Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Pharmaceutical Solutions

All Drugs and Chemicals

Antineoplastic Agents

Anti-Infective Agents

Ixazomib

HIV Protease Inhibitors

Protease Inhibitors

Enzyme Inhibitors

Part A: Participants will receive a single dose of 4.1-milligram (mg) \[14C\]-IXAZOMIB oral solution containing approximately 500-nCurie (nCi) of total radioactivity on Day 1 and remain at the clinic for 8 days. On Days 14 and 21, participants may be administered a single 4.0-mg capsule of IXAZOMIB. Participants will return to the clinic in the evening before Days 14, 21, 28, and 35 for a 24-hour overnight clinic visit.

Part B: Eligible participants from Part A may continue into Part B once they have completed their Day 35 assessments in Part A. Participants may receive IXAZOMIB capsules administered orally at a dose of 4.0-mg once weekly on Days 1, 8, and 15 of 28-day cycles. Participants will continue in this study until disease progression or unacceptable toxicity.

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.

IXAZOMIB

Medical Monitor

This is a phase 1, 2-part, open-label study in 4 to 6 pharmacokinetic-evaluable participants with advanced solid tumors or lymphoma.

Mass Balance, Pharmacokinetics and Metabolism Study of IXAZOMIB

A Phase 1 Study of [ 14 C]-Ixazomib to Assess Mass Balance, Pharmacokinetics, and Metabolism in Patients With Advanced Solid Tumors or Lymphoma

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

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.

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.

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

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.

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.

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 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.

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.

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

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

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

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.

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".

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".

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".

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

Millennium Pharmaceuticals, Inc.

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.

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

Sex: Female, Male

Race/Ethnicity, Customized

United States

Region of Enrollment

Height

Weight

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

Medical Director

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.

Part A: Cmax: Maximum Observed Plasma Concentration for Ixazomib

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.

Part A: Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for Ixazomib

Part A: AUC(0-312): Area Under the Plasma Concentration-time Curve From Time 0 to 312 Hrs Post-dose for Ixazomib

Part A: Cmax: Maximum Observed Plasma Concentration of TRA

Part A: Tmax: Time to Reach the Cmax for TRA

Part A: AUC(0-816): Area Under the Plasma Concentration-time Curve From Time 0 to 816 Hrs Post-dose for TRA

Part A: Cmax: Maximum Observed Whole Blood Concentration of TRA

Part A: Tmax: Time to Reach the Maximum Observed Whole Blood Concentration (Cmax) for TRA

Part A: AUC(0-816): Area Under the Whole Blood Concentration-time Curve From Time 0 to 816 Hrs Post-dose for TRA

Part A: Cumulative Percentage of Ixazomib Dose Recovered in the Urine

Part A: Cumulative Percentage of the Total Radioactivity Dose Excreted in Feces

Part A: Cumulative Percentage of the Total Radioactivity Dose Excreted in Urine

Part A: Renal Clearance of Ixazomib

P4, ixazomib

P2, ML00701258

P3, ML00701201

P6, ML00749506

P7, ML00752034

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.

Spots Global Cancer Trial Database for Mass Balance, Pharmacokinetics and Metabolism Study of IXAZOMIB

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Study Description

Keywords

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