Phase Ib Study of the Soluble Guanylate Cyclase Activator BI 685509 in Patients with Diabetic Kidney Disease
Bibliographic record
Abstract
Background: Soluble guanylate cyclase (sGC) plays a key role in the kidney nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway. Increased albuminuria is associated with kidney function loss. The NO-independent sGC activator BI 685509 lowers albuminuria in experimental models. This Phase Ib study (NCT03165227) assessed the safety and efficacy of BI 685509 in patients with diabetic kidney disease and albuminuria. Methods: This placebo (PBO)-controlled, multiple dose study enrolled patients with type 1 or 2 diabetes, estimated glomerular filtration rate (eGFR) 20-75 mL/min/1.73m2 and urinary albumin creatinine ratio (UACR) 200-3500 mg/g. Patients (N=74) were randomised to three active dose groups receiving oral BI 685509 (tested doses after titration: 1 mg three times daily [TID], n=20; 3 mg once daily [QD], n=19; 3 mg TID, n=20) or PBO (n=15) for 28 days. Efficacy was assessed by the proportion of responders, defined as patients with ≥20% decrease from baseline in UACR measured in first morning void (UACRFMV) and 10-h (UACR10h) (PBO, 3 mg QD and 3 mg TID only) urine. Results: At baseline, median eGFR was 47.0 mL/min/1.73m2 and median UACR was 641.5 mg/g, although this varied between groups. Drug-related adverse events (AEs) occurred in 12 patients (16.2%; BI 685509 15.3%, PBO 20.0%); the most frequent were hypotension (4.1%) and diarrhoea (2.7%). AEs leading to study discontinuation occurred in 4 patients (5.4%; BI 685509 5.1%, PBO 6.7%). Compared with PBO, the proportion of patients receiving BI 685509 classed as responders was higher (Figure). Conclusions: BI 685509 treatment was generally well-tolerated with over 50% of patients in the 3 mg QD and 3 mg TID dose groups appearing to show a response in UACR10h. Funding: Commercial Support - Boehringer IngelheimProportion of responders (≥20% decrease from baseline in UACR)
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".