A pharmacokinetics and safety phase 1/1b study of oral ixazomib in patients with multiple myeloma and severe renal impairment or end‐stage renal disease requiring haemodialysis
Bibliographic record
Abstract
Renal impairment (RI) is a major complication of multiple myeloma (MM). This study aimed to characterize the single-dose pharmacokinetics (PK) of the oral proteasome inhibitor, ixazomib, in cancer patients with normal renal function [creatinine clearance (CrCl) ≥90 ml/min; n = 20), severe RI (CrCl <30 ml/min; n = 14), or end-stage renal disease requiring haemodialysis (ESRD; n = 7). PK and adverse events (AEs) were assessed after a single 3 mg dose of ixazomib. Ixazomib was highly bound to plasma proteins (~99%) in all renal function groups. Unbound and total systemic exposures of ixazomib were 38% and 39% higher, respectively, in severe RI/ESRD patients versus patients with normal renal function. Total ixazomib concentrations were similar in pre- and post-dialyser samples collected from ESRD patients; therefore, ixazomib can be administered without regard to haemodialysis timing. Except for anaemia, the incidence of the most common AEs was generally similar across groups, but grade 3 and 4 AEs were more frequent in the severe RI/ESRD groups versus the normal group (79%/57% vs. 45%), as were serious AEs (43%/43% vs. 15%). The PK and safety results support a reduced ixazomib dose of 3 mg in patients with severe RI/ESRD.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".