A Study to Assess the Safety, Tolerability and Efficacy of IONIS-AGT-LRx in Hypertensive Participants With Uncontrolled Blood Pressure

Exclusion Criteria

• •Clinically significant abnormalities in screening laboratory results, medical history according to Investigator judgment
• •History of secondary hypertension (HTN) including, but not limited to any of the following: renovascular HTN (unilateral or bilateral renal artery stenosis), coarctation of the aorta, primary hyperaldosteronism, Cushing's disease, pheochromocytoma, polycystic kidney disease, and drug-induced HTN
• •The use of the following at time of screening and during the course of the study:
• •* Other medications for the treatment of HTN (e.g., minoxidil, diazoxide, renin inhibitors)
• •* Medications that may cause hyperkalemia unless on a stable dose at least 1 month prior to the screening visit and no known history of hyperkalemia per Investigator judgement
• •* Use of oral anticoagulants, unless stable for 4 weeks prior to the first dose of study drug and regular monitoring must be performed per clinical practice during the study unless the participant is receiving vitamin K agonists. If the participant is receiving vitamin K antagonists (e.g., warfarin) international normalized ratio (INR) should be in therapeutic range, as established by the Investigator, for 4 weeks prior to the first dose
• •* Chronic administration of non-steroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase 2 (COX-2) inhibitors (except aspirin for cardiovascular disease provided the total daily dose does not exceed 325 mg)
• •History of bleeding diathesis, coagulopathy, immune thrombocytopenic purpura (ITP), thrombotic cytopenic purpura (TTP), or any qualitative or quantitative platelet defect
• •Unstable/underlying known cardiovascular disease defined as:
• •* Any history of congestive heart failure (New York Heart Association \[NYHA\] Class III-IV)
• •* Any history of previous myocardial infarction, coronary revascularization, unstable or stable angina pectoris ˂ 1 year prior to screening
• •* Any hemodynamically unstable atrial or ventricular arrhythmias
• •* Significant uncorrected valvular heart disease
• •* Any history of stroke or transient ischemic attack \< 1 year prior to screening
• •A cardiac valve repair, cardiac device implantation, and/or a hospitalization for heart failure within 3 months of screening
• •Participant works nighttime shifts (e.g., 11 PM to 7 AM)