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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1155-6072 | Other Identifier | World Health Organization |
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The purpose of this study is to evaluate the effect of moderate or severe hepatic impairment on the single-dose pharmacokinetics of alisertib in adult participants with cancer.
The drug being tested in this study is called alisertib. Alisertib was tested to assess how it was processed by the body in participants with advanced solid tumors or relapsed/refractory lymphoma with varying degrees of liver function. This study also assessed laboratory results and safety.
The study enrolled 36 participants. Participants were assigned to 1 of the 3 treatment groups based on the status of their liver function: Normal hepatic function (Total bilirubin ≤ upper limit of the normal range [ULN] and alanine aminotransferase [ALT] level ≤ ULN), moderate hepatic impairment (Total bilirubin > 1.5-3 x ULN and ALT level = Any), or severe hepatic impairment (Total bilirubin > 3 x ULN and ALT level = Any). All participants were administered one 50 mg dose of alisertib on Day 1, Cycle 1. Alisertib was administered again on Days 8 through 14 of Cycle 1, followed by a 14-day rest period. Doses administered on Days 8-14 were 50, 30, or 20 mg of alisertib, depending on hepatic function. Alisertib was then continued at the same dose as in Cycle 1, Days 8-14 in 21-day cycles (7 days of alisertib followed by a 14-day rest period) for up to 1 year (approximately 16 cycles).
This multicenter trial was conducted in USA only. The overall time to participate in this study was up to 312 Days. Participants made multiple visits to the clinic including an end-of-study visit 30 days after the last dose of study drug for a follow-up assessment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Alisertib: Normal Hepatic Function | Experimental | Alisertib 50 mg, orally, once, on Cycle 1 Day 1, followed by, alisertib 50 mg, orally, twice daily (BID) for 7 days (Cycle 1 Day 8 to 14) followed by a 14-day rest period. Starting at Cycle 2 Day 1, alisertib 50 mg, BID for 7 days, followed by a 14-day rest period unless a dose reduction is indicated. Participants may continue to receive alisertib until they experience progressive disease or unacceptable alisertib-related toxicities for up to 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. Normal hepatic function includes participants with total bilirubin ≤ upper limit of the normal range [ULN] and alanine aminotransferase [ALT] level ≤ ULN. |
|
| Alisertib: Moderate Hepatic Impairment | Experimental | Alisertib 50 mg, orally, once, on Cycle 1 Day 1, followed by alisertib 30 mg, BID for 7 days (Cycle 1 Day 8 to 14), followed by a 14-day rest period. Starting at Cycle 2 Day 1, alisertib 30 mg, BID for 7 days followed by a 14-day rest period unless a dose reduction is indicated. Participants may continue to receive alisertib until they experience progressive disease or unacceptable alisertib-related toxicities for up to 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. Moderate hepatic impairment includes participants with total bilirubin > 1.5-3 x ULN and any ALT level. |
|
| Alisertib: Severe Hepatic Impairment | Experimental | Alisertib 50 mg, orally, once, on Cycle 1 Day 1, followed by, alisertib 20 mg, BID for 7 days (Cycle 1 Day 8 to 14) followed by a 14-day rest period. Starting at Cycle 2 Day 1, alisertib 20 mg, BID for 7 days followed by a 14-day rest period unless a dose reduction is indicated. Participants may continue to receive alisertib until they experience progressive disease or unacceptable alisertib-related toxicities for up to 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. Severe hepatic impairment includes participants with total bilirubin > 3 x ULN and any ALT level. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Alisertib | Drug | Alisertib will be supplied as enteric coated tablets. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Unbound Cmax: Maximum Observed Plasma Concentration for Alisertib | Cycle 1 Day 1 Pre-dose and, and at multiple timepoints (up to 168 hours) post-dose | |
| Unbound AUClast: Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Alisertib | Cycle 1 Day 1 Pre-dose and, and at multiple timepoints (up to 168 hours) post-dose | |
| Unbound AUC0-∞: Area Under the Concentration-Time Curve From Time 0 to Infinity for Alisertib | Cycle 1 Day 1 Pre-dose and, and at multiple timepoints (up to 168 hours) post-dose |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event | An adverse event is any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event is defined as an adverse event with an onset that occurs after receiving study drug. |
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Inclusion Criteria:
Male or female participants 18 years of age or older.
Histologically or cytologically confirmed metastatic and/or advanced solid tumors or lymphomas for which standard curative or life-prolonging treatment does not exist or is no longer effective or tolerable.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
Female participants who:
Male participants, even if surgically sterilized (ie, status postvasectomy), who:
Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care.
Suitable venous access for the study-required blood sampling, including pharmacokinetics.
Ability to swallow tablets.
Participants with biliary obstruction for which a stent had been placed are eligible provided that the stent has been in place for more than 14 days before the first dose of alisertib and liver function has stabilized.
Recovered from the reversible effects of prior antineoplastic therapy (ie, ≤ Grade 1 toxicity or baseline).
Clinical laboratory values as specified below:
Absolute neutrophil count (ANC) ≥ 1500/μL and platelet count ≥ 75,000/μL.
Exclusion Criteria:
Participants of North/East Asian ethnicity (ie, Japanese, Chinese, Korean) will be excluded.
Recurrent nausea and/or vomiting within 14 days before the first dose of alisertib or known gastrointestinal (GI) abnormality or GI procedure that could interfere with or modify the oral absorption or tolerance of alisertib. Examples include, but are not limited to, disease-related bowel obstruction, pancreatic insufficiency, use of pancreatic enzymes, a gastric condition (such as severe reflux or active peptic ulcer disease) that requires chronic and uninterrupted use of proton pump inhibitors, partial gastrectomy, history of small intestine surgery, and celiac disease.
Participants requiring treatment with clinically significant enzyme inducers, such as the enzyme-inducing anti-epileptic drugs phenytoin, carbamazepine, phenobarbital, oxcarbazepine, primidone, rifampin, rifabutin, rifapentine, or St. John's wort within 14 days before the first dose of alisertib or requiring the use of these medications during the study.
A medical condition requiring use of pancreatic enzymes; daily, chronic, or regular use of proton pump inhibitors (PPIs); or histamine 2 (H2) receptor antagonists. Participants who intermittently use these medications, must meet the following criteria:
Inadequate bone marrow or other organ function (excluding hepatic impairment per eligibility criteria).
Female participants who are lactating and breastfeeding or have a positive serum pregnancy test during the Screening period or a positive urine pregnancy test on Day 1 before first dose of alisertib.
Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
Treatment with any anticancer therapy or any investigational products within 3 weeks before the first dose of study drug.
Exposure to nitrosoureas or mitomycin C within 42 days before the first dose of study drug.
Radiotherapy within 14 days before the first dose of study drug.
Prior treatment with radiation therapy involving ≥ 25% of the hematopoietically active bone marrow within 42 days before the first dose of study drug.
Major surgery within 14 days before the first dose of study drug.
Serious infection within 14 days before the first dose of study drug. Participant must have recovered from infection before first dose.
Life-threatening illness unrelated to cancer.
Symptomatic brain metastasis. Participants with brain metastases:
Clinically significant coagulopathy or bleeding disorder.
Severe central nervous system, pulmonary, or renal disease not related to the participant's cancer.
Known human immunodeficiency virus (HIV) positive.
Known history of hepatitis C infection or suspected currently active hepatitis C infection, or known or suspected history of hepatitis B infection. Participants with known or suspected history of hepatitis B infection were to be screened and excluded when any of the following conditions were met:
Any of the following cardiovascular conditions:
History of uncontrolled sleep apnea syndrome or other condition that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease.
Use of moderate or strong cytochrome P450 (CYP) 3A inhibitors or CYP3A inducers within 2 weeks before the first dose of study drug.
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director Clinical Science | Millennium Pharmaceuticals, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Miami | Florida | United States | ||||
Participants with a diagnosis of advanced solid tumors or relapsed/refractory lymphoma were assigned to 1 of 3 hepatic function groups (normal hepatic function, moderate hepatic impairment, or severe hepatic impairment) on the basis of their total bilirubin and alanine aminotransferase (ALT) values. All participants received alisertib.
Participants took part in the study at 6 investigative sites in the United States from 21 August 2014 to 18 July 2016.
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| ID | Title | Description |
|---|---|---|
| FG000 | Alisertib: Normal Hepatic Function | Alisertib 50 mg, orally, once, on Cycle 1 Day 1, followed by, alisertib 50 mg, orally, twice daily (BID) for 7 days (Cycle 1 Day 8 to 14) followed by a 14-day rest period. Starting at Cycle 2 Day 1, alisertib 50 mg, BID for 7 days, followed by a 14-day rest period unless a dose reduction is indicated. Participants may continue to receive alisertib until they experience progressive disease or unacceptable alisertib-related toxicities for up to 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. Normal hepatic function includes participants with total bilirubin ≤ upper limit of the normal range [ULN] and alanine aminotransferase [ALT] level ≤ ULN. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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|
| Baseline to 30 days after last dose (Up to 312 Days) |
| Percentage of Participants Who Experienced at Least 1 Serious Adverse Event | A serious adverse event is any untoward medical occurrence or effect that at any dose of a drug results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is medically important due to other reasons than the above mentioned criteria. | Baseline to 30 days after last dose (Up to 312 Days) |
| Percentage of Participants With Clinically Significant Laboratory Values | Laboratory assessments include serum chemistry and hematology. An abnormal laboratory value was assessed as an AE if that value led to discontinuation or delay in treatment, dose modification, therapeutic intervention, or was considered by the investigator to be a clinically significant change from baseline. | Baseline to the end of the study (Up to 312 Days) |
| Percentage of Participants With Clinically Significant Vital Signs | Vital signs include measurements of sitting diastolic and systolic blood pressure, heart rate, and temperature. Any vital signs determined by the investigator to be clinically significant were recorded as AEs. | Baseline to the end of the study (Up to 312 days) |
| Cmax: Maximum Observed Plasma Concentration for Alisertib Metabolites M1 and M2 | Cycle 1 Day 1 Pre-dose and, and at multiple timepoints (up to 168 hours) post-dose |
| Tmax: Time of First Occurrence of Cmax for Alisertib Metabolites M1 and M2 | Cycle 1 Day 1 Pre-dose and, and at multiple timepoints (up to 168 hours) post-dose |
| AUClast: Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Alisertib Metabolites M1 and M2 | The area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration (AUC0-last) of the alisertib metabolites M1 and M2 was determined from the concentration-time curve of each participant using non-compartmental methods. | Cycle 1 Day 1 Pre-dose and, and at multiple timepoints (up to 168 hours) post-dose |
| Dose-normalized Trough Concentration of Alisertib on Cycle 1 Day 14 | A single blood sample will be collected pre-dose on Cycle 1 Day 14. The concentration of alisertib was determined in the plasma sample and dose-normalized. | Pre-dose on Day 14 of Cycle 1 |
| Chicago |
| Illinois |
| United States |
| Ann Arbor | Michigan | United States |
| St Louis | Missouri | United States |
| Dallas | Texas | United States |
| Houston | Texas | United States |
| San Antonio | Texas | United States |
| FG001 | Alisertib: Moderate Hepatic Impairment | Alisertib 50 mg, orally, once, on Cycle 1 Day 1, followed by alisertib 30 mg, BID for 7 days (Cycle 1 Day 8 to 14), followed by a 14-day rest period. Starting at Cycle 2 Day 1, alisertib 30 mg, BID for 7 days followed by a 14-day rest period unless a dose reduction is indicated. Participants may continue to receive alisertib until they experience progressive disease or unacceptable alisertib-related toxicities for up to 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. Moderate hepatic impairment includes participants with total bilirubin > 1.5-3 x ULN and any ALT level. |
| FG002 | Alisertib: Severe Hepatic Impairment | Alisertib 50 mg, orally, once, on Cycle 1 Day 1, followed by, alisertib 20 mg, BID for 7 days (Cycle 1 Day 8 to 14) followed by a 14-day rest period. Starting at Cycle 2 Day 1, alisertib 20 mg, BID for 7 days followed by a 14-day rest period unless a dose reduction is indicated. Participants may continue to receive alisertib until they experience progressive disease or unacceptable alisertib-related toxicities for up to 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. Severe hepatic impairment includes participants with total bilirubin > 3 x ULN and any ALT level. |
| COMPLETED | Completed=Completed protocol-specified dosing and PK assessment. |
|
| NOT COMPLETED |
|
Safety population was defined as all participants who received at least 1 dose of alisertib.
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| ID | Title | Description |
|---|---|---|
| BG000 | Alisertib: Normal Hepatic Function | Alisertib 50 mg, orally, once, on Cycle 1 Day 1, followed by, alisertib 50 mg, orally, twice daily (BID) for 7 days (Cycle 1 Day 8 to 14) followed by a 14-day rest period. Starting at Cycle 2 Day 1, alisertib 50 mg, BID for 7 days, followed by a 14-day rest period unless a dose reduction is indicated. Participants may continue to receive alisertib until they experience progressive disease or unacceptable alisertib-related toxicities for up to 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. Normal hepatic function includes participants with total bilirubin ≤ upper limit of the normal range [ULN] and alanine aminotransferase [ALT] level ≤ ULN. |
| BG001 | Alisertib: Moderate Hepatic Impairment | Alisertib 50 mg, orally, once, on Cycle 1 Day 1, followed by alisertib 30 mg, BID for 7 days (Cycle 1 Day 8 to 14), followed by a 14-day rest period. Starting at Cycle 2 Day 1, alisertib 30 mg, BID for 7 days followed by a 14-day rest period unless a dose reduction is indicated. Participants may continue to receive alisertib until they experience progressive disease or unacceptable alisertib-related toxicities for up to 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. Moderate hepatic impairment includes participants with total bilirubin > 1.5-3 x ULN and any ALT level. |
| BG002 | Alisertib: Severe Hepatic Impairment | Alisertib 50 mg, orally, once, on Cycle 1 Day 1, followed by, alisertib 20 mg, BID for 7 days (Cycle 1 Day 8 to 14) followed by a 14-day rest period. Starting at Cycle 2 Day 1, alisertib 20 mg, BID for 7 days followed by a 14-day rest period unless a dose reduction is indicated. Participants may continue to receive alisertib until they experience progressive disease or unacceptable alisertib-related toxicities for up to 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. Severe hepatic impairment includes participants with total bilirubin > 3 x ULN and any ALT level. |
| BG003 | 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 |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| Height | Height data is only available for n=14,11,5 participants. | Mean | Standard Deviation | cm |
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| Weight | Mean | Standard Deviation | kg |
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| Body surface area | Body surface area=square root[height(cm)*weight(kg)/3600] | Body surface area data is only available for n=14,11,5 participants. | Mean | Standard Deviation | m^2 |
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| 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 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Unbound Cmax: Maximum Observed Plasma Concentration for Alisertib | Pharmacokinetic (PK)-evaluable population was defined as all participants who had completed protocol-specified dosing and PK assessment in Cycle 1 with sufficient dosing and PK data to reliably estimate PK parameters. | Posted | Mean | Standard Deviation | nmol/L | Cycle 1 Day 1 Pre-dose and, and at multiple timepoints (up to 168 hours) post-dose |
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| Primary | Unbound AUClast: Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Alisertib | Participants from the PK-evaluable population, all participants who had completed protocol-specified dosing and PK assessment in Cycle 1 with sufficient dosing and PK data to reliably estimate PK parameters, with data available for analysis. | Posted | Mean | Standard Deviation | h*nmol/L | Cycle 1 Day 1 Pre-dose and, and at multiple timepoints (up to 168 hours) post-dose |
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| Primary | Unbound AUC0-∞: Area Under the Concentration-Time Curve From Time 0 to Infinity for Alisertib | Participants from the PK-evaluable population, all participants who had completed protocol-specified dosing and PK assessment in Cycle 1 with sufficient dosing and PK data to reliably estimate PK parameters, with data available for analysis. | Posted | Mean | Standard Deviation | h*nmol/L | Cycle 1 Day 1 Pre-dose and, and at multiple timepoints (up to 168 hours) post-dose |
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| Secondary | Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event | An adverse event is any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event is defined as an adverse event with an onset that occurs after receiving study drug. | Safety population was defined as all participants who received at least 1 dose of alisertib. | Posted | Number | percentage of participants | Baseline to 30 days after last dose (Up to 312 Days) |
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| Secondary | Percentage of Participants Who Experienced at Least 1 Serious Adverse Event | A serious adverse event is any untoward medical occurrence or effect that at any dose of a drug results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is medically important due to other reasons than the above mentioned criteria. | Safety population was defined as all participants who received at least 1 dose of alisertib. | Posted | Number | percentage of participants | Baseline to 30 days after last dose (Up to 312 Days) |
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| Secondary | Percentage of Participants With Clinically Significant Laboratory Values | Laboratory assessments include serum chemistry and hematology. An abnormal laboratory value was assessed as an AE if that value led to discontinuation or delay in treatment, dose modification, therapeutic intervention, or was considered by the investigator to be a clinically significant change from baseline. | Safety population was defined as all participants who received at least 1 dose of alisertib. | Posted | Number | percentage of participants | Baseline to the end of the study (Up to 312 Days) |
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| Secondary | Percentage of Participants With Clinically Significant Vital Signs | Vital signs include measurements of sitting diastolic and systolic blood pressure, heart rate, and temperature. Any vital signs determined by the investigator to be clinically significant were recorded as AEs. | Safety population was defined as all participants who received at least 1 dose of alisertib. | Posted | Number | percentage of participants | Baseline to the end of the study (Up to 312 days) |
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| Secondary | Cmax: Maximum Observed Plasma Concentration for Alisertib Metabolites M1 and M2 | PK-evaluable population was defined as all participants who had completed protocol-specified dosing and PK assessment in Cycle 1 with sufficient dosing and PK data to reliably estimate PK parameters. | Posted | Mean | Standard Deviation | nmol/L | Cycle 1 Day 1 Pre-dose and, and at multiple timepoints (up to 168 hours) post-dose |
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| Secondary | Tmax: Time of First Occurrence of Cmax for Alisertib Metabolites M1 and M2 | PK-evaluable population was defined as all participants who had completed protocol-specified dosing and PK assessment in Cycle 1 with sufficient dosing and PK data to reliably estimate PK parameters. | Posted | Median | Full Range | hours | Cycle 1 Day 1 Pre-dose and, and at multiple timepoints (up to 168 hours) post-dose |
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| Secondary | AUClast: Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Alisertib Metabolites M1 and M2 | The area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration (AUC0-last) of the alisertib metabolites M1 and M2 was determined from the concentration-time curve of each participant using non-compartmental methods. | Participants from the PK-evaluable population, all participants who had completed protocol-specified dosing and PK assessment in Cycle 1 with sufficient dosing and PK data to reliably estimate PK parameters, with data available for analysis. | Posted | Mean | Standard Deviation | h*nmol/L | Cycle 1 Day 1 Pre-dose and, and at multiple timepoints (up to 168 hours) post-dose |
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| Secondary | Dose-normalized Trough Concentration of Alisertib on Cycle 1 Day 14 | A single blood sample will be collected pre-dose on Cycle 1 Day 14. The concentration of alisertib was determined in the plasma sample and dose-normalized. | Data was not collected, as many participants dropped out of the study prior to Day 14 trough concentration collection. | Posted | Pre-dose on Day 14 of Cycle 1 |
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First dose of study drug to 30 days past last dose (Up to 312 Days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
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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 | Alisertib: Normal Hepatic Function | Alisertib 50 mg, orally, once, on Cycle 1 Day 1, followed by, alisertib 50 mg, orally, twice daily (BID) for 7 days (Cycle 1 Day 8 to 14) followed by a 14-day rest period. Starting at Cycle 2 Day 1, alisertib 50 mg, BID for 7 days, followed by a 14-day rest period unless a dose reduction is indicated. Participants may continue to receive alisertib until they experience progressive disease or unacceptable alisertib-related toxicities for up to 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. Normal hepatic function includes participants with total bilirubin ≤ upper limit of the normal range [ULN] and alanine aminotransferase [ALT] level ≤ ULN. | 2 | 16 | 7 | 16 | 15 | 16 |
| EG001 | Alisertib: Moderate Hepatic Impairment | Alisertib 50 mg, orally, once, on Cycle 1 Day 1, followed by alisertib 30 mg, BID for 7 days (Cycle 1 Day 8 to 14), followed by a 14-day rest period. Starting at Cycle 2 Day 1, alisertib 30 mg, BID for 7 days followed by a 14-day rest period unless a dose reduction is indicated. Participants may continue to receive alisertib until they experience progressive disease or unacceptable alisertib-related toxicities for up to 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. Moderate hepatic impairment includes participants with total bilirubin > 1.5-3 x ULN and any ALT level. | 3 | 12 | 8 | 12 | 12 | 12 |
| EG002 | Alisertib: Severe Hepatic Impairment | Alisertib 50 mg, orally, once, on Cycle 1 Day 1, followed by, alisertib 20 mg, BID for 7 days (Cycle 1 Day 8 to 14) followed by a 14-day rest period. Starting at Cycle 2 Day 1, alisertib 20 mg, BID for 7 days followed by a 14-day rest period unless a dose reduction is indicated. Participants may continue to receive alisertib until they experience progressive disease or unacceptable alisertib-related toxicities for up to 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. Severe hepatic impairment includes participants with total bilirubin > 3 x ULN and any ALT level. | 4 | 8 | 7 | 8 | 8 | 8 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Colon cancer metastatic | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version: 19.0 | Systematic Assessment | One treatment-emergent death occurred during treatment with alisertib and is not related. |
|
| Colorectal adenocarcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version: 19.0 | Systematic Assessment | One treatment-emergent death occurred during treatment with alisertib and is not related. |
|
| Rectal cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version: 19.0 | Systematic Assessment | One treatment-emergent death occurred during treatment with alisertib and is not related. |
|
| Breast cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version: 19.0 | Systematic Assessment | One treatment-emergent death occurred during treatment with alisertib and is not related. |
|
| Pancreatic neuroendocrine tumour metastatic | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version: 19.0 | Systematic Assessment | One treatment-emergent death occurred during treatment with alisertib and is not related. |
|
| Ovarian cancer metastatic | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version: 19.0 | Systematic Assessment | One treatment-emergent death occurred during treatment with alisertib and is not related. |
|
| Pancreatic carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version: 19.0 | Systematic Assessment | One treatment-emergent death occurred during treatment with alisertib and is not related. |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Malaise | General disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Hyperbilirubinaemia | Hepatobiliary 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 alisertib and is not related. |
|
| Bile duct obstruction | Hepatobiliary disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Bacterial sepsis | Infections and infestations | MedDRA version: 19.0 | Systematic Assessment |
| |
| Biliary tract infection | Infections and infestations | MedDRA version: 19.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA version: 19.0 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA version: 19.0 | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Delirium | Psychiatric disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Hydronephrosis | Renal and urinary disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Cerebral haemorrhage | Nervous system disorders | MedDRA version: 19.0 | Systematic Assessment | One treatment-emergent death occurred during treatment with alisertib and is not related. |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Dermatitis bullous | Skin and subcutaneous tissue disorders | MedDRA version: 19.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Ascites | Gastrointestinal disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Retching | Gastrointestinal disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Gingival pain | Gastrointestinal disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Epigastric discomfort | Gastrointestinal disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Eructation | Gastrointestinal disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Haematochezia | Gastrointestinal disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Haemorrhoids | Gastrointestinal disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Oral pain | Gastrointestinal disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Tongue discolouration | Gastrointestinal disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Chills | General disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Mass | General disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Pain | General disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Peripheral swelling | General disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition 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 |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Lactic acidosis | Metabolism and nutrition disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Choking sensation | Respiratory, thoracic and mediastinal disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Anaemia of malignant disease | Blood and lymphatic system disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Haemolytic anaemia | Blood and lymphatic system disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Pancytopenia | Blood and lymphatic system disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Presyncope | Nervous system disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Amnesia | Nervous system disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Balance disorder | Nervous system disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Cervical radiculopathy | Nervous system disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Tongue biting | Nervous system disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Eczema | Skin and subcutaneous tissue disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Pain of skin | 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 maculo-papular | Skin and subcutaneous tissue disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Skin exfoliation | Skin and subcutaneous tissue disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Delirium | Psychiatric disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Stress | Psychiatric disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA version: 19.0 | Systematic Assessment |
| |
| Blood sodium decreased | Investigations | MedDRA version: 19.0 | Systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA version: 19.0 | Systematic Assessment |
| |
| Platelet count decreased | 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 |
| |
| Blood bilirubin increased | Investigations | MedDRA version: 19.0 | Systematic Assessment |
| |
| Blood calcium increased | Investigations | MedDRA version: 19.0 | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA version: 19.0 | Systematic Assessment |
| |
| Blood phosphorus decreased | Investigations | MedDRA version: 19.0 | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA version: 19.0 | Systematic Assessment |
| |
| Transaminases increased | Investigations | MedDRA version: 19.0 | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA version: 19.0 | Systematic Assessment |
| |
| Flank pain | Musculoskeletal and connective tissue 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 |
| |
| Muscular weakness | 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 |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Neck mass | Musculoskeletal and connective tissue disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Neck 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 |
| |
| Polymyalgia rheumatica | Musculoskeletal and connective tissue disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Hepatic failure | Hepatobiliary disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Hepatorenal syndrome | Hepatobiliary disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Portal hypertension | Hepatobiliary disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Portal vein thrombosis | Hepatobiliary disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA version: 19.0 | Systematic Assessment |
| |
| Oral candidiasis | Infections and infestations | MedDRA version: 19.0 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA version: 19.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA version: 19.0 | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Dysuria | Renal and urinary disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Nephrolithiasis | Renal and urinary disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Pollakiuria | Renal and urinary disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Hot flush | Vascular disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Jugular vein thrombosis | Vascular disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Cerumen impaction | Ear and labyrinth disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Deafness | Ear and labyrinth disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Dry eye | Eye disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Eye irritation | Eye disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA version: 19.0 | Systematic Assessment |
| |
| Pelvic fracture | Injury, poisoning and procedural complications | MedDRA version: 19.0 | Systematic Assessment |
| |
| Sinus tachycardia | Cardiac disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version: 19.0 | Systematic Assessment |
| |
| Pelvic pain | Reproductive system and breast disorders | MedDRA version: 19.0 | Systematic Assessment |
| |
| Bile duct obstruction | Hepatobiliary disorders | MedDRA version: 19.0 | Systematic Assessment |
|
The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
| 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 |
Not provided
Not provided
Not provided
|
|
|
| Not Hispanic or Latino |
|
|
| Not Reported |
|
|
|
| Black or African American |
|
|
|
|
|
|
| OG002 | Alisertib: Severe Hepatic Impairment | Alisertib 50 mg, orally, once, on Cycle 1 Day 1, followed by, alisertib 20 mg, BID for 7 days (Cycle 1 Day 8 to 14) followed by a 14-day rest period. Starting at Cycle 2 Day 1, alisertib 20 mg, BID for 7 days followed by a 14-day rest period unless a dose reduction is indicated. Participants may continue to receive alisertib until they experience progressive disease or unacceptable alisertib-related toxicities for up to 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. Severe hepatic impairment includes participants with total bilirubin > 3 x ULN and any ALT level. |
|
|
|
| OG002 | Alisertib: Severe Hepatic Impairment | Alisertib 50 mg, orally, once, on Cycle 1 Day 1, followed by, alisertib 20 mg, BID for 7 days (Cycle 1 Day 8 to 14) followed by a 14-day rest period. Starting at Cycle 2 Day 1, alisertib 20 mg, BID for 7 days followed by a 14-day rest period unless a dose reduction is indicated. Participants may continue to receive alisertib until they experience progressive disease or unacceptable alisertib-related toxicities for up to 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. Severe hepatic impairment includes participants with total bilirubin > 3 x ULN and any ALT level. |
|
|
|
Alisertib 50 mg, orally, once, on Cycle 1 Day 1, followed by alisertib 30 mg, BID for 7 days (Cycle 1 Day 8 to 14), followed by a 14-day rest period. Starting at Cycle 2 Day 1, alisertib 30 mg, BID for 7 days followed by a 14-day rest period unless a dose reduction is indicated. Participants may continue to receive alisertib until they experience progressive disease or unacceptable alisertib-related toxicities for up to 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. Moderate hepatic impairment includes participants with total bilirubin > 1.5-3 x ULN and any ALT level. |
| OG002 | Alisertib: Severe Hepatic Impairment | Alisertib 50 mg, orally, once, on Cycle 1 Day 1, followed by, alisertib 20 mg, BID for 7 days (Cycle 1 Day 8 to 14) followed by a 14-day rest period. Starting at Cycle 2 Day 1, alisertib 20 mg, BID for 7 days followed by a 14-day rest period unless a dose reduction is indicated. Participants may continue to receive alisertib until they experience progressive disease or unacceptable alisertib-related toxicities for up to 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. Severe hepatic impairment includes participants with total bilirubin > 3 x ULN and any ALT level. |
|
|
Alisertib 50 mg, orally, once, on Cycle 1 Day 1, followed by alisertib 30 mg, BID for 7 days (Cycle 1 Day 8 to 14), followed by a 14-day rest period. Starting at Cycle 2 Day 1, alisertib 30 mg, BID for 7 days followed by a 14-day rest period unless a dose reduction is indicated. Participants may continue to receive alisertib until they experience progressive disease or unacceptable alisertib-related toxicities for up to 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. Moderate hepatic impairment includes participants with total bilirubin > 1.5-3 x ULN and any ALT level. |
| OG002 | Alisertib: Severe Hepatic Impairment | Alisertib 50 mg, orally, once, on Cycle 1 Day 1, followed by, alisertib 20 mg, BID for 7 days (Cycle 1 Day 8 to 14) followed by a 14-day rest period. Starting at Cycle 2 Day 1, alisertib 20 mg, BID for 7 days followed by a 14-day rest period unless a dose reduction is indicated. Participants may continue to receive alisertib until they experience progressive disease or unacceptable alisertib-related toxicities for up to 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. Severe hepatic impairment includes participants with total bilirubin > 3 x ULN and any ALT level. |
|
|
Alisertib 50 mg, orally, once, on Cycle 1 Day 1, followed by alisertib 30 mg, BID for 7 days (Cycle 1 Day 8 to 14), followed by a 14-day rest period. Starting at Cycle 2 Day 1, alisertib 30 mg, BID for 7 days followed by a 14-day rest period unless a dose reduction is indicated. Participants may continue to receive alisertib until they experience progressive disease or unacceptable alisertib-related toxicities for up to 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. Moderate hepatic impairment includes participants with total bilirubin > 1.5-3 x ULN and any ALT level.
| OG002 | Alisertib: Severe Hepatic Impairment | Alisertib 50 mg, orally, once, on Cycle 1 Day 1, followed by, alisertib 20 mg, BID for 7 days (Cycle 1 Day 8 to 14) followed by a 14-day rest period. Starting at Cycle 2 Day 1, alisertib 20 mg, BID for 7 days followed by a 14-day rest period unless a dose reduction is indicated. Participants may continue to receive alisertib until they experience progressive disease or unacceptable alisertib-related toxicities for up to 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. Severe hepatic impairment includes participants with total bilirubin > 3 x ULN and any ALT level. |
|
|
| OG002 | Alisertib: Severe Hepatic Impairment | Alisertib 50 mg, orally, once, on Cycle 1 Day 1, followed by, alisertib 20 mg, BID for 7 days (Cycle 1 Day 8 to 14) followed by a 14-day rest period. Starting at Cycle 2 Day 1, alisertib 20 mg, BID for 7 days followed by a 14-day rest period unless a dose reduction is indicated. Participants may continue to receive alisertib until they experience progressive disease or unacceptable alisertib-related toxicities for up to 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. Severe hepatic impairment includes participants with total bilirubin > 3 x ULN and any ALT level. |
|
|
| OG002 | Alisertib: Severe Hepatic Impairment | Alisertib 50 mg, orally, once, on Cycle 1 Day 1, followed by, alisertib 20 mg, BID for 7 days (Cycle 1 Day 8 to 14) followed by a 14-day rest period. Starting at Cycle 2 Day 1, alisertib 20 mg, BID for 7 days followed by a 14-day rest period unless a dose reduction is indicated. Participants may continue to receive alisertib until they experience progressive disease or unacceptable alisertib-related toxicities for up to 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. Severe hepatic impairment includes participants with total bilirubin > 3 x ULN and any ALT level. |
|
|
| OG002 | Alisertib: Severe Hepatic Impairment | Alisertib 50 mg, orally, once, on Cycle 1 Day 1, followed by, alisertib 20 mg, BID for 7 days (Cycle 1 Day 8 to 14) followed by a 14-day rest period. Starting at Cycle 2 Day 1, alisertib 20 mg, BID for 7 days followed by a 14-day rest period unless a dose reduction is indicated. Participants may continue to receive alisertib until they experience progressive disease or unacceptable alisertib-related toxicities for up to 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. Severe hepatic impairment includes participants with total bilirubin > 3 x ULN and any ALT level. |
|
|
| OG001 | Alisertib: Moderate Hepatic Impairment | Alisertib 50 mg, orally, once, on Cycle 1 Day 1, followed by alisertib 30 mg, BID for 7 days (Cycle 1 Day 8 to 14), followed by a 14-day rest period. Starting at Cycle 2 Day 1, alisertib 30 mg, BID for 7 days followed by a 14-day rest period unless a dose reduction is indicated. Participants may continue to receive alisertib until they experience progressive disease or unacceptable alisertib-related toxicities for up to 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. Moderate hepatic impairment includes participants with total bilirubin > 1.5-3 x ULN and any ALT level. |
| OG002 | Alisertib: Severe Hepatic Impairment | Alisertib 50 mg, orally, once, on Cycle 1 Day 1, followed by, alisertib 20 mg, BID for 7 days (Cycle 1 Day 8 to 14) followed by a 14-day rest period. Starting at Cycle 2 Day 1, alisertib 20 mg, BID for 7 days followed by a 14-day rest period unless a dose reduction is indicated. Participants may continue to receive alisertib until they experience progressive disease or unacceptable alisertib-related toxicities for up to 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. Severe hepatic impairment includes participants with total bilirubin > 3 x ULN and any ALT level. |
|
|
| OG002 | Alisertib: Severe Hepatic Impairment | Alisertib 50 mg, orally, once, on Cycle 1 Day 1, followed by, alisertib 20 mg, BID for 7 days (Cycle 1 Day 8 to 14) followed by a 14-day rest period. Starting at Cycle 2 Day 1, alisertib 20 mg, BID for 7 days followed by a 14-day rest period unless a dose reduction is indicated. Participants may continue to receive alisertib until they experience progressive disease or unacceptable alisertib-related toxicities for up to 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. Severe hepatic impairment includes participants with total bilirubin > 3 x ULN and any ALT level. |
|