A Study to Assess the Safety, Tolerability and Efficacy of IONIS-AGT-LRx
Condition: Hypertension
MeSH terms: Hypertension
Intervention: Placebo; ISIS 757456
Intervention description: ISIS 757456-matching placebo solution administered as SC injection.; ISIS 757456 administered as SC injection.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 26.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Hypertension; Hypertensive; AGT; Angiotensinogen; Blood Pressure

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.
    

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