BMS-986308 / BMS - LARVOL DELTA

Potassium-sparing Diuresis and Natriuresis With a Novel Renal Outer Medullary Potassium Channel Inhibitor, in Healthy Adult Participants (AHA 2024) - P1 | "BMS-986308, a novel inhibitor of the Renal Outer Medullary Potassium Channel (ROMK), is predicted to enhance potassium-sparring diuresis and natriuresis in HF patients with persistent congestion and edema despite SOC treatment...No meaningful change was observed for the other biomarkers tested.ConclusionBMS-986308 significantly increased diuresis and natriuresis in healthy participants while sparing potassium. In line with the substantial natriuresis, activation of the RAAS pathway and transient elevations of serum creatinine and cystatin C (with no change in kidney injury markers) was observed."

Clinical • Cardiovascular • Congestive Heart Failure • Heart Failure • Renal Disease • CST3 • KIM1

First-in-Human Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of BMS-986308: A Renal Outer Medullary Potassium Channel Inhibitor. (PubMed, Clin Pharmacol Ther) - "The largest mean changes from baseline in diuresis and natriuresis occurred in both the 6- and -24 h post-dose period following administration of 100 mg (1683.0 mL and 2055.3 mL, and 231.7 mmol and 213.7 mmol, respectively; ***P < 0.001). Overall, single-dose BMS-986308 was found to be safe, well-tolerated, with an excellent PK profile, and substantial diuretic and natriuretic activity."

Journal • P1 data • PK/PD data • Cardiovascular • Congestive Heart Failure • Heart Failure

Discovery of BMS-986308: A Renal Outer Medullary Potassium Channel Inhibitor for the Treatment of Heart Failure. (PubMed, J Med Chem) - "A series of piperazine-based ROMK inhibitors were designed and optimized to achieve excellent ROMK potency, hERG selectivity, and ADME properties, which led to the identification of compound 28 (BMS-986308). BMS-986308 demonstrated efficacy in the volume-loaded rat diuresis model as well as promising in vitro and in vivo profiles and was therefore advanced to clinical development."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure

A Study to Evaluate the Safety, Tolerability, Drug Levels, and Drug Effects of BMS-986308 in Healthy Participants (clinicaltrials.gov) - P1 | N=46 | Completed | Sponsor: Bristol-Myers Squibb | Recruiting ➔ Completed

Trial completion