Table 3. Adverse Events and Serum Potassium Changes.
| Measures | Cohort 1 (PRA ≤1.0 ng/mL/h) | Exploratory cohort 2 (PRA >1.0 ng/mL/h) | ||||||
|---|---|---|---|---|---|---|---|---|
| Lorundrostat | Placebo (n = 30) | Lorundrostat, 100 mg once daily (n = 31) | Placebo (n = 6) | |||||
| 100 mg once daily (n = 30) | 50 mg once daily (n = 28) | 25 mg twice daily (n = 30) | 12.5 mg twice daily (n = 22) | 12.5 mg once daily (n = 23) | ||||
| Participants with any serious adverse event, No. (%) | 0 | 0 | 0 | 0 | 2 (9)a | 0 | 1 (3)b | 0 |
| Participants with any adverse event, No. (%)c | 17 (57) | 12 (43) | 20 (67) | 13 (59) | 16 (70) | 12 (40) | 19 (61) | 1 (17) |
| Participants with hypotension, No. (%) | 1 (3) | 0 | 0 | 1 (5) | 0 | 0 | 1 (3) | 0 |
| Potassium-related eventsd | ||||||||
| Change from baseline in serum potassium level, mean (SD), mmol/L | 0.29 (0.59) | 0.25 (0.36) | 0.34 (0.46) | 0.32 (0.53) | 0.31 (0.44) | 0.03 (0.37) | 0.21 (0.54) | −0.05 (0.28) |
| Participants with serum potassium level 5.6-6.0 mmol/L, No. (%) | 5 (16) | 1 (4) | 2 (7) | 2 (9) | 3 (13) | 0 | 2 (6) | 0 |
| Participants with serum potassium level 6.1-6.5 mmol/L, No. (%) | 0 | 0 | 1 (3) | 1 (5) | 1 (4) | 0 | 1 (3) | 0 |
| Participants with serum potassium level >6.5 mmol/L, No. (%) | 1 (3) | 1 (4) | 0 | 0 | 0 | 0 | 0 | 0 |
Abbreviation: PRA, plasma renin activity.
One participant was identified with worsening of preexisting coronary artery disease and 1 participant was found to have metastatic cancer in their peritoneum.
Participant had hyponatremia that resolved on drug discontinuation.
Site investigators were requested to assess the relationship between study intervention and each occurrence of each adverse event. Investigators were directed to use clinical judgment to determine the relationship as either unlikely related, unrelated, possibly related, or definitely related. Criteria for deeming possibly or definitely related (and thus treatment related) include that there is a reasonable possibility that the adverse event may have been caused by the study drug. Examples of more prevalent adverse events included hyperkalemia and decline in estimated glomerular filtration rate.
Affected individuals were counted once at highest-grade abnormality. Hemolyzed blood samples with serum potassium levels that were not reproducible on repeat testing were not included.