Advanced Solid Tumors, Lymphoma
Conditions
Brief summary
This is a phase 1, 2-part, open-label study in 4 to 6 pharmacokinetic-evaluable participants with advanced solid tumors or lymphoma.
Interventions
DRUGIXAZOMIB
Part A: Ixazomib 4.1 mg containing approximately 500-nCi \[14C\]-ixazomib, solution, orally on Day 1 and ixazomib 4 mg, capsule, orally on Days 14 and 21. 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.
Sponsors
Millennium Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Each participant must meet all of the following inclusion criteria to be enrolled in the study: * 18 years or older * Histologic or cytologic diagnosis of advanced or metastatic solid tumor or lymphoma for which no standard, curative, or life-prolonging therapies exist or are effective * Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 * Female participants who are postmenopausal for at least 1 year OR are surgically sterile OR if of childbearing potential, agree to practice 2 effective methods of contraception at the same time during the entire study through 90 days after the last dose of study drug OR agree to practice true abstinence * Male participants who agree to practice effective barrier contraception during the entire study and through 90 days after the last dose of study drug OR agree to practice true abstinence * Voluntary written consent * Suitable venous access for the conduct of blood sampling * Recovered from the reversible effects of prior anticancer therapy
Exclusion criteria
Participants meeting any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: AUC(0-816): Area Under the Plasma Concentration-time Curve From Time 0 to 816 Hrs Post-dose for TRA | 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. |
| Part A: Cmax: Maximum Observed Whole Blood Concentration of TRA | 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. |
| Part A: Tmax: Time to Reach the Maximum Observed Whole Blood Concentration (Cmax) for TRA | 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. |
| Part A: AUC(0-816): Area Under the Whole Blood Concentration-time Curve From Time 0 to 816 Hrs Post-dose for TRA | 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. |
| Part A: Cumulative Percentage of Ixazomib Dose Recovered in the Urine | 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. |
| Part A: Cumulative Percentage of the Total Radioactivity Dose Excreted in Feces | 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 |
| Part A: Cumulative Percentage of the Total Radioactivity Dose Excreted in Urine | 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. |
| Part A: Renal Clearance of Ixazomib | 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. |
| Part A: Cmax: Maximum Observed Plasma Concentration for Ixazomib | Day 1 of Part A pre-dose and at multiple timepoints (up to Day 14) post-dose | Maximum observed plasma concentration (Cmax) is the peak plasma concentration of ixazomib, obtained directly from the plasma concentration-time curve. |
| Part A: Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for Ixazomib | Day 1 of Part A pre-dose and at multiple timepoints (up to Day 14) post-dose | 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. |
| Part A: AUC(0-312): Area Under the Plasma Concentration-time Curve From Time 0 to 312 Hrs Post-dose for Ixazomib | 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. |
| Part A: Cmax: Maximum Observed Plasma Concentration of TRA | 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. |
| Part A: Tmax: Time to Reach the Cmax for TRA | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With TEAEs Related to Vital Signs | Baseline up to Cycle 5 Day 25 | Vital signs included oral body temperature, heart rate, and blood pressure. |
| Ixazomib and Metabolites as Percent of Total Radioactivity in Plasma | Day 1 pre-dose and at multiple time points (up to 816 hrs) post-dose | 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. |
| Ixazomib and Metabolites as Percent of Total Dose Administered in Urine | 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. |
| Ixazomib and Metabolites as Percent of Total Dose Administered in Feces | 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. |
| Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Baseline up to Cycle 5 Day 45 | — |
| Number of Participants With TEAEs Related to Investigations System Organ Class for Laboratory Values | Baseline up to Cycle 5 Day 45 | — |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 1 investigative site in the United States from 19 March 2014 to 09 February 2016.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 7 |
| Total | 7 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Progressive disease | 2 |
Baseline characteristics
| Characteristic | Ixazomib |
|---|---|
| Age, Continuous | 64.6 years STANDARD_DEVIATION 9.95 |
| Height | 164.4 centimeter (cm) STANDARD_DEVIATION 8.64 |
| Race/Ethnicity, Customized Black or African American | 1 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 6 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 1 Participants |
| Race/Ethnicity, Customized White | 5 Participants |
| Region of Enrollment United States | 7 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 2 Participants |
| Weight | 82.16 kilogram (kg) STANDARD_DEVIATION 16.772 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 7 / 7 |
| serious Total, serious adverse events | 1 / 7 |
Outcome results
Primary
Part A: AUC(0-312): Area Under the Plasma Concentration-time Curve From Time 0 to 312 Hrs Post-dose for Ixazomib
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.
Time frame: Day 1 of Part A pre-dose and at multiple timepoints (up to 312 hrs) 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ixazomib | Part A: AUC(0-312): Area Under the Plasma Concentration-time Curve From Time 0 to 312 Hrs Post-dose for Ixazomib | 1181 nanogram*hour per milliliter (ng*hr/mL) | Standard Deviation 600.53 |
Primary
Part A: AUC(0-816): Area Under the Plasma Concentration-time Curve From Time 0 to 816 Hrs Post-dose for TRA
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.
Time frame: Day 1 of Part A pre-dose and at multiple timepoints (up to 816 hrs) 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ixazomib | 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
Part A: AUC(0-816): Area Under the Whole Blood Concentration-time Curve From Time 0 to 816 Hrs Post-dose for TRA
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.
Time frame: Day 1 of Part A pre-dose and at multiple timepoints (up to 816 hrs) 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ixazomib | 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
Part A: Cmax: Maximum Observed Plasma Concentration for Ixazomib
Maximum observed plasma concentration (Cmax) is the peak plasma concentration of ixazomib, obtained directly from the plasma concentration-time curve.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ixazomib | Part A: Cmax: Maximum Observed Plasma Concentration for Ixazomib | 89.06 nanogram per milliliter (ng/mL) | Standard Deviation 67.834 |
Primary
Part A: Cmax: Maximum Observed Plasma Concentration of TRA
Maximum observed plasma concentration (Cmax) of TRA is the peak plasma concentration of TRA, obtained directly from the plasma TRA concentration-time curve.
Time frame: Day 1 of Part A pre-dose and at multiple timepoints (up to Day 35) 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ixazomib | Part A: Cmax: Maximum Observed Plasma Concentration of TRA | 78.80 nanogram-equivalent per milliliter | Standard Deviation 48.814 |
Primary
Part A: Cmax: Maximum Observed Whole Blood Concentration of TRA
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.
Time frame: Day 1 of Part A pre-dose and at multiple timepoints (up to Day 35) 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ixazomib | Part A: Cmax: Maximum Observed Whole Blood Concentration of TRA | 181.6 nanogram-equivalent per milliliter | Standard Deviation 75.58 |
Primary
Part A: Cumulative Percentage of Ixazomib Dose Recovered in the Urine
Percentage of the ixazomib dose excreted unchanged in the urine from 0 to 168 hrs post-dose.
Time frame: Day 1 of Part A from 0 to pre-dose and at multiple timepoints (up to 168 hrs) 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ixazomib | Part A: Cumulative Percentage of Ixazomib Dose Recovered in the Urine | 3.226 percentage of dose | Standard Deviation 2.1274 |
Primary
Part A: Cumulative Percentage of the Total Radioactivity Dose Excreted in Feces
Percentage of the TRA dose excreted in feces from Day 1 to Day 35 of Part A
Time frame: Day 1 of Part A pre-dose and at multiple timepoints (up to Day 35) 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ixazomib | Part A: Cumulative Percentage of the Total Radioactivity Dose Excreted in Feces | 21.80 percentage of dose | Standard Deviation 3.4147 |
Primary
Part A: Cumulative Percentage of the Total Radioactivity Dose Excreted in Urine
Percentage of the TRA dose excreted in urine from Day 1 to Day 35 of Part A.
Time frame: Day 1 of Part A pre-dose and at multiple timepoints (up to Day 35) 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ixazomib | Part A: Cumulative Percentage of the Total Radioactivity Dose Excreted in Urine | 62.06 percentage of dose | Standard Deviation 21.17 |
Primary
Part A: Renal Clearance of Ixazomib
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.
Time frame: Day 1 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ixazomib | Part A: Renal Clearance of Ixazomib | 0.1191 liter per hour (L/hr) | Standard Deviation 0.068763 |
Primary
Part A: Tmax: Time to Reach the Cmax for TRA
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.
Time frame: Day 1 of Part A pre-dose and at multiple timepoints (up to Day 35) 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.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Ixazomib | Part A: Tmax: Time to Reach the Cmax for TRA | 0.5000 hr | Full Range 1.5547 |
Primary
Part A: Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for Ixazomib
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Ixazomib | Part A: Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for Ixazomib | 0.5000 hour (hr) | Full Range 0.044721 |
Primary
Part A: Tmax: Time to Reach the Maximum Observed Whole Blood Concentration (Cmax) for TRA
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.
Time frame: Day 1 of Part A pre-dose and at multiple timepoints (up to Day 35) 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.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Ixazomib | Part A: Tmax: Time to Reach the Maximum Observed Whole Blood Concentration (Cmax) for TRA | 0.6000 hr | Full Range 0.80436 |
Secondary
Ixazomib and Metabolites as Percent of Total Dose Administered in Feces
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.
Time frame: Day 1 pre-dose and at multiple time points (up to Day 35) 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ixazomib | Ixazomib and Metabolites as Percent of Total Dose Administered in Feces | FH6, ixazomib | 13.8 percentage of dose |
| Ixazomib | Ixazomib and Metabolites as Percent of Total Dose Administered in Feces | FH1 | 0.900 percentage of dose |
| Ixazomib | Ixazomib and Metabolites as Percent of Total Dose Administered in Feces | FH2 | 0.111 percentage of dose |
| Ixazomib | Ixazomib and Metabolites as Percent of Total Dose Administered in Feces | FH3, ML00701258 | 0.620 percentage of dose |
| Ixazomib | Ixazomib and Metabolites as Percent of Total Dose Administered in Feces | FH4, ML00701201 | 0.901 percentage of dose |
| Ixazomib | Ixazomib and Metabolites as Percent of Total Dose Administered in Feces | FH5 | 1.14 percentage of dose |
| Ixazomib | Ixazomib and Metabolites as Percent of Total Dose Administered in Feces | FH7, ML00752034 | 1.58 percentage of dose |
| Ixazomib | Ixazomib and Metabolites as Percent of Total Dose Administered in Feces | FH8 | 0.502 percentage of dose |
| Ixazomib | Ixazomib and Metabolites as Percent of Total Dose Administered in Feces | FH9 | 0.112 percentage of dose |
Secondary
Ixazomib and Metabolites as Percent of Total Dose Administered in Urine
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.
Time frame: Day 1 pre-dose and at multiple time points (up to Day 35) 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ixazomib | Ixazomib and Metabolites as Percent of Total Dose Administered in Urine | U11, ML00749506 | 1.28 percentage of dose |
| Ixazomib | Ixazomib and Metabolites as Percent of Total Dose Administered in Urine | U12, ML00752034 | 0.069 percentage of dose |
| Ixazomib | Ixazomib and Metabolites as Percent of Total Dose Administered in Urine | U13 | 0.974 percentage of dose |
| Ixazomib | Ixazomib and Metabolites as Percent of Total Dose Administered in Urine | U9, ixazomib | 1.30 percentage of dose |
| Ixazomib | Ixazomib and Metabolites as Percent of Total Dose Administered in Urine | U1 | 0.391 percentage of dose |
| Ixazomib | Ixazomib and Metabolites as Percent of Total Dose Administered in Urine | U2 | 0.926 percentage of dose |
| Ixazomib | Ixazomib and Metabolites as Percent of Total Dose Administered in Urine | U3 | 1.61 percentage of dose |
| Ixazomib | Ixazomib and Metabolites as Percent of Total Dose Administered in Urine | U4 | 1.33 percentage of dose |
| Ixazomib | Ixazomib and Metabolites as Percent of Total Dose Administered in Urine | U5, ML00701258 | 2.72 percentage of dose |
| Ixazomib | Ixazomib and Metabolites as Percent of Total Dose Administered in Urine | U6, ML00701201 | 30.2 percentage of dose |
| Ixazomib | Ixazomib and Metabolites as Percent of Total Dose Administered in Urine | U7 | 2.75 percentage of dose |
| Ixazomib | Ixazomib and Metabolites as Percent of Total Dose Administered in Urine | U8 | 0.695 percentage of dose |
| Ixazomib | Ixazomib and Metabolites as Percent of Total Dose Administered in Urine | U10, ML00751996 | 5.93 percentage of dose |
Secondary
Ixazomib and Metabolites as Percent of Total Radioactivity in Plasma
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ixazomib | Ixazomib and Metabolites as Percent of Total Radioactivity in Plasma | P2, ML00701258 | 7.91 percent of total radioactivity in plasma |
| Ixazomib | Ixazomib and Metabolites as Percent of Total Radioactivity in Plasma | P3, ML00701201 | 18.9 percent of total radioactivity in plasma |
| Ixazomib | Ixazomib and Metabolites as Percent of Total Radioactivity in Plasma | P6, ML00749506 | 10.6 percent of total radioactivity in plasma |
| Ixazomib | Ixazomib and Metabolites as Percent of Total Radioactivity in Plasma | P7, ML00752034 | 3.20 percent of total radioactivity in plasma |
| Ixazomib | Ixazomib and Metabolites as Percent of Total Radioactivity in Plasma | P4, ixazomib | 54.2 percent of total radioactivity in plasma |
Secondary
Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: Baseline up to Cycle 5 Day 45
Population: The safety population included all participants who received at least 1 dose of ixazomib.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ixazomib | Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 7 participants |
| Ixazomib | Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 1 participants |
Secondary
Number of Participants With TEAEs Related to Investigations System Organ Class for Laboratory Values
Time frame: Baseline up to Cycle 5 Day 45
Population: The safety population included all participants who received at least 1 dose of ixazomib.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Ixazomib | Number of Participants With TEAEs Related to Investigations System Organ Class for Laboratory Values | Blood bilirubin increased | 1 participants | 9.9 |
| Ixazomib | Number of Participants With TEAEs Related to Investigations System Organ Class for Laboratory Values | Platelet count decreased | 1 participants | 25.53 |
| Ixazomib | Number of Participants With TEAEs Related to Investigations System Organ Class for Laboratory Values | Lymphocyte count decreased | 1 participants | 117.64 |
Secondary
Number of Participants With TEAEs Related to Vital Signs
Vital signs included oral body temperature, heart rate, and blood pressure.
Time frame: Baseline up to Cycle 5 Day 25
Population: The safety population included all participants who received at least 1 dose of ixazomib.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ixazomib | Number of Participants With TEAEs Related to Vital Signs | 0 participants |