A Phase 1 pharmacokinetic study in 14 healthy adults found that balcinrenone (a novel mineralocorticoid receptor antagonist) maintains consistent blood levels whether taken with food or on an empty stomach, and is not significantly affected by P-glycoprotein inhibitors .
Balcinrenone is a new selective non-steroidal mineralocorticoid receptor antagonist currently in development as a fixed-dose combination with dapagliflozin (an SGLT2 inhibitor) for heart failure with reduced kidney function and chronic kidney disease. Before advancing to larger clinical trials, researchers need to understand how food and drug interactions affect the absorption and metabolism of new compounds. This Phase 1 study evaluated those questions in healthy volunteers.
The research team administered the balcinrenone/dapagliflozin combination (40 mg/10 mg) to 14 healthy participants in three separate dosing periods using a randomized crossover design. The first period involved a fasted state (reference), the second involved dosing after a high-fat, high-calorie meal, and the third involved co-administration with quinidine (a P-glycoprotein inhibitor dosed at 300 mg twice). The researchers then measured drug concentrations in blood plasma over time to determine absorption patterns and exposure levels.
For balcinrenone specifically, food had minimal impact. Maximum plasma concentration (Cmax) was essentially identical between fed and fasted states (geometric mean ratio 1.05), and total drug exposure over time (AUCinf) showed only a 12% increase with food, which fell within acceptable ranges. This suggests the body absorbs balcinrenone similarly regardless of whether it's taken with meals. Dapagliflozin showed the expected pattern from previous studies: food reduced peak concentrations by 41% but did not meaningfully change total exposure, indicating the drug is still absorbed adequately.
When balcinrenone was co-administered with quinidine, a P-glycoprotein inhibitor, drug exposure increased modestly. Peak concentration rose 48% and total exposure increased 24%. However, this increase remained below the threshold (2-fold) used to classify a drug as a "sensitive" P-glycoprotein substrate, meaning balcinrenone is not considered highly dependent on this transporter for elimination. The authors concluded that no dose adjustments or special precautions are needed when balcinrenone is used with P-glycoprotein inhibitors. All interventions were well tolerated with no serious adverse events reported.
This study addresses practical questions about drug administration that matter once balcinrenone enters clinical use. The finding that food does not significantly affect balcinrenone absorption means patients would have flexibility in dosing: the medication can be taken with breakfast, lunch, dinner, or between meals without loss of efficacy. This removes a common barrier to medication adherence, as patients don't need to remember specific meal timing.
The P-glycoprotein data is relevant primarily for patients who take other medications that inhibit this transporter. Common P-glycoprotein inhibitors include certain antibiotics (like erythromycin), antifungals, and some cardiovascular drugs. The modest increase in balcinrenone exposure when combined with these agents appears manageable and doesn't necessitate dose reductions based on this evidence.
However, this is a Phase 1 study in healthy adults, not patients with heart failure or kidney disease. Pharmacokinetics can differ in disease states, so these findings serve as preliminary safety and dosing guidance rather than definitive clinical recommendations. Larger Phase 2 and Phase 3 trials will be needed to confirm these patterns hold in the intended patient populations and to establish whether food and drug interactions have clinical significance for outcomes.
| Parameter | Details |
|---|---|
| Study Type | Randomized, open-label, three-way crossover Phase 1 trial |
| Sample Size | 14 healthy adult participants |
| Intervention | Balcinrenone/dapagliflozin 40 mg/10 mg oral capsule in three conditions: fasted, fed (high-fat meal), and with quinidine 300 mg twice daily |
| Primary Outcome | Pharmacokinetic parameters (Cmax, AUCinf) for both compounds |
| Key Finding (Balcinrenone) | Cmax GMR fed vs. fasted: 1.05 (90% CI 0.88-1.25); AUCinf GMR: 1.12 (90% CI 1.06-1.19) |
| Key Finding (Quinidine Co-administration) | Cmax GMR: 1.48 (90% CI 1.24-1.76); AUCinf GMR: 1.24 (90% CI 1.17-1.31) |
| Safety | All interventions well tolerated; no serious adverse events |
| Publication | Journal of Clinical Pharmacology |
| Study Quality | Phase 1 pharmacokinetic studies use small healthy samples to establish preliminary safety and dosing parameters; limited generalization to disease populations |
Eriksson AL, et al. Effect of Food on Balcinrenone/Dapagliflozin Pharmacokinetics and the Pharmacokinetics of Balcinrenone When Dosed with a P-gp Inhibitor. *Journal of Clinical Pharmacology*. 2025. PubMed: 42687606
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