P0001EFFECTS OF VEVERIMER ON SERUM BICARBONATE AND PHYSICAL FUNCTION IN PATIENTS WITH CHRONIC KIDNEY DISEASE AND METABOLIC ACIDOSIS ARE INDEPENDENT OF ALBUMINURIA: SUBGROUP ANALYSES FROM A RANDOMIZED TRIAL
Bibliographic record
Abstract
Abstract Background and Aims Veverimer, an investigational, novel, orally-administered, non-absorbed polymer that binds gastrointestinal hydrochloric acid and results in an increase in serum bicarbonate, is being developed as a treatment for metabolic acidosis in patients with chronic kidney disease (CKD). Metabolic acidosis is a complication of CKD that has deleterious effects on kidney function, bone (demineralization), and muscle (protein catabolism).1 Albuminuria and metabolic acidosis are independently associated with CKD progression and treatment of each may reduce the risk of kidney failure.2,3 We sought to assess (post-hoc) if albuminuria impacts the ability of veverimer to increase serum bicarbonate level and improve physical functioning. Method TRCA-301E is a multicenter, Phase 3, randomized, blinded, placebo-controlled trial in 196 patients with CKD (eGFR 20 - 40 ml/min/1.73 m2) and metabolic acidosis (serum bicarbonate 12 - 20 mEq/L) who were treated for up to 1 year with veverimer (previously TRC101) or placebo, with dose titration targeted to achieve a normal serum bicarbonate. 4 The randomization was performed in a ratio of 4:3 (veverimer:placebo). Results We previously reported4 that, compared with placebo, veverimer significantly increased serum bicarbonate and significantly improved physical function as reported on the Kidney Disease and Quality of Life-Physical Function Domain (KDQOL-PFD) (e.g., walking several blocks, climbing stairs) and as measured objectively using the 5-times repeated chair stand test with a safety profile that was similar to placebo. Baseline characteristics of the subgroups of patients by baseline urine albumin to creatinine ratio (UACR) ≤ 300 vs. >300 mg/g are shown in the Table. Neither albuminuria (log UACR) as a continuous covariate nor the presence of UACR > 300 mg/g had an effect on the efficacy of veverimer treatment in correction of acidosis or improvement of physical function (interaction p-values >0.4). In patients with UACR > 300 mg/g, at Week 52, serum bicarbonate increased by 4.1 (0.5) mEq/L on veverimer (p = 0.047 vs. placebo) and a significantly higher percentage (vs. placebo) had a ≥ 4 mEq/L increase or normalization of serum bicarbonate (59% vs. 30%, p = 0.014). Patient-reported limitations of physical function (KDQOL-PFD) improved in the veverimer vs. placebo group (+10.4 vs. +1.2 seconds, respectively, p = 0.034). Objective physical performance on the chair stand test at Week 52 also improved in the veverimer group vs. placebo (p < 0.001). In patients with UACR ≤ 300 mg/g, at Week 52, serum bicarbonate increased by 5.2 (0.5) mEq/L on veverimer (p = 0.003 vs. placebo) and a numerically higher percentage (vs. placebo) had a ≥ 4 mEq/L increase or normalization of serum bicarbonate (65% vs. 45%, p = 0.063). KDQOL-PFD improved in the veverimer vs. placebo group (+12.5 vs. -2.8 seconds, respectively, p = 0.001). The chair stand test at Week 52 also improved in the veverimer group vs. placebo (p = 0.002). Conclusion The drug candidate veverimer effectively treated metabolic acidosis and improved the ability to repeatedly stand from a seated position and physical function related to daily activities independent of albuminuria, and therefore independent of the kidney injury reflected by albuminuria.
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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".