Long-Term Safety of Azilsartan Medoxomil and Chlorthalidone Compared to Olmesartan Medoxomil and Hydrochlorothiazide in Participants With Hypertension and Kidney Disease.

A major component of blood pressure regulation is the renin-angiotensin-aldosterone system
(RAAS). Drugs that modulate the RAAS are used commonly worldwide for the treatment of
hypertension. TAK-491 (azilsartan medoxomil) is a prodrug of TAK-536 (azilsartan), an
angiotensin II receptor blocker (ARB). Azilsartan medoxomil is being evaluated by Takeda to
treat participants with essential hypertension.

Chlorthalidone is an orally administered thiazide-type diuretic agent, and some long-term
outcomes trials show blood pressure reductions associated with chlorthalidone treatment
reduce risk of cardiovascular morbidity and mortality.

Hypertensive patients with moderate renal impairment are a relatively more severe and
resistant hypertension population, and may benefit from effective fixed-dose combination
treatments such as an ARB plus a thiazide-type diuretic for blood pressure control.

Participants will be randomized to receive azilsartan medoxomil and chlorthalidone or
olmesartan medoxomil and hydrochlorothiazide for up to 52 weeks to evaluate long term safety
of azilsartan medoxomil and chlorthalidone. A titration-to-target blood pressure approach
will be used to guide the titration of study medication in this trial.