The purpose of this study is to evaluate the effect of zilebesiran on systolic and
diastolic blood pressure and to characterize the pharmacodynamic (PD) effects and safety
of zilebesiran as add-on therapy.

Zilebesiran as Add-on Therapy in Patients With Hypertension Not Adequately Controlled by a Standard of Care Antihypertensive Medication (KARDIA-2)

Hypertension

Zilebesiran

Clinical Trial Site

Clinical Trials Site

A Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of Zilebesiran Used as Add-on Therapy in Patients With Hypertension Not Adequately Controlled by a Standard of Care Antihypertensive Medication

Daytime is defined as 6 am to 9:59 pm and nighttime is defined as 10 pm to 5:59 am.

Following a run-in on olmesartan, eligible participants will receive zilebesiran on Day 1
of a 6-month double-blind treatment period as add-on to olmesartan. Thereafter,
participants will receive zilebesiran once every 6 months during the open-label extension
period. Upon implementation of Amendment 3, the open-label extension (OLE) period will be
closed and participants will not receive any further treatment with zilebesiran in the
OLE period.

Following a run-in on olmesartan, eligible participants will receive placebo on Day 1 of
a 6-month double-blind treatment period as add-on to olmesartan. Thereafter, participants
will receive zilebesiran once every 6 months during the open-label extension period. Upon
implementation of Amendment 3, the OLE period will be closed and participants will not
receive any further treatment with zilebesiran in the OLE period.

Following a run-in on amlodipine, eligible participants will receive zilebesiran on Day 1
of a 6-month double-blind treatment period as add-on to amlodipine. Thereafter,
participants will receive zilebesiran once every 6 months during the open-label extension
period. Upon implementation of Amendment 3, the OLE period will be closed and
participants will not receive any further treatment with zilebesiran in the OLE period.

Following a run-in on amlodipine, eligible participants will receive placebo on Day 1 of
a 6-month double-blind treatment period as add-on to amlodipine. Thereafter, participants
will receive zilebesiran once every 6 months during the open-label extension period. Upon
implementation of Amendment 3, the OLE period will be closed and participants will not
receive any further treatment with zilebesiran in the OLE period.

Following a run-in on indapamide, eligible participants will receive zilebesiran on Day 1
of a 6-month double-blind treatment period as add-on to indapamide. Thereafter,
participants will receive zilebesiran once every 6 months during the open-label extension
period. Upon implementation of Amendment 3, the OLE period will be closed and
participants will not receive any further treatment with zilebesiran in the OLE period.

Following a run-in on indapamide, eligible participants will receive placebo on Day 1 of
a 6-month double-blind treatment period as add-on to indapamide. Thereafter, participants
will receive zilebesiran once every 6 months during the open-label extension period. Upon
implementation of Amendment 3, the OLE period will be closed and participants will not
receive any further treatment with zilebesiran in the OLE period.