical or psychiatric condition * Known or suspected human immunodeficiency virus (HIV) positive or hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection Please note there are additional inclusion and
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From the Time-matched Baseline in the Individually Corrected QTc Interval (QTcI) | Baseline, Days 1 and 10 multiple timepoints postdose (up to 24 hours) in Cycle 1 |
| Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Alisertib in Presence and Absence of Rifampin | Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 1 for alisertib without rifampin arm; Day 8 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 2 for alisertib with rifampin arm |
| Phase Elimination Half-life (T1/2) for Alisertib in Presence and Absence of Rifampin | Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 1 for alisertib without rifampin arm; Day 8 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 2 for alisertib with rifampin arm |
| Cmax: Maximum Observed Concentration for Alisertib in Presence and Absence of Esomeprazole | Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 1 for alisertib without esomeprazole arm; Day 8 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 2 for alisertib with esomeprazole arm |
| AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Alisertib in Presence and Absence of Esomeprazole | Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 1 for alisertib without esomeprazole arm; Day 8 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 2 for alisertib with esomeprazole arm |
| AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Alisertib in Presence and Absence of Esomeprazole | Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 1 for alisertib without esomeprazole arm; Day 8 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 2 for alisertib with esomeprazole arm |
| Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Alisertib in Presence and Absence of Esomeprazole | Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 1 for alisertib without esomeprazole arm; Day 8 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 2 for alisertib with esomeprazole arm |
| Terminal Phase Elimination Half-life (T1/2) for Alisertib in Presence and Absence of Esomeprazole | Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 1 for alisertib without esomeprazole arm; Day 8 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 2 for alisertib with esomeprazole arm |
| Cmax: Maximum Observed Concentration for Alisertib in Presence and Absence of Rifampin | Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 1 for alisertib without rifampin arm; Day 8 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 2 for alisertib with rifampin arm |
| AUC(Last): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Alisertib in Presence and Absence of Rifampin | Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 1 for alisertib without rifampin arm; Day 8 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 2 for alisertib with rifampin arm |
| AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Alisertib in Presence or Absence of Rifampin | Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 1 for alisertib without rifampin arm; Day 8 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 2 for alisertib with rifampin arm |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) | An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A Serious Adverse Event (SAE) A serious 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. |
| Change From the Time-matched Baseline in the Fridericia Correction of QTc (QTcF) | Baseline, Days 1 and 10 multiple timepoints postdose (up to 24 hours) in Cycle 1 | — |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 6 investigative sites in the United States from 25 June 2013 to 06 September 2016. Data cut-off for primary analysis was 04 August 2014.
Pre-assignment details
Participants with a diagnosis of advanced solid tumors or lymphomas were enrolled to receive alisertib 50 mg tablets, orally along with esomeprazole 40 mg, delayed release capsule once daily and alisertib 50 mg along with rifampin 600 mg capsule.
Participants by arm
| Arm | Count |
|---|---|
| Esomeprazole 40 mg + Alisertib 50 mg Alisertib 50 mg, tablets, orally, once on Day 1, followed by twice daily on Days 4 to 10, followed by a 14-day rest period in Cycle 1. Esomeprazole, 40 mg, delayed-release capsules, orally, once daily on Days 1 to 10 plus alisertib, 50 mg, tablets, orally, once on Day 8, followed by twice daily on Days 11 to 17, followed by a 14-day rest period in Cycle 2. Alisertib 50 mg, tablets, orally, twice daily on Days 1 to 7 beginning with Cycle 3 (21-day cycles) to the end of study (Up to 15 Cycles). | 26 |
| Rifampin 600 mg + Alisertib 50 mg Alisertib 50 mg, tablets, orally, once on Day 1, followed by twice daily on Days 4 to 10, followed by a 14-day rest period in Cycle 1. Rifampin 600 mg, capsules, orally, once daily on Days 1 to 10 in Cycle 2 plus alisertib, 50 mg, tablets, orally, once on Day 8, followed by twice daily on Days 11 to 17, followed by a 14-day rest period in Cycle 2. Alisertib 50 mg, tablets, orally, twice daily on Days 1 to 7 beginning with Cycle 3 (21-day cycles) to the end of study (Up to 15 Cycles). | 29 |
| Total | 55 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Didn't complete dosing;PK/ECG assessment | 8 | 10 |
Baseline characteristics
| Characteristic | Esomeprazole 40 mg + Alisertib 50 mg | Rifampin 600 mg + Alisertib 50 mg | Total |
|---|---|---|---|
| Age, Continuous | 62.2 years STANDARD_DEVIATION 6.9 | 60.4 years STANDARD_DEVIATION 10.58 | 61.3 years STANDARD_DEVIATION 8.99 |
| Body Mass Index | 29.557 kg/m^2 STANDARD_DEVIATION 7.2787 | 28.026 kg/m^2 STANDARD_DEVIATION 9.4175 | 28.750 kg/m^2 STANDARD_DEVIATION 8.4327 |
| Height | 166.6 cm STANDARD_DEVIATION 8.9 | 164.8 cm STANDARD_DEVIATION 9.09 | 165.7 cm STANDARD_DEVIATION 8.97 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 3 Participants | 4 Participants | 7 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 22 Participants | 24 Participants | 46 Participants |
| Race/Ethnicity, Customized Not Reported | 1 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 22 Participants | 26 Participants | 48 Participants |
| Region of Enrollment United States | 26 Participants | 29 Participants | 55 Participants |
| Sex: Female, Male Female | 14 Participants | 21 Participants | 35 Participants |
| Sex: Female, Male Male | 12 Participants | 8 Participants | 20 Participants |
| Weight | 82.07 kg STANDARD_DEVIATION 20.765 | 77.37 kg STANDARD_DEVIATION 33.801 | 79.59 kg STANDARD_DEVIATION 28.242 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 26 | 3 / 29 |
| other Total, other adverse events | 25 / 26 | 25 / 29 |
| serious Total, serious adverse events | 9 / 26 | 11 / 29 |
Outcome results
Primary
AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Alisertib in Presence and Absence of Esomeprazole
Time frame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 1 for alisertib without esomeprazole arm; Day 8 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 2 for alisertib with esomeprazole arm
Population: The PK Population included participants who completed protocol-specified dosing and PK sampling requirements in Cycle 1 and 2 to have sufficient dosing and plasma concentration-time data to permit calculation of PK parameters. Here number of participants analyzed are participants who were evaluable for this outcome measure at specified time points.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alisertib Without Esomeprazole | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Alisertib in Presence and Absence of Esomeprazole | 21371.4 hr*nmol/L | Standard Deviation 8138.55 |
| Alisertib With Esomeprazole | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Alisertib in Presence and Absence of Esomeprazole | 26612.5 hr*nmol/L | Standard Deviation 6626.4 |
90% CI: [1.07, 1.53]
Primary
AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Alisertib in Presence or Absence of Rifampin
Time frame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 1 for alisertib without rifampin arm; Day 8 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 2 for alisertib with rifampin arm
Population: The PK Population included participants who completed protocol-specified dosing and PK sampling requirements in Cycle 1 and 2 to have sufficient dosing and plasma concentration-time data to permit calculation of PK parameters. Here number of participants analyzed are participants who were evaluable for this outcome measure at specified time points.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alisertib Without Esomeprazole | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Alisertib in Presence or Absence of Rifampin | 17258.3 hr*nmol/L | Standard Deviation 6163.6 |
| Alisertib With Esomeprazole | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Alisertib in Presence or Absence of Rifampin | 8955.0 hr*nmol/L | Standard Deviation 2389.25 |
90% CI: [0.41, 0.7]
Primary
AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Alisertib in Presence and Absence of Esomeprazole
Time frame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 1 for alisertib without esomeprazole arm; Day 8 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 2 for alisertib with esomeprazole arm
Population: The PK Population included participants who completed the protocol-specified dosing and PK sampling requirements in Cycle 1 and Cycle 2 to have sufficient dosing and plasma concentration-time data to permit calculation of PK parameters.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alisertib Without Esomeprazole | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Alisertib in Presence and Absence of Esomeprazole | 20427.8 hr*nmol/L | Standard Deviation 6813.46 |
| Alisertib With Esomeprazole | AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Alisertib in Presence and Absence of Esomeprazole | 25094.4 hr*nmol/L | Standard Deviation 5574.04 |
90% CI: [1.08, 1.45]
Primary
AUC(Last): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Alisertib in Presence and Absence of Rifampin
Time frame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 1 for alisertib without rifampin arm; Day 8 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 2 for alisertib with rifampin arm
Population: The PK Population included participants who completed the protocol-specified dosing and PK sampling requirements in Cycle 1 and Cycle 2 to have sufficient dosing and plasma concentration-time data to permit calculation of PK parameters.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alisertib Without Esomeprazole | AUC(Last): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Alisertib in Presence and Absence of Rifampin | 19732.0 hr*nmol/L | Standard Deviation 8489.24 |
| Alisertib With Esomeprazole | AUC(Last): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Alisertib in Presence and Absence of Rifampin | 9470.5 hr*nmol/L | Standard Deviation 2653.6 |
90% CI: [0.41, 0.62]
Primary
Change From the Time-matched Baseline in the Individually Corrected QTc Interval (QTcI)
Time frame: Baseline, Days 1 and 10 multiple timepoints postdose (up to 24 hours) in Cycle 1
Population: The electrocardiogram (ECG) QTc population included participants who received at least 1 dose of alisertib and have at least 1 post-baseline ECG.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Alisertib Without Esomeprazole | Change From the Time-matched Baseline in the Individually Corrected QTc Interval (QTcI) | Day 10, 0 hour postdose | -2.2 milliseconds (msec) |
| Alisertib Without Esomeprazole | Change From the Time-matched Baseline in the Individually Corrected QTc Interval (QTcI) | Day 1, 0.5 hour postdose | -3.7 milliseconds (msec) |
| Alisertib Without Esomeprazole | Change From the Time-matched Baseline in the Individually Corrected QTc Interval (QTcI) | Day 10, 0.5 hour postdose | -5.4 milliseconds (msec) |
| Alisertib Without Esomeprazole | Change From the Time-matched Baseline in the Individually Corrected QTc Interval (QTcI) | Day 1, 1 hour postdose | -4.5 milliseconds (msec) |
| Alisertib Without Esomeprazole | Change From the Time-matched Baseline in the Individually Corrected QTc Interval (QTcI) | Day 10, 1 hour postdose | -3.5 milliseconds (msec) |
| Alisertib Without Esomeprazole | Change From the Time-matched Baseline in the Individually Corrected QTc Interval (QTcI) | Day 1, 2 hours postdose | -4.0 milliseconds (msec) |
| Alisertib Without Esomeprazole | Change From the Time-matched Baseline in the Individually Corrected QTc Interval (QTcI) | Day 10, 2 hours postdose | -1.6 milliseconds (msec) |
| Alisertib Without Esomeprazole | Change From the Time-matched Baseline in the Individually Corrected QTc Interval (QTcI) | Day 1, 3 hours postdose | -2.5 milliseconds (msec) |
| Alisertib Without Esomeprazole | Change From the Time-matched Baseline in the Individually Corrected QTc Interval (QTcI) | Day 10, 3 hours postdose | -2.3 milliseconds (msec) |
| Alisertib Without Esomeprazole | Change From the Time-matched Baseline in the Individually Corrected QTc Interval (QTcI) | Day 1, 4 hours postdose | -1.2 milliseconds (msec) |
| Alisertib Without Esomeprazole | Change From the Time-matched Baseline in the Individually Corrected QTc Interval (QTcI) | Day 10, 4 hours postdose | -1.2 milliseconds (msec) |
| Alisertib Without Esomeprazole | Change From the Time-matched Baseline in the Individually Corrected QTc Interval (QTcI) | Day 1, 6 hours postdose | -0.9 milliseconds (msec) |
| Alisertib Without Esomeprazole | Change From the Time-matched Baseline in the Individually Corrected QTc Interval (QTcI) | Day 10, 6 hours postdose | -3.5 milliseconds (msec) |
| Alisertib Without Esomeprazole | Change From the Time-matched Baseline in the Individually Corrected QTc Interval (QTcI) | Day 1, 8 hours postdose | -0.5 milliseconds (msec) |
| Alisertib Without Esomeprazole | Change From the Time-matched Baseline in the Individually Corrected QTc Interval (QTcI) | Day 10, 8 hours postdose | -0.4 milliseconds (msec) |
| Alisertib Without Esomeprazole | Change From the Time-matched Baseline in the Individually Corrected QTc Interval (QTcI) | Day 1, 10 hours postdose | -1.5 milliseconds (msec) |
| Alisertib Without Esomeprazole | Change From the Time-matched Baseline in the Individually Corrected QTc Interval (QTcI) | Day 10, 10 hours postdose | -2.4 milliseconds (msec) |
| Alisertib Without Esomeprazole | Change From the Time-matched Baseline in the Individually Corrected QTc Interval (QTcI) | Day 1, 24 hours postdose | -3.3 milliseconds (msec) |
Primary
Cmax: Maximum Observed Concentration for Alisertib in Presence and Absence of Esomeprazole
Time frame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 1 for alisertib without esomeprazole arm; Day 8 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 2 for alisertib with esomeprazole arm
Population: The pharmacokinetic (PK) population included participants who completed the protocol-specified dosing and PK sampling requirements in cycle 1 and cycle 2 to have sufficient dosing and plasma concentration-time data to permit calculation of PK parameters.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alisertib Without Esomeprazole | Cmax: Maximum Observed Concentration for Alisertib in Presence and Absence of Esomeprazole | 1542.6 nmol/L | Standard Deviation 357.19 |
| Alisertib With Esomeprazole | Cmax: Maximum Observed Concentration for Alisertib in Presence and Absence of Esomeprazole | 1804.8 nmol/L | Standard Deviation 571.89 |
90% CI: [0.97, 1.35]
Primary
Cmax: Maximum Observed Concentration for Alisertib in Presence and Absence of Rifampin
Time frame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 1 for alisertib without rifampin arm; Day 8 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 2 for alisertib with rifampin arm
Population: The PK Population included participants who completed the protocol-specified dosing and PK sampling requirements in Cycle 1 and Cycle 2 to have sufficient dosing and plasma concentration-time data to permit calculation of PK parameters.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alisertib Without Esomeprazole | Cmax: Maximum Observed Concentration for Alisertib in Presence and Absence of Rifampin | 1561.4 nmol/L | Standard Deviation 661.81 |
| Alisertib With Esomeprazole | Cmax: Maximum Observed Concentration for Alisertib in Presence and Absence of Rifampin | 1581.5 nmol/L | Standard Deviation 519.68 |
90% CI: [0.84, 1.26]
Primary
Phase Elimination Half-life (T1/2) for Alisertib in Presence and Absence of Rifampin
Time frame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 1 for alisertib without rifampin arm; Day 8 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 2 for alisertib with rifampin arm
Population: The PK Population included participants who completed the protocol-specified dosing and PK sampling requirements in Cycle 1 and Cycle 2 to have sufficient dosing and plasma concentration-time data to permit calculation of PK parameters.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alisertib Without Esomeprazole | Phase Elimination Half-life (T1/2) for Alisertib in Presence and Absence of Rifampin | 16.30 hours | Standard Deviation 6.608 |
| Alisertib With Esomeprazole | Phase Elimination Half-life (T1/2) for Alisertib in Presence and Absence of Rifampin | 8.17 hours | Standard Deviation 5.476 |
Primary
Terminal Phase Elimination Half-life (T1/2) for Alisertib in Presence and Absence of Esomeprazole
Time frame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 1 for alisertib without esomeprazole arm; Day 8 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 2 for alisertib with esomeprazole arm
Population: The PK Population included participants who completed the protocol-specified dosing and PK sampling requirements in Cycle 1 and Cycle 2 to have sufficient dosing and plasma concentration-time data to permit calculation of PK parameters.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alisertib Without Esomeprazole | Terminal Phase Elimination Half-life (T1/2) for Alisertib in Presence and Absence of Esomeprazole | 16.06 hours | Standard Deviation 5.398 |
| Alisertib With Esomeprazole | Terminal Phase Elimination Half-life (T1/2) for Alisertib in Presence and Absence of Esomeprazole | 15.96 hours | Standard Deviation 5.234 |
Primary
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Alisertib in Presence and Absence of Esomeprazole
Time frame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 1 for alisertib without esomeprazole arm; Day 8 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 2 for alisertib with esomeprazole arm
Population: The PK Population included participants who completed the protocol-specified dosing and PK sampling requirements in Cycle 1 and Cycle 2 to have sufficient dosing and plasma concentration-time data to permit calculation of PK parameters.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Alisertib Without Esomeprazole | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Alisertib in Presence and Absence of Esomeprazole | 4.0 hours |
| Alisertib With Esomeprazole | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Alisertib in Presence and Absence of Esomeprazole | 3.0 hours |
Primary
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Alisertib in Presence and Absence of Rifampin
Time frame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 1 for alisertib without rifampin arm; Day 8 pre-dose and at multiple time points (up to 72 hours) post-dose in Cycle 2 for alisertib with rifampin arm
Population: The PK Population included participants who completed the protocol-specified dosing and PK sampling requirements in Cycle 1 and Cycle 2 to have sufficient dosing and plasma concentration-time data to permit calculation of PK parameters.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Alisertib Without Esomeprazole | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Alisertib in Presence and Absence of Rifampin | 4.0 hours |
| Alisertib With Esomeprazole | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Alisertib in Presence and Absence of Rifampin | 2.1 hours |
Secondary
Change From the Time-matched Baseline in the Fridericia Correction of QTc (QTcF)
Time frame: Baseline, Days 1 and 10 multiple timepoints postdose (up to 24 hours) in Cycle 1
Population: The electrocardiogram (ECG) QTc population included participants who received at least 1 dose of alisertib and have at least 1 post-baseline ECG.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Alisertib Without Esomeprazole | Change From the Time-matched Baseline in the Fridericia Correction of QTc (QTcF) | Day 10, 0 hour postdose | -2.4 milliseconds (msec) |
| Alisertib Without Esomeprazole | Change From the Time-matched Baseline in the Fridericia Correction of QTc (QTcF) | Day 1, 0.5 hour postdose | -3.9 milliseconds (msec) |
| Alisertib Without Esomeprazole | Change From the Time-matched Baseline in the Fridericia Correction of QTc (QTcF) | Day 10, 0.5 hour postdose | -5.3 milliseconds (msec) |
| Alisertib Without Esomeprazole | Change From the Time-matched Baseline in the Fridericia Correction of QTc (QTcF) | Day 1, 1 hour postdose | -4.6 milliseconds (msec) |
| Alisertib Without Esomeprazole | Change From the Time-matched Baseline in the Fridericia Correction of QTc (QTcF) | Day 10, 1 hour postdose | -3.9 milliseconds (msec) |
| Alisertib Without Esomeprazole | Change From the Time-matched Baseline in the Fridericia Correction of QTc (QTcF) | Day 1, 2 hours postdose | -3.5 milliseconds (msec) |
| Alisertib Without Esomeprazole | Change From the Time-matched Baseline in the Fridericia Correction of QTc (QTcF) | Day 10, 2 hours postdose | -2.5 milliseconds (msec) |
| Alisertib Without Esomeprazole | Change From the Time-matched Baseline in the Fridericia Correction of QTc (QTcF) | Day 1, 3 hours postdose | -2.1 milliseconds (msec) |
| Alisertib Without Esomeprazole | Change From the Time-matched Baseline in the Fridericia Correction of QTc (QTcF) | Day 10, 3 hours postdose | -2.6 milliseconds (msec) |
| Alisertib Without Esomeprazole | Change From the Time-matched Baseline in the Fridericia Correction of QTc (QTcF) | Day 1, 4 hours postdose | 0 milliseconds (msec) |
| Alisertib Without Esomeprazole | Change From the Time-matched Baseline in the Fridericia Correction of QTc (QTcF) | Day 10, 4 hours postdose | -1.3 milliseconds (msec) |
| Alisertib Without Esomeprazole | Change From the Time-matched Baseline in the Fridericia Correction of QTc (QTcF) | Day 1, 6 hours postdose | -0.5 milliseconds (msec) |
| Alisertib Without Esomeprazole | Change From the Time-matched Baseline in the Fridericia Correction of QTc (QTcF) | Day 10, 6 hours postdose | -4.1 milliseconds (msec) |
| Alisertib Without Esomeprazole | Change From the Time-matched Baseline in the Fridericia Correction of QTc (QTcF) | Day 1, 8 hours postdose | 0 milliseconds (msec) |
| Alisertib Without Esomeprazole | Change From the Time-matched Baseline in the Fridericia Correction of QTc (QTcF) | Day 10, 8 hours postdose | -1.6 milliseconds (msec) |
| Alisertib Without Esomeprazole | Change From the Time-matched Baseline in the Fridericia Correction of QTc (QTcF) | Day 1, 10 hours postdose | -1.2 milliseconds (msec) |
| Alisertib Without Esomeprazole | Change From the Time-matched Baseline in the Fridericia Correction of QTc (QTcF) | Day 10, 10 hours postdose | -3.5 milliseconds (msec) |
| Alisertib Without Esomeprazole | Change From the Time-matched Baseline in the Fridericia Correction of QTc (QTcF) | Day 1, 24 hours postdose | -3.8 milliseconds (msec) |
Secondary
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A Serious Adverse Event (SAE) A serious 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.
Time frame: From the first dose through 30 days after administration of the last dose of study drug (up to 328 days)
Population: The safety population included all participants who received at least 1 dose of alisertib. According to the protocol analysis planned, primary purpose of the study was to observe the drug-drug interaction of either esomeprazole or rifampin on the single-dose of alisertib.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alisertib Without Esomeprazole | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 25 participants |
| Alisertib Without Esomeprazole | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 9 participants |
| Alisertib With Esomeprazole | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 27 participants |
| Alisertib With Esomeprazole | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 11 participants |