Dimopoulos M, Grosicki S, Jędrzejczak W, Nahi H, Gruber A, Hansson M, et al
. All-oral ixazomib, cyclophosphamide, and dexamethasone for transplant-ineligible patients with newly diagnosed multiple myeloma. Eur J Cancer. 2018;106:89-98 pubmed publisher
..Grade ≥3 AEs were reported by 73% of patients. Five on-study deaths occurred (not treatment-related). ICd treatment followed by ixazomib maintenance is tolerable and active in elderly, transplant-ineligible NDMM patients. NCT02046070. ..
Gupta N, Hanley M, Xia C, Labotka R, Harvey R, Venkatakrishnan K. Clinical Pharmacology of Ixazomib: The First Oral Proteasome Inhibitor. Clin Pharmacokinet. 2018;: pubmed publisher
..Exposure-response analyses of data from the phase III TOURMALINE-MM1 registrational study demonstrate a favorable benefit-risk profile for the approved dose and regimen of weekly ixazomib 4 mg on days 1, 8, and 15 of each 28-day cycle. ..
Gupta N, Huh Y, Hutmacher M, Ottinger S, Hui A, Venkatakrishnan K. Integrated nonclinical and clinical risk assessment of the investigational proteasome inhibitor ixazomib on the QTc interval in cancer patients. Cancer Chemother Pharmacol. 2015;76:507-16 pubmed publisher
..Integrating preclinical data and concentration-QTc modeling of phase 1 data may obviate the need for a dedicated QTc study in oncology. A framework for QT assessment in oncology drug development is proposed. ..
Gupta N, Goh Y, Min C, Lee J, Kim K, Wong R, et al
. Pharmacokinetics and safety of ixazomib plus lenalidomide-dexamethasone in Asian patients with relapsed/refractory myeloma: a phase 1 study. J Hematol Oncol. 2015;8:103 pubmed publisher
..0 mg. Consequently, East Asian patients enrolled in phase 3 studies are receiving the same ixazomib dose as patients in other regions. This study is registered at NCT01645930. ..
Gupta N, Hanley M, Venkatakrishnan K, Wang B, Sharma S, Bessudo A, et al
. The Effect of a High-Fat Meal on the Pharmacokinetics of Ixazomib, an Oral Proteasome Inhibitor, in Patients With Advanced Solid Tumors or Lymphoma. J Clin Pharmacol. 2016;56:1288-95 pubmed publisher
..These recommendations are reflected in the United States Prescribing Information for ixazomib (clinicaltrials.gov identifier NCT01454076). ..
Gupta N, Labotka R, Liu G, Hui A, Venkatakrishnan K. Exposure-safety-efficacy analysis of single-agent ixazomib, an oral proteasome inhibitor, in relapsed/refractory multiple myeloma: dose selection for a phase 3 maintenance study. Invest New Drugs. 2016;34:338-46 pubmed publisher
Gupta N, Diderichsen P, Hanley M, Berg D, van de Velde H, Harvey R, et al
. Population Pharmacokinetic Analysis of Ixazomib, an Oral Proteasome Inhibitor, Including Data from the Phase III TOURMALINE-MM1 Study to Inform Labelling. Clin Pharmacokinet. 2017;56:1355-1368 pubmed publisher
..The geometric mean terminal disposition phase half-life was 9.5 days, steady-state volume of distribution was 543 L and systemic clearance was 1.86 L/h. The absolute bioavailability of an oral dose was estimated to be 58%. ..
Gupta N, Yang H, Hanley M, Zhang S, Liu R, Kumar S, et al
. Dose and Schedule Selection of the Oral Proteasome Inhibitor Ixazomib in Relapsed/Refractory Multiple Myeloma: Clinical and Model-Based Analyses. Target Oncol. 2017;12:643-654 pubmed publisher
..0 mg on days 1, 8, and 15 of 28-day cycles, which was selected for the phase III TOURMALINE registration program. ClinicalTrials.gov NCT00932698, NCT00963820, NCT01217957, NCT01564537. ..
Gupta N, Zhang S, Pusalkar S, Plesescu M, Chowdhury S, Hanley M, et al
. 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;36:407-415 pubmed publisher
..These findings suggest that ixazomib is extensively metabolized, with urine representing the predominant route of excretion of drug-related material.Trial ID: ClinicalTrials.gov # NCT01953783. ..