a study to assess the safety, tolerability and efficacy of ionis-agt-lrx

Conditions: Hypertension

Summary: this study evaluated the effect of isis 757456 (ionis-agt-lrx) on plasma angiotensinogen (agt) and systolic blood pressure (sbp) in uncontrolled hypertensive participants who were on two to three antihypertensive medications.

this study was a phase 2, double-blind, randomized, placebo-controlled study in 26 participants. participants were randomized in a 2:1 ratio and received a once-weekly subcutaneous (sc) treatment with either ionis-agt-lrx or placebo, with an additional loading dose administered on study day 3. the treatment lasted for 8 weeks and the post-treatment period lasted for 13 weeks.

Eligibility criteria:
inclusion criteria: * males or females aged 18-75 inclusive and weighing ≥ 50 kilograms (kg) at the time of informed consent * 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 (wocbp), the participant or participant's non-pregnant female partner must be using a highly effective contraceptive method * body mass index (bmi) ≤ 35.0 kg/square meter (m\^2) * participant must have been diagnosed with essential hypertension for a minimum of 3 months prior to screening * at screening, the participant must have been on a stable regimen of 2 to 3 antihypertensive medications for at least 1 month prior to screening and will be required to maintain this regimen throughout the study, using either an angiotensin-converting enzyme inhibitor (acei) or an angiotensin ii receptor blocker (arb), as well as 1 or 2 additional antihypertensive medications in the following categories: beta blocker, acebutolol, atenolol, betaxolol, bisoprolol, carvedilol, labetalol, metoprolol, nadolol, nebivolol, propranolol, pindolol, calcium channel blocker or, non-potassium sparing diuretic exclusion criteria: * clinically significant abnormalities in medical history, screening laboratory results, or physical examination that would render the participant unsuitable for inclusion * history of secondary hypertension (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., clonidine, guanfacine, guanabenz, alpha-methyldopa, hydralazine, minoxidil, diazoxide, renin inhibitors) * medications that may cause hyperkalemia (e.g., cyclosporine or tacrolimus, pentamidine, trimethoprim-sulfamethoxazole, all heparins) * oral or sc anticoagulants (e.g., warfarin, rivaroxaban, apixaban, heparin, lovenox) * organic nitrate preparations (e.g., nitroglycerin, isosorbide mononitrate, isosorbide dinitrate, or pentaerythritol) * phosphodiesterase 5 inhibitors (e.g., sildenafil, tadalafil, vardenafil, avanafil) * potassium-sparing diuretics (e.g., eplerenone, spironolactone, amiloride, triamterene) unstable/underlying cardiovascular disease defined as: * any history of congestive heart failure (new york heart association \[nyha\] class ii-iv) * any history of previous stroke, transient ischemic attack, unstable or stable angina pectoris, or myocardial infarction prior to screening * 12-lead electrocardiogram (ecg) corrected using fridericia's formula (qtcf) \> 450 milliseconds (msec) in males and \> 470 msec in females at screening, or a history or evidence of long qt syndrome * any clinically significant active atrial or ventricular arrhythmias * any history of coronary bypass or percutaneous coronary intervention

Keywords: hypertension hypertensive agt angiotensinogen blood pressure