Trial Outcomes & Findings for Mass Balance, Pharmacokinetics and Metabolism Study of Alisertib (NCT NCT01714947)
NCT ID: NCT01714947
Last Updated: 2018-10-31
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
3 participants
Primary outcome timeframe
Predose and multiple timepoints post-dose (up to 240 hours)
Results posted on
2018-10-31
Participant Flow
Participants took part in the study at 1 investigative site in the United States from 24 January 2013 to 14 June 2013.
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.
Participant milestones
| Measure |
Alisertib
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).
|
|---|---|
|
Part A
STARTED
|
3
|
|
Part A
COMPLETED
|
3
|
|
Part A
NOT COMPLETED
|
0
|
|
Part B
STARTED
|
3
|
|
Part B
COMPLETED
|
0
|
|
Part B
NOT COMPLETED
|
3
|
Reasons for withdrawal
| Measure |
Alisertib
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).
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|---|---|
|
Part B
Progressive Disease
|
3
|
Baseline Characteristics
Mass Balance, Pharmacokinetics and Metabolism Study of Alisertib
Baseline characteristics by cohort
| Measure |
Alisertib
n=3 Participants
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).
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|---|---|
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Age, Continuous
|
64.0 years
STANDARD_DEVIATION 13.11 • n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
3 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
2 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
1 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
3 participants
n=5 Participants
|
|
Height
|
173.5 cm
STANDARD_DEVIATION 7.15 • n=5 Participants
|
|
Weight
|
80.27 kg
STANDARD_DEVIATION 20.760 • n=5 Participants
|
|
Body Mass Index (BMI)
|
26.91 kg/m^2
STANDARD_DEVIATION 8.346 • n=5 Participants
|
PRIMARY outcome
Timeframe: Predose and multiple timepoints post-dose (up to 240 hours)Population: Pharmacokinetic (PK) Population included all participants with sufficient dosing and PK concentration-time data to reliably estimate PK parameters and mass balance.
Outcome measures
| Measure |
Alisertib
n=3 Participants
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).
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|---|---|
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Cmax: Maximum Observed Plasma Concentration for Alisertib and Drug-Related Material Following a Single Dose of [^14C]-Alisertib Oral Solution
Alisertib
|
2183.3 nanomole (nmol)/liter (L)
Standard Deviation 161.97
|
|
Cmax: Maximum Observed Plasma Concentration for Alisertib and Drug-Related Material Following a Single Dose of [^14C]-Alisertib Oral Solution
Drug-Related Material
|
2606.7 nanomole (nmol)/liter (L)
Standard Deviation 228.98
|
PRIMARY outcome
Timeframe: Predose and multiple timepoints post-dose (up to 240 hours)Population: Pharmacokinetic (PK) Population included all participants with sufficient dosing and PK concentration-time data to reliably estimate PK parameters and mass balance.
Outcome measures
| Measure |
Alisertib
n=3 Participants
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).
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|---|---|
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Tmax: Time of First Occurrence of Cmax for Alisertib and Drug-Related Material in Plasma Following a Single Dose of [^14C]-Alisertib Oral Solution
Alisertib
|
1.00 hr
Full Range 161.97 • Interval 0.5 to 2.0
|
|
Tmax: Time of First Occurrence of Cmax for Alisertib and Drug-Related Material in Plasma Following a Single Dose of [^14C]-Alisertib Oral Solution
Drug-Related Material
|
1.00 hr
Full Range 228.98 • Interval 0.5 to 2.0
|
PRIMARY outcome
Timeframe: Predose and multiple timepoints post-dose (up to 240 hours)Population: PK Population included all participants with sufficient dosing and PK concentration-time data to reliably estimate PK parameters and mass balance.
Outcome measures
| Measure |
Alisertib
n=3 Participants
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).
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|---|---|
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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
Alisertib
|
16800.0 hour (hr)*nmol/L
Standard Deviation 4936.60
|
|
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
Drug-Related Material
|
37033.3 hour (hr)*nmol/L
Standard Deviation 20545.15
|
PRIMARY outcome
Timeframe: Predose and multiple timepoints post-dose (up to 240 hours)Population: PK Population included all participants with sufficient dosing and PK concentration-time data to reliably estimate PK parameters and mass balance.
Outcome measures
| Measure |
Alisertib
n=3 Participants
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).
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|---|---|
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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
Alisertib
|
17266.7 hr*nmol/L
Standard Deviation 5138.42
|
|
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
Drug-Related Material
|
42233.3 hr*nmol/L
Standard Deviation 23302.43
|
PRIMARY outcome
Timeframe: Predose and multiple timepoints post-dose (up to 240 hours)Population: PK Population included all participants with sufficient dosing and PK concentration-time data to reliably estimate PK parameters and mass balance.
Outcome measures
| Measure |
Alisertib
n=3 Participants
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).
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|---|---|
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T1/2: Terminal Half Life for Alisertib and Drug-Related Material in Plasma Following a Single Dose of [^14C]-Alisertib Oral Solution
Alisertib
|
23.40 hour
Standard Deviation 7.041
|
|
T1/2: Terminal Half Life for Alisertib and Drug-Related Material in Plasma Following a Single Dose of [^14C]-Alisertib Oral Solution
Drug-Related Material
|
42.03 hour
Standard Deviation 25.255
|
PRIMARY outcome
Timeframe: Predose and multiple timepoints post-dose (up to 240 hours)Population: PK Population included all participants with sufficient dosing and PK concentration-time data to reliably estimate PK parameters and mass balance.
Outcome measures
| Measure |
Alisertib
n=3 Participants
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).
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|---|---|
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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
|
4.06 L/hr
Geometric Coefficient of Variation 25.6
|
PRIMARY outcome
Timeframe: Predose and multiple timepoints post-dose (up to 240 hours)Population: PK Population included all participants with sufficient dosing and PK concentration-time data to reliably estimate PK parameters and mass balance.
Outcome measures
| Measure |
Alisertib
n=3 Participants
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).
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|---|---|
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Ratio of Whole Blood Total Radioactivity (TRA) Cmax to Plasma TRA Cmax
|
0.6550 ratio
Standard Deviation 0.0671
|
PRIMARY outcome
Timeframe: Predose and multiple timepoints post-dose (up to 240 hours)Population: PK Population included all participants with sufficient dosing and PK concentration-time data to reliably estimate PK parameters and mass balance.
Outcome measures
| Measure |
Alisertib
n=3 Participants
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).
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|---|---|
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Ratio of Alisertib Plasma Cmax to Drug-Related Material TRA Plasma Cmax
|
0.8397 ratio
Standard Deviation 0.0589
|
PRIMARY outcome
Timeframe: Predose and multiple timepoints post-dose (up to 240 hours)Population: PK Population included all participants with sufficient dosing and PK concentration-time data to reliably estimate PK parameters and mass balance.
Outcome measures
| Measure |
Alisertib
n=3 Participants
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).
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|---|---|
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Ratio of Whole Blood TRA AUClast to Plasma TRA AUClast
|
0.5950 ratio
Standard Deviation 0.1010
|
PRIMARY outcome
Timeframe: Predose and multiple timepoints post-dose (up to 240 hours)Population: PK population included all participants with sufficient dosing and PK concentration-time data to reliably estimate PK parameters and mass balance.
Outcome measures
| Measure |
Alisertib
n=3 Participants
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).
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|---|---|
|
Ratio of Alisertib Plasma AUClast to Drug-Related Material TRA Plasma AUClast
|
0.4997 ratio
Standard Deviation 0.1364
|
PRIMARY outcome
Timeframe: Predose and multiple timepoints post-dose (up to 240 hours)Population: PK Population included all participants with sufficient dosing and PK concentration-time data to reliably estimate PK parameters and mass balance.
Outcome measures
| Measure |
Alisertib
n=3 Participants
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).
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|---|---|
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Ratio of Whole Blood TRA AUC∞ to Plasma TRA AUC∞
|
0.6750 ratio
Standard Deviation 0.0170
|
PRIMARY outcome
Timeframe: Predose and multiple timepoints post-dose (up to 240 hours)Population: PK Population included all participants with sufficient dosing and PK concentration-time data to reliably estimate PK parameters and mass balance.
Outcome measures
| Measure |
Alisertib
n=3 Participants
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).
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|---|---|
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Ratio of Alisertib Plasma AUC∞ to Drug-Related Material TRA Plasma AUC∞
|
0.4490 ratio
Standard Deviation 0.1204
|
PRIMARY outcome
Timeframe: Predose and multiple timepoints post-dose (up to 240 hours)Population: PK Population included all participants with sufficient dosing and PK concentration-time data to reliably estimate PK parameters and mass balance.
Outcome measures
| Measure |
Alisertib
n=3 Participants
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).
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|---|---|
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Fe: Fraction of Administered Dose of [^14C]-Alisertib Excreted in Urine
|
2.650 percent of dose
Standard Deviation 1.7935
|
PRIMARY outcome
Timeframe: Predose and multiple timepoints post-dose (up to 240 hours)Population: PK Population included all participants with sufficient dosing and PK concentration-time data to reliably estimate PK parameters and mass balance.
Outcome measures
| Measure |
Alisertib
n=3 Participants
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).
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|---|---|
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Fe: Fraction of Administered Dose of [^14C]-Alisertib Excreted in Feces
|
87.833 percent of dose
Standard Deviation 2.2898
|
PRIMARY outcome
Timeframe: Predose and multiple timepoints post-dose (up to 240 hours)Population: PK Population included all participants with sufficient dosing and PK concentration-time data to reliably estimate PK parameters and mass balance.
Outcome measures
| Measure |
Alisertib
n=3 Participants
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).
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|---|---|
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Ae: Amount of [^14C]-Alisertib Excreted in Urine
|
939420.7 nanogram equivalent [ng(eq)]
Standard Deviation 632770.92
|
PRIMARY outcome
Timeframe: Predose and multiple timepoints post-dose (up to 240 hours)Population: PK Population included all participants with sufficient dosing and PK concentration-time data to reliably estimate PK parameters and mass balance.
Outcome measures
| Measure |
Alisertib
n=3 Participants
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).
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|---|---|
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Ae: Amount of [^14C]-Alisertib Excreted in Feces
|
31156703.0 ng(eq)
Standard Deviation 764243.97
|
PRIMARY outcome
Timeframe: Predose and multiple timepoints post-dose (up to 240 hours)Population: PK population included all participants with sufficient dosing and PK concentration-time data to reliably estimate PK parameters and mass balance.
Outcome measures
| Measure |
Alisertib
n=3 Participants
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).
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|---|---|
|
Percent of Total Radioactivity (TRA) in Urine and Feces
|
90.500 percent of TRA
Standard Deviation 1.3115
|
PRIMARY outcome
Timeframe: Predose and multiple timepoints post-dose (up to 240 hours)Population: 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.
Outcome measures
| Measure |
Alisertib
n=2 Participants
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).
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|---|---|
|
Fe: Fraction of Administered Dose of Alisertib Excreted in Urine
|
0.009045 percent of dose
Standard Deviation 0.000714
|
PRIMARY outcome
Timeframe: Predose and multiple timepoints post-dose (up to 240 hours)Population: 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.
Outcome measures
| Measure |
Alisertib
n=2 Participants
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).
|
|---|---|
|
Ae: Amount of Alisertib Excretion in Urine
|
3215.0 ng
Standard Deviation 219.20
|
PRIMARY outcome
Timeframe: Predose and multiple timepoints post-dose (up to 240 hours)Population: 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.
Outcome measures
| Measure |
Alisertib
n=2 Participants
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).
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|---|---|
|
Renal Clearance (CLR) of Alisertib
|
0.000687 L/hr
Standard Deviation 0.000013
|
SECONDARY outcome
Timeframe: Predose and multiple timepoints post-dose (0 to 192 hours)Population: PK Population included all participants with sufficient dosing and PK concentration-time data to reliably estimate PK parameters and mass balance.
Total radioactive peak distributions of metabolites in 0 to 192 hours pooled plasma samples from participants.
Outcome measures
| Measure |
Alisertib
n=3 Participants
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).
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|---|---|
|
Percentage of Alisertib Metabolites in Plasma Following a Single Dose of [^14C]-Alisertib Oral Solution
Metabolite M1
|
12.0 percent of plasma AUC0-192hr
|
|
Percentage of Alisertib Metabolites in Plasma Following a Single Dose of [^14C]-Alisertib Oral Solution
Metabolite M2
|
34.6 percent of plasma AUC0-192hr
|
|
Percentage of Alisertib Metabolites in Plasma Following a Single Dose of [^14C]-Alisertib Oral Solution
Metabolite M3
|
5.6 percent of plasma AUC0-192hr
|
SECONDARY outcome
Timeframe: Predose and multiple timepoints post-dose (0 to 192 hours)Population: PK Population included all participants with sufficient dosing and PK concentration-time data to reliably estimate PK parameters and mass balance.
Total radioactive peak distributions of metabolites in 0 to 192 hours pooled urine samples from participants.
Outcome measures
| Measure |
Alisertib
n=3 Participants
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).
|
|---|---|
|
Percentage of Alisertib Metabolites in Urine Following a Single Dose of [^14C]-Alisertib Oral Solution
Unknown
|
0.24 percent of dose
|
|
Percentage of Alisertib Metabolites in Urine Following a Single Dose of [^14C]-Alisertib Oral Solution
M8a
|
0.28 percent of dose
|
|
Percentage of Alisertib Metabolites in Urine Following a Single Dose of [^14C]-Alisertib Oral Solution
M9
|
0.66 percent of dose
|
|
Percentage of Alisertib Metabolites in Urine Following a Single Dose of [^14C]-Alisertib Oral Solution
M536
|
0.14 percent of dose
|
|
Percentage of Alisertib Metabolites in Urine Following a Single Dose of [^14C]-Alisertib Oral Solution
M1
|
0.84 percent of dose
|
|
Percentage of Alisertib Metabolites in Urine Following a Single Dose of [^14C]-Alisertib Oral Solution
M8
|
0.37 percent of dose
|
|
Percentage of Alisertib Metabolites in Urine Following a Single Dose of [^14C]-Alisertib Oral Solution
Others
|
0.05 percent of dose
|
SECONDARY outcome
Timeframe: Predose and multiple timepoints post-dose (0 to 192 hours)Population: PK Population included all participants with sufficient dosing and PK concentration-time data to reliably estimate PK parameters and mass balance.
Total radioactive peak distributions of metabolites in 0 to 192 hours pooled fecal samples from participants.
Outcome measures
| Measure |
Alisertib
n=3 Participants
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).
|
|---|---|
|
Percentage of Alisertib Metabolites in Feces Following a Single Dose of [^14C]-Alisertib Oral Solution
M3
|
20.82 percent of dose
|
|
Percentage of Alisertib Metabolites in Feces Following a Single Dose of [^14C]-Alisertib Oral Solution
M520c
|
5.94 percent of dose
|
|
Percentage of Alisertib Metabolites in Feces Following a Single Dose of [^14C]-Alisertib Oral Solution
M2
|
8.62 percent of dose
|
|
Percentage of Alisertib Metabolites in Feces Following a Single Dose of [^14C]-Alisertib Oral Solution
Others
|
0 percent of dose
|
|
Percentage of Alisertib Metabolites in Feces Following a Single Dose of [^14C]-Alisertib Oral Solution
Alisertib
|
26.27 percent of dose
|
|
Percentage of Alisertib Metabolites in Feces Following a Single Dose of [^14C]-Alisertib Oral Solution
M536
|
4.45 percent of dose
|
|
Percentage of Alisertib Metabolites in Feces Following a Single Dose of [^14C]-Alisertib Oral Solution
M520a
|
1.19 percent of dose
|
|
Percentage of Alisertib Metabolites in Feces Following a Single Dose of [^14C]-Alisertib Oral Solution
M3a
|
2.22 percent of dose
|
|
Percentage of Alisertib Metabolites in Feces Following a Single Dose of [^14C]-Alisertib Oral Solution
M550
|
2.96 percent of dose
|
|
Percentage of Alisertib Metabolites in Feces Following a Single Dose of [^14C]-Alisertib Oral Solution
M537
|
9.17 percent of dose
|
|
Percentage of Alisertib Metabolites in Feces Following a Single Dose of [^14C]-Alisertib Oral Solution
M520b
|
1.72 percent of dose
|
SECONDARY outcome
Timeframe: From first dose of study drug through 30 days after the last dose of study drug (Up to 117 days)Population: Safety Population included all participants who received at least 1 dose of study drug.
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.
Outcome measures
| Measure |
Alisertib
n=3 Participants
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).
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|---|---|
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Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events
Any AE
|
3 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events
SAE
|
0 Participants
|
SECONDARY outcome
Timeframe: 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)Population: Safety Population included all participants who received at least 1 dose of study drug.
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.
Outcome measures
| Measure |
Alisertib
n=3 Participants
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).
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|---|---|
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Number of Participants With Clinically Significant Changes or Abnormalities in Clinical Laboratory Values Reported as AEs
Neutrophil Count Decreased
|
1 Participants
|
|
Number of Participants With Clinically Significant Changes or Abnormalities in Clinical Laboratory Values Reported as AEs
Neutropenia
|
1 Participants
|
|
Number of Participants With Clinically Significant Changes or Abnormalities in Clinical Laboratory Values Reported as AEs
Blood Magnesium Decreased
|
1 Participants
|
SECONDARY outcome
Timeframe: 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)Population: Safety population included all participants who received at least 1 dose of study drug.
Vital signs included body temperature, heart rate, and sitting blood pressure. The investigator determined if the changes were clinically significant.
Outcome measures
| Measure |
Alisertib
n=3 Participants
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).
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|---|---|
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Number of Participants With Clinically Significant Changes or Abnormalities in Vital Sign Measurements
|
0 Participants
|
Adverse Events
Alisertib
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Alisertib
n=3 participants at risk
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).
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|---|---|
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Gastrointestinal disorders
Nausea
|
33.3%
1/3 • From first dose of study drug through 30 days after the last dose of study drug (Up to 117 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Gastrointestinal disorders
Vomiting
|
33.3%
1/3 • From first dose of study drug through 30 days after the last dose of study drug (Up to 117 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Gastrointestinal disorders
Glossodynia
|
33.3%
1/3 • From first dose of study drug through 30 days after the last dose of study drug (Up to 117 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
General disorders
Fatigue
|
66.7%
2/3 • From first dose of study drug through 30 days after the last dose of study drug (Up to 117 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
General disorders
Pyrexia
|
33.3%
1/3 • From first dose of study drug through 30 days after the last dose of study drug (Up to 117 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
General disorders
Chills
|
33.3%
1/3 • From first dose of study drug through 30 days after the last dose of study drug (Up to 117 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
General disorders
Oedema peripheral
|
33.3%
1/3 • From first dose of study drug through 30 days after the last dose of study drug (Up to 117 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
33.3%
1/3 • From first dose of study drug through 30 days after the last dose of study drug (Up to 117 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
33.3%
1/3 • From first dose of study drug through 30 days after the last dose of study drug (Up to 117 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
33.3%
1/3 • From first dose of study drug through 30 days after the last dose of study drug (Up to 117 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
66.7%
2/3 • From first dose of study drug through 30 days after the last dose of study drug (Up to 117 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Blood and lymphatic system disorders
Neutropenia
|
33.3%
1/3 • From first dose of study drug through 30 days after the last dose of study drug (Up to 117 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Injury, poisoning and procedural complications
Ligament sprain
|
33.3%
1/3 • From first dose of study drug through 30 days after the last dose of study drug (Up to 117 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Investigations
Blood magnesium decreased
|
33.3%
1/3 • From first dose of study drug through 30 days after the last dose of study drug (Up to 117 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Investigations
Neutrophil count decreased
|
33.3%
1/3 • From first dose of study drug through 30 days after the last dose of study drug (Up to 117 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Nervous system disorders
Headache
|
33.3%
1/3 • From first dose of study drug through 30 days after the last dose of study drug (Up to 117 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Reproductive system and breast disorders
Scrotal swelling
|
33.3%
1/3 • From first dose of study drug through 30 days after the last dose of study drug (Up to 117 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
33.3%
1/3 • From first dose of study drug through 30 days after the last dose of study drug (Up to 117 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory tract congestion
|
33.3%
1/3 • From first dose of study drug through 30 days after the last dose of study drug (Up to 117 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
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Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER