Mass Balance, Pharmacokinetics and Metabolism Study of IXAZOMIB

NCT01953783 | Completed Phase 1 Results

• 1 other identifier: C16016
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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.

Conditions

Advanced Solid Tumors; Lymphoma

Outcome Measures

Primary Outcomes (13)

• 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.

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

• 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.

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

• 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.

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

• 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.

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

• 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.

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

• 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.

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

• 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.

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

• 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.

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

• 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.

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

• 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.

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

• 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

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

• 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.

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

• 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.

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

Secondary Outcomes (6)

• 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

• 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

• 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

• 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

Study Arms (1)

IXAZOMIB

EXPERIMENTAL

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.

Drug: IXAZOMIB

Interventions

IXAZOMIB DRUG

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Female participants who are lactating or breastfeeding or have a positive serum pregnancy test
• Serious medical or psychiatric illness that could interfere with the study
• Treatment with any investigational products or radiotherapy within 21 days before the first dose of study drug
• Peripheral neuropathy greater than (\>) Grade 2
• Systemic treatment with strong and moderate inhibitors of CYP1A2, strong and moderate inhibitors of CYP3A, or clinically significant CYP3A inducers or use of Ginkgo biloba or St. John's wort within 14 days before the first dose of study drug
• Symptomatic brain metastasis. Participants with brain metastases: must have stable neurologic status following local therapy (surgery or radiation) for at least 2 weeks after completion of the definitive therapy; and must be without neurologic dysfunction that would confound the evaluation of neurologic and other adverse events (AEs)
• Ongoing treatment with corticosteroids
• Major surgery within the 14 days preceding the first dose of study drug
• Infection requiring systemic intravenous antibiotic therapy or other serious infection within 14 days before the first dose of study drug
• Life-threatening illness unrelated to cancer
• Known hepatitis B surface antigen -positive, or known or suspected active hepatitis C infection or human immunodeficiency virus (HIV) positive
• Diagnosed or treated for another malignancy within 2 years before the first dose, OR previously diagnosed with another malignancy and have any evidence of residual disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection
• Any cardiovascular condition specified in the study protocol
• Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of IXAZOMIB
• History of urinary and/or fecal incontinence

Sponsors & Collaborators

• Millennium Pharmaceuticals, Inc.: lead

Study Sites (1)

Unknown Facility

Cleveland, Ohio, United States

Location

Related Publications (1)

• Gupta N, Zhang S, Pusalkar S, Plesescu M, Chowdhury S, Hanley MJ, Wang B, Xia C, Zhang X, Venkatakrishnan K, Shepard DR. A phase I study to assess the mass balance, excretion, and pharmacokinetics of [14C]-ixazomib, an oral proteasome inhibitor, in patients with advanced solid tumors. Invest New Drugs. 2018 Jun;36(3):407-415. doi: 10.1007/s10637-017-0509-1. Epub 2017 Sep 21.

  PMID: 28932928 DERIVED

MeSH Terms

Conditions

Lymphoma

Interventions

ixazomib

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Monitor

  Millennium Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2013
• First Posted: October 1, 2013
• Study Start: March 19, 2014
• Primary Completion: December 17, 2014
• Study Completion: February 9, 2016
• Last Updated: August 26, 2020
• Results First Posted: August 26, 2020

Record last verified: 2020-08

Locations

US (1)