A Study to Assess the Safety, Tolerability and Efficacy of IONIS-AGT-LRx, an Antisense Inhibitor Administered Subcutaneously to Hypertensive Participants With Controlled Blood Pressure

Participants were randomized in a 2:1 ratio to receive a once-weekly subcutaneous treatment and an additional loading dose on Study Day 3 with either IONIS-AGT-LRx or placebo for 6 weeks.

All participants completed a 13-week Post-Treatment Period.

Inclusion criteria

• Females must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal.
• Males must be surgically sterile or, abstinent or, if engaged in sexual relations with a woman of child-bearing potential, the participant or the participant's non-pregnant female partner must be using a highly effective contraceptive method
• Body Mass Index (BMI) ≤ 35.0 kg/m2
• Participant must have been diagnosed with essential hypertension for a minimum of 3 months prior to screening
• At Screening, on a stable regimen of antihypertensive medications for at least 1 month prior to screening
• Agree to conduct at home Blood Pressure (BP) and Heart Rate (HR) monitoring three times weekly and document the average of the triplicate measurements assessed on a day in the patient diary

Exclusion criteria

• Clinically-significant (CS) abnormalities in medical history, screening laboratory results, physical or physical examination that would render a participant unsuitable for inclusion
• The use of the following at time of screening and during the course of the study:

• Other medications for the treatment of hypertension (e.g., clonidine, guanfacine, guanabenz, alpha-methyldopa, hydralazine, minoxidil, diazoxide, renin inhibitors)
• Medications that also may cause hyperkalemia (e.g., cyclosporine or tacrolimus, pentamidine, trimethoprim-sulfamethoxazole, all heparins)
• Oral or subcutaneous anticoagulants (e.g., warfarin, rivaroxaban, apixaban, heparin, lovenox)
• Organic nitrate preparations (e.g., nitroglycerin, isosorbide mononitrate, isosorbide dinitrate, or pentaerythritol)
• Sildenafil, tadalafil, vardenafil
• Unwilling to discontinue antihypertensive mediations during Wash Out (WO) and Treatment Period of study
• Participant has a history of secondary hypertension
• Unstable/underlying cardiovascular disease defined as:

• Any history of congestive heart failure (NYHA class II-IV)
• Any history of previous stroke, transient ischemic attack, unstable or stable angina pectoris, or myocardial infarction prior to screening
• a history or evidence of long QT syndrome
• Any CS active atrial or ventricular arrhythmias
• Any history of coronary bypass or percutaneous coronary intervention