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A Study of MLN8237, a Novel Aurora A Kinase Inhibitor, in Participants With Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT00500903
Recruitment Status : Completed
First Posted : July 13, 2007
Results First Posted : March 14, 2019
Last Update Posted : March 14, 2019
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
Condition Advanced Malignancies
Intervention Drug: Alisertib
Enrollment 87
Recruitment Details Participants took part in the study at 3 investigative sites in the United States from 15 May 2007 to 23 February 2011.
Pre-assignment Details Participants with a diagnosis of advanced malignancies were enrolled in 1 of 3 treatment groups, alisertib 5 to 150 mg Powder-in-Capsule (PIC) dose escalation cohort, alisertib 10 or 20 mg Enteric-coated Tablet (ECT) dose escalation cohort, or alisertib 40 mg PIC/ECT in a crossover design followed by alisertib 50 mg relative bioavailability cohort.
Arm/Group Title PIC Dose Escalation ECT Dose Escalation Relative Bioavailability
Hide Arm/Group Description Alisertib 5, 10, 20, 40, 80, 110 or 150 mg, PIC, orally, once daily (QD) for 7 days, followed by a 14-day recovery period or alisertib 25 mg, PIC, orally, QD for 14 days, followed by a 14-day recovery period or alisertib 25, 50 or 70 mg, PIC, orally, QD for 21 days followed by a 14-day recovery period or alisertib 50 or 60 mg, PIC, orally, twice daily (BID) for 7 days followed by a 14-day recovery period or alisertib 40 mg, PIC, orally, BID for 14 days followed by a 14-day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles). Alisertib 10 or 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-­related toxicity (up to 2 cycles). Alisertib 40 mg ECT or PIC formulation, orally, twice daily (BID) for 7 days followed by a 14-­day recovery period in cycle 1, followed by alisertib 40 mg in the opposite formulation (PIC or ECT) orally, twice daily (BID) for 7 days followed by a 14-­day recovery period in cycle 2, followed by alisertib 50 mg PIC formulation orally, twice daily (BID) for 7 days followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-­related toxicity (up to 9 cycles).
Period Title: Overall Study
Started 65 2 20
Completed 0 0 0
Not Completed 65 2 20
Reason Not Completed
Occurrence of Adverse Event(s)             10             0             0
Unsatisfactory Therapeutic Response             2             0             0
Progressive Disease             41             2             15
Patient Declined Further Treatment             0             0             3
Symptomatic Deterioration             2             0             0
Reason Not Specified             10             0             2
Arm/Group Title PIC Dose Escalation ECT Dose Escalation Relative Bioavailability Total
Hide Arm/Group Description Alisertib 5, 10, 20, 40, 80, 110 or 150 mg, PIC, orally, once daily (QD) for 7 days, followed by a 14-day recovery period or alisertib 25 mg, PIC, orally, QD for 14 days, followed by a 14-day recovery period or alisertib 25, 50 or 70 mg, PIC, orally, QD for 21 days followed by a 14-day recovery period or alisertib 50 or 60 mg, PIC, orally, twice daily (BID) for 7 days followed by a 14-day recovery period or alisertib 40 mg, PIC, orally, BID for 14 days followed by a 14-day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles). Alisertib 10 or 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-­related toxicity (up to 2 cycles). Alisertib 40 mg ECT or PIC formulation, orally, twice daily (BID) for 7 days followed by a 14-­day recovery period in cycle 1, followed by alisertib 40 mg in the opposite formulation (PIC or ECT) orally, twice daily (BID) for 7 days followed by a 14-­day recovery period in cycle 2, followed by alisertib 50 mg PIC formulation orally, twice daily (BID) for 7 days followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-­related toxicity (up to 9 cycles). Total of all reporting groups
Overall Number of Baseline Participants 65 2 20 87
Hide Baseline Analysis Population Description
The Safety Population included all participants who received any amount of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 65 participants 2 participants 20 participants 87 participants
61.6  (10.44) 57.0  (15.56) 56.9  (11.71) 60.4  (10.88)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 65 participants 2 participants 20 participants 87 participants
Female
33
  50.8%
1
  50.0%
9
  45.0%
43
  49.4%
Male
32
  49.2%
1
  50.0%
11
  55.0%
44
  50.6%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 65 participants 2 participants 20 participants 87 participants
Not Hispanic or Latino 56 2 20 78
Not Reported 7 0 0 7
Hispanic or Latino 2 0 0 2
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 65 participants 2 participants 20 participants 87 participants
White 55 2 18 75
Black or African American 9 0 2 11
Other 1 0 0 1
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 65 participants 2 participants 20 participants 87 participants
65 2 20 87
Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 65 participants 2 participants 20 participants 87 participants
169.3  (10.06) 165.1  (0.00) 171.5  (12.51) 169.7  (10.55)
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 65 participants 2 participants 20 participants 87 participants
78.24  (18.130) 67.36  (11.226) 83.97  (21.706) 79.33  (18.976)
Body Surface Area (BSA)   [1] 
Mean (Standard Deviation)
Unit of measure:  M^2
Number Analyzed 65 participants 2 participants 20 participants 87 participants
1.91  (0.263) 1.75  (0.147) 1.99  (0.294) 1.92  (0.270)
[1]
Measure Description: BSA=square root[height (cm) x weight (kg)/3600]
1.Primary Outcome
Title Number of Participants With Dose-Limiting Toxicity (DLT)
Hide Description

DLT was evaluated according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0 and was defined as any of the following events related to therapy with alisertib:

  1. Grade 4 neutropenia lasting ≥7 consecutive days
  2. Grade 4 neutropenia with fever and/or infection
  3. Platelet count <25,000/mm^3
  4. Grade 3 or greater nausea and/or emesis despite use of optimal antiemetic prophylaxis
  5. Grade 3 or greater diarrhea despite maximal supportive therapy with loperamide
  6. Any other Grade 3 or greater nonhematologic toxicity, with the following exceptions: Grade 3 arthralgia/myalgias, Any grade of alopecia, Brief (<1 week) Grade 3 fatigue
  7. Treatment delay of >1 week due to failure of adequate hematologic or nonhematologic recovery from previous cycle of treatment
  8. Other alisertib-related nonhematologic toxicities ≥Grade 2 that, in the opinion of the investigator, required a dose reduction or discontinuation of therapy with alisertib.
Time Frame Cycle 1 Day 1 up to Day 35 (alisertib daily for 7 to 21 days followed by a 14-day recovery period)
Hide Outcome Measure Data
Hide Analysis Population Description
DLT-Evaluable Population included all participants who received at least 75% of their planned alisertib doses for their first cycle of treatment (unless interrupted by DLT) and had sufficient follow-up data to allow the investigators and sponsor to determine whether DLT occurred.
Arm/Group Title Alisertib 5 mg PIC QD 7D Alisertib 10 mg PIC QD 7D Alisertib 20 mg PIC QD 7D Alisertib 40 mg PIC QD 7D Alisertib 80 mg PIC QD 7D Alisertib 110 mg PIC QD 7D Alisertib 150 mg PIC QD 7D Alisertib 25 mg PIC QD 14D Alisertib 25 mg PIC QD 21D Alisertib 50 mg PIC QD 21D Alisertib 70 mg PIC QD 21D Alisertib 50 mg PIC BID 7D Alisertib 60 mg PIC BID 7D Alisertib 40 mg PIC BID 14D Alisertib 10 mg ECT QD7 Alisertib 20 mg ECT QD7
Hide Arm/Group Description:
Alisertib 5 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
Alisertib 10 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Alisertib 10 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-­related toxicity (up to 2 cycles).
Alisertib 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-­related toxicity (up to 2 cycles).
Overall Number of Participants Analyzed 3 3 3 3 3 6 6 3 3 6 7 11 6 2 1 1
Measure Type: Number
Unit of Measure: participants
0 0 0 0 0 1 3 0 0 0 1 2 2 2 0 0
2.Primary Outcome
Title Maximum Tolerated Dose (MTD) of Alisertib
Hide Description MTD was defined as the highest dose at which DLT occurred in 0/3 or 1/6 patients.
Time Frame From first dose of study drug to 30 days after the last dose (up to 1011 days)
Hide Outcome Measure Data
Hide Analysis Population Description
DLT-Evaluable Population included all participants who received at least 75% of their planned alisertib doses for their first cycle of treatment (unless interrupted by DLT) and had sufficient follow-up data to allow the investigators and sponsor to determine whether DLT occurred.
Arm/Group Title Alisertib
Hide Arm/Group Description:
Alisertib 5, 10, 20, 40, 80, 110 or 150 mg, PIC, orally, once daily (QD) for 7 days, followed by a 14-day recovery period or alisertib 25 mg, PIC, orally, QD for 14 days, followed by a 14-day recovery period or alisertib 25, 50 or 70 mg, PIC, orally, QD for 21 days followed by a 14-day recovery period or alisertib 50 or 60 mg, PIC, orally, twice daily (BID) for 7 days followed by a 14-day recovery period or alisertib 40 mg, PIC, orally, BID for 14 days followed by a 14-day recovery period or alisertib 10 or 20 mg ECT, orally QD for 7 days followed by a 14-day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
Overall Number of Participants Analyzed 65
Measure Type: Number
Unit of Measure: mg BID for 7 Days
50
3.Primary Outcome
Title Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Hide Description An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A Serious Adverse Event (SAE) A serious is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.
Time Frame From first dose of study drug to 30 days after the last dose (up to 1011 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population included all participants who received any amount of study drug.
Arm/Group Title PIC Dose Escalation ECT Dose Escalation Relative Bioavailability
Hide Arm/Group Description:
Alisertib 5, 10, 20, 40, 80, 110 or 150 mg, PIC, orally, once daily (QD) for 7 days, followed by a 14-day recovery period or alisertib 25 mg, PIC, orally, QD for 14 days, followed by a 14-day recovery period or alisertib 25, 50 or 70 mg, PIC, orally, QD for 21 days followed by a 14-day recovery period or alisertib 50 or 60 mg, PIC, orally, twice daily (BID) for 7 days followed by a 14-day recovery period or alisertib 40 mg, PIC, orally, BID for 14 days followed by a 14-day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
Alisertib 10 or 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-­related toxicity (up to 2 cycles).
Alisertib 40 mg ECT or PIC formulation, orally, twice daily (BID) for 7 days followed by a 14-­day recovery period in cycle 1, followed by alisertib 40 mg in the opposite formulation (PIC or ECT) orally, twice daily (BID) for 7 days followed by a 14-­day recovery period in cycle 2, followed by alisertib 50 mg PIC formulation orally, twice daily (BID) for 7 days followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-­related toxicity (up to 9 cycles).
Overall Number of Participants Analyzed 65 2 20
Measure Type: Number
Unit of Measure: participants
AEs 65 2 20
SAEs 26 0 1
4.Secondary Outcome
Title Cmax: Maximum Observed Concentration for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 7 Days (QD7D) Dosing
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1 predose and at multiple time-points (up to 24 hours) postdose and Day 7 predose and at multiple time-points (up to 10 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis. Here number analyzed is the number of participants with data available for analysis at the given time point.
Arm/Group Title Alisertib 5 mg PIC QD 7D Alisertib 10 mg PIC QD 7D Alisertib 20 mg PIC QD 7D Alisertib 40 mg PIC QD 7D Alisertib 80 mg PIC QD 7D Alisertib 110 mg PIC QD 7D Alisertib 150 mg PIC QD 7D
Hide Arm/Group Description:
Alisertib 5 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
Alisertib 10 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
Overall Number of Participants Analyzed 3 3 3 3 3 6 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nM
Day 1 Number Analyzed 3 participants 3 participants 3 participants 3 participants 3 participants 6 participants 6 participants
208.4
(27.96%)
279.1
(46.20%)
759.3
(11.82%)
1245.4
(20.60%)
1661.3
(45.20%)
2717.8
(44.62%)
4260.3
(42.62%)
Day 7 Number Analyzed 3 participants 2 participants 3 participants 3 participants 3 participants 6 participants 5 participants
285.7
(32.74%)
931.5
(81.68%)
1114.1
(36.96%)
1681.6
(64.62%)
2376.3
(51.06%)
3586.4
(48.28%)
4467.8
(24.58%)
5.Secondary Outcome
Title Tmax: Time of First Occurrence of Cmax for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 7 Days (QD7D) Dosing
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1 predose and at multiple time-points (up to 24 hours) postdose and Day 7 predose and at multiple time-points (up to 10 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis. Here number analyzed is the number of participants with data available for analysis at the given time point.
Arm/Group Title Alisertib 5 mg PIC QD 7D Alisertib 10 mg PIC QD 7D Alisertib 20 mg PIC QD 7D Alisertib 40 mg PIC QD 7D Alisertib 80 mg PIC QD 7D Alisertib 110 mg PIC QD 7D Alisertib 150 mg PIC QD 7D
Hide Arm/Group Description:
Alisertib 5 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
Alisertib 10 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
Overall Number of Participants Analyzed 3 3 3 3 3 6 6
Median (Full Range)
Unit of Measure: hours (h)
Day 1 Number Analyzed 3 participants 3 participants 3 participants 3 participants 3 participants 6 participants 6 participants
2.000
(1.50 to 3.00)
2.000
(1.50 to 3.00)
1.500
(1.50 to 1.50)
2.000
(1.50 to 6.00)
2.000
(1.50 to 3.00)
2.000
(1.48 to 5.57)
2.000
(1.45 to 3.00)
Day 7 Number Analyzed 3 participants 2 participants 3 participants 3 participants 3 participants 6 participants 5 participants
1.500
(1.00 to 1.50)
3.750
(1.50 to 6.00)
1.500
(1.50 to 2.00)
2.000
(1.97 to 6.00)
2.000
(1.98 to 3.05)
3.710
(1.42 to 6.02)
2.000
(1.48 to 3.93)
6.Secondary Outcome
Title AUCt: Area Under the Concentration­Time Curve From Time 0 to Time t for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 7 Days (QD7D) Dosing
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1 predose and at multiple time-points (up to 24 hours) postdose and Day 7 predose and at multiple time-points (up to 10 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis. Here number analyzed is the number of participants with data available for analysis at the given time point.
Arm/Group Title Alisertib 5 mg PIC QD 7D Alisertib 10 mg PIC QD 7D Alisertib 20 mg PIC QD 7D Alisertib 40 mg PIC QD 7D Alisertib 80 mg PIC QD 7D Alisertib 110 mg PIC QD 7D Alisertib 150 mg PIC QD 7D
Hide Arm/Group Description:
Alisertib 5 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
Alisertib 10 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
Overall Number of Participants Analyzed 3 3 3 3 3 6 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nM*h
Day 1 Number Analyzed 3 participants 3 participants 3 participants 3 participants 2 participants 6 participants 6 participants
1682.4
(31.06%)
2525.8
(21.87%)
5772.1
(10.68%)
12045.4
(57.01%)
20958.1
(38.92%)
29460.7
(39.43%)
38582.1
(45.95%)
Day 7 Number Analyzed 3 participants 2 participants 3 participants 3 participants 3 participants 6 participants 5 participants
2919.5
(32.31%)
10602.9
(107.87%)
10927.5
(45.27%)
21976.0
(96.64%)
27825.5
(53.59%)
46271.1
(33.38%)
53031.9
(26.22%)
7.Secondary Outcome
Title Terminal Half-Life (t1/2) for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 7 Days (QD7D) Dosing
Hide Description [Not Specified]
Time Frame Cycle 1 Day 7 predose and at multiple time-points (up to 10 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis, with data available at the given timepoint.
Arm/Group Title Alisertib 5 mg PIC QD 7D Alisertib 10 mg PIC QD 7D Alisertib 20 mg PIC QD 7D Alisertib 40 mg PIC QD 7D Alisertib 80 mg PIC QD 7D Alisertib 110 mg PIC QD 7D Alisertib 150 mg PIC QD 7D
Hide Arm/Group Description:
Alisertib 5 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
Alisertib 10 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
Overall Number of Participants Analyzed 2 2 3 2 3 6 5
Mean (Standard Deviation)
Unit of Measure: h
24.950  (20.4354) 35.150  (23.4052) 26.400  (19.7684) 18.155  (12.5087) 39.333  (18.8006) 13.427  (4.3465) 16.766  (9.7804)
8.Secondary Outcome
Title Accumulation Ratio (Rac) for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 7 Days (QD7D) Dosing
Hide Description [Not Specified]
Time Frame Cycle 1 Day 7 predose and at multiple time-points (up to 10 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis, with data available at the given timepoint.
Arm/Group Title Alisertib 5 mg PIC QD 7D Alisertib 10 mg PIC QD 7D Alisertib 20 mg PIC QD 7D Alisertib 40 mg PIC QD 7D Alisertib 80 mg PIC QD 7D Alisertib 110 mg PIC QD 7D Alisertib 150 mg PIC QD 7D
Hide Arm/Group Description:
Alisertib 5 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
Alisertib 10 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
Overall Number of Participants Analyzed 3 2 3 3 2 6 5
Mean (Standard Deviation)
Unit of Measure: ratio
1.753  (0.2754) 6.350  (7.2408) 2.037  (0.9708) 1.997  (0.9393) 1.535  (0.3323) 1.677  (0.6788) 1.588  (0.4129)
9.Secondary Outcome
Title Peak/Trough Ratio for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 7 Days (QD7D) Dosing
Hide Description [Not Specified]
Time Frame Cycle 1 Day 7 predose and at multiple time-points (up to 10 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis, with data available at the given timepoint.
Arm/Group Title Alisertib 5 mg PIC QD 7D Alisertib 10 mg PIC QD 7D Alisertib 20 mg PIC QD 7D Alisertib 40 mg PIC QD 7D Alisertib 80 mg PIC QD 7D Alisertib 110 mg PIC QD 7D Alisertib 150 mg PIC QD 7D
Hide Arm/Group Description:
Alisertib 5 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
Alisertib 10 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
Overall Number of Participants Analyzed 3 2 3 3 3 6 5
Mean (Standard Deviation)
Unit of Measure: ratio
4.107  (0.8460) 5.195  (3.9527) 5.430  (2.4856) 3.907  (2.3944) 3.850  (2.0612) 4.922  (2.5890) 4.610  (0.5314)
10.Secondary Outcome
Title CLss/F: Apparent Oral Clearance at Steady State for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 7 Days (QD7D) Dosing
Hide Description [Not Specified]
Time Frame Cycle 1 Day 7 predose and at multiple time-points (up to 10 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis, with data available at the given timepoint.
Arm/Group Title Alisertib 5 mg PIC QD 7D Alisertib 10 mg PIC QD 7D Alisertib 20 mg PIC QD 7D Alisertib 40 mg PIC QD 7D Alisertib 80 mg PIC QD 7D Alisertib 110 mg PIC QD 7D Alisertib 150 mg PIC QD 7D
Hide Arm/Group Description:
Alisertib 5 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
Alisertib 10 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
Overall Number of Participants Analyzed 3 2 3 3 3 6 5
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: liters (L)/h
3.302
(35.8915%)
1.817
(107.8347%)
3.525
(49.1267%)
3.511
(72.1346%)
5.545
(41.0258%)
4.348
(61.5266%)
5.450
(37.3021%)
11.Secondary Outcome
Title Ae: Amount of Alisertib Excreted in Urine Over the Collection Period for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 7 Days (QD7D) Dosing
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1 predose and at multiple time-points (up to 24 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis.
Arm/Group Title Alisertib 5 mg PIC QD 7D Alisertib 10 mg PIC QD 7D Alisertib 20 mg PIC QD 7D Alisertib 40 mg PIC QD 7D Alisertib 80 mg PIC QD 7D Alisertib 110 mg PIC QD 7D Alisertib 150 mg PIC QD 7D
Hide Arm/Group Description:
Alisertib 5 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
Alisertib 10 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
Overall Number of Participants Analyzed 3 3 3 3 2 6 6
Mean (Standard Deviation)
Unit of Measure: ng
0.0  (0.00) 0.0  (0.00) 0.0  (0.00) 4806.7  (8325.39) 18815.0  (1675.84) 13813.3  (16387.22) 14473.3  (15603.71)
12.Secondary Outcome
Title CLr: Renal Clearance of Alisertib as Powder-in-Capsule (PIC) With Once Daily for 7 Days (QD7D) Dosing
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1 predose and at multiple time-points (up to 24 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis.
Arm/Group Title Alisertib 40 mg PIC QD 7D Alisertib 80 mg PIC QD 7D Alisertib 110 mg PIC QD 7D Alisertib 150 mg PIC QD 7D
Hide Arm/Group Description:
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
Overall Number of Participants Analyzed 1 1 5 5
Mean (Standard Deviation)
Unit of Measure: L/h
0.0012630 [1]   (NA) 0.0013860 [1]   (NA) 0.0009414  (0.00063956) 0.0006710  (0.00060091)
[1]
Cannot be calculated for 1 participant
13.Secondary Outcome
Title Cmax: Maximum Observed Concentration for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1 predose and at multiple time-points (up to 24 hours) postdose and Day 7 predose and at multiple time-points (up to 10 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis.
Arm/Group Title Alisertib 25 mg PIC QD 14D
Hide Arm/Group Description:
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
Overall Number of Participants Analyzed 3
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nM
Day 1
778.7
(24.28%)
Day 7
995.5
(43.21%)
Day 14
808.9
(37.96%)
14.Secondary Outcome
Title Tmax: Time of First Occurrence of Cmax for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1 predose and at multiple time-points (up to 24 hours) postdose and Day 7 predose and at multiple time-points (up to 10 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis.
Arm/Group Title Alisertib 25 mg PIC QD 14D
Hide Arm/Group Description:
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
Overall Number of Participants Analyzed 3
Median (Full Range)
Unit of Measure: h
Day 1
4.000
(2.00 to 8.88)
Day 7
2.000
(2.00 to 2.00)
Day 14
2.000
(1.098 to 2.00)
15.Secondary Outcome
Title AUCt: Area Under the Concentration-­Time Curve From Time 0 to Time t for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1 predose and at multiple time-points (up to 24 hours) postdose and Day 7 predose and at multiple time-points (up to 10 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis.
Arm/Group Title Alisertib 25 mg PIC QD 14D
Hide Arm/Group Description:
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
Overall Number of Participants Analyzed 3
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nM*h
Day 1
8061.6
(17.30%)
Day 7
8634.0
(42.70%)
Day 14
8978.0
(20.15%)
16.Secondary Outcome
Title Terminal Half-Life for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing
Hide Description [Not Specified]
Time Frame Cycle 1 Day 14 predose and at multiple time-points (up to 10 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis.
Arm/Group Title Alisertib 25 mg PIC QD 14D
Hide Arm/Group Description:
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
Overall Number of Participants Analyzed 3
Mean (Standard Deviation)
Unit of Measure: h
65.67  (43.859)
17.Secondary Outcome
Title Accumulation Ratio (Rac) for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing
Hide Description [Not Specified]
Time Frame Cycle 1 Days 7 and 14 predose and at multiple time-points (up to 10 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis.
Arm/Group Title Alisertib 25 mg PIC QD 14D
Hide Arm/Group Description:
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
Overall Number of Participants Analyzed 3
Mean (Standard Deviation)
Unit of Measure: ratio
Day 7 1.203  (0.6964)
Day 14 1.133  (0.2303)
18.Secondary Outcome
Title Peak/Trough Ratio for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing
Hide Description [Not Specified]
Time Frame Cycle 1 Days 7 and 14 predose and at multiple time-points (up to 10 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis.
Arm/Group Title Alisertib 25 mg PIC QD 14D
Hide Arm/Group Description:
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
Overall Number of Participants Analyzed 3
Mean (Standard Deviation)
Unit of Measure: ratio
Day 7 6.877  (1.1151)
Day 14 5.073  (2.2113)
19.Secondary Outcome
Title CLss/F: Apparent Oral Clearance at Steady State for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing
Hide Description [Not Specified]
Time Frame Cycle 1 Days 7 and 14 predose and at multiple time-points (up to 10 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis.
Arm/Group Title Alisertib 25 mg PIC QD 14D
Hide Arm/Group Description:
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
Overall Number of Participants Analyzed 3
Mean (Standard Deviation)
Unit of Measure: L/h
Day 7 6.030  (2.9963)
Day 14 5.433  (0.9808)
20.Secondary Outcome
Title Ae: Amount of Alisertib Excreted in Urine Over the Collection Period for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1 predose and at multiple time-points (up to 24 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis.
Arm/Group Title Alisertib 25 mg PIC QD 14D
Hide Arm/Group Description:
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
Overall Number of Participants Analyzed 3
Mean (Standard Deviation)
Unit of Measure: ng
800.0  (1385.64)
21.Secondary Outcome
Title CLr: Renal Clearance of Alisertib as Powder-in-Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1 predose and at multiple time-points (up to 24 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis.
Arm/Group Title Alisertib 25 mg PIC QD 14D
Hide Arm/Group Description:
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
Overall Number of Participants Analyzed 1
Mean (Standard Deviation)
Unit of Measure: L/h
0.0004930 [1]   (NA)
[1]
Cannot be calculated for 1 participant
22.Secondary Outcome
Title Cmax: Maximum Observed Concentration for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1 predose and at multiple timepoints up to 24 hours postdose and Days 14 and 21 predose and at multiple time points (up to 10 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis. Here number analyzed is the number of participants with data available for analysis at the given time point.
Arm/Group Title Alisertib 25 mg PIC QD 21D Alisertib 50 mg PIC QD 21D Alisertib 70 mg PIC QD 21D
Hide Arm/Group Description:
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Overall Number of Participants Analyzed 3 6 7
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nM
Day 1 Number Analyzed 3 participants 6 participants 7 participants
898.2
(86.35%)
1725.9
(54.70%)
2237.0
(54.18%)
Day 14 Number Analyzed 3 participants 6 participants 5 participants
1343.3
(60.32%)
1722.0
(38.82%)
2598.3
(12.49%)
Day 21 Number Analyzed 3 participants 6 participants 5 participants
1104.7
(45.15%)
1564.2
(38.80%)
1974.5
(59.49%)
23.Secondary Outcome
Title Tmax: Time of First Occurrence of Cmax for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1 predose and at multiple timepoints up to 24 hours postdose and Days 14 and 21 predose and at multiple time points (up to 10 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis. Here number analyzed is the number of participants with data available for analysis at the given time point.
Arm/Group Title Alisertib 25 mg PIC QD 21D Alisertib 50 mg PIC QD 21D Alisertib 70 mg PIC QD 21D
Hide Arm/Group Description:
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Overall Number of Participants Analyzed 3 6 7
Median (Full Range)
Unit of Measure: h
Day 1 Number Analyzed 3 participants 6 participants 7 participants
2.020
(2.00 to 4.00)
2.285
(2.00 to 4.00)
2.000
(2.00 to 2.02)
Day 14 Number Analyzed 3 participants 6 participants 5 participants
2.000
(2.00 to 2.18)
2.000
(1.98 to 2.03)
2.000
(2.00 to 2.05)
Day 21 Number Analyzed 3 participants 6 participants 5 participants
2.000
(1.00 to 2.02)
2.000
(1.93 to 9.92)
2.000
(1.00 to 6.00)
24.Secondary Outcome
Title AUCt: Area Under the Concentration-time Curve From Time 0 to Time t for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1 predose and at multiple timepoints up to 24 hours postdose and Days 14 and 21 predose and at multiple time points (up to 10 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis. Here number analyzed is the number of participants with data available for analysis at the given time point.
Arm/Group Title Alisertib 25 mg PIC QD 21D Alisertib 50 mg PIC QD 21D Alisertib 70 mg PIC QD 21D
Hide Arm/Group Description:
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Overall Number of Participants Analyzed 3 6 7
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nM*h
Day 1 Number Analyzed 3 participants 6 participants 6 participants
10058.0
(66.85%)
14686.6
(44.04%)
22114.8
(68.66%)
Day 14 Number Analyzed 3 participants 6 participants 4 participants
15131.7
(49.89%)
17168.2
(32.09%)
23197.2
(17.75%)
Day 21 Number Analyzed 3 participants 6 participants 5 participants
13199.3
(70.05%)
19336.3
(26.85%)
23499.8
(65.64%)
25.Secondary Outcome
Title Terminal Half-Life (t1/2) for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing
Hide Description [Not Specified]
Time Frame Cycle 1 Day 21 predose and at multiple time points (up to 10 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis, with data available at the given time­point.
Arm/Group Title Alisertib 25 mg PIC QD 21D Alisertib 50 mg PIC QD 21D Alisertib 70 mg PIC QD 21D
Hide Arm/Group Description:
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Overall Number of Participants Analyzed 3 6 5
Mean (Standard Deviation)
Unit of Measure: h
31.667  (6.7122) 23.650  (16.9487) 22.378  (19.8802)
26.Secondary Outcome
Title Accumulation Ratio (Rac) for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing
Hide Description [Not Specified]
Time Frame Cycle 1 Days 14 and 21 predose and at multiple timepoints (up to 10 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis. Here number analyzed is the number of participants with data available for analysis at the given time point.
Arm/Group Title Alisertib 25 mg PIC QD 21D Alisertib 50 mg PIC QD 21D Alisertib 70 mg PIC QD 21D
Hide Arm/Group Description:
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Overall Number of Participants Analyzed 3 6 7
Mean (Standard Deviation)
Unit of Measure: ratio
Day 14 Number Analyzed 3 participants 6 participants 3 participants
1.560  (0.5543) 1.230  (0.4193) 1.440  (0.1493)
Day 21 Number Analyzed 3 participants 6 participants 4 participants
1.560  (1.0516) 1.373  (0.4474) 1.335  (0.4749)
27.Secondary Outcome
Title Peak/Trough Ratio for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing
Hide Description [Not Specified]
Time Frame Cycle 1 Days 14 and 21 predose and at multiple timepoints up to 10 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis. Here number analyzed is the number of participants with data available for analysis at the given time point.
Arm/Group Title Alisertib 25 mg PIC QD 21D Alisertib 50 mg PIC QD 21D Alisertib 70 mg PIC QD 21D
Hide Arm/Group Description:
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Overall Number of Participants Analyzed 3 6 7
Mean (Standard Deviation)
Unit of Measure: ratio
Day 14 Number Analyzed 3 participants 6 participants 5 participants
4.773  (0.9001) 7.543  (5.4982) 6.392  (2.0824)
Day 21 Number Analyzed 3 participants 6 participants 5 participants
3.637  (1.8675) 4.157  (2.1051) 5.570  (2.5772)
28.Secondary Outcome
Title CLss/F: Apparent Oral Clearance at Steady State for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing
Hide Description [Not Specified]
Time Frame Cycle 1 Days 14 and 21 predose and at multiple timepoints up to 10 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis. Here number analyzed is the number of participants with data available for analysis at the given time point.
Arm/Group Title Alisertib 25 mg PIC QD 21D Alisertib 50 mg PIC QD 21D Alisertib 70 mg PIC QD 21D
Hide Arm/Group Description:
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Overall Number of Participants Analyzed 3 6 7
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: L/h
Day 14 Number Analyzed 3 participants 6 participants 4 participants
3.181
(42.5706%)
5.612
(28.6881%)
5.825
(17.7291%)
Day 21 Number Analyzed 3 participants 6 participants 5 participants
3.656
(89.5750%)
4.984
(25.6945%)
5.745
(42.3818%)
29.Secondary Outcome
Title Ae: Amount of Alisertib Excreted in Urine Over the Collection Period for Alisertib as Powder-in-Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1 predose and at multiple time points (up to 24 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis.
Arm/Group Title Alisertib 25 mg PIC QD 21D Alisertib 50 mg PIC QD 21D Alisertib 70 mg PIC QD 21D
Hide Arm/Group Description:
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Overall Number of Participants Analyzed 3 6 7
Mean (Standard Deviation)
Unit of Measure: ng
3047.7  (5278.71) 5766.7  (7971.95) 9391.4  (11410.18)
30.Secondary Outcome
Title CLr: Renal Clearance of Alisertib as Powder-in-Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1 predose and at multiple time points (up to 24 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis.
Arm/Group Title Alisertib 25 mg PIC QD 21D Alisertib 50 mg PIC QD 21D Alisertib 70 mg PIC QD 21D
Hide Arm/Group Description:
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Overall Number of Participants Analyzed 1 3 4
Mean (Standard Deviation)
Unit of Measure: L/h
0.0008640 [1]   (NA) 0.0012323  (0.00111840) 0.0007865  (0.00042447)
[1]
Cannot be calculated for 1 participant
31.Secondary Outcome
Title Cmax: Maximum Observed Concentration for Alisertib as Powder-in-Capsule (PIC) With Twice Daily for 7 Days (BID7D) Dosing
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1 predose and at multiple time-points (up to 24 hours) postdose and Day 7 predose and at multiple time-points (up to 10 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis. Here number analyzed is the number of participants with data available for analysis at the given time point.
Arm/Group Title Alisertib 50 mg PIC BID 7D Alisertib 60 mg PIC BID 7D
Hide Arm/Group Description:
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
Overall Number of Participants Analyzed 11 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nM
Day 1 Number Analyzed 11 participants 6 participants
1581.1
(37.34%)
1867.1
(29.03%)
Day 7 Number Analyzed 10 participants 5 participants
3376.4
(41.74%)
3080.8
(38.79%)
32.Secondary Outcome
Title Tmax: Time of First Occurrence of Cmax for Alisertib as Powder-in-Capsule (PIC) With Twice Daily for 7 Days (BID7D) Dosing
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1 predose and at multiple time-points (up to 24 hours) postdose and Day 7 predose and at multiple time-points (up to 10 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis. Here number analyzed is the number of participants with data available for analysis at the given time point.
Arm/Group Title Alisertib 50 mg PIC BID 7D Alisertib 60 mg PIC BID 7D
Hide Arm/Group Description:
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
Overall Number of Participants Analyzed 11 6
Median (Full Range)
Unit of Measure: h
Day 1 Number Analyzed 11 participants 6 participants
2.000
(1.98 to 8.00)
2.000
(1.60 to 4.00)
Day 7 Number Analyzed 10 participants 5 participants
2.015
(0.98 to 6.05)
2.000
(1.98 to 6.03)
33.Secondary Outcome
Title AUCt: Area Under the Concentration-time Curve From Time 0 to Time t for Alisertib as Powder-in-Capsule (PIC) With Twice Daily for 7 Days (BID7D) Dosing
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1 predose and at multiple time-points (up to 24 hours) postdose and Day 7 predose and at multiple time-points (up to 10 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis. Here number analyzed is the number of participants with data available for analysis at the given time point.
Arm/Group Title Alisertib 50 mg PIC BID 7D Alisertib 60 mg PIC BID 7D
Hide Arm/Group Description:
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
Overall Number of Participants Analyzed 11 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nM*h
Day 1 Number Analyzed 8 participants 3 participants
11166.3
(37.45%)
13200.4
(26.70%)
Day 7 Number Analyzed 5 participants 4 participants
32291.5
(40.82%)
27386.1
(37.43%)
34.Secondary Outcome
Title Terminal Half-Life (t1/2) for Alisertib as Powder-in-Capsule (PIC) With Twice Daily for 7 Days (BID7D) Dosing
Hide Description [Not Specified]
Time Frame Cycle 1 Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis, with data available at the given time­point.
Arm/Group Title Alisertib 50 mg PIC BID 7D Alisertib 60 mg PIC BID 7D
Hide Arm/Group Description:
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
Overall Number of Participants Analyzed 10 6
Mean (Standard Deviation)
Unit of Measure: h
20.215  (15.5083) 18.200  (3.2212)
35.Secondary Outcome
Title Accumulation Ratio (Rac) for Alisertib as Powder-in-Capsule (PIC) With Twice Daily for 7 Days (BID7D) Dosing
Hide Description [Not Specified]
Time Frame Cycle 1 Day 7 predose and at multiple time-points (up to 10 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis, with data available at the given time­point.
Arm/Group Title Alisertib 50 mg PIC BID 7D Alisertib 60 mg PIC BID 7D
Hide Arm/Group Description:
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
Overall Number of Participants Analyzed 5 3
Mean (Standard Deviation)
Unit of Measure: ratio
2.474  (1.0467) 2.543  (0.1950)
36.Secondary Outcome
Title Peak/Trough Ratio for Alisertib as Powder-in-Capsule (PIC) With Twice Daily for 7 Days (BID7D) Dosing
Hide Description [Not Specified]
Time Frame Cycle 1 Day 7 predose and at multiple time-points (up to 10 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis, with data available at the given time­point.
Arm/Group Title Alisertib 50 mg PIC BID 7D Alisertib 60 mg PIC BID 7D
Hide Arm/Group Description:
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
Overall Number of Participants Analyzed 6 4
Mean (Standard Deviation)
Unit of Measure: ratio
2.193  (1.1346) 1.890  (0.2012)
37.Secondary Outcome
Title CLss/F: Apparent Oral Clearance at Steady State for Alisertib as Powder-in-Capsule (PIC) With Twice Daily for 7 Days (BID7D) Dosing
Hide Description [Not Specified]
Time Frame Cycle 1 Day 7 predose and at multiple time-points (up to 10 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis, with data available at the given time­point.
Arm/Group Title Alisertib 50 mg PIC BID 7D Alisertib 60 mg PIC BID 7D
Hide Arm/Group Description:
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
Overall Number of Participants Analyzed 5 4
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: L/h
2.984
(43.8719%)
4.220
(47.9681%)
38.Secondary Outcome
Title Ae: Amount of Alisertib Excreted in Urine Over the Collection Period for Alisertib as Powder-in-Capsule (PIC) With Twice Daily for 7 Days (BID7D) Dosing
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1 predose and at multiple time-points (up to 24 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis.
Arm/Group Title Alisertib 50 mg PIC BID 7D Alisertib 60 mg PIC BID 7D
Hide Arm/Group Description:
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
Overall Number of Participants Analyzed 10 5
Mean (Standard Deviation)
Unit of Measure: ng
13775.0  (7937.14) 8498.3  (6866.09)
39.Secondary Outcome
Title CLr: Renal Clearance of Alisertib as Powder-in-Capsule (PIC) With Twice Daily for 7 Days (BID7D) Dosing
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1 predose and at multiple time-points (up to 24 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis.
Arm/Group Title Alisertib 50 mg PIC BID 7D Alisertib 60 mg PIC BID 7D
Hide Arm/Group Description:
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
Overall Number of Participants Analyzed 10 5
Mean (Standard Deviation)
Unit of Measure: ng
0.001  (0.0011) 0.001  (0.0004)
40.Secondary Outcome
Title Cmax: Maximum Observed Concentration for Alisertib as Powder-in-Capsule (PIC) With Twice Daily for 14 Days (BID14D) Dosing
Hide Description [Not Specified]
Time Frame Cycle 1 Days 1 and 7 predose and at multiple time-points (up to 10 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis. Here number analyzed is the number of participants with data available for analysis at the given time point.
Arm/Group Title Alisertib 40 mg PIC BID 14D
Hide Arm/Group Description:
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Overall Number of Participants Analyzed 2
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nM
Day 1 Number Analyzed 2 participants
1236.6
(37.29%)
Day 7 Number Analyzed 1 participants
2060.0 [1] 
(NA%)
[1]
Geometric Coefficient of Variation cannot be calculated for 1 participant.
41.Secondary Outcome
Title Tmax: Time of First Occurrence of Cmax for Alisertib as Powder-in-Capsule (PIC) With Twice Daily for 14 Days (BID14D) Dosing
Hide Description [Not Specified]
Time Frame Cycle 1 Days 1 and 7 predose and at multiple time-points (up to 10 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis. Here number analyzed is the number of participants with data available for analysis at the given time point.
Arm/Group Title Alisertib 40 mg PIC BID 14D
Hide Arm/Group Description:
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Overall Number of Participants Analyzed 2
Median (Full Range)
Unit of Measure: h
Day 1 Number Analyzed 2 participants
3.00
(2.0 to 4.0)
Day 7 Number Analyzed 1 participants
1.70
(1.7 to 1.7)
42.Secondary Outcome
Title AUCt: Area Under the Concentration-time Curve From Time 0 to Time t for Alisertib as Powder-in-Capsule (PIC) With Twice Daily for 14 Days (BID14D) Dosing
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1 predose and at multiple time-points (up to 24 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis.
Arm/Group Title Alisertib 40 mg PIC BID 14D
Hide Arm/Group Description:
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Overall Number of Participants Analyzed 2
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nM*h
9684.8
(71.50%)
43.Secondary Outcome
Title AUCt: Area Under the Concentration-time Curve From Time 0 to Time t as Assessment of Relative Bioavailability for Alisertib as Enteric-coated Tablet (ECT) Versus PIC at Day 7
Hide Description [Not Specified]
Time Frame Cycle 1 Day 7 predose and at multiple time-points (up to 10 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis.
Arm/Group Title Alisertib 40 mg ECT BID 7D Alisertib 40 mg PIC BID 7D
Hide Arm/Group Description:
Alisertib 40 mg, Enteric-coated tablet (ECT), orally, twice daily (BID) for 7 days (D) followed by a 14-­day recovery period for 1 cycle.
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14-­day recovery period for 1 cycle.
Overall Number of Participants Analyzed 14 14
Mean (Standard Deviation)
Unit of Measure: nM*h
12700.0  (6557.58) 14190.7  (7097.72)
44.Secondary Outcome
Title Cmax: Maximum Observed Concentration as Assessment of Relative Bioavailability for Alisertib as Enteric-coated Tablet (ECT) Versus PIC at Day 7
Hide Description [Not Specified]
Time Frame Cycle 1 Day 7 predose and at multiple time-points (up to 10 hours) postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis.
Arm/Group Title Alisertib 40 mg ECT BID 7D Alisertib 40 mg PIC BID 7D
Hide Arm/Group Description:
Alisertib 40 mg, Enteric-coated tablet (ECT), orally, twice daily (BID) for 7 days (D) followed by a 14-­day recovery period for 1 cycle.
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14-­day recovery period for 1 cycle.
Overall Number of Participants Analyzed 14 14
Mean (Standard Deviation)
Unit of Measure: nM
1666.1  (765.28) 2027.9  (928.96)
45.Secondary Outcome
Title Change From Baseline in Alisertib Skin Punch Biopsy as Measured by Mitotic Index With PIC Once Daily for 7 Days (QD7D) Dosing
Hide Description Mitotic index was defined as the mean number of mitotic cells per millimeter (mm) length of the basoepithelial layer (BEL). Mitotic cells were counted manually within the BEL of 4, 5 µM skin sections by staining with fluorescent-tagged antibodies specific to 2 mitotic markers—serine 10 phosphohistone H3 (pHistH3) and MPM2. Deoxyribonucleic acid (DNA) was stained with a fluorescent marker as well. A positive change from Baseline indicates improvement.
Time Frame Baseline and Cycle 1 Day 1, 6 hours and 24 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis, with data available at the given time­points.
Arm/Group Title Alisertib 5 mg PIC QD 7D Alisertib 10 mg PIC QD 7D Alisertib 20 mg PIC QD 7D Alisertib 40 mg PIC QD 7D Alisertib 80 mg PIC QD 7D Alisertib 110 mg PIC QD 7D Alisertib 150 mg PIC QD 7D
Hide Arm/Group Description:
Alisertib 5 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
Alisertib 10 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
Overall Number of Participants Analyzed 3 2 3 3 3 5 6
Mean (Standard Deviation)
Unit of Measure: mitotic cells/millimeter of BEL
Day 1, Hour 6 0.405  (0.2701) 0.614  (0.5437) 0.263  (0.1461) 0.168  (0.5146) 0.488  (1.0215) 0.261  (0.4597) 0.865  (0.9420)
Day 1, Hour 24 0.019  (0.1914) -0.103  (0.0186) 0.005  (0.0709) 0.141  (0.3852) 0.108  (0.4081) 1.764  (2.6380) 0.239  (0.6992)
46.Secondary Outcome
Title Change From Baseline in Alisertib Skin Punch Biopsy as Measured by Apoptotic Index With PIC Once Daily for 7 Days (QD7D) Dosing
Hide Description Apoptotic index was defined as the mean number of apoptotic cells per millimeter (mm) length of the basoepithelial layer (BEL). Apoptotic cells were counted manually within the BEL of 4, 5 µM skin sections by staining with hematoxylin-eosin. A positive change from Baseline indicates improvement.
Time Frame Baseline and Cycle 1 Day 1, 6 hours and 24 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis, with data available at the given time­points.
Arm/Group Title Alisertib 5 mg PIC QD 7D Alisertib 10 mg PIC QD 7D Alisertib 20 mg PIC QD 7D Alisertib 40 mg PIC QD 7D Alisertib 80 mg PIC QD 7D Alisertib 110 mg PIC QD 7D Alisertib 150 mg PIC QD 7D
Hide Arm/Group Description:
Alisertib 5 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
Alisertib 10 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
Alisertib 20 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 31 cycles).
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 8 cycles).
Alisertib 80 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
Alisertib 110 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
Alisertib 150 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
Overall Number of Participants Analyzed 3 2 3 3 3 5 6
Mean (Standard Deviation)
Unit of Measure: apoptotic cells/millimeter of BEL
Day 1, Hour 6 0.010  (0.1175) -0.090  (0.1278) 0.042  (0.0731) 0.040  (0.0701) 0.121  (0.1317) 0.036  (0.0530) -0.042  (0.1262)
Day 1, Hour 24 0.009  (0.1164) 0.065  (0.1404) 0.000  (0.0000) 0.037  (0.0634) 0.074  (0.1286) 0.151  (0.1721) 0.139  (0.2069)
47.Secondary Outcome
Title Change From Baseline in Alisertib Skin Punch Biopsy as Measured by Mitotic Index With PIC Once Daily for 14 Days (QD14D) Dosing
Hide Description Mitotic index was defined as the mean number of mitotic cells per millimeter (mm) length of the basoepithelial layer (BEL). Mitotic cells were counted manually within the BEL of 4, 5 µM skin sections by staining with fluorescent-tagged antibodies specific to 2 mitotic markers—serine 10 phosphohistone H3 (pHistH3) and MPM2. Deoxyribonucleic acid (DNA) was stained with a fluorescent marker as well. A positive change from Baseline indicates improvement.
Time Frame Baseline and Cycle 1 Day 1, 6 hours and 24 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis, with data available at the given time­points.
Arm/Group Title Alisertib 25 mg PIC QD 14D
Hide Arm/Group Description:
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
Overall Number of Participants Analyzed 3
Mean (Standard Deviation)
Unit of Measure: mitotic cells/millimeter of BEL
Day 1, Hour 6 0.134  (0.1723)
Day 1, Hour 24 0.047  (0.0589)
48.Secondary Outcome
Title Change From Baseline in Alisertib Skin Punch Biopsy as Measured by Apoptotic Index With PIC Once Daily for 14 Days (QD14D) Dosing
Hide Description Apoptotic index was defined as the mean number of apoptotic cells per millimeter (mm) length of the basoepithelial layer (BEL). Apoptotic cells were counted manually within the BEL of 4, 5 µM skin sections by staining with hematoxylin-eosin. A positive change from Baseline indicates improvement.
Time Frame Baseline and Cycle 1 Day 1, 6 hours and 24 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis, with data available at the given time­points.
Arm/Group Title Alisertib 25 mg PIC QD 14D
Hide Arm/Group Description:
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 14 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles).
Overall Number of Participants Analyzed 3
Mean (Standard Deviation)
Unit of Measure: apoptotic cells/millimeter of BEL
Day 1, Hour 6 0.000  (0.0000)
Day 1, Hour 24 0.000  (0.0000)
49.Secondary Outcome
Title Change From Baseline in Alisertib Skin Punch Biopsy as Measured by Mitotic Index With PIC Once Daily for 21 Days (QD21D) Dosing
Hide Description Mitotic index was defined as the mean number of mitotic cells per millimeter (mm) length of the basoepithelial layer (BEL). Mitotic cells were counted manually within the BEL of 4, 5 µM skin sections by staining with fluorescent-tagged antibodies specific to 2 mitotic markers—serine 10 phosphohistone H3 (pHistH3) and MPM2. Deoxyribonucleic acid (DNA) was stained with a fluorescent marker as well. A positive change from Baseline indicates improvement.
Time Frame Baseline and Cycle 1 Day 1, 6 hours and 24 hours postdose and Days 7 and 21, 6 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis. Here number analyzed is the number of participants with data available for analysis at the given time point.
Arm/Group Title Alisertib 25 mg PIC QD 21D Alisertib 50 mg PIC QD 21D Alisertib 70 mg PIC QD 21D
Hide Arm/Group Description:
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Overall Number of Participants Analyzed 3 6 7
Mean (Standard Deviation)
Unit of Measure: mitotic cells/millimeter of BEL
Day 1, Hour 6 Number Analyzed 3 participants 3 participants 1 participants
0.380  (0.4165) 0.405  (0.4690) 0.510 [1]   (NA)
Day 1, Hour 24 Number Analyzed 3 participants 3 participants 2 participants
0.021  (0.1081) 0.082  (0.1796) 0.289  (0.5746)
Day 7, Hour 6 Number Analyzed 0 participants 0 participants 3 participants
0.479  (0.3040)
Day 21, Hour 6 Number Analyzed 0 participants 1 participants 3 participants
0.045 [2]   (NA) 0.742  (0.5782)
[1]
Cannot be calculated for 1 participant
[2]
Cannot be calculated for 1 participant.
50.Secondary Outcome
Title Change From Baseline in Alisertib Skin Punch Biopsy as Measured by Apoptotic Index With PIC Once Daily for 21 Days (QD21D) Dosing
Hide Description Apoptotic index was defined as the mean number of apoptotic cells per millimeter (mm) length of the basoepithelial layer (BEL). Apoptotic cells were counted manually within the BEL of 4, 5 µM skin sections by staining with hematoxylin-eosin. A positive change from Baseline indicates improvement.
Time Frame Baseline and Cycle 1 Day 1, 6 hours and 24 hours postdose and Days 7 and 21, 6 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis. Here number analyzed is the number of participants with data available for analysis at the given time point.
Arm/Group Title Alisertib 25 mg PIC QD 21D Alisertib 50 mg PIC QD 21D Alisertib 70 mg PIC QD 21D
Hide Arm/Group Description:
Alisertib 25 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles).
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 7 cycles).
Alisertib 70 mg, Powder-in-Capsule (PIC), orally, once daily (QD) for 21 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Overall Number of Participants Analyzed 3 6 7
Mean (Standard Deviation)
Unit of Measure: apoptotic cells/millimeter of BEL
Day 1, Hour 6 Number Analyzed 3 participants 3 participants 1 participants
0.122  (0.2117) 0.000  (0.0000) 0.000 [1]   (NA)
Day 1, Hour 24 Number Analyzed 3 participants 3 participants 2 participants
0.042  (0.0722) 0.042  (0.0719) 0.000  (0.0000)
Day 7, Hour 6 Number Analyzed 0 participants 0 participants 3 participants
0.000  (0.0000)
Day 21, Hour 6 Number Analyzed 0 participants 1 participants 3 participants
0.099 [2]   (NA) 0.032  (0.0552)
[1]
Cannot be calculated for 1 participant
[2]
Cannot be calculated for 1 participant.
51.Secondary Outcome
Title Change From Baseline in Alisertib Skin Punch Biopsy as Measured by Mitotic Index With PIC Twice Daily for 7 Days (BID7D) Dosing
Hide Description Mitotic index was defined as the mean number of mitotic cells per millimeter (mm) length of the basoepithelial layer (BEL). Mitotic cells were counted manually within the BEL of 4, 5 µM skin sections by staining with fluorescent-tagged antibodies specific to 2 mitotic markers—serine 10 phosphohistone H3 (pHistH3) and MPM2. Deoxyribonucleic acid (DNA) was stained with a fluorescent marker as well. A positive change from Baseline indicates improvement.
Time Frame Baseline and Cycle 1 Day 1, 6 hours and 24 hours postdose and Day 7, 6 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis. Here number analyzed is the number of participants with data available for analysis at the given time point.
Arm/Group Title Alisertib 50 mg PIC BID 7D Alisertib 60 mg PIC BID 7D
Hide Arm/Group Description:
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
Overall Number of Participants Analyzed 11 6
Mean (Standard Deviation)
Unit of Measure: mitotic cells/millimeter of BEL
Day 1, Hour 6 Number Analyzed 9 participants 6 participants
0.054  (0.3022) 0.364  (0.2574)
Day 1, Hour 24 Number Analyzed 6 participants 6 participants
2.578  (2.2875) 1.435  (0.8329)
Day 7, Hour 6 Number Analyzed 3 participants 0 participants
5.486  (5.8688)
52.Secondary Outcome
Title Change From Baseline in Alisertib Skin Punch Biopsy as Measured by Apoptotic Index With PIC Twice Daily for 7 Days (BID7D) Dosing
Hide Description Apoptotic index was defined as the mean number of apoptotic cells per millimeter (mm) length of the basoepithelial layer (BEL). Apoptotic cells were counted manually within the BEL of 4, 5 µM skin sections by staining with hematoxylin-eosin. A positive change from Baseline indicates improvement.
Time Frame Baseline and Cycle 1 Day 1, 6 hours and 24 hours postdose and Day 7, 6 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis. Here number analyzed is the number of participants with data available for analysis at the given time point.
Arm/Group Title Alisertib 50 mg PIC BID 7D Alisertib 60 mg PIC BID 7D
Hide Arm/Group Description:
Alisertib 50 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 4 cycles).
Alisertib 60 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 35 cycles).
Overall Number of Participants Analyzed 11 6
Mean (Standard Deviation)
Unit of Measure: apoptotic cells/millimeter of BEL
Day 1, Hour 6 Number Analyzed 9 participants 6 participants
-0.016  (0.0494) 0.020  (0.0491)
Day 1, Hour 24 Number Analyzed 6 participants 6 participants
0.055  (0.1691) 0.080  (0.1958)
Day 7, Hour 6 Number Analyzed 3 participants 0 participants
2.142  (3.2510)
53.Secondary Outcome
Title Change From Baseline in Alisertib Skin Punch Biopsy as Measured by Mitotic Index With PIC Twice Daily for 14 Days (BID14D) Dosing
Hide Description Mitotic index was defined as the mean number of mitotic cells per millimeter (mm) length of the basoepithelial layer (BEL). Mitotic cells were counted manually within the BEL of 4, 5 µM skin sections by staining with fluorescent-tagged antibodies specific to 2 mitotic markers—serine 10 phosphohistone H3 (pHistH3) and MPM2. Deoxyribonucleic acid (DNA) was stained with a fluorescent marker as well. A positive change from Baseline indicates improvement.
Time Frame Baseline and Cycle 1 Day 7, 6 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis, with data available at the given time­point.
Arm/Group Title Alisertib 40 mg PIC BID 14D
Hide Arm/Group Description:
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Overall Number of Participants Analyzed 1
Mean (Standard Deviation)
Unit of Measure: mitotic cells/millimeter of BEL
1.507 [1]   (NA)
[1]
Cannot be calculated for 1 participant
54.Secondary Outcome
Title Change From Baseline in Alisertib Skin Punch Biopsy as Measured by Apoptotic Index With PIC Twice Daily for 14 Days (BID14D) Dosing
Hide Description Apoptotic index was defined as the mean number of apoptotic cells per millimeter (mm) length of the basoepithelial layer (BEL). Apoptotic cells were counted manually within the BEL of 4, 5 µM skin sections by staining with hematoxylin-eosin. A positive change from Baseline indicates improvement.
Time Frame Baseline and Cycle 1 Day 7, 6 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK)-Evaluable Population included all participants for whom there were sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis, with data available at the given time­point.
Arm/Group Title Alisertib 40 mg PIC BID 14D
Hide Arm/Group Description:
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 14 days (D) followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Overall Number of Participants Analyzed 1
Mean (Standard Deviation)
Unit of Measure: apoptotic cells/millimeter of BEL
2.837 [1]   (NA)
[1]
Cannot be calculated for 1 participant
55.Secondary Outcome
Title Number of Participants With Polymorphisms in Gene Encoding Enzyme UGT1A1
Hide Description

One peripheral blood sample (approximately 4 mL) was to be obtained on Day 1 of Cycle 1 prior to the first dose of alisertib to genotype patients for polymorphisms in UGT1A1 because UGT1A1 is one of the enzymes responsible for glucuronidation of alisertib, which is expected to contribute to the clearance of alisertib.

wt=wild type

*28=polymorphism in the promoter region of a UGT1A1 allele resulting in reduced UGT1A1 expression.

Time Frame Cycle 1 Day 1 predose
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population included all participants who received any amount of study drug.
Arm/Group Title Alisertib
Hide Arm/Group Description:
Alisertib 5, 10, 20, 40, 80, 110 or 150 mg, PIC, orally, once daily (QD) for 7 days, followed by a 14-day recovery period or alisertib 25 mg, PIC, orally, QD for 14 days, followed by a 14-day recovery period or alisertib 25, 50 or 70 mg, PIC, orally, QD for 21 days followed by a 14-day recovery period or alisertib 50 or 60 mg, PIC, orally, twice daily (BID) for 7 days followed by a 14-day recovery period or alisertib 40 mg, PIC, orally, BID for 14 days followed by a 14-day recovery period or alisertib 10 or 20 mg ECT, orally QD for 7 days followed by a 14-day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
Overall Number of Participants Analyzed 87
Measure Type: Number
Unit of Measure: participants
wt/wt 38
wt/*28 30
*28/*28 9
*28/other 4
other/other 2
Not Determined 1
Missing 3
56.Secondary Outcome
Title Best Overall Response Based on Investigator Assessment
Hide Description Best overall response is defined as the percentage of participants with Complete Response (CR) + Partial Response (PR) as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1. According to RECIST: CR is defined as disappearance of all target and nontarget lesions and normalization of tumor marker level (if applicable); PR is defined as ≥30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter, persistence of 1 or more nontarget lesion(s) and/or maintenance of tumor marker level above the normal limits.
Time Frame Beginning at the end of Cycle 2, every 2 cycles until progressive disease (PD); Participants who discontinue study drug before PD: Follow-Up (FU) every 8-12 weeks until PD or as per institutional practice (Up to 33.2 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population included all participants who received any amount of study drug.
Arm/Group Title Alisertib
Hide Arm/Group Description:
Alisertib 5, 10, 20, 40, 80, 110 or 150 mg, PIC, orally, once daily (QD) for 7 days, followed by a 14-day recovery period or alisertib 25 mg, PIC, orally, QD for 14 days, followed by a 14-day recovery period or alisertib 25, 50 or 70 mg, PIC, orally, QD for 21 days followed by a 14-day recovery period or alisertib 50 or 60 mg, PIC, orally, twice daily (BID) for 7 days followed by a 14-day recovery period or alisertib 40 mg, PIC, orally, BID for 14 days followed by a 14-day recovery period or alisertib 10 or 20 mg ECT, orally QD for 7 days followed by a 14-day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
Overall Number of Participants Analyzed 87
Measure Type: Number
Unit of Measure: percentage of participants
1
57.Secondary Outcome
Title Duration Of Response (DOR)
Hide Description DOR is defined as the time from the date of first documentation of a confirmed response to the date of first documented PD. PD is defined as 20% increase in the sum of the longest diameter of target lesions.
Time Frame Beginning at the end of Cycle 2, every 2 cycles until progressive disease (PD); Participants who discontinue study drug before PD: Follow-Up (FU) every 8-12 weeks until PD or as per institutional practice (Up to 33.2 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population included all participants who received any amount of study drug.
Arm/Group Title Alisertib
Hide Arm/Group Description:
Alisertib 5, 10, 20, 40, 80, 110 or 150 mg, PIC, orally, once daily (QD) for 7 days, followed by a 14-day recovery period or alisertib 25 mg, PIC, orally, QD for 14 days, followed by a 14-day recovery period or alisertib 25, 50 or 70 mg, PIC, orally, QD for 21 days followed by a 14-day recovery period or alisertib 50 or 60 mg, PIC, orally, twice daily (BID) for 7 days followed by a 14-day recovery period or alisertib 40 mg, PIC, orally, BID for 14 days followed by a 14-day recovery period or alisertib 10 or 20 mg ECT, orally QD for 7 days followed by a 14-day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles).
Overall Number of Participants Analyzed 1
Measure Type: Number
Unit of Measure: days
470
58.Secondary Outcome
Title Effect of Food on the Pharmacokinetics (PK) of Alisertib
Hide Description The effects of food on the PK of alisertib were to be evaluated using the preferred alisertib regimen (unit dose and formulation) based on the results from the relative bioavailability study.
Time Frame Up to 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
The effects of food on the PK of alisertib was not conducted. As the development of alisertib was transitioned from the PIC to the ECT formulation and the clinical dose of alisertib ECT had not been determined yet, it was decided that the effect of food would be evaluated in a different study at the appropriate clinical dose, administered as ECT.
Arm/Group Title Alisertib 40 mg ECT BID 7D Alisertib 40 mg PIC BID 7D
Hide Arm/Group Description:
Alisertib 40 mg, Enteric-coated tablet (ECT), orally, twice daily (BID) for 7 days (D) followed by a 14-­day recovery period for 1 cycle.
Alisertib 40 mg, Powder-in-Capsule (PIC), orally, twice daily (BID) for 7 days (D) followed by a 14-­day recovery period for 1 cycle.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame From first dose of study drug to 30 days after the last dose (up to 1011 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 PIC Dose Escalation ECT Dose Escalation Relative Bioavailability
Hide Arm/Group Description Alisertib 5, 10, 20, 40, 80, 110 or 150 mg, PIC, orally, once daily (QD) for 7 days, followed by a 14-day recovery period or alisertib 25 mg, PIC, orally, QD for 14 days, followed by a 14-day recovery period or alisertib 25, 50 or 70 mg, PIC, orally, QD for 21 days followed by a 14-day recovery period or alisertib 50 or 60 mg, PIC, orally, twice daily (BID) for 7 days followed by a 14-day recovery period or alisertib 40 mg, PIC, orally, BID for 14 days followed by a 14-day recovery period in each cycle until disease progression or unacceptable alisertib-related toxicity (up to 51 cycles). Alisertib 10 or 20 mg, Enteric-coated Tablet (ECT) formulation, orally, once daily (QD) for 7 days followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-­related toxicity (up to 2 cycles). Alisertib 40 mg ECT or PIC formulation, orally, twice daily (BID) for 7 days followed by a 14-­day recovery period in cycle 1, followed by alisertib 40 mg in the opposite formulation (PIC or ECT) orally, twice daily (BID) for 7 days followed by a 14-­day recovery period in cycle 2, followed by alisertib 50 mg PIC formulation orally, twice daily (BID) for 7 days followed by a 14-­day recovery period in each cycle until disease progression or unacceptable alisertib-­related toxicity (up to 9 cycles).
All-Cause Mortality
PIC Dose Escalation ECT Dose Escalation Relative Bioavailability
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
PIC Dose Escalation ECT Dose Escalation Relative Bioavailability
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   26/65 (40.00%)   0/2 (0.00%)   1/20 (5.00%) 
Blood and lymphatic system disorders       
Febrile neutropenia  1  5/65 (7.69%)  0/2 (0.00%)  1/20 (5.00%) 
Neutropenia  1  3/65 (4.62%)  0/2 (0.00%)  0/20 (0.00%) 
Anaemia  1  4/65 (6.15%)  0/2 (0.00%)  0/20 (0.00%) 
Thrombocytopenia  1  4/65 (6.15%)  0/2 (0.00%)  0/20 (0.00%) 
Cardiac disorders       
Restrictive cardiomyopathy  1  1/65 (1.54%)  0/2 (0.00%)  0/20 (0.00%) 
Ventricular dysfunction  1  1/65 (1.54%)  0/2 (0.00%)  0/20 (0.00%) 
Arrhythmia supraventricular  1  1/65 (1.54%)  0/2 (0.00%)  0/20 (0.00%) 
Atrial fibrillation  1  1/65 (1.54%)  0/2 (0.00%)  0/20 (0.00%) 
Gastrointestinal disorders       
Diarrhoea  1  3/65 (4.62%)  0/2 (0.00%)  0/20 (0.00%) 
Nausea  1  3/65 (4.62%)  0/2 (0.00%)  0/20 (0.00%) 
Vomiting  1  2/65 (3.08%)  0/2 (0.00%)  0/20 (0.00%) 
Intestinal obstruction  1  2/65 (3.08%)  0/2 (0.00%)  0/20 (0.00%) 
Small intestinal obstruction  1 [1]  1/65 (1.54%)  0/2 (0.00%)  0/20 (0.00%) 
Abdominal pain  1  1/65 (1.54%)  0/2 (0.00%)  0/20 (0.00%) 
Gastrointestinal haemorrhage  1  1/65 (1.54%)  0/2 (0.00%)  0/20 (0.00%) 
Stomatitis  1  1/65 (1.54%)  0/2 (0.00%)  0/20 (0.00%) 
General disorders       
Asthenia  1  1/65 (1.54%)  0/2 (0.00%)  0/20 (0.00%) 
Fatigue  1  1/65 (1.54%)  0/2 (0.00%)  0/20 (0.00%) 
Disease progression  1 [2]  1/65 (1.54%)  0/2 (0.00%)  0/20 (0.00%) 
Hepatobiliary disorders       
Hyperbilirubinaemia  1  1/65 (1.54%)  0/2 (0.00%)  0/20 (0.00%) 
Jaundice cholestatic  1  1/65 (1.54%)  0/2 (0.00%)  0/20 (0.00%) 
Bile duct obstruction  1  0/65 (0.00%)  0/2 (0.00%)  1/20 (5.00%) 
Bile duct stenosis  1  1/65 (1.54%)  0/2 (0.00%)  0/20 (0.00%) 
Infections and infestations       
Klebsiella bacteraemia  1  1/65 (1.54%)  0/2 (0.00%)  1/20 (5.00%) 
Urinary tract infection  1  2/65 (3.08%)  0/2 (0.00%)  0/20 (0.00%) 
Enterococcal bacteraemia  1  0/65 (0.00%)  0/2 (0.00%)  1/20 (5.00%) 
Pneumonia  1  1/65 (1.54%)  0/2 (0.00%)  0/20 (0.00%) 
Staphylococcal infection  1  1/65 (1.54%)  0/2 (0.00%)  0/20 (0.00%) 
Bacteraemia  1  1/65 (1.54%)  0/2 (0.00%)  0/20 (0.00%) 
Injury, poisoning and procedural complications       
Radius fracture  1  1/65 (1.54%)  0/2 (0.00%)  0/20 (0.00%) 
Musculoskeletal and connective tissue disorders       
Back pain  1  0/65 (0.00%)  0/2 (0.00%)  1/20 (5.00%) 
Neck pain  1  0/65 (0.00%)  0/2 (0.00%)  1/20 (5.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Metastases to central nervous system  1  1/65 (1.54%)  0/2 (0.00%)  0/20 (0.00%) 
Pancreatic carcinoma metastatic  1 [3]  0/65 (0.00%)  0/2 (0.00%)  1/20 (5.00%) 
Nervous system disorders       
Syncope  1  1/65 (1.54%)  0/2 (0.00%)  0/20 (0.00%) 
Headache  1  1/65 (1.54%)  0/2 (0.00%)  0/20 (0.00%) 
Mental impairment  1  1/65 (1.54%)  0/2 (0.00%)  0/20 (0.00%) 
Psychiatric disorders       
Hallucination, visual  1  1/65 (1.54%)  0/2 (0.00%)  0/20 (0.00%) 
Renal and urinary disorders       
Renal failure acute  1 [4]  1/65 (1.54%)  0/2 (0.00%)  0/20 (0.00%) 
Reproductive system and breast disorders       
Vaginal haemorrhage  1  1/65 (1.54%)  0/2 (0.00%)  0/20 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Dyspnoea  1  2/65 (3.08%)  0/2 (0.00%)  0/20 (0.00%) 
Pulmonary embolism  1  1/65 (1.54%)  0/2 (0.00%)  0/20 (0.00%) 
Vascular disorders       
Deep vein thrombosis  1  0/65 (0.00%)  0/2 (0.00%)  1/20 (5.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 8.1
[1]
One treatment-emergent death occurred during treatment with alisertib 40 mg PIC BID14D (PIC dose escalation reporting group) and is not related.
[2]
One treatment-emergent death occurred during treatment with alisertib 80 mg PIC QD7D (PIC dose escalation reporting group) and is not related.
[3]
One treatment-emergent death occurred during treatment with alisertib 40 mg PIC BID7D (PIC dose escalation reporting group) and is not related.
[4]
One treatment-emergent death occurred during treatment with alisertib 40 mg PIC QD7D (PIC dose escalation reporting group) and is not related.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
PIC Dose Escalation ECT Dose Escalation Relative Bioavailability
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   65/65 (100.00%)   2/2 (100.00%)   20/20 (100.00%) 
Blood and lymphatic system disorders       
Neutropenia  1  28/65 (43.08%)  0/2 (0.00%)  7/20 (35.00%) 
Anaemia  1  24/65 (36.92%)  2/2 (100.00%)  6/20 (30.00%) 
Thrombocytopenia  1  8/65 (12.31%)  0/2 (0.00%)  0/20 (0.00%) 
Leukopenia  1  2/65 (3.08%)  0/2 (0.00%)  4/20 (20.00%) 
Lymphopenia  1  1/65 (1.54%)  0/2 (0.00%)  3/20 (15.00%) 
Cardiac disorders       
Atrial flutter  1  0/65 (0.00%)  0/2 (0.00%)  1/20 (5.00%) 
Ear and labyrinth disorders       
Ear pain  1  1/65 (1.54%)  0/2 (0.00%)  1/20 (5.00%) 
Endocrine disorders       
Hypothyroidism  1  0/65 (0.00%)  0/2 (0.00%)  1/20 (5.00%) 
Eye disorders       
Vision blurred  1  4/65 (6.15%)  0/2 (0.00%)  0/20 (0.00%) 
Eye swelling  1  0/65 (0.00%)  0/2 (0.00%)  1/20 (5.00%) 
Visual disturbance  1  0/65 (0.00%)  0/2 (0.00%)  1/20 (5.00%) 
Gastrointestinal disorders       
Nausea  1  39/65 (60.00%)  1/2 (50.00%)  6/20 (30.00%) 
Diarrhoea  1  34/65 (52.31%)  1/2 (50.00%)  6/20 (30.00%) 
Vomiting  1  24/65 (36.92%)  1/2 (50.00%)  2/20 (10.00%) 
Stomatitis  1  15/65 (23.08%)  1/2 (50.00%)  5/20 (25.00%) 
Constipation  1  12/65 (18.46%)  0/2 (0.00%)  4/20 (20.00%) 
Abdominal pain  1  13/65 (20.00%)  0/2 (0.00%)  2/20 (10.00%) 
Flatulence  1  5/65 (7.69%)  0/2 (0.00%)  1/20 (5.00%) 
Abdominal distension  1  5/65 (7.69%)  0/2 (0.00%)  0/20 (0.00%) 
Ascites  1  4/65 (6.15%)  0/2 (0.00%)  0/20 (0.00%) 
Oral pain  1  3/65 (4.62%)  1/2 (50.00%)  0/20 (0.00%) 
Abdominal pain lower  1  1/65 (1.54%)  0/2 (0.00%)  2/20 (10.00%) 
Dyspepsia  1  1/65 (1.54%)  0/2 (0.00%)  1/20 (5.00%) 
Abdominal discomfort  1  0/65 (0.00%)  0/2 (0.00%)  1/20 (5.00%) 
Frequent bowel movements  1  0/65 (0.00%)  0/2 (0.00%)  1/20 (5.00%) 
Gastrooesophageal reflux disease  1  0/65 (0.00%)  0/2 (0.00%)  1/20 (5.00%) 
Gingival pain  1  0/65 (0.00%)  0/2 (0.00%)  1/20 (5.00%) 
General disorders       
Fatigue  1  32/65 (49.23%)  2/2 (100.00%)  12/20 (60.00%) 
Oedema peripheral  1  13/65 (20.00%)  0/2 (0.00%)  4/20 (20.00%) 
Pyrexia  1  12/65 (18.46%)  0/2 (0.00%)  5/20 (25.00%) 
Asthenia  1  11/65 (16.92%)  1/2 (50.00%)  1/20 (5.00%) 
Chills  1  4/65 (6.15%)  0/2 (0.00%)  2/20 (10.00%) 
Gait disturbance  1  3/65 (4.62%)  0/2 (0.00%)  1/20 (5.00%) 
Chest discomfort  1  2/65 (3.08%)  0/2 (0.00%)  1/20 (5.00%) 
Pain  1  1/65 (1.54%)  1/2 (50.00%)  1/20 (5.00%) 
Malaise  1  1/65 (1.54%)  0/2 (0.00%)  1/20 (5.00%) 
Non-cardiac chest pain  1  1/65 (1.54%)  0/2 (0.00%)  1/20 (5.00%) 
Catheter site inflammation  1  0/65 (0.00%)  0/2 (0.00%)  1/20 (5.00%) 
Irritability  1  0/65 (0.00%)  0/2 (0.00%)  1/20 (5.00%) 
Hepatobiliary disorders       
Hepatobiliary disorders  1  4/65 (6.15%)  0/2 (0.00%)  0/20 (0.00%) 
Infections and infestations       
Urinary tract infection  1  6/65 (9.23%)  0/2 (0.00%)  0/20 (0.00%) 
Escherichia infection  1  0/65 (0.00%)  0/2 (0.00%)  1/20 (5.00%) 
Folliculitis  1  0/65 (0.00%)  0/2 (0.00%)  1/20 (5.00%) 
Investigations       
White blood cell count decreased  1  21/65 (32.31%)  0/2 (0.00%)  3/20 (15.00%) 
Blood alkaline phosphatase increased  1  6/65 (9.23%)  0/2 (0.00%)  1/20 (5.00%) 
Blood creatinine increased  1  5/65 (7.69%)  0/2 (0.00%)  1/20 (5.00%) 
Weight decreased  1  6/65 (9.23%)  0/2 (0.00%)  0/20 (0.00%) 
Alanine aminotransferase increased  1  4/65 (6.15%)  0/2 (0.00%)  1/20 (5.00%) 
Aspartate aminotransferase increased  1  4/65 (6.15%)  0/2 (0.00%)  1/20 (5.00%) 
Platelet count decreased  1  3/65 (4.62%)  0/2 (0.00%)  1/20 (5.00%) 
Weight increased  1  3/65 (4.62%)  0/2 (0.00%)  1/20 (5.00%) 
Blood bilirubin increased  1  2/65 (3.08%)  0/2 (0.00%)  1/20 (5.00%) 
Neutrophil count decreased  1  1/65 (1.54%)  0/2 (0.00%)  1/20 (5.00%) 
Activated partial thromboplastin time prolonged  1  0/65 (0.00%)  0/2 (0.00%)  1/20 (5.00%) 
Blood sodium decreased  1  0/65 (0.00%)  0/2 (0.00%)  1/20 (5.00%) 
Metabolism and nutrition disorders       
Anorexia  1  30/65 (46.15%)  1/2 (50.00%)  3/20 (15.00%) 
Dehydration  1  9/65 (13.85%)  0/2 (0.00%)  1/20 (5.00%) 
Hypokalaemia  1  8/65 (12.31%)  0/2 (0.00%)  1/20 (5.00%) 
Hyperglycaemia  1  7/65 (10.77%)  0/2 (0.00%)  0/20 (0.00%) 
Hypocalcaemia  1  7/65 (10.77%)  0/2 (0.00%)  0/20 (0.00%) 
Hyponatraemia  1  7/65 (10.77%)  0/2 (0.00%)  0/20 (0.00%) 
Hyperkalaemia  1  6/65 (9.23%)  0/2 (0.00%)  0/20 (0.00%) 
Hypernatraemia  1  1/65 (1.54%)  0/2 (0.00%)  1/20 (5.00%) 
Hypomagnesaemia  1  1/65 (1.54%)  0/2 (0.00%)  1/20 (5.00%) 
Musculoskeletal and connective tissue disorders       
Muscle spasms  1  6/65 (9.23%)  0/2 (0.00%)  2/20 (10.00%) 
Back pain  1  5/65 (7.69%)  0/2 (0.00%)  2/20 (10.00%) 
Arthralgia  1  4/65 (6.15%)  0/2 (0.00%)  2/20 (10.00%) 
Myalgia  1  4/65 (6.15%)  1/2 (50.00%)  1/20 (5.00%) 
Shoulder pain  1  5/65 (7.69%)  0/2 (0.00%)  1/20 (5.00%) 
Neck pain  1  3/65 (4.62%)  0/2 (0.00%)  2/20 (10.00%) 
Pain in extremity  1  1/65 (1.54%)  0/2 (0.00%)  3/20 (15.00%) 
Chest wall pain  1  2/65 (3.08%)  0/2 (0.00%)  1/20 (5.00%) 
Joint swelling  1  0/65 (0.00%)  0/2 (0.00%)  1/20 (5.00%) 
Groin pain  1  1/65 (1.54%)  0/2 (0.00%)  1/20 (5.00%) 
Nervous system disorders       
Somnolence  1  27/65 (41.54%)  0/2 (0.00%)  6/20 (30.00%) 
Dizziness  1  13/65 (20.00%)  0/2 (0.00%)  3/20 (15.00%) 
Headache  1  9/65 (13.85%)  0/2 (0.00%)  0/20 (0.00%) 
Paraesthesia  1  6/65 (9.23%)  0/2 (0.00%)  1/20 (5.00%) 
Peripheral sensory neuropathy  1  4/65 (6.15%)  0/2 (0.00%)  0/20 (0.00%) 
Grand mal convulsion  1  0/65 (0.00%)  0/2 (0.00%)  1/20 (5.00%) 
Psychiatric disorders       
Insomnia  1  7/65 (10.77%)  0/2 (0.00%)  0/20 (0.00%) 
Anxiety  1  1/65 (1.54%)  0/2 (0.00%)  3/20 (15.00%) 
Confusional state  1  3/65 (4.62%)  0/2 (0.00%)  1/20 (5.00%) 
Depression  1  1/65 (1.54%)  0/2 (0.00%)  1/20 (5.00%) 
Agitation  1  0/65 (0.00%)  0/2 (0.00%)  1/20 (5.00%) 
Mood altered  1  0/65 (0.00%)  0/2 (0.00%)  1/20 (5.00%) 
Renal and urinary disorders       
Pollakiuria  1  1/65 (1.54%)  0/2 (0.00%)  2/20 (10.00%) 
Reproductive system and breast disorders       
Vaginal haemorrhage  1  4/65 (6.15%)  0/2 (0.00%)  1/20 (5.00%) 
Erectile dysfunction  1  0/65 (0.00%)  0/2 (0.00%)  1/20 (5.00%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  10/65 (15.38%)  0/2 (0.00%)  1/20 (5.00%) 
Dyspnoea  1  9/65 (13.85%)  0/2 (0.00%)  0/20 (0.00%) 
Dyspnoea exertional  1  5/65 (7.69%)  1/2 (50.00%)  1/20 (5.00%) 
Rhinorrhoea  1  3/65 (4.62%)  0/2 (0.00%)  1/20 (5.00%) 
Pharyngolaryngeal pain  1  1/65 (1.54%)  0/2 (0.00%)  1/20 (5.00%) 
Skin and subcutaneous tissue disorders       
Alopecia  1  25/65 (38.46%)  1/2 (50.00%)  10/20 (50.00%) 
Rash  1  5/65 (7.69%)  0/2 (0.00%)  1/20 (5.00%) 
Pruritus  1  5/65 (7.69%)  0/2 (0.00%)  0/20 (0.00%) 
Dermatitis acneiform  1  0/65 (0.00%)  0/2 (0.00%)  1/20 (5.00%) 
Hyperhidrosis  1  0/65 (0.00%)  0/2 (0.00%)  1/20 (5.00%) 
Onychorrhexis  1  0/65 (0.00%)  0/2 (0.00%)  1/20 (5.00%) 
Swelling face  1  0/65 (0.00%)  0/2 (0.00%)  1/20 (5.00%) 
Urticaria  1  0/65 (0.00%)  0/2 (0.00%)  1/20 (5.00%) 
Vascular disorders       
Hot flush  1  1/65 (1.54%)  0/2 (0.00%)  1/20 (5.00%) 
Hypotension  1  1/65 (1.54%)  0/2 (0.00%)  1/20 (5.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 8.1
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.
In general, Investigators may publish clinical data after the earlier of (i) publication by the Sponsor or (ii) 12 months following the abandonment, early termination or database lock; provided a copy of the publication provided to Sponsor at least 30 days ahead of publication, the Sponsor’s confidential information is removed as may be requested by Sponsor and Investigator defers publication for up to 60 days in the event Sponsor provides notice that it intends to file a patent application.
Results Point of Contact
Name/Title: Medical Director
Organization: Takeda
Phone: +1-877-825-3327
Responsible Party: Takeda ( Millennium Pharmaceuticals, Inc. )
ClinicalTrials.gov Identifier: NCT00500903     History of Changes
Other Study ID Numbers: C14001
U1111-1187-1087 ( Registry Identifier: WHO )
First Submitted: July 12, 2007
First Posted: July 13, 2007
Results First Submitted: January 4, 2018
Results First Posted: March 14, 2019
Last Update Posted: March 14, 2019