Trial Outcomes & Findings for Mass Balance, Pharmacokinetics and Metabolism Study of IXAZOMIB (NCT NCT01953783)

NCT ID: NCT01953783

Last Updated: 2020-08-26

Results Overview

Maximum observed plasma concentration (Cmax) is the peak plasma concentration of ixazomib, obtained directly from the plasma concentration-time curve.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

7 participants

Primary outcome timeframe

Day 1 of Part A pre-dose and at multiple timepoints (up to Day 14) post-dose

Results posted on

2020-08-26

Participant Flow

Participants took part in the study at 1 investigative site in the United States from 19 March 2014 to 09 February 2016.

Participants with a historical diagnosis of advanced solid tumors or lymphoma were enrolled in 1 treatment group of this 2-part study to receive ixazomib.

Participant milestones

Participant milestones
Measure	Ixazomib Ixazomib 4.1 milligram (mg) containing approximately 500-nCurie (nCi) of total radioactivity \[14C\]-ixazomib, solution, orally on Day 1 and ixazomib 4 mg, capsule, orally on Days 14 and 21 in Part A. Participants who had completed their Day 35 assessments in Part A were eligible to continue in Part B. Ixazomib 4 mg, capsule, orally, once weekly, on Days 1, 8 and 15 in 28-day cycles until disease progression or unacceptable toxicity in Part B.
Overall Study STARTED	7
Overall Study COMPLETED	5
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Ixazomib Ixazomib 4.1 milligram (mg) containing approximately 500-nCurie (nCi) of total radioactivity \[14C\]-ixazomib, solution, orally on Day 1 and ixazomib 4 mg, capsule, orally on Days 14 and 21 in Part A. Participants who had completed their Day 35 assessments in Part A were eligible to continue in Part B. Ixazomib 4 mg, capsule, orally, once weekly, on Days 1, 8 and 15 in 28-day cycles until disease progression or unacceptable toxicity in Part B.
Overall Study Progressive disease	2

Baseline Characteristics

Mass Balance, Pharmacokinetics and Metabolism Study of IXAZOMIB

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ixazomib n=7 Participants Ixazomib 4.1 milligram (mg) containing approximately 500-nCurie (nCi) of total radioactivity \[14C\]-ixazomib, solution, orally on Day 1 and ixazomib 4 mg, capsule, orally on Days 14 and 21 in Part A. Participants who had completed their Day 35 assessments in Part A were eligible to continue in Part B. Ixazomib 4 mg, capsule, orally, once weekly, on Days 1, 8 and 15 in 28-day cycles until disease progression or unacceptable toxicity in Part B.
Age, Continuous	64.6 years STANDARD_DEVIATION 9.95 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	1 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	6 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants
Race/Ethnicity, Customized White	5 Participants n=5 Participants
Race/Ethnicity, Customized Unknown or Not Reported	1 Participants n=5 Participants
Region of Enrollment United States	7 Participants n=5 Participants
Height	164.4 centimeter (cm) STANDARD_DEVIATION 8.64 • n=5 Participants
Weight	82.16 kilogram (kg) STANDARD_DEVIATION 16.772 • n=5 Participants

PRIMARY outcome

Timeframe: Day 1 of Part A pre-dose and at multiple timepoints (up to Day 14) post-dose

Population: Pharmacokinetic(PK)-evaluable population included all participants who received protocol-specified single\[14C\]-ixazomib dose(Part A), did not receive any excluded concomitant medications till completion(Part A), had sufficient concentration-time and total radioactivity(TRA)-time data to permit reliable estimation of PK parameters and mass balance.

Maximum observed plasma concentration (Cmax) is the peak plasma concentration of ixazomib, obtained directly from the plasma concentration-time curve.

Outcome measures

Outcome measures
Measure	Ixazomib n=5 Participants Ixazomib 4.1 milligram (mg) containing approximately 500-nCurie (nCi) of total radioactivity \[14C\]-ixazomib, solution, orally on Day 1 and ixazomib 4 mg, capsule, orally on Days 14 and 21 in Part A. Participants who had completed their Day 35 assessments in Part A were eligible to continue in Part B. Ixazomib 4 mg, capsule, orally, once weekly, on Days 1, 8 and 15 in 28-day cycles until disease progression or unacceptable toxicity in Part B.
Part A: Cmax: Maximum Observed Plasma Concentration for Ixazomib	89.06 nanogram per milliliter (ng/mL) Standard Deviation 67.834

PRIMARY outcome

Timeframe: Day 1 of Part A pre-dose and at multiple timepoints (up to Day 14) post-dose

Population: The PK-evaluable population included all participants who received the protocol-specified single \[14C\]-ixazomib dose in Part A, did not receive any excluded concomitant medications through the completion of Part A, and had sufficient concentration-time and TRA-time data to permit reliable estimation of PK parameters and mass balance.

Time to reach the maximum observed plasma concentration (Cmax), equal to time (hours) to Cmax of ixazomib after administration, obtained directly from the plasma concentration-time curve.

Outcome measures

Outcome measures
Measure	Ixazomib n=5 Participants Ixazomib 4.1 milligram (mg) containing approximately 500-nCurie (nCi) of total radioactivity \[14C\]-ixazomib, solution, orally on Day 1 and ixazomib 4 mg, capsule, orally on Days 14 and 21 in Part A. Participants who had completed their Day 35 assessments in Part A were eligible to continue in Part B. Ixazomib 4 mg, capsule, orally, once weekly, on Days 1, 8 and 15 in 28-day cycles until disease progression or unacceptable toxicity in Part B.
Part A: Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for Ixazomib	0.5000 hour (hr) Full Range 0.044721 • Interval 0.5 to 0.6

PRIMARY outcome

Timeframe: Day 1 of Part A pre-dose and at multiple timepoints (up to 312 hrs) post-dose

AUC(0-312) is a measure of the area under the plasma concentration time-curve from time zero to 312 hrs post-dose for ixazomib.

Outcome measures

Outcome measures
Measure	Ixazomib n=5 Participants Ixazomib 4.1 milligram (mg) containing approximately 500-nCurie (nCi) of total radioactivity \[14C\]-ixazomib, solution, orally on Day 1 and ixazomib 4 mg, capsule, orally on Days 14 and 21 in Part A. Participants who had completed their Day 35 assessments in Part A were eligible to continue in Part B. Ixazomib 4 mg, capsule, orally, once weekly, on Days 1, 8 and 15 in 28-day cycles until disease progression or unacceptable toxicity in Part B.
Part A: AUC(0-312): Area Under the Plasma Concentration-time Curve From Time 0 to 312 Hrs Post-dose for Ixazomib	1181 nanogramhour per milliliter (nghr/mL) Standard Deviation 600.53

PRIMARY outcome

Timeframe: Day 1 of Part A pre-dose and at multiple timepoints (up to Day 35) post-dose

Maximum observed plasma concentration (Cmax) of TRA is the peak plasma concentration of TRA, obtained directly from the plasma TRA concentration-time curve.

Outcome measures

Outcome measures
Measure	Ixazomib n=5 Participants Ixazomib 4.1 milligram (mg) containing approximately 500-nCurie (nCi) of total radioactivity \[14C\]-ixazomib, solution, orally on Day 1 and ixazomib 4 mg, capsule, orally on Days 14 and 21 in Part A. Participants who had completed their Day 35 assessments in Part A were eligible to continue in Part B. Ixazomib 4 mg, capsule, orally, once weekly, on Days 1, 8 and 15 in 28-day cycles until disease progression or unacceptable toxicity in Part B.
Part A: Cmax: Maximum Observed Plasma Concentration of TRA	78.80 nanogram-equivalent per milliliter Standard Deviation 48.814

PRIMARY outcome

Timeframe: Day 1 of Part A pre-dose and at multiple timepoints (up to Day 35) post-dose

Time to reach the maximum observed plasma concentration (Cmax) for TRA, equal to time (hours) to Cmax for TRA after administration, obtained directly from the plasma TRA concentration-time curve.

Outcome measures

Outcome measures
Measure	Ixazomib n=5 Participants Ixazomib 4.1 milligram (mg) containing approximately 500-nCurie (nCi) of total radioactivity \[14C\]-ixazomib, solution, orally on Day 1 and ixazomib 4 mg, capsule, orally on Days 14 and 21 in Part A. Participants who had completed their Day 35 assessments in Part A were eligible to continue in Part B. Ixazomib 4 mg, capsule, orally, once weekly, on Days 1, 8 and 15 in 28-day cycles until disease progression or unacceptable toxicity in Part B.
Part A: Tmax: Time to Reach the Cmax for TRA	0.5000 hr Full Range 1.5547 • Interval 0.5 to 4.0

PRIMARY outcome

Timeframe: Day 1 of Part A pre-dose and at multiple timepoints (up to 816 hrs) post-dose

AUC(0-816) is a measure of the area under the plasma concentration time-curve from time zero to 816 hrs post-dose for TRA.

Outcome measures

Outcome measures
Measure	Ixazomib n=5 Participants Ixazomib 4.1 milligram (mg) containing approximately 500-nCurie (nCi) of total radioactivity \[14C\]-ixazomib, solution, orally on Day 1 and ixazomib 4 mg, capsule, orally on Days 14 and 21 in Part A. Participants who had completed their Day 35 assessments in Part A were eligible to continue in Part B. Ixazomib 4 mg, capsule, orally, once weekly, on Days 1, 8 and 15 in 28-day cycles until disease progression or unacceptable toxicity in Part B.
Part A: AUC(0-816): Area Under the Plasma Concentration-time Curve From Time 0 to 816 Hrs Post-dose for TRA	2981 nanogram-equivalent*hour per milliliter Standard Deviation 1898.7

PRIMARY outcome

Timeframe: Day 1 of Part A pre-dose and at multiple timepoints (up to Day 35) post-dose

Maximum observed whole blood concentration (Cmax) of a TRA is the peak whole blood concentration of TRA, obtained directly from the whole blood TRA concentration-time curve.

Outcome measures

Outcome measures
Measure	Ixazomib n=5 Participants Ixazomib 4.1 milligram (mg) containing approximately 500-nCurie (nCi) of total radioactivity \[14C\]-ixazomib, solution, orally on Day 1 and ixazomib 4 mg, capsule, orally on Days 14 and 21 in Part A. Participants who had completed their Day 35 assessments in Part A were eligible to continue in Part B. Ixazomib 4 mg, capsule, orally, once weekly, on Days 1, 8 and 15 in 28-day cycles until disease progression or unacceptable toxicity in Part B.
Part A: Cmax: Maximum Observed Whole Blood Concentration of TRA	181.6 nanogram-equivalent per milliliter Standard Deviation 75.580

PRIMARY outcome

Timeframe: Day 1 of Part A pre-dose and at multiple timepoints (up to Day 35) post-dose

Time to reach the maximum observed whole blood concentration (Cmax) for TRA, equal to time (hours) to Cmax for TRA after administration, obtained directly from the whole blood TRA concentration-time curve.

Outcome measures

Outcome measures
Measure	Ixazomib n=5 Participants Ixazomib 4.1 milligram (mg) containing approximately 500-nCurie (nCi) of total radioactivity \[14C\]-ixazomib, solution, orally on Day 1 and ixazomib 4 mg, capsule, orally on Days 14 and 21 in Part A. Participants who had completed their Day 35 assessments in Part A were eligible to continue in Part B. Ixazomib 4 mg, capsule, orally, once weekly, on Days 1, 8 and 15 in 28-day cycles until disease progression or unacceptable toxicity in Part B.
Part A: Tmax: Time to Reach the Maximum Observed Whole Blood Concentration (Cmax) for TRA	0.6000 hr Full Range 0.80436 • Interval 0.5 to 2.0

PRIMARY outcome

Timeframe: Day 1 of Part A pre-dose and at multiple timepoints (up to 816 hrs) post-dose

AUC(0-816) is a measure of the area under the whole blood concentration time-curve from time zero to 816 hrs post-dose for TRA.

Outcome measures

Outcome measures
Measure	Ixazomib n=5 Participants Ixazomib 4.1 milligram (mg) containing approximately 500-nCurie (nCi) of total radioactivity \[14C\]-ixazomib, solution, orally on Day 1 and ixazomib 4 mg, capsule, orally on Days 14 and 21 in Part A. Participants who had completed their Day 35 assessments in Part A were eligible to continue in Part B. Ixazomib 4 mg, capsule, orally, once weekly, on Days 1, 8 and 15 in 28-day cycles until disease progression or unacceptable toxicity in Part B.
Part A: AUC(0-816): Area Under the Whole Blood Concentration-time Curve From Time 0 to 816 Hrs Post-dose for TRA	29200 nanogram-equivalent* hour per milliliter Standard Deviation 4712.2

PRIMARY outcome

Timeframe: Day 1 of Part A from 0 to pre-dose and at multiple timepoints (up to 168 hrs) post-dose

Percentage of the ixazomib dose excreted unchanged in the urine from 0 to 168 hrs post-dose.

Outcome measures

Outcome measures
Measure	Ixazomib n=5 Participants Ixazomib 4.1 milligram (mg) containing approximately 500-nCurie (nCi) of total radioactivity \[14C\]-ixazomib, solution, orally on Day 1 and ixazomib 4 mg, capsule, orally on Days 14 and 21 in Part A. Participants who had completed their Day 35 assessments in Part A were eligible to continue in Part B. Ixazomib 4 mg, capsule, orally, once weekly, on Days 1, 8 and 15 in 28-day cycles until disease progression or unacceptable toxicity in Part B.
Part A: Cumulative Percentage of Ixazomib Dose Recovered in the Urine	3.226 percentage of dose Standard Deviation 2.1274

PRIMARY outcome

Timeframe: Day 1 of Part A pre-dose and at multiple timepoints (up to Day 35) post-dose

Percentage of the TRA dose excreted in feces from Day 1 to Day 35 of Part A

Outcome measures

Outcome measures
Measure	Ixazomib n=5 Participants Ixazomib 4.1 milligram (mg) containing approximately 500-nCurie (nCi) of total radioactivity \[14C\]-ixazomib, solution, orally on Day 1 and ixazomib 4 mg, capsule, orally on Days 14 and 21 in Part A. Participants who had completed their Day 35 assessments in Part A were eligible to continue in Part B. Ixazomib 4 mg, capsule, orally, once weekly, on Days 1, 8 and 15 in 28-day cycles until disease progression or unacceptable toxicity in Part B.
Part A: Cumulative Percentage of the Total Radioactivity Dose Excreted in Feces	21.80 percentage of dose Standard Deviation 3.4147

PRIMARY outcome

Timeframe: Day 1 of Part A pre-dose and at multiple timepoints (up to Day 35) post-dose

Percentage of the TRA dose excreted in urine from Day 1 to Day 35 of Part A.

Outcome measures

Outcome measures
Measure	Ixazomib n=5 Participants Ixazomib 4.1 milligram (mg) containing approximately 500-nCurie (nCi) of total radioactivity \[14C\]-ixazomib, solution, orally on Day 1 and ixazomib 4 mg, capsule, orally on Days 14 and 21 in Part A. Participants who had completed their Day 35 assessments in Part A were eligible to continue in Part B. Ixazomib 4 mg, capsule, orally, once weekly, on Days 1, 8 and 15 in 28-day cycles until disease progression or unacceptable toxicity in Part B.
Part A: Cumulative Percentage of the Total Radioactivity Dose Excreted in Urine	62.06 percentage of dose Standard Deviation 21.170

PRIMARY outcome

Timeframe: Day 1 pre-dose and at multiple timepoints (up to Day 14) post-dose

Renal clearance is the volume of plasma from which ixazomib is completely removed by the kidney in a given amount of time, calculated as the amount of ixazomib excreted in the urine divided by the area under the plasma ixazomib concentration-time curve.

Outcome measures

Outcome measures
Measure	Ixazomib n=5 Participants Ixazomib 4.1 milligram (mg) containing approximately 500-nCurie (nCi) of total radioactivity \[14C\]-ixazomib, solution, orally on Day 1 and ixazomib 4 mg, capsule, orally on Days 14 and 21 in Part A. Participants who had completed their Day 35 assessments in Part A were eligible to continue in Part B. Ixazomib 4 mg, capsule, orally, once weekly, on Days 1, 8 and 15 in 28-day cycles until disease progression or unacceptable toxicity in Part B.
Part A: Renal Clearance of Ixazomib	0.1191 liter per hour (L/hr) Standard Deviation 0.068763

SECONDARY outcome

Timeframe: Day 1 pre-dose and at multiple time points (up to 816 hrs) post-dose

Population: PK-evaluable population with acceptable excretion recovery included all participants who received protocol-specified single\[14C\]-ixazomib dose(Part A), did not receive any excluded concomitant medications till completion(Part A), and had sufficient concentration-time and TRA-time data to permit reliable estimation of PK parameters and mass balance.

The plasma samples were pooled for participants over 816 hrs post-dose, and data was analysed using the Hamilton method time-proportional pooling, and therefore the data is reported as "percent of total radioactivity in plasma" with measure type as "number" and measure dispersion as "Not applicable, NA".

Outcome measures

Outcome measures
Measure	Ixazomib n=4 Participants Ixazomib 4.1 milligram (mg) containing approximately 500-nCurie (nCi) of total radioactivity \[14C\]-ixazomib, solution, orally on Day 1 and ixazomib 4 mg, capsule, orally on Days 14 and 21 in Part A. Participants who had completed their Day 35 assessments in Part A were eligible to continue in Part B. Ixazomib 4 mg, capsule, orally, once weekly, on Days 1, 8 and 15 in 28-day cycles until disease progression or unacceptable toxicity in Part B.
Ixazomib and Metabolites as Percent of Total Radioactivity in Plasma P4, ixazomib	54.2 percent of total radioactivity in plasma
Ixazomib and Metabolites as Percent of Total Radioactivity in Plasma P2, ML00701258	7.91 percent of total radioactivity in plasma
Ixazomib and Metabolites as Percent of Total Radioactivity in Plasma P3, ML00701201	18.9 percent of total radioactivity in plasma
Ixazomib and Metabolites as Percent of Total Radioactivity in Plasma P6, ML00749506	10.6 percent of total radioactivity in plasma
Ixazomib and Metabolites as Percent of Total Radioactivity in Plasma P7, ML00752034	3.20 percent of total radioactivity in plasma

SECONDARY outcome

Timeframe: Day 1 pre-dose and at multiple time points (up to Day 35) post-dose

The 35-day post-dose data is extrapolated from the average of four participant data from 0-168-hr pooled urine. The data is therefore reported as "percentage of dose" with measure type as "number" and measure dispersion as "NA".

Outcome measures

Outcome measures
Measure	Ixazomib n=4 Participants Ixazomib 4.1 milligram (mg) containing approximately 500-nCurie (nCi) of total radioactivity \[14C\]-ixazomib, solution, orally on Day 1 and ixazomib 4 mg, capsule, orally on Days 14 and 21 in Part A. Participants who had completed their Day 35 assessments in Part A were eligible to continue in Part B. Ixazomib 4 mg, capsule, orally, once weekly, on Days 1, 8 and 15 in 28-day cycles until disease progression or unacceptable toxicity in Part B.
Ixazomib and Metabolites as Percent of Total Dose Administered in Urine U9, ixazomib	1.30 percentage of dose
Ixazomib and Metabolites as Percent of Total Dose Administered in Urine U1	0.391 percentage of dose
Ixazomib and Metabolites as Percent of Total Dose Administered in Urine U2	0.926 percentage of dose
Ixazomib and Metabolites as Percent of Total Dose Administered in Urine U3	1.61 percentage of dose
Ixazomib and Metabolites as Percent of Total Dose Administered in Urine U4	1.33 percentage of dose
Ixazomib and Metabolites as Percent of Total Dose Administered in Urine U5, ML00701258	2.72 percentage of dose
Ixazomib and Metabolites as Percent of Total Dose Administered in Urine U6, ML00701201	30.2 percentage of dose
Ixazomib and Metabolites as Percent of Total Dose Administered in Urine U7	2.75 percentage of dose
Ixazomib and Metabolites as Percent of Total Dose Administered in Urine U8	0.695 percentage of dose
Ixazomib and Metabolites as Percent of Total Dose Administered in Urine U10, ML00751996	5.93 percentage of dose
Ixazomib and Metabolites as Percent of Total Dose Administered in Urine U11, ML00749506	1.28 percentage of dose
Ixazomib and Metabolites as Percent of Total Dose Administered in Urine U12, ML00752034	0.069 percentage of dose
Ixazomib and Metabolites as Percent of Total Dose Administered in Urine U13	0.974 percentage of dose

SECONDARY outcome

Timeframe: Day 1 pre-dose and at multiple time points (up to Day 35) post-dose

The 35-day post-dose data is extrapolated from the average of four participant data from 0-168-hr pooled feces. The data is therefore reported as "percentage of dose" with measure type as "number" and measure dispersion as "NA".

Outcome measures

Outcome measures
Measure	Ixazomib n=4 Participants Ixazomib 4.1 milligram (mg) containing approximately 500-nCurie (nCi) of total radioactivity \[14C\]-ixazomib, solution, orally on Day 1 and ixazomib 4 mg, capsule, orally on Days 14 and 21 in Part A. Participants who had completed their Day 35 assessments in Part A were eligible to continue in Part B. Ixazomib 4 mg, capsule, orally, once weekly, on Days 1, 8 and 15 in 28-day cycles until disease progression or unacceptable toxicity in Part B.
Ixazomib and Metabolites as Percent of Total Dose Administered in Feces FH6, ixazomib	13.8 percentage of dose
Ixazomib and Metabolites as Percent of Total Dose Administered in Feces FH1	0.900 percentage of dose
Ixazomib and Metabolites as Percent of Total Dose Administered in Feces FH2	0.111 percentage of dose
Ixazomib and Metabolites as Percent of Total Dose Administered in Feces FH3, ML00701258	0.620 percentage of dose
Ixazomib and Metabolites as Percent of Total Dose Administered in Feces FH4, ML00701201	0.901 percentage of dose
Ixazomib and Metabolites as Percent of Total Dose Administered in Feces FH5	1.14 percentage of dose
Ixazomib and Metabolites as Percent of Total Dose Administered in Feces FH7, ML00752034	1.58 percentage of dose
Ixazomib and Metabolites as Percent of Total Dose Administered in Feces FH8	0.502 percentage of dose
Ixazomib and Metabolites as Percent of Total Dose Administered in Feces FH9	0.112 percentage of dose

SECONDARY outcome

Timeframe: Baseline up to Cycle 5 Day 45

Population: The safety population included all participants who received at least 1 dose of ixazomib.

Outcome measures

Outcome measures
Measure	Ixazomib n=7 Participants Ixazomib 4.1 milligram (mg) containing approximately 500-nCurie (nCi) of total radioactivity \[14C\]-ixazomib, solution, orally on Day 1 and ixazomib 4 mg, capsule, orally on Days 14 and 21 in Part A. Participants who had completed their Day 35 assessments in Part A were eligible to continue in Part B. Ixazomib 4 mg, capsule, orally, once weekly, on Days 1, 8 and 15 in 28-day cycles until disease progression or unacceptable toxicity in Part B.
Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) TEAEs	7 participants
Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) SAEs	1 participants

SECONDARY outcome

Timeframe: Baseline up to Cycle 5 Day 45

Population: The safety population included all participants who received at least 1 dose of ixazomib.

Outcome measures

Outcome measures
Measure	Ixazomib n=7 Participants Ixazomib 4.1 milligram (mg) containing approximately 500-nCurie (nCi) of total radioactivity \[14C\]-ixazomib, solution, orally on Day 1 and ixazomib 4 mg, capsule, orally on Days 14 and 21 in Part A. Participants who had completed their Day 35 assessments in Part A were eligible to continue in Part B. Ixazomib 4 mg, capsule, orally, once weekly, on Days 1, 8 and 15 in 28-day cycles until disease progression or unacceptable toxicity in Part B.
Number of Participants With TEAEs Related to Investigations System Organ Class for Laboratory Values Blood bilirubin increased	1 participants 9.90
Number of Participants With TEAEs Related to Investigations System Organ Class for Laboratory Values Platelet count decreased	1 participants 25.53
Number of Participants With TEAEs Related to Investigations System Organ Class for Laboratory Values Lymphocyte count decreased	1 participants 117.64

SECONDARY outcome

Timeframe: Baseline up to Cycle 5 Day 25

Population: The safety population included all participants who received at least 1 dose of ixazomib.

Vital signs included oral body temperature, heart rate, and blood pressure.

Outcome measures

Outcome measures
Measure	Ixazomib n=7 Participants Ixazomib 4.1 milligram (mg) containing approximately 500-nCurie (nCi) of total radioactivity \[14C\]-ixazomib, solution, orally on Day 1 and ixazomib 4 mg, capsule, orally on Days 14 and 21 in Part A. Participants who had completed their Day 35 assessments in Part A were eligible to continue in Part B. Ixazomib 4 mg, capsule, orally, once weekly, on Days 1, 8 and 15 in 28-day cycles until disease progression or unacceptable toxicity in Part B.
Number of Participants With TEAEs Related to Vital Signs	0 participants

Adverse Events

Ixazomib

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Ixazomib n=7 participants at risk Ixazomib 4.1 milligram (mg) containing approximately 500-nCurie (nCi) of total radioactivity \[14C\]-ixazomib, solution, orally on Day 1 and ixazomib 4 mg, capsule, orally on Days 14 and 21 in Part A. Participants who had completed their Day 35 assessments in Part A were eligible to continue in Part B. Ixazomib 4 mg, capsule, orally, once weekly, on Days 1, 8 and 15 in 28-day cycles until disease progression or unacceptable toxicity in Part B.
Infections and infestations Influenza	14.3% 1/7 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Cycle 5 Day 45). 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.

Other adverse events

Other adverse events
Measure	Ixazomib n=7 participants at risk Ixazomib 4.1 milligram (mg) containing approximately 500-nCurie (nCi) of total radioactivity \[14C\]-ixazomib, solution, orally on Day 1 and ixazomib 4 mg, capsule, orally on Days 14 and 21 in Part A. Participants who had completed their Day 35 assessments in Part A were eligible to continue in Part B. Ixazomib 4 mg, capsule, orally, once weekly, on Days 1, 8 and 15 in 28-day cycles until disease progression or unacceptable toxicity in Part B.
Gastrointestinal disorders Diarrhoea	71.4% 5/7 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Cycle 5 Day 45). 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 Abdominal pain upper	28.6% 2/7 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Cycle 5 Day 45). 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 Constipation	28.6% 2/7 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Cycle 5 Day 45). 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 Nausea	28.6% 2/7 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Cycle 5 Day 45). 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	28.6% 2/7 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Cycle 5 Day 45). 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 Abdominal pain	14.3% 1/7 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Cycle 5 Day 45). 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 Dry mouth	14.3% 1/7 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Cycle 5 Day 45). 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	28.6% 2/7 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Cycle 5 Day 45). 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 Muscle spasms	14.3% 1/7 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Cycle 5 Day 45). 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 Neck pain	14.3% 1/7 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Cycle 5 Day 45). 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	14.3% 1/7 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Cycle 5 Day 45). 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 bilirubin increased	14.3% 1/7 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Cycle 5 Day 45). 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 Lymphocyte count decreased	14.3% 1/7 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Cycle 5 Day 45). 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 Platelet count decreased	14.3% 1/7 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Cycle 5 Day 45). 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 Weight decreased	14.3% 1/7 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Cycle 5 Day 45). 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.
Metabolism and nutrition disorders Decreased appetite	42.9% 3/7 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Cycle 5 Day 45). 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.
Metabolism and nutrition disorders Hyperuricaemia	14.3% 1/7 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Cycle 5 Day 45). 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	42.9% 3/7 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Cycle 5 Day 45). 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 Dizziness	28.6% 2/7 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Cycle 5 Day 45). 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 Dysgeusia	14.3% 1/7 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Cycle 5 Day 45). 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 Peripheral sensory neuropathy	14.3% 1/7 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Cycle 5 Day 45). 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 Catheter site erythema	14.3% 1/7 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Cycle 5 Day 45). 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	14.3% 1/7 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Cycle 5 Day 45). 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 Gait disturbance	14.3% 1/7 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Cycle 5 Day 45). 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 Influenza like illness	14.3% 1/7 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Cycle 5 Day 45). 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 Malaise	14.3% 1/7 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Cycle 5 Day 45). 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 Medical device complication	14.3% 1/7 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Cycle 5 Day 45). 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	28.6% 2/7 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Cycle 5 Day 45). 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 Dyspnoea	14.3% 1/7 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Cycle 5 Day 45). 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 Dyspnoea exertional	14.3% 1/7 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Cycle 5 Day 45). 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 Pruritus	28.6% 2/7 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Cycle 5 Day 45). 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 Rash maculo-papular	28.6% 2/7 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Cycle 5 Day 45). 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 Skin discolouration	14.3% 1/7 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Cycle 5 Day 45). 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.
Infections and infestations Urinary tract infection	14.3% 1/7 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Cycle 5 Day 45). 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.
Infections and infestations Viral infection	14.3% 1/7 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Cycle 5 Day 45). 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.
Immune system disorders Drug hypersensitivity	14.3% 1/7 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Cycle 5 Day 45). 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.
Renal and urinary disorders Bladder spasm	14.3% 1/7 • Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days after the last dose of study drug (Cycle 5 Day 45). 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.

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

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.
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Restriction type: OTHER