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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.
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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Esomeprazole 40 mg + Alisertib 50 mg | Experimental | 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). |
|
| Rifampin 600 mg + Alisertib 50 mg | Experimental | 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). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Alisertib | Drug | Alisertib tablets |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | |
| 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. |
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Inclusion Criteria:
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 exclusion criteria. The study center will determine if you meet all of the criteria.
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| Name | Affiliation | Role |
|---|---|---|
| Medical Monitor | Millennium Pharmaceuticals, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sarasota | Florida | United States | ||||
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 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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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). |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Esomeprazole | Drug | Esomeprazole capsules |
|
| Rifampin | Drug | Rifampin capsules |
|
| 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 |
| 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 |
| 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 |
| From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) |
| St Louis |
| Missouri |
| United States |
| Oklahoma City | Oklahoma | United States |
| Nashville | Tennessee | United States |
| Dallas | Texas | United States |
| San Antonio | Texas | United States |
| Madison | Wisconsin | United States |
| FG001 | 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). |
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| NOT COMPLETED |
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The safety population included all participants who received at least 1 dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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). |
| BG001 | 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). |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Count of Participants | Participants |
| ||||||||||||||||
| Height | Mean | Standard Deviation | cm |
| |||||||||||||||
| Weight | Mean | Standard Deviation | kg |
| |||||||||||||||
| Body Mass Index | Body Mass Index = weight (kg)/ height (m^2). | Mean | Standard Deviation | kg/m^2 |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Cmax: Maximum Observed Concentration for Alisertib in Presence and Absence of Esomeprazole | 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. | Posted | Mean | Standard Deviation | nmol/L | 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 |
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| 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 | 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. | Posted | Mean | Standard Deviation | hr*nmol/L | 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 |
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| Primary | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Alisertib in Presence and Absence of Esomeprazole | 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. | Posted | Mean | Standard Deviation | hr*nmol/L | 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 |
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| Primary | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Alisertib in Presence and Absence of Esomeprazole | 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. | Posted | Median | Full Range | hours | 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 |
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| Primary | Terminal Phase Elimination Half-life (T1/2) for Alisertib in Presence and Absence of Esomeprazole | 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. | Posted | Mean | Standard Deviation | hours | 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 |
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| Primary | Cmax: Maximum Observed Concentration for Alisertib in Presence and Absence of Rifampin | 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. | Posted | Mean | Standard Deviation | nmol/L | 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 |
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| 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 | 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. | Posted | Mean | Standard Deviation | hr*nmol/L | 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 |
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| Primary | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Alisertib in Presence or Absence of Rifampin | 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. | Posted | Mean | Standard Deviation | hr*nmol/L | 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 |
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| Primary | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Alisertib in Presence and Absence of Rifampin | 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. | Posted | Median | Full Range | hours | 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 |
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| Primary | Phase Elimination Half-life (T1/2) for Alisertib in Presence and Absence of Rifampin | 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. | Posted | Mean | Standard Deviation | hours | 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 |
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| Primary | Change From the Time-matched Baseline in the Individually Corrected QTc Interval (QTcI) | The electrocardiogram (ECG) QTc population included participants who received at least 1 dose of alisertib and have at least 1 post-baseline ECG. | Posted | Mean | 95% Confidence Interval | milliseconds (msec) | Baseline, Days 1 and 10 multiple timepoints postdose (up to 24 hours) in Cycle 1 |
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| Secondary | Change From the Time-matched Baseline in the Fridericia Correction of QTc (QTcF) | The electrocardiogram (ECG) QTc population included participants who received at least 1 dose of alisertib and have at least 1 post-baseline ECG. | Posted | Mean | 95% Confidence Interval | milliseconds (msec) | Baseline, Days 1 and 10 multiple timepoints postdose (up to 24 hours) in Cycle 1 |
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| 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. | 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. | Posted | Number | participants | From the first dose through 30 days after administration of the last dose of study drug (up to 328 days) |
|
From the first dose through 30 days after administration of the last dose of study drug (up to 328 days)
Any AE spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. 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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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). | 1 | 26 | 9 | 26 | 25 | 26 |
| EG001 | 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). | 3 | 29 | 11 | 29 | 25 | 29 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Vomiting | Gastrointestinal disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Gastric ulcer perforation | Gastrointestinal disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Ascites | Gastrointestinal disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Pyelonephritis | Infections and infestations | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Septic shock | Infections and infestations | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Cervix carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA, Version 19.0 | Systematic Assessment | One treatment-emergent death occurred during treatment with rifampin and alisertib and is not related. |
|
| Non-small cell lung cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA, Version 19.0 | Systematic Assessment | One treatment-emergent death occurred during treatment with esomeprazole and alisertib and is not related. |
|
| Pancreatic carcinoma metastatic | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA, Version 19.0 | Systematic Assessment | One treatment-emergent death occurred during treatment with rifampin and alisertib and is not related. |
|
| Cerebrovascular accident | Nervous system disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Hepatic encephalopathy | Nervous system disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA, Version 19.0 | Systematic Assessment |
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| Orthostatic hypotension | Vascular disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA, Version 19.0 | Systematic Assessment |
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| Neutropenia | Blood and lymphatic system disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Pancytopenia | Blood and lymphatic system disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Hepatic failure | Hepatobiliary disorders | MedDRA, Version 19.0 | Systematic Assessment | One treatment-emergent death occurred during treatment with rifampin and alisertib and is not related. |
|
| Hip fracture | Injury, poisoning and procedural complications | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Mental status changes | Psychiatric disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA, Version 19.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Rash macular | Skin and subcutaneous tissue disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA, Version 19.0 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA, Version 19.0 | Systematic Assessment |
|
In general, Investigators may publish clinical data after the earlier of (i) publication by the Sponsor or (ii) 12 months following the abandonment, early termination or database lock; provided a copy of the publication provided to Sponsor at least 30 days ahead of publication, the Sponsor's confidential information is removed as may be requested by Sponsor and Investigator defers publication for up to 60 days in the event Sponsor provides notice that it intends to file a patent application.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Takeda | +1-877-825-3327 | trialdisclosures@takeda.com |
| ID | Term |
|---|---|
| D008223 | Lymphoma |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C550258 | MLN 8237 |
| D064098 | Esomeprazole |
| D012293 | Rifampin |
| ID | Term |
|---|---|
| D009853 | Omeprazole |
| D053799 | 2-Pyridinylmethylsulfinylbenzimidazoles |
| D013454 | Sulfoxides |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001562 | Benzimidazoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D012294 | Rifamycins |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D047029 | Lactams, Macrocyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Not Reported |
|
| Black or African American |
|
| Native Hawaiian or Other Pacific Islander |
|
| Asian |
|
| American Indian or Alaska Native |
|
| Other |
|
| Not Reported |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
| Title | Denominators | Categories | ||||
|---|---|---|---|---|---|---|
| Day 10, 0 hour postdose |
| |||||
| Day 1, 0.5 hour postdose |
| |||||
| Day 10, 0.5 hour postdose |
| |||||
| Day 1, 1 hour postdose |
| |||||
| Day 10, 1 hour postdose |
| |||||
| Day 1, 2 hours postdose |
| |||||
| Day 10, 2 hours postdose |
| |||||
| Day 1, 3 hours postdose |
| |||||
| Day 10, 3 hours postdose |
| |||||
| Day 1, 4 hours postdose |
| |||||
| Day 10, 4 hours postdose |
| |||||
| Day 1, 6 hours postdose |
| |||||
| Day 10, 6 hours postdose |
| |||||
| Day 1, 8 hours postdose |
| |||||
| Day 10, 8 hours postdose |
| |||||
| Day 1, 10 hours postdose |
| |||||
| Day 10, 10 hours postdose |
| |||||
| Day 1, 24 hours postdose |
|
| Title | Denominators | Categories | ||||
|---|---|---|---|---|---|---|
| Day 10, 0 hour postdose |
| |||||
| Day 1, 0.5 hour postdose |
| |||||
| Day 10, 0.5 hour postdose |
| |||||
| Day 1, 1 hour postdose |
| |||||
| Day 10, 1 hour postdose |
| |||||
| Day 1, 2 hours postdose |
| |||||
| Day 10, 2 hours postdose |
| |||||
| Day 1, 3 hours postdose |
| |||||
| Day 10, 3 hours postdose |
| |||||
| Day 1, 4 hours postdose |
| |||||
| Day 10, 4 hours postdose |
| |||||
| Day 1, 6 hours postdose |
| |||||
| Day 10, 6 hours postdose |
| |||||
| Day 1, 8 hours postdose |
| |||||
| Day 10, 8 hours postdose |
| |||||
| Day 1, 10 hours postdose |
| |||||
| Day 10, 10 hours postdose |
| |||||
| Day 1, 24 hours postdose |
|
| OG001 | 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). |
|
|