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Trial record 30 of 59 for:    MLN8237

Mass Balance, Pharmacokinetics and Metabolism Study of Alisertib

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ClinicalTrials.gov Identifier: NCT01714947
Recruitment Status : Completed
First Posted : October 26, 2012
Results First Posted : October 31, 2018
Last Update Posted : October 31, 2018
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Advanced Solid Tumors
Lymphoma
Interventions Drug: [^14C]-alisertib
Drug: alisertib
Enrollment 3
Recruitment Details Participants took part in the study at 1 investigative site in the United States from 24 January 2013 to 14 June 2013.
Pre-assignment Details Participants with a diagnosis of advanced solid tumors or lymphomas received [^14C]-alisertib 35 mg oral solution single dose in Part A and alisertib 50 mg for 7 days in 21-day cycles in Part B.
Arm/Group Title Alisertib
Hide Arm/Group Description Part A: [^14C]-alisertib 35 mg, oral solution containing 80 - 100 microcuries (μCi) of total radioactivity (1.19 - 1.48 mCi/mmol), orally, single dose on Day 1. Part B: Alisertib 50 mg, enteric coated tablets, orally, twice daily for 7 days, followed by 14-day washout period in 21-day cycles until disease progression or unacceptable treatment-related toxicity (Up to 3 Cycles).
Period Title: Part A
Started 3
Completed 3
Not Completed 0
Period Title: Part B
Started 3
Completed 0
Not Completed 3
Reason Not Completed
Progressive Disease             3
Arm/Group Title Alisertib
Hide Arm/Group Description Part A: [^14C]-alisertib 35 mg, oral solution containing 80 - 100 microcuries (μCi) of total radioactivity (1.19 - 1.48 mCi/mmol), orally, single dose on Day 1. Part B: Alisertib 50 mg, enteric coated tablets, orally, twice daily for 7 days, followed by 14-day washout period in 21-day cycles until disease progression or unacceptable treatment-related toxicity (Up to 3 Cycles).
Overall Number of Baseline Participants 3
Hide Baseline Analysis Population Description
Safety Population included all participants who received at least 1 dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 3 participants
64.0  (13.11)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants
Female
1
  33.3%
Male
2
  66.7%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Not Hispanic or Latino Number Analyzed 3 participants
3
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 3 participants
White 2
Black or African American 1
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 3 participants
3
Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 3 participants
173.5  (7.15)
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 3 participants
80.27  (20.760)
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 3 participants
26.91  (8.346)
1.Primary Outcome
Title Cmax: Maximum Observed Plasma Concentration for Alisertib and Drug-Related Material Following a Single Dose of [^14C]-Alisertib Oral Solution
Hide Description [Not Specified]
Time Frame Predose and multiple timepoints post-dose (up to 240 hours)
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) Population included all participants with sufficient dosing and PK concentration-time data to reliably estimate PK parameters and mass balance.
Arm/Group Title Alisertib
Hide Arm/Group Description:
Part A: [^14C]-alisertib 35 mg, oral solution containing 80 - 100 microcuries (μCi) of total radioactivity (1.19 - 1.48 mCi/mmol), orally, single dose on Day 1. Part B: Alisertib 50 mg, enteric coated tablets, orally, twice daily for 7 days, followed by 14-day washout period in 21-day cycles until disease progression or unacceptable treatment-related toxicity (Up to 3 Cycles).
Overall Number of Participants Analyzed 3
Mean (Standard Deviation)
Unit of Measure: nanomole (nmol)/liter (L)
Alisertib 2183.3  (161.97)
Drug-Related Material 2606.7  (228.98)
2.Primary Outcome
Title Tmax: Time of First Occurrence of Cmax for Alisertib and Drug-Related Material in Plasma Following a Single Dose of [^14C]-Alisertib Oral Solution
Hide Description [Not Specified]
Time Frame Predose and multiple timepoints post-dose (up to 240 hours)
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) Population included all participants with sufficient dosing and PK concentration-time data to reliably estimate PK parameters and mass balance.
Arm/Group Title Alisertib
Hide Arm/Group Description:
Part A: [^14C]-alisertib 35 mg, oral solution containing 80 - 100 microcuries (μCi) of total radioactivity (1.19 - 1.48 mCi/mmol), orally, single dose on Day 1. Part B: Alisertib 50 mg, enteric coated tablets, orally, twice daily for 7 days, followed by 14-day washout period in 21-day cycles until disease progression or unacceptable treatment-related toxicity (Up to 3 Cycles).
Overall Number of Participants Analyzed 3
Median (Full Range)
Unit of Measure: hr
Alisertib
1.00
(0.5 to 2.0)
Drug-Related Material
1.00
(0.5 to 2.0)
3.Primary Outcome
Title AUClast: Area Under the Concentration-Time Curve From Time 0 to Time of the Last Quantifiable Plasma Concentration for Alisertib and Drug-Related Material Following a Single Dose of [^14C]-Alisertib Oral Solution
Hide Description [Not Specified]
Time Frame Predose and multiple timepoints post-dose (up to 240 hours)
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population included all participants with sufficient dosing and PK concentration-time data to reliably estimate PK parameters and mass balance.
Arm/Group Title Alisertib
Hide Arm/Group Description:
Part A: [^14C]-alisertib 35 mg, oral solution containing 80 - 100 microcuries (μCi) of total radioactivity (1.19 - 1.48 mCi/mmol), orally, single dose on Day 1. Part B: Alisertib 50 mg, enteric coated tablets, orally, twice daily for 7 days, followed by 14-day washout period in 21-day cycles until disease progression or unacceptable treatment-related toxicity (Up to 3 Cycles).
Overall Number of Participants Analyzed 3
Mean (Standard Deviation)
Unit of Measure: hour (hr)*nmol/L
Alisertib 16800.0  (4936.60)
Drug-Related Material 37033.3  (20545.15)
4.Primary Outcome
Title AUC∞: Area Under the Concentration-Time Curve From Time 0 to Infinity, Calculated Using the Observed Value of the Last Quantifiable Plasma Concentration for Alisertib and Drug-Related Material Following a Single Dose of [^14C]-Alisertib Oral Solution
Hide Description [Not Specified]
Time Frame Predose and multiple timepoints post-dose (up to 240 hours)
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population included all participants with sufficient dosing and PK concentration-time data to reliably estimate PK parameters and mass balance.
Arm/Group Title Alisertib
Hide Arm/Group Description:
Part A: [^14C]-alisertib 35 mg, oral solution containing 80 - 100 microcuries (μCi) of total radioactivity (1.19 - 1.48 mCi/mmol), orally, single dose on Day 1. Part B: Alisertib 50 mg, enteric coated tablets, orally, twice daily for 7 days, followed by 14-day washout period in 21-day cycles until disease progression or unacceptable treatment-related toxicity (Up to 3 Cycles).
Overall Number of Participants Analyzed 3
Mean (Standard Deviation)
Unit of Measure: hr*nmol/L
Alisertib 17266.7  (5138.42)
Drug-Related Material 42233.3  (23302.43)
5.Primary Outcome
Title T1/2: Terminal Half Life for Alisertib and Drug-Related Material in Plasma Following a Single Dose of [^14C]-Alisertib Oral Solution
Hide Description [Not Specified]
Time Frame Predose and multiple timepoints post-dose (up to 240 hours)
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population included all participants with sufficient dosing and PK concentration-time data to reliably estimate PK parameters and mass balance.
Arm/Group Title Alisertib
Hide Arm/Group Description:
Part A: [^14C]-alisertib 35 mg, oral solution containing 80 - 100 microcuries (μCi) of total radioactivity (1.19 - 1.48 mCi/mmol), orally, single dose on Day 1. Part B: Alisertib 50 mg, enteric coated tablets, orally, twice daily for 7 days, followed by 14-day washout period in 21-day cycles until disease progression or unacceptable treatment-related toxicity (Up to 3 Cycles).
Overall Number of Participants Analyzed 3
Mean (Standard Deviation)
Unit of Measure: hour
Alisertib 23.40  (7.041)
Drug-Related Material 42.03  (25.255)
6.Primary Outcome
Title CL/F: Apparent Clearance After Extravascular Administration, Calculated Using the Observed Value of the Last Quantifiable Plasma Concentration for Alisertib Following a Single Dose of [^14C]-Alisertib Oral Solution
Hide Description [Not Specified]
Time Frame Predose and multiple timepoints post-dose (up to 240 hours)
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population included all participants with sufficient dosing and PK concentration-time data to reliably estimate PK parameters and mass balance.
Arm/Group Title Alisertib
Hide Arm/Group Description:
Part A: [^14C]-alisertib 35 mg, oral solution containing 80 - 100 microcuries (μCi) of total radioactivity (1.19 - 1.48 mCi/mmol), orally, single dose on Day 1. Part B: Alisertib 50 mg, enteric coated tablets, orally, twice daily for 7 days, followed by 14-day washout period in 21-day cycles until disease progression or unacceptable treatment-related toxicity (Up to 3 Cycles).
Overall Number of Participants Analyzed 3
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: L/hr
4.06
(25.6%)
7.Primary Outcome
Title Ratio of Whole Blood Total Radioactivity (TRA) Cmax to Plasma TRA Cmax
Hide Description [Not Specified]
Time Frame Predose and multiple timepoints post-dose (up to 240 hours)
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population included all participants with sufficient dosing and PK concentration-time data to reliably estimate PK parameters and mass balance.
Arm/Group Title Alisertib
Hide Arm/Group Description:
Part A: [^14C]-alisertib 35 mg, oral solution containing 80 - 100 microcuries (μCi) of total radioactivity (1.19 - 1.48 mCi/mmol), orally, single dose on Day 1. Part B: Alisertib 50 mg, enteric coated tablets, orally, twice daily for 7 days, followed by 14-day washout period in 21-day cycles until disease progression or unacceptable treatment-related toxicity (Up to 3 Cycles).
Overall Number of Participants Analyzed 3
Mean (Standard Deviation)
Unit of Measure: ratio
0.6550  (0.0671)
8.Primary Outcome
Title Ratio of Alisertib Plasma Cmax to Drug-Related Material TRA Plasma Cmax
Hide Description [Not Specified]
Time Frame Predose and multiple timepoints post-dose (up to 240 hours)
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population included all participants with sufficient dosing and PK concentration-time data to reliably estimate PK parameters and mass balance.
Arm/Group Title Alisertib
Hide Arm/Group Description:
Part A: [^14C]-alisertib 35 mg, oral solution containing 80 - 100 microcuries (μCi) of total radioactivity (1.19 - 1.48 mCi/mmol), orally, single dose on Day 1. Part B: Alisertib 50 mg, enteric coated tablets, orally, twice daily for 7 days, followed by 14-day washout period in 21-day cycles until disease progression or unacceptable treatment-related toxicity (Up to 3 Cycles).
Overall Number of Participants Analyzed 3
Mean (Standard Deviation)
Unit of Measure: ratio
0.8397  (0.0589)
9.Primary Outcome
Title Ratio of Whole Blood TRA AUClast to Plasma TRA AUClast
Hide Description [Not Specified]
Time Frame Predose and multiple timepoints post-dose (up to 240 hours)
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population included all participants with sufficient dosing and PK concentration-time data to reliably estimate PK parameters and mass balance.
Arm/Group Title Alisertib
Hide Arm/Group Description:
Part A: [^14C]-alisertib 35 mg, oral solution containing 80 - 100 microcuries (μCi) of total radioactivity (1.19 - 1.48 mCi/mmol), orally, single dose on Day 1. Part B: Alisertib 50 mg, enteric coated tablets, orally, twice daily for 7 days, followed by 14-day washout period in 21-day cycles until disease progression or unacceptable treatment-related toxicity (Up to 3 Cycles).
Overall Number of Participants Analyzed 3
Mean (Standard Deviation)
Unit of Measure: ratio
0.5950  (0.1010)
10.Primary Outcome
Title Ratio of Alisertib Plasma AUClast to Drug-Related Material TRA Plasma AUClast
Hide Description [Not Specified]
Time Frame Predose and multiple timepoints post-dose (up to 240 hours)
Hide Outcome Measure Data
Hide Analysis Population Description
PK population included all participants with sufficient dosing and PK concentration-time data to reliably estimate PK parameters and mass balance.
Arm/Group Title Alisertib
Hide Arm/Group Description:
Part A: [^14C]-alisertib 35 mg, oral solution containing 80 - 100 microcuries (μCi) of total radioactivity (1.19 - 1.48 mCi/mmol), orally, single dose on Day 1. Part B: Alisertib 50 mg, enteric coated tablets, orally, twice daily for 7 days, followed by 14-day washout period in 21-day cycles until disease progression or unacceptable treatment-related toxicity (Up to 3 Cycles).
Overall Number of Participants Analyzed 3
Mean (Standard Deviation)
Unit of Measure: ratio
0.4997  (0.1364)
11.Primary Outcome
Title Ratio of Whole Blood TRA AUC∞ to Plasma TRA AUC∞
Hide Description [Not Specified]
Time Frame Predose and multiple timepoints post-dose (up to 240 hours)
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population included all participants with sufficient dosing and PK concentration-time data to reliably estimate PK parameters and mass balance.
Arm/Group Title Alisertib
Hide Arm/Group Description:
Part A: [^14C]-alisertib 35 mg, oral solution containing 80 - 100 microcuries (μCi) of total radioactivity (1.19 - 1.48 mCi/mmol), orally, single dose on Day 1. Part B: Alisertib 50 mg, enteric coated tablets, orally, twice daily for 7 days, followed by 14-day washout period in 21-day cycles until disease progression or unacceptable treatment-related toxicity (Up to 3 Cycles).
Overall Number of Participants Analyzed 3
Mean (Standard Deviation)
Unit of Measure: ratio
0.6750  (0.0170)
12.Primary Outcome
Title Ratio of Alisertib Plasma AUC∞ to Drug-Related Material TRA Plasma AUC∞
Hide Description [Not Specified]
Time Frame Predose and multiple timepoints post-dose (up to 240 hours)
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population included all participants with sufficient dosing and PK concentration-time data to reliably estimate PK parameters and mass balance.
Arm/Group Title Alisertib
Hide Arm/Group Description:
Part A: [^14C]-alisertib 35 mg, oral solution containing 80 - 100 microcuries (μCi) of total radioactivity (1.19 - 1.48 mCi/mmol), orally, single dose on Day 1. Part B: Alisertib 50 mg, enteric coated tablets, orally, twice daily for 7 days, followed by 14-day washout period in 21-day cycles until disease progression or unacceptable treatment-related toxicity (Up to 3 Cycles).
Overall Number of Participants Analyzed 3
Mean (Standard Deviation)
Unit of Measure: ratio
0.4490  (0.1204)
13.Primary Outcome
Title Fe: Fraction of Administered Dose of [^14C]-Alisertib Excreted in Urine
Hide Description [Not Specified]
Time Frame Predose and multiple timepoints post-dose (up to 240 hours)
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population included all participants with sufficient dosing and PK concentration-time data to reliably estimate PK parameters and mass balance.
Arm/Group Title Alisertib
Hide Arm/Group Description:
Part A: [^14C]-alisertib 35 mg, oral solution containing 80 - 100 microcuries (μCi) of total radioactivity (1.19 - 1.48 mCi/mmol), orally, single dose on Day 1. Part B: Alisertib 50 mg, enteric coated tablets, orally, twice daily for 7 days, followed by 14-day washout period in 21-day cycles until disease progression or unacceptable treatment-related toxicity (Up to 3 Cycles).
Overall Number of Participants Analyzed 3
Mean (Standard Deviation)
Unit of Measure: percent of dose
2.650  (1.7935)
14.Primary Outcome
Title Fe: Fraction of Administered Dose of [^14C]-Alisertib Excreted in Feces
Hide Description [Not Specified]
Time Frame Predose and multiple timepoints post-dose (up to 240 hours)
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population included all participants with sufficient dosing and PK concentration-time data to reliably estimate PK parameters and mass balance.
Arm/Group Title Alisertib
Hide Arm/Group Description:
Part A: [^14C]-alisertib 35 mg, oral solution containing 80 - 100 microcuries (μCi) of total radioactivity (1.19 - 1.48 mCi/mmol), orally, single dose on Day 1. Part B: Alisertib 50 mg, enteric coated tablets, orally, twice daily for 7 days, followed by 14-day washout period in 21-day cycles until disease progression or unacceptable treatment-related toxicity (Up to 3 Cycles).
Overall Number of Participants Analyzed 3
Mean (Standard Deviation)
Unit of Measure: percent of dose
87.833  (2.2898)
15.Primary Outcome
Title Ae: Amount of [^14C]-Alisertib Excreted in Urine
Hide Description [Not Specified]
Time Frame Predose and multiple timepoints post-dose (up to 240 hours)
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population included all participants with sufficient dosing and PK concentration-time data to reliably estimate PK parameters and mass balance.
Arm/Group Title Alisertib
Hide Arm/Group Description:
Part A: [^14C]-alisertib 35 mg, oral solution containing 80 - 100 microcuries (μCi) of total radioactivity (1.19 - 1.48 mCi/mmol), orally, single dose on Day 1. Part B: Alisertib 50 mg, enteric coated tablets, orally, twice daily for 7 days, followed by 14-day washout period in 21-day cycles until disease progression or unacceptable treatment-related toxicity (Up to 3 Cycles).
Overall Number of Participants Analyzed 3
Mean (Standard Deviation)
Unit of Measure: nanogram equivalent [ng(eq)]
939420.7  (632770.92)
16.Primary Outcome
Title Ae: Amount of [^14C]-Alisertib Excreted in Feces
Hide Description [Not Specified]
Time Frame Predose and multiple timepoints post-dose (up to 240 hours)
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population included all participants with sufficient dosing and PK concentration-time data to reliably estimate PK parameters and mass balance.
Arm/Group Title Alisertib
Hide Arm/Group Description:
Part A: [^14C]-alisertib 35 mg, oral solution containing 80 - 100 microcuries (μCi) of total radioactivity (1.19 - 1.48 mCi/mmol), orally, single dose on Day 1. Part B: Alisertib 50 mg, enteric coated tablets, orally, twice daily for 7 days, followed by 14-day washout period in 21-day cycles until disease progression or unacceptable treatment-related toxicity (Up to 3 Cycles).
Overall Number of Participants Analyzed 3
Mean (Standard Deviation)
Unit of Measure: ng(eq)
31156703.0  (764243.97)
17.Primary Outcome
Title Percent of Total Radioactivity (TRA) in Urine and Feces
Hide Description [Not Specified]
Time Frame Predose and multiple timepoints post-dose (up to 240 hours)
Hide Outcome Measure Data
Hide Analysis Population Description
PK population included all participants with sufficient dosing and PK concentration-time data to reliably estimate PK parameters and mass balance.
Arm/Group Title Alisertib
Hide Arm/Group Description:
Part A: [^14C]-alisertib 35 mg, oral solution containing 80 - 100 microcuries (μCi) of total radioactivity (1.19 - 1.48 mCi/mmol), orally, single dose on Day 1. Part B: Alisertib 50 mg, enteric coated tablets, orally, twice daily for 7 days, followed by 14-day washout period in 21-day cycles until disease progression or unacceptable treatment-related toxicity (Up to 3 Cycles).
Overall Number of Participants Analyzed 3
Mean (Standard Deviation)
Unit of Measure: percent of TRA
90.500  (1.3115)
18.Primary Outcome
Title Fe: Fraction of Administered Dose of Alisertib Excreted in Urine
Hide Description [Not Specified]
Time Frame Predose and multiple timepoints post-dose (up to 240 hours)
Hide Outcome Measure Data
Hide Analysis Population Description
Participant from the PK Population, all participants with sufficient dosing and PK concentration-time data to reliably estimate PK parameters and mass balance, with data available for Fe.
Arm/Group Title Alisertib
Hide Arm/Group Description:
Part A: [^14C]-alisertib 35 mg, oral solution containing 80 - 100 microcuries (μCi) of total radioactivity (1.19 - 1.48 mCi/mmol), orally, single dose on Day 1. Part B: Alisertib 50 mg, enteric coated tablets, orally, twice daily for 7 days, followed by 14-day washout period in 21-day cycles until disease progression or unacceptable treatment-related toxicity (Up to 3 Cycles).
Overall Number of Participants Analyzed 2
Mean (Standard Deviation)
Unit of Measure: percent of dose
0.009045  (0.000714)
19.Primary Outcome
Title Ae: Amount of Alisertib Excretion in Urine
Hide Description [Not Specified]
Time Frame Predose and multiple timepoints post-dose (up to 240 hours)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the PK Population, all participants with sufficient dosing and PK concentration-time data to reliably estimate PK parameters and mass balance, with data available for Ae.
Arm/Group Title Alisertib
Hide Arm/Group Description:
Part A: [^14C]-alisertib 35 mg, oral solution containing 80 - 100 microcuries (μCi) of total radioactivity (1.19 - 1.48 mCi/mmol), orally, single dose on Day 1. Part B: Alisertib 50 mg, enteric coated tablets, orally, twice daily for 7 days, followed by 14-day washout period in 21-day cycles until disease progression or unacceptable treatment-related toxicity (Up to 3 Cycles).
Overall Number of Participants Analyzed 2
Mean (Standard Deviation)
Unit of Measure: ng
3215.0  (219.20)
20.Primary Outcome
Title Renal Clearance (CLR) of Alisertib
Hide Description [Not Specified]
Time Frame Predose and multiple timepoints post-dose (up to 240 hours)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the PK Population, all participants with sufficient dosing and PK concentration-time data to reliably estimate PK parameters and mass balance, with data for CLR.
Arm/Group Title Alisertib
Hide Arm/Group Description:
Part A: [^14C]-alisertib 35 mg, oral solution containing 80 - 100 microcuries (μCi) of total radioactivity (1.19 - 1.48 mCi/mmol), orally, single dose on Day 1. Part B: Alisertib 50 mg, enteric coated tablets, orally, twice daily for 7 days, followed by 14-day washout period in 21-day cycles until disease progression or unacceptable treatment-related toxicity (Up to 3 Cycles).
Overall Number of Participants Analyzed 2
Mean (Standard Deviation)
Unit of Measure: L/hr
0.000687  (0.000013)
21.Secondary Outcome
Title Percentage of Alisertib Metabolites in Plasma Following a Single Dose of [^14C]-Alisertib Oral Solution
Hide Description Total radioactive peak distributions of metabolites in 0 to 192 hours pooled plasma samples from participants.
Time Frame Predose and multiple timepoints post-dose (0 to 192 hours)
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population included all participants with sufficient dosing and PK concentration-time data to reliably estimate PK parameters and mass balance.
Arm/Group Title Alisertib
Hide Arm/Group Description:
Part A: [^14C]-alisertib 35 mg, oral solution containing 80 - 100 microcuries (μCi) of total radioactivity (1.19 - 1.48 mCi/mmol), orally, single dose on Day 1. Part B: Alisertib 50 mg, enteric coated tablets, orally, twice daily for 7 days, followed by 14-day washout period in 21-day cycles until disease progression or unacceptable treatment-related toxicity (Up to 3 Cycles).
Overall Number of Participants Analyzed 3
Measure Type: Number
Unit of Measure: percent of plasma AUC0-192hr
Metabolite M1 12.0
Metabolite M2 34.6
Metabolite M3 5.6
22.Secondary Outcome
Title Percentage of Alisertib Metabolites in Urine Following a Single Dose of [^14C]-Alisertib Oral Solution
Hide Description Total radioactive peak distributions of metabolites in 0 to 192 hours pooled urine samples from participants.
Time Frame Predose and multiple timepoints post-dose (0 to 192 hours)
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population included all participants with sufficient dosing and PK concentration-time data to reliably estimate PK parameters and mass balance.
Arm/Group Title Alisertib
Hide Arm/Group Description:
Part A: [^14C]-alisertib 35 mg, oral solution containing 80 - 100 microcuries (μCi) of total radioactivity (1.19 - 1.48 mCi/mmol), orally, single dose on Day 1. Part B: Alisertib 50 mg, enteric coated tablets, orally, twice daily for 7 days, followed by 14-day washout period in 21-day cycles until disease progression or unacceptable treatment-related toxicity (Up to 3 Cycles).
Overall Number of Participants Analyzed 3
Measure Type: Number
Unit of Measure: percent of dose
Unknown 0.24
M8a 0.28
M9 0.66
M536 0.14
M1 0.84
M8 0.37
Others 0.05
23.Secondary Outcome
Title Percentage of Alisertib Metabolites in Feces Following a Single Dose of [^14C]-Alisertib Oral Solution
Hide Description Total radioactive peak distributions of metabolites in 0 to 192 hours pooled fecal samples from participants.
Time Frame Predose and multiple timepoints post-dose (0 to 192 hours)
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population included all participants with sufficient dosing and PK concentration-time data to reliably estimate PK parameters and mass balance.
Arm/Group Title Alisertib
Hide Arm/Group Description:
Part A: [^14C]-alisertib 35 mg, oral solution containing 80 - 100 microcuries (μCi) of total radioactivity (1.19 - 1.48 mCi/mmol), orally, single dose on Day 1. Part B: Alisertib 50 mg, enteric coated tablets, orally, twice daily for 7 days, followed by 14-day washout period in 21-day cycles until disease progression or unacceptable treatment-related toxicity (Up to 3 Cycles).
Overall Number of Participants Analyzed 3
Measure Type: Number
Unit of Measure: percent of dose
M536 4.45
M520a 1.19
M3a 2.22
M550 2.96
M537 9.17
M520b 1.72
M3 20.82
M520c 5.94
Alisertib 26.27
M2 8.62
Others 0
24.Secondary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events
Hide Description An Adverse Event (AE) was 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) was defined as any AE at any dose that: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in a persistent or significant disability/incapacity or resulted in congenital anomaly/birth defect. A treatment-emergent adverse event is defined as an adverse event with an onset that occurs after receiving study drug.
Time Frame From first dose of study drug through 30 days after the last dose of study drug (Up to 117 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population included all participants who received at least 1 dose of study drug.
Arm/Group Title Alisertib
Hide Arm/Group Description:
Part A: [^14C]-alisertib 35 mg, oral solution containing 80 - 100 microcuries (μCi) of total radioactivity (1.19 - 1.48 mCi/mmol), orally, single dose on Day 1. Part B: Alisertib 50 mg, enteric coated tablets, orally, twice daily for 7 days, followed by 14-day washout period in 21-day cycles until disease progression or unacceptable treatment-related toxicity (Up to 3 Cycles).
Overall Number of Participants Analyzed 3
Measure Type: Number
Unit of Measure: Participants
Any AE 3
SAE 0
25.Secondary Outcome
Title Number of Participants With Clinically Significant Changes or Abnormalities in Clinical Laboratory Values Reported as AEs
Hide Description An abnormal laboratory was assessed to be an AE if the value lead to discontinuation or delay in treatment, dose modification, therapeutic intervention, or was considered by the investigator to be a clinically significant change from Baseline.
Time Frame Part A: Day 1 and End of Study (EOS) Day 31 if not continuing to Part B, Part B: Days 8 and 15 of each cycle and EOS (Up to 117 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population included all participants who received at least 1 dose of study drug.
Arm/Group Title Alisertib
Hide Arm/Group Description:
Part A: [^14C]-alisertib 35 mg, oral solution containing 80 - 100 microcuries (μCi) of total radioactivity (1.19 - 1.48 mCi/mmol), orally, single dose on Day 1. Part B: Alisertib 50 mg, enteric coated tablets, orally, twice daily for 7 days, followed by 14-day washout period in 21-day cycles until disease progression or unacceptable treatment-related toxicity (Up to 3 Cycles).
Overall Number of Participants Analyzed 3
Measure Type: Number
Unit of Measure: Participants
Neutrophil Count Decreased 1
Neutropenia 1
Blood Magnesium Decreased 1
26.Secondary Outcome
Title Number of Participants With Clinically Significant Changes or Abnormalities in Vital Sign Measurements
Hide Description Vital signs included body temperature, heart rate, and sitting blood pressure. The investigator determined if the changes were clinically significant.
Time Frame Part A: Day 1 and EOS (Day 31 if not continuing to Part B), Part B: Day 1 of each cycle and EOS (Up to 117 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants who received at least 1 dose of study drug.
Arm/Group Title Alisertib
Hide Arm/Group Description:
Part A: [^14C]-alisertib 35 mg, oral solution containing 80 - 100 microcuries (μCi) of total radioactivity (1.19 - 1.48 mCi/mmol), orally, single dose on Day 1. Part B: Alisertib 50 mg, enteric coated tablets, orally, twice daily for 7 days, followed by 14-day washout period in 21-day cycles until disease progression or unacceptable treatment-related toxicity (Up to 3 Cycles).
Overall Number of Participants Analyzed 3
Measure Type: Number
Unit of Measure: Participants
0
Time Frame From first dose of study drug through 30 days after the last dose of study drug (Up to 117 days)
Adverse Event Reporting Description At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
 
Arm/Group Title Alisertib
Hide Arm/Group Description Part A: [^14C]-alisertib 35 mg, oral solution containing 80 - 100 microcuries (μCi) of total radioactivity (1.19 - 1.48 mCi/mmol), orally, single dose on Day 1. Part B: Alisertib 50 mg, enteric coated tablets, orally, twice daily for 7 days, followed by 14-day washout period in 21-day cycles until disease progression or unacceptable treatment-related toxicity (Up to 3 Cycles).
All-Cause Mortality
Alisertib
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Alisertib
Affected / at Risk (%)
Total   0/3 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Alisertib
Affected / at Risk (%)
Total   3/3 (100.00%) 
Blood and lymphatic system disorders   
Neutropenia  1  1/3 (33.33%) 
Gastrointestinal disorders   
Nausea  1  1/3 (33.33%) 
Vomiting  1  1/3 (33.33%) 
Glossodynia  1  1/3 (33.33%) 
General disorders   
Fatigue  1  2/3 (66.67%) 
Pyrexia  1  1/3 (33.33%) 
Chills  1  1/3 (33.33%) 
Oedema peripheral  1  1/3 (33.33%) 
Injury, poisoning and procedural complications   
Ligament sprain  1  1/3 (33.33%) 
Investigations   
Blood magnesium decreased  1  1/3 (33.33%) 
Neutrophil count decreased  1  1/3 (33.33%) 
Musculoskeletal and connective tissue disorders   
Back pain  1  1/3 (33.33%) 
Musculoskeletal pain  1  1/3 (33.33%) 
Pain in extremity  1  1/3 (33.33%) 
Nervous system disorders   
Headache  1  1/3 (33.33%) 
Reproductive system and breast disorders   
Scrotal swelling  1  1/3 (33.33%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  1/3 (33.33%) 
Respiratory tract congestion  1  1/3 (33.33%) 
Skin and subcutaneous tissue disorders   
Alopecia  1  2/3 (66.67%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (15.0)
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: NCT01714947     History of Changes
Other Study ID Numbers: C14014
U1111-1187-6760 ( Other Identifier: WHO )
First Submitted: October 17, 2012
First Posted: October 26, 2012
Results First Submitted: February 20, 2018
Results First Posted: October 31, 2018
Last Update Posted: October 31, 2018