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Pharmacokinetics of Alisertib in Adults With Advanced Solid Tumors or Relapsed/Refractory Lymphoma With Varying Degrees of Hepatic Function

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ClinicalTrials.gov Identifier: NCT02214147
Recruitment Status : Completed
First Posted : August 12, 2014
Results First Posted : November 15, 2018
Last Update Posted : November 15, 2018
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Advanced Solid Tumors
Relapsed/Refractory Lymphoma
Intervention Drug: Alisertib
Enrollment 36
Recruitment Details Participants took part in the study at 6 investigative sites in the United States from 21 August 2014 to 18 July 2016.
Pre-assignment Details 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.
Arm/Group Title Alisertib: Normal Hepatic Function Alisertib: Moderate Hepatic Impairment Alisertib: Severe Hepatic Impairment
Hide Arm/Group Description 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 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 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.
Period Title: Overall Study
Started 16 12 8
Completed [1] 16 12 8
Not Completed 0 0 0
[1]
Completed=Completed protocol-specified dosing and PK assessment.
Arm/Group Title Alisertib: Normal Hepatic Function Alisertib: Moderate Hepatic Impairment Alisertib: Severe Hepatic Impairment Total
Hide Arm/Group Description 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 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 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. Total of all reporting groups
Overall Number of Baseline Participants 16 12 8 36
Hide Baseline Analysis Population Description
Safety population was defined as all participants who received at least 1 dose of alisertib.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 16 participants 12 participants 8 participants 36 participants
61.2  (10.07) 54.9  (9.89) 54.0  (7.05) 57.5  (9.77)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants 12 participants 8 participants 36 participants
Female
5
  31.3%
7
  58.3%
2
  25.0%
14
  38.9%
Male
11
  68.8%
5
  41.7%
6
  75.0%
22
  61.1%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Hispanic or Latino Number Analyzed 16 participants 12 participants 8 participants 36 participants
1
   6.3%
1
   8.3%
2
  25.0%
4
  11.1%
Not Hispanic or Latino Number Analyzed 16 participants 12 participants 8 participants 36 participants
14
  87.5%
11
  91.7%
6
  75.0%
31
  86.1%
Not Reported Number Analyzed 16 participants 12 participants 8 participants 36 participants
1
   6.3%
0
   0.0%
0
   0.0%
1
   2.8%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
White Number Analyzed 16 participants 12 participants 8 participants 36 participants
14
  87.5%
11
  91.7%
6
  75.0%
31
  86.1%
Black or African American Number Analyzed 16 participants 12 participants 8 participants 36 participants
2
  12.5%
1
   8.3%
2
  25.0%
5
  13.9%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 16 participants 12 participants 8 participants 36 participants
16
 100.0%
12
 100.0%
8
 100.0%
36
 100.0%
Height   [1] 
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 14 participants 11 participants 5 participants 30 participants
172.9  (14.62) 162.9  (7.79) 178.2  (8.10) 170.1  (12.66)
[1]
Measure Analysis Population Description: Height data is only available for n=14,11,5 participants.
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 16 participants 12 participants 8 participants 36 participants
84.6  (20.997) 85.5  (33.881) 85.8  (11.847) 85.2  (24.044)
Body surface area   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  M^2
Number Analyzed 14 participants 11 participants 5 participants 30 participants
2.030  (0.3073) 1.897  (0.4028) 2.056  (0.1970) 1.986  (0.3292)
[1]
Measure Description: Body surface area=square root[height(cm)*weight(kg)/3600]
[2]
Measure Analysis Population Description: Body surface area data is only available for n=14,11,5 participants.
1.Primary Outcome
Title Unbound Cmax: Maximum Observed Plasma Concentration for Alisertib
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1 Pre-dose and, and at multiple timepoints (up to 168 hours) post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Alisertib: Normal Hepatic Function Alisertib: Moderate Hepatic Impairment Alisertib: Severe Hepatic Impairment
Hide Arm/Group Description:
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 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 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.
Overall Number of Participants Analyzed 16 12 8
Mean (Standard Deviation)
Unit of Measure: nmol/L
17.3  (9.09) 28.1  (7.82) 18.5  (5.80)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alisertib: Normal Hepatic Function, Alisertib: Moderate Hepatic Impairment, Alisertib: Severe Hepatic Impairment
Comments [Not Specified]
Type of Statistical Test Other
Comments The effect of hepatic impairment on alisertib PK. Combined analysis of moderate and severe hepatic impairment in reference to normal hepatic function.
Method of Estimation Estimation Parameter Least Squares Geometric Mean Ratio
Estimated Value 1.42
Confidence Interval (2-Sided) 90%
1.12 to 1.80
Estimation Comments Least Squares Geometric Means Ratio= Moderate + Severe Hepatic Impairment/Normal Hepatic Function
2.Primary Outcome
Title Unbound AUClast: Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Alisertib
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1 Pre-dose and, and at multiple timepoints (up to 168 hours) post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Alisertib: Normal Hepatic Function Alisertib: Moderate Hepatic Impairment Alisertib: Severe Hepatic Impairment
Hide Arm/Group Description:
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 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 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.
Overall Number of Participants Analyzed 16 10 8
Mean (Standard Deviation)
Unit of Measure: h*nmol/L
248.5  (131.41) 859.1  (387.85) 735.4  (444.61)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alisertib: Normal Hepatic Function, Alisertib: Moderate Hepatic Impairment, Alisertib: Severe Hepatic Impairment
Comments [Not Specified]
Type of Statistical Test Other
Comments The effect of hepatic impairment on alisertib PK. Combined analysis of moderate and severe hepatic impairment in reference to normal hepatic function.
Method of Estimation Estimation Parameter Least Squares Geometric Mean Ratio
Estimated Value 3.21
Confidence Interval (2-Sided) 90%
2.33 to 4.43
Estimation Comments Least Squares Geometric Mean Ratio=Moderate + Severe Hepatic Impairment/Normal Hepatic Function
3.Primary Outcome
Title Unbound AUC0-∞: Area Under the Concentration-Time Curve From Time 0 to Infinity for Alisertib
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1 Pre-dose and, and at multiple timepoints (up to 168 hours) post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Alisertib: Normal Hepatic Function Alisertib: Moderate Hepatic Impairment Alisertib: Severe Hepatic Impairment
Hide Arm/Group Description:
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 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 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.
Overall Number of Participants Analyzed 12 10 7
Mean (Standard Deviation)
Unit of Measure: h*nmol/L
304.3  (119.09) 937.6  (428.98) 778.0  (610.51)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alisertib: Normal Hepatic Function, Alisertib: Moderate Hepatic Impairment, Alisertib: Severe Hepatic Impairment
Comments [Not Specified]
Type of Statistical Test Other
Comments The effect of hepatic impairment on alisertib PK. Combined analysis of moderate and severe hepatic impairment in reference to normal hepatic function.
Method of Estimation Estimation Parameter Least Squares Geometric Mean Ratio
Estimated Value 2.54
Confidence Interval (2-Sided) 90%
1.84 to 3.53
Estimation Comments Least Squares Geometric Mean Ratio=Moderate + Severe Hepatic Impairment/Normal Hepatic Function
4.Secondary Outcome
Title Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event
Hide Description 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.
Time Frame Baseline to 30 days after last dose (Up to 312 Days)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population was defined as all participants who received at least 1 dose of alisertib.
Arm/Group Title Alisertib: Normal Hepatic Function Alisertib: Moderate Hepatic Impairment Alisertib: Severe Hepatic Impairment
Hide Arm/Group Description:
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 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 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.
Overall Number of Participants Analyzed 16 12 8
Measure Type: Number
Unit of Measure: percentage of participants
100 100 100
5.Secondary Outcome
Title Percentage of Participants Who Experienced at Least 1 Serious Adverse Event
Hide Description 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.
Time Frame Baseline to 30 days after last dose (Up to 312 Days)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population was defined as all participants who received at least 1 dose of alisertib.
Arm/Group Title Alisertib: Normal Hepatic Function Alisertib: Moderate Hepatic Impairment Alisertib: Severe Hepatic Impairment
Hide Arm/Group Description:
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 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 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.
Overall Number of Participants Analyzed 16 12 8
Measure Type: Number
Unit of Measure: percentage of participants
44 67 88
6.Secondary Outcome
Title Percentage of Participants With Clinically Significant Laboratory Values
Hide Description 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.
Time Frame Baseline to the end of the study (Up to 312 Days)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population was defined as all participants who received at least 1 dose of alisertib.
Arm/Group Title Alisertib: Normal Hepatic Function Alisertib: Moderate Hepatic Impairment Alisertib: Severe Hepatic Impairment
Hide Arm/Group Description:
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 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 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.
Overall Number of Participants Analyzed 16 12 8
Measure Type: Number
Unit of Measure: percentage of participants
Gamma-glutamyltransferase increased 13 0 0
Alanine aminotransferase increased 0 8 0
Aspartate aminotransferase increased 0 8 0
Blood bilirubin increased 0 8 0
Transaminases increased 0 8 0
Blood sodium decreased 6 8 0
Blood calcium increased 6 0 0
Blood phosphorus decreased 6 0 0
Platelet count decreased 6 8 0
Blood alkaline phosphatase increased 6 8 0
Blood creatinine increased 0 8 0
Neutrophil count decreased 0 8 0
White blood cell count decreased 0 8 0
7.Secondary Outcome
Title Percentage of Participants With Clinically Significant Vital Signs
Hide Description 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.
Time Frame Baseline to the end of the study (Up to 312 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population was defined as all participants who received at least 1 dose of alisertib.
Arm/Group Title Alisertib: Normal Hepatic Function Alisertib: Moderate Hepatic Impairment Alisertib: Severe Hepatic Impairment
Hide Arm/Group Description:
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 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 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.
Overall Number of Participants Analyzed 16 12 8
Measure Type: Number
Unit of Measure: percentage of participants
Pyrexia 25 8 38
Sinus tachycardia 6 0 0
8.Secondary Outcome
Title Cmax: Maximum Observed Plasma Concentration for Alisertib Metabolites M1 and M2
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1 Pre-dose and, and at multiple timepoints (up to 168 hours) post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Alisertib: Normal Hepatic Function Alisertib: Moderate Hepatic Impairment Alisertib: Severe Hepatic Impairment
Hide Arm/Group Description:
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 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 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.
Overall Number of Participants Analyzed 16 12 8
Mean (Standard Deviation)
Unit of Measure: nmol/L
Metabolite M1 370.3  (282.02) 1774.0  (904.10) 2001.9  (1094.75)
Metabolite M2 154.6  (82.54) 173.8  (54.39) 207.3  (151.60)
9.Secondary Outcome
Title Tmax: Time of First Occurrence of Cmax for Alisertib Metabolites M1 and M2
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1 Pre-dose and, and at multiple timepoints (up to 168 hours) post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Alisertib: Normal Hepatic Function Alisertib: Moderate Hepatic Impairment Alisertib: Severe Hepatic Impairment
Hide Arm/Group Description:
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 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 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.
Overall Number of Participants Analyzed 16 12 8
Median (Full Range)
Unit of Measure: hours
Metabolite M1
3.500
(1.88 to 7.92)
24.000
(1.00 to 48.30)
24.150
(9.08 to 96.70)
Metabolite M2
9.000
(5.88 to 49.30)
24.050
(9.00 to 72.10)
24.150
(9.08 to 96.70)
10.Secondary Outcome
Title AUClast: Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Alisertib Metabolites M1 and M2
Hide Description 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.
Time Frame Cycle 1 Day 1 Pre-dose and, and at multiple timepoints (up to 168 hours) post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Alisertib: Normal Hepatic Function Alisertib: Moderate Hepatic Impairment Alisertib: Severe Hepatic Impairment
Hide Arm/Group Description:
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 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 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.
Overall Number of Participants Analyzed 16 10 8
Mean (Standard Deviation)
Unit of Measure: h*nmol/L
Metabolite M1 8366.3  (10790.88) 159665.0  (116960.23) 196750.0  (117472.08)
Metabolite M2 8923.1  (6539.00) 17326.0  (8562.96) 16987.5  (9384.25)
11.Secondary Outcome
Title Dose-normalized Trough Concentration of Alisertib on Cycle 1 Day 14
Hide Description 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.
Time Frame Pre-dose on Day 14 of Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
Data was not collected, as many participants dropped out of the study prior to Day 14 trough concentration collection.
Arm/Group Title Alisertib: Normal Hepatic Function Alisertib: Moderate Hepatic Impairment Alisertib: Severe Hepatic Impairment
Hide Arm/Group Description:
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 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 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.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame First dose of study drug to 30 days past last dose (Up to 312 Days)
Adverse Event Reporting Description 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.
 
Arm/Group Title Alisertib: Normal Hepatic Function Alisertib: Moderate Hepatic Impairment Alisertib: Severe Hepatic Impairment
Hide Arm/Group Description 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 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 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.
All-Cause Mortality
Alisertib: Normal Hepatic Function Alisertib: Moderate Hepatic Impairment Alisertib: Severe Hepatic Impairment
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/16 (12.50%)   3/12 (25.00%)   4/8 (50.00%) 
Hide Serious Adverse Events
Alisertib: Normal Hepatic Function Alisertib: Moderate Hepatic Impairment Alisertib: Severe Hepatic Impairment
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   7/16 (43.75%)   8/12 (66.67%)   7/8 (87.50%) 
Blood and lymphatic system disorders       
Anaemia  1  0/16 (0.00%)  1/12 (8.33%)  1/8 (12.50%) 
Cardiac disorders       
Atrial fibrillation  1  1/16 (6.25%)  0/12 (0.00%)  0/8 (0.00%) 
Gastrointestinal disorders       
Abdominal pain  1  0/16 (0.00%)  2/12 (16.67%)  3/8 (37.50%) 
Gastrointestinal haemorrhage  1  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
Stomatitis  1  0/16 (0.00%)  0/12 (0.00%)  1/8 (12.50%) 
General disorders       
Pyrexia  1  2/16 (12.50%)  0/12 (0.00%)  1/8 (12.50%) 
Malaise  1  1/16 (6.25%)  1/12 (8.33%)  0/8 (0.00%) 
Hepatobiliary disorders       
Hyperbilirubinaemia  1  0/16 (0.00%)  0/12 (0.00%)  1/8 (12.50%) 
Hepatic failure  1 [1]  0/16 (0.00%)  0/12 (0.00%)  1/8 (12.50%) 
Bile duct obstruction  1  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
Infections and infestations       
Bacterial sepsis  1  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
Biliary tract infection  1  0/16 (0.00%)  0/12 (0.00%)  1/8 (12.50%) 
Pneumonia  1  1/16 (6.25%)  0/12 (0.00%)  0/8 (0.00%) 
Sepsis  1  0/16 (0.00%)  0/12 (0.00%)  1/8 (12.50%) 
Metabolism and nutrition disorders       
Hyperkalaemia  1  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
Hyponatraemia  1  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Colon cancer metastatic  1 [1]  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
Colorectal adenocarcinoma  1 [1]  0/16 (0.00%)  0/12 (0.00%)  1/8 (12.50%) 
Rectal cancer  1 [1]  0/16 (0.00%)  0/12 (0.00%)  1/8 (12.50%) 
Breast cancer  1 [1]  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
Pancreatic neuroendocrine tumour metastatic  1 [1]  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
Ovarian cancer metastatic  1 [1]  1/16 (6.25%)  0/12 (0.00%)  0/8 (0.00%) 
Pancreatic carcinoma  1 [1]  0/16 (0.00%)  0/12 (0.00%)  1/8 (12.50%) 
Nervous system disorders       
Cerebral haemorrhage  1 [1]  1/16 (6.25%)  0/12 (0.00%)  0/8 (0.00%) 
Psychiatric disorders       
Confusional state  1  1/16 (6.25%)  0/12 (0.00%)  0/8 (0.00%) 
Delirium  1  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
Renal and urinary disorders       
Acute kidney injury  1  0/16 (0.00%)  0/12 (0.00%)  1/8 (12.50%) 
Hydronephrosis  1  1/16 (6.25%)  0/12 (0.00%)  0/8 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Dyspnoea  1  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
Skin and subcutaneous tissue disorders       
Dermatitis bullous  1  0/16 (0.00%)  0/12 (0.00%)  1/8 (12.50%) 
1
Term from vocabulary, MedDRA version: 19.0
Indicates events were collected by systematic assessment
[1]
One treatment-emergent death occurred during treatment with alisertib and is not related.
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Alisertib: Normal Hepatic Function Alisertib: Moderate Hepatic Impairment Alisertib: Severe Hepatic Impairment
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   15/16 (93.75%)   12/12 (100.00%)   8/8 (100.00%) 
Blood and lymphatic system disorders       
Thrombocytopenia  1  1/16 (6.25%)  5/12 (41.67%)  0/8 (0.00%) 
Anaemia  1  1/16 (6.25%)  3/12 (25.00%)  1/8 (12.50%) 
Neutropenia  1  4/16 (25.00%)  1/12 (8.33%)  0/8 (0.00%) 
Leukopenia  1  2/16 (12.50%)  1/12 (8.33%)  1/8 (12.50%) 
Anaemia of malignant disease  1  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
Haemolytic anaemia  1  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
Lymphadenopathy  1  1/16 (6.25%)  0/12 (0.00%)  0/8 (0.00%) 
Pancytopenia  1  1/16 (6.25%)  0/12 (0.00%)  0/8 (0.00%) 
Cardiac disorders       
Sinus tachycardia  1  1/16 (6.25%)  0/12 (0.00%)  0/8 (0.00%) 
Ear and labyrinth disorders       
Cerumen impaction  1  0/16 (0.00%)  2/12 (16.67%)  0/8 (0.00%) 
Deafness  1  0/16 (0.00%)  0/12 (0.00%)  1/8 (12.50%) 
Eye disorders       
Dry eye  1  0/16 (0.00%)  0/12 (0.00%)  1/8 (12.50%) 
Eye irritation  1  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
Vision blurred  1  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
Gastrointestinal disorders       
Nausea  1  9/16 (56.25%)  3/12 (25.00%)  0/8 (0.00%) 
Diarrhoea  1  6/16 (37.50%)  4/12 (33.33%)  0/8 (0.00%) 
Vomiting  1  4/16 (25.00%)  4/12 (33.33%)  0/8 (0.00%) 
Ascites  1  0/16 (0.00%)  6/12 (50.00%)  1/8 (12.50%) 
Constipation  1  5/16 (31.25%)  2/12 (16.67%)  0/8 (0.00%) 
Stomatitis  1  5/16 (31.25%)  2/12 (16.67%)  0/8 (0.00%) 
Abdominal pain  1  1/16 (6.25%)  3/12 (25.00%)  2/8 (25.00%) 
Dyspepsia  1  3/16 (18.75%)  0/12 (0.00%)  0/8 (0.00%) 
Retching  1  1/16 (6.25%)  2/12 (16.67%)  0/8 (0.00%) 
Gingival pain  1  2/16 (12.50%)  0/12 (0.00%)  0/8 (0.00%) 
Abdominal distension  1  0/16 (0.00%)  0/12 (0.00%)  1/8 (12.50%) 
Abdominal pain upper  1  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
Dysphagia  1  1/16 (6.25%)  0/12 (0.00%)  0/8 (0.00%) 
Epigastric discomfort  1  1/16 (6.25%)  0/12 (0.00%)  0/8 (0.00%) 
Eructation  1  0/16 (0.00%)  0/12 (0.00%)  1/8 (12.50%) 
Haematochezia  1  0/16 (0.00%)  0/12 (0.00%)  1/8 (12.50%) 
Haemorrhoids  1  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
Oral pain  1  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
Tongue discolouration  1  1/16 (6.25%)  0/12 (0.00%)  0/8 (0.00%) 
General disorders       
Fatigue  1  6/16 (37.50%)  3/12 (25.00%)  3/8 (37.50%) 
Pyrexia  1  4/16 (25.00%)  1/12 (8.33%)  2/8 (25.00%) 
Oedema peripheral  1  2/16 (12.50%)  3/12 (25.00%)  1/8 (12.50%) 
Chills  1  4/16 (25.00%)  0/12 (0.00%)  1/8 (12.50%) 
Chest pain  1  1/16 (6.25%)  0/12 (0.00%)  0/8 (0.00%) 
Influenza like illness  1  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
Mass  1  1/16 (6.25%)  0/12 (0.00%)  0/8 (0.00%) 
Non-cardiac chest pain  1  1/16 (6.25%)  0/12 (0.00%)  0/8 (0.00%) 
Pain  1  1/16 (6.25%)  0/12 (0.00%)  0/8 (0.00%) 
Peripheral swelling  1  0/16 (0.00%)  0/12 (0.00%)  1/8 (12.50%) 
Hepatobiliary disorders       
Hyperbilirubinaemia  1  0/16 (0.00%)  5/12 (41.67%)  0/8 (0.00%) 
Hepatic failure  1  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
Hepatorenal syndrome  1  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
Portal hypertension  1  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
Portal vein thrombosis  1  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
Bile duct obstruction  1  0/16 (0.00%)  1/12 (8.33%)  1/8 (12.50%) 
Infections and infestations       
Pneumonia  1  2/16 (12.50%)  0/12 (0.00%)  0/8 (0.00%) 
Oral candidiasis  1  0/16 (0.00%)  0/12 (0.00%)  1/8 (12.50%) 
Sepsis  1  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
Urinary tract infection  1  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
Injury, poisoning and procedural complications       
Fall  1  1/16 (6.25%)  0/12 (0.00%)  1/8 (12.50%) 
Pelvic fracture  1  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
Investigations       
Blood alkaline phosphatase increased  1  1/16 (6.25%)  1/12 (8.33%)  0/8 (0.00%) 
Blood sodium decreased  1  1/16 (6.25%)  1/12 (8.33%)  0/8 (0.00%) 
Gamma-glutamyltransferase increased  1  2/16 (12.50%)  0/12 (0.00%)  0/8 (0.00%) 
Platelet count decreased  1  1/16 (6.25%)  1/12 (8.33%)  0/8 (0.00%) 
Alanine aminotransferase increased  1  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
Aspartate aminotransferase increased  1  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
Blood bilirubin increased  1  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
Blood calcium increased  1  1/16 (6.25%)  0/12 (0.00%)  0/8 (0.00%) 
Blood creatinine increased  1  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
Blood phosphorus decreased  1  1/16 (6.25%)  0/12 (0.00%)  0/8 (0.00%) 
Neutrophil count decreased  1  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
Transaminases increased  1  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
White blood cell count decreased  1  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
Metabolism and nutrition disorders       
Decreased appetite  1  4/16 (25.00%)  3/12 (25.00%)  1/8 (12.50%) 
Hyponatraemia  1  3/16 (18.75%)  2/12 (16.67%)  1/8 (12.50%) 
Dehydration  1  1/16 (6.25%)  4/12 (33.33%)  0/8 (0.00%) 
Hyperkalaemia  1  2/16 (12.50%)  1/12 (8.33%)  0/8 (0.00%) 
Hypoalbuminaemia  1  0/16 (0.00%)  1/12 (8.33%)  1/8 (12.50%) 
Hypokalaemia  1  1/16 (6.25%)  1/12 (8.33%)  0/8 (0.00%) 
Hypercalcaemia  1  1/16 (6.25%)  0/12 (0.00%)  0/8 (0.00%) 
Hypocalcaemia  1  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
Hypoglycaemia  1  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
Hypomagnesaemia  1  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
Lactic acidosis  1  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
Musculoskeletal and connective tissue disorders       
Flank pain  1  0/16 (0.00%)  2/12 (16.67%)  1/8 (12.50%) 
Back pain  1  1/16 (6.25%)  1/12 (8.33%)  0/8 (0.00%) 
Arthralgia  1  1/16 (6.25%)  0/12 (0.00%)  0/8 (0.00%) 
Muscular weakness  1  0/16 (0.00%)  0/12 (0.00%)  1/8 (12.50%) 
Musculoskeletal chest pain  1  1/16 (6.25%)  0/12 (0.00%)  0/8 (0.00%) 
Myalgia  1  0/16 (0.00%)  0/12 (0.00%)  1/8 (12.50%) 
Neck mass  1  1/16 (6.25%)  0/12 (0.00%)  0/8 (0.00%) 
Neck pain  1  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
Pain in extremity  1  0/16 (0.00%)  0/12 (0.00%)  1/8 (12.50%) 
Polymyalgia rheumatica  1  1/16 (6.25%)  0/12 (0.00%)  0/8 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Tumour pain  1  0/16 (0.00%)  0/12 (0.00%)  1/8 (12.50%) 
Nervous system disorders       
Headache  1  4/16 (25.00%)  1/12 (8.33%)  1/8 (12.50%) 
Dizziness  1  2/16 (12.50%)  3/12 (25.00%)  0/8 (0.00%) 
Presyncope  1  1/16 (6.25%)  1/12 (8.33%)  0/8 (0.00%) 
Amnesia  1  1/16 (6.25%)  0/12 (0.00%)  0/8 (0.00%) 
Balance disorder  1  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
Cervical radiculopathy  1  0/16 (0.00%)  0/12 (0.00%)  1/8 (12.50%) 
Dysgeusia  1  1/16 (6.25%)  0/12 (0.00%)  0/8 (0.00%) 
Somnolence  1  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
Tongue biting  1  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
Psychiatric disorders       
Confusional state  1  0/16 (0.00%)  3/12 (25.00%)  2/8 (25.00%) 
Anxiety  1  1/16 (6.25%)  2/12 (16.67%)  0/8 (0.00%) 
Insomnia  1  3/16 (18.75%)  0/12 (0.00%)  0/8 (0.00%) 
Delirium  1  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
Stress  1  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
Renal and urinary disorders       
Acute kidney injury  1  0/16 (0.00%)  1/12 (8.33%)  1/8 (12.50%) 
Dysuria  1  0/16 (0.00%)  2/12 (16.67%)  0/8 (0.00%) 
Nephrolithiasis  1  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
Pollakiuria  1  0/16 (0.00%)  0/12 (0.00%)  1/8 (12.50%) 
Reproductive system and breast disorders       
Pelvic pain  1  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  3/16 (18.75%)  1/12 (8.33%)  1/8 (12.50%) 
Dyspnoea  1  2/16 (12.50%)  1/12 (8.33%)  1/8 (12.50%) 
Pleural effusion  1  2/16 (12.50%)  1/12 (8.33%)  0/8 (0.00%) 
Dyspnoea exertional  1  1/16 (6.25%)  1/12 (8.33%)  0/8 (0.00%) 
Nasal congestion  1  1/16 (6.25%)  1/12 (8.33%)  0/8 (0.00%) 
Choking sensation  1  1/16 (6.25%)  0/12 (0.00%)  0/8 (0.00%) 
Haemoptysis  1  1/16 (6.25%)  0/12 (0.00%)  0/8 (0.00%) 
Hypoxia  1  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
Oropharyngeal pain  1  1/16 (6.25%)  0/12 (0.00%)  0/8 (0.00%) 
Pulmonary embolism  1  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
Rhinorrhoea  1  1/16 (6.25%)  0/12 (0.00%)  0/8 (0.00%) 
Skin and subcutaneous tissue disorders       
Alopecia  1  6/16 (37.50%)  3/12 (25.00%)  1/8 (12.50%) 
Dry skin  1  1/16 (6.25%)  1/12 (8.33%)  0/8 (0.00%) 
Hyperhidrosis  1  2/16 (12.50%)  0/12 (0.00%)  0/8 (0.00%) 
Palmar-plantar erythrodysaesthesia syndrome  1  0/16 (0.00%)  1/12 (8.33%)  1/8 (12.50%) 
Dermatitis acneiform  1  1/16 (6.25%)  0/12 (0.00%)  0/8 (0.00%) 
Eczema  1  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
Pain of skin  1  1/16 (6.25%)  0/12 (0.00%)  0/8 (0.00%) 
Pruritus  1  0/16 (0.00%)  0/12 (0.00%)  1/8 (12.50%) 
Rash  1  0/16 (0.00%)  0/12 (0.00%)  1/8 (12.50%) 
Rash maculo-papular  1  0/16 (0.00%)  0/12 (0.00%)  1/8 (12.50%) 
Skin exfoliation  1  1/16 (6.25%)  0/12 (0.00%)  0/8 (0.00%) 
Vascular disorders       
Hypotension  1  0/16 (0.00%)  2/12 (16.67%)  1/8 (12.50%) 
Deep vein thrombosis  1  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
Hot flush  1  1/16 (6.25%)  0/12 (0.00%)  0/8 (0.00%) 
Jugular vein thrombosis  1  0/16 (0.00%)  1/12 (8.33%)  0/8 (0.00%) 
1
Term from vocabulary, MedDRA version: 19.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Director
Organization: Takeda
Phone: +1-877-825-3327
EMail: trialdisclosures@takeda.com
Layout table for additonal information
Responsible Party: Takeda ( Millennium Pharmaceuticals, Inc. )
ClinicalTrials.gov Identifier: NCT02214147    
Other Study ID Numbers: C14019
U1111-1155-6072 ( Other Identifier: World Health Organization )
First Submitted: July 30, 2014
First Posted: August 12, 2014
Results First Submitted: April 9, 2018
Results First Posted: November 15, 2018
Last Update Posted: November 15, 2018