A Study to Investigate Tonlamarsen for the Treatment of Adults With Uncontrolled Hypertension (KARDINAL)

To assess the safety and tolerability of tonlamarsen

Incidence and severity of treatment emergent adverse events (TEAEs). Incidence of clinically significant abnormalities in laboratory assessments, ECGs and vital signs. Incidence of: (1) Hyperkalemia, defined as serum potassium \>5.5 mmol/L. (2) Hypotension, defined as systolic blood pressure \<90 mmHg, or systolic blood pressure \<100 mmHg and symptomatic and/or requiring clinical intervention. (3) Renal dysfunction, defined as a decrease of eGFR \>30% from baseline value. (4) Increased proteinuria, defined as UPCR \>0.5 mg/mg from baseline value.

Time frame: Week 28

To assess the efficacy of tonlamarsen in achieving office seated systolic blood pressure <130 mmHg

Proportion of participants with mean office seated systolic blood pressure \<130 mmHg at Week 20

Time frame: Week 20

To assess the systolic blood pressure-lowering efficacy of tonlamarsen

Change from baseline (Week 0) in mean self-assessed home systolic blood pressure through Week 20

Time frame: Week 20

To assess the effect of tonlamarsen on severe systolic blood pressure elevations

Proportion of participants with any daily average home systolic blood pressure ≥150 mmHg at Week 20