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
Condition: Mild Hypertension
MeSH terms: Hypertension
Intervention: Placebo; ISIS 757456
Intervention description: Placebo matching solution administered as SC injection.; Administered as SC injection.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 25.0
Sex: All
Minimum age: 18 Years
Maximum age: 72 Years
Healthy volunteers: No
Keywords: Hypertension; Hypertensive; AGT; Angiotensinogen; Blood Pressure; High Blood Pressure

Summary:

      This was a Phase 2, double-blind, randomized, placebo-controlled study of IONIS-AGT-LRx
      conducted in mild hypertensive participants.
    

Eligibility criteria:

        Inclusion Criteria

          1. Females must be non-pregnant and non-lactating, and either surgically sterile or
             post-menopausal.

          2. 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

          3. Body Mass Index (BMI) ≤ 35.0 kg/m2

          4. Participant must have been diagnosed with essential hypertension for a minimum of 3
             months prior to screening

          5. At Screening, on a stable regimen of antihypertensive medications for at least 1 month
             prior to screening

          6. 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

          1. Clinically-significant (CS) abnormalities in medical history, screening laboratory
             results, physical or physical examination that would render a participant unsuitable
             for inclusion

          2. The use of the following at time of screening and during the course of the study:

               1. Other medications for the treatment of hypertension (e.g., clonidine, guanfacine,
                  guanabenz, alpha-methyldopa, hydralazine, minoxidil, diazoxide, renin inhibitors)

               2. Medications that also may cause hyperkalemia (e.g., cyclosporine or tacrolimus,
                  pentamidine, trimethoprim-sulfamethoxazole, all heparins)

               3. Oral or subcutaneous anticoagulants (e.g., warfarin, rivaroxaban, apixaban,
                  heparin, lovenox)

               4. Organic nitrate preparations (e.g., nitroglycerin, isosorbide mononitrate,
                  isosorbide dinitrate, or pentaerythritol)

               5. Sildenafil, tadalafil, vardenafil

          3. Unwilling to discontinue antihypertensive mediations during Wash Out (WO) and
             Treatment Period of study

          4. Participant has a history of secondary hypertension

          5. Unstable/underlying cardiovascular disease defined as:

               1. Any history of congestive heart failure (NYHA class II-IV)

               2. Any history of previous stroke, transient ischemic attack, unstable or stable
                  angina pectoris, or myocardial infarction prior to screening

               3. a history or evidence of long QT syndrome

               4. Any CS active atrial or ventricular arrhythmias

               5. Any history of coronary bypass or percutaneous coronary intervention