Table 2. Primary and Secondary Efficacy End Pointsa.
| End points | Cohort 1 (PRA ≤1.0 ng/mL/h) | Exploratory cohort 2 (PRA >1.0 ng/mL/h)b | ||||||
|---|---|---|---|---|---|---|---|---|
| Lorundrostat | Placebo (n = 29) | Lorundrostat, 100 mg once daily (n = 31) | Placebo (n = 6) | |||||
| 100 mg once daily (n = 25) | 50 mg once daily (n = 28) | 25 mg twice daily (n = 28) | 12.5 mg twice daily (n = 19) | 12.5 mg once daily (n = 19) | ||||
| Primary end point | ||||||||
| Automated office SBP, baseline to wk 8 | ||||||||
| Baseline SBP, mean (SD), mm Hg | 143.8 (12.0) | 141.8 (10.9) | 140.9 (9.6) | 144.6 (10.5) | 147.1 (11.6) | 142.7 (10.2) | 140.4 (8.6) | 132.9 (8.4) |
| Wk 8 SBP, mean (SD), mm Hg | 131.3 (14.1) | 128.6 (13.7) | 131.3 (16.6) | 131.9 (12.9) | 140.8 (22.0) | 139.1 (14.2) | 129.3 (15.4) | 128.3 (18.9) |
| Change in SBP, least-squares mean (SE), mm Hg | −11.9 (2.8) | −13.7 (2.7) | −11.1 (2.7) | −11.3 (3.2) | −5.6 (3.2) | −4.1 (2.6) | −11.4 (2.5) | |
| Difference from placebo in SBP change, least-squares mean, (90% CI), mm Hg | −7.8 (−14.1 to −1.5) | −9.6 (−15.8 to −3.4) | −7.0 (−13.1 to −0.8) | −7.2 (−14.0 to −0.4) | −1.5 (−8.3 to 5.3) | |||
| P value | .04 | .01 | .06 | .08 | .71 | |||
| Secondary end point | ||||||||
| Automated office DBP, baseline to wk 8 | ||||||||
| Baseline DBP, mean (SD), mm Hg | 78.9 (9.6) | 84.9 (6.4) | 78.9 (8.0) | 81.6 (7.6) | 82.4 (10.7) | 83.4 (8.8) | 78.1 (7.6) | 78.3 (7.6) |
| Wk 8 DBP, mean (SD), mm Hg | 73.0 (9.4) | 76.8 (9.8) | 75.4 (13.1) | 75.2 (10.1) | 81.4 (17.2) | 81.3 (9.4) | 72.2 (8.4) | 76.2 (11.0) |
| Change in DBP, least-squares mean (SE), mm Hg | −5.8 (1.8) | −7.1 (1.7) | −4.1 (1.7) | −5.5 (2.0) | −3.8 (2.0) | −1.6 (1.7) | −5.6 (1.4) | |
| Difference from placebo in DBP change, least-squares mean, (90% CI), mm Hg | −4.1 (−8.1 to −0.1) | −5.5 (−9.4 to −1.5) | −2.5 (−6.4 to 1.4) | −3.8 (−8.2 to 0.5) | −2.1 (−6.5 to 2.2) | |||
| P value | .09 | .02 | .30 | .14 | .42 | |||
Abbreviations: DBP, diastolic blood pressure; PRA, plasma renin activity; SBP, systolic blood pressure.
a
Analysis used a mixed-model repeated-measures approach with fixed effects for categorical terms for treatment and baseline SBP as a fixed continuous covariate.
b
Because cohort 2 was an exploratory end point, no formal statistical testing was performed comparing lorundrostat with placebo.