Long-Term Safety of Azilsartan Medoxomil and Chlorthalidone Compared to Olmesartan Medoxomil and Hydrochlorothiazide in Participants With Hypertension and Kidney Disease
|Safety||Drug: Azilsartan medoxomil and chlorthalidone Drug: Olmesartan medoxomil and hydrochlorothiazide||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Randomized, Open-Label, Phase 3 Study to Compare Long-Term Safety and Tolerability of the TAK-491 and Chlorthalidone Fixed-Dose Combination Versus Olmesartan Medoxomil and Hydrochlorothiazide Fixed-Dose Combination in Hypertensive Subjects With Moderate Renal Impairment|
- Number of Participants With at Least 1 Adverse Event (AE) [ Time Frame: From the first dose of open-label study drug until 14 days (or 30 days for a serious adverse event) after the last dose of open- label study drug (up to 56 weeks). ]An AE is any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have a causal relationship with this treatment. A serious AE is defined as any untoward medical occurrence that resulted in death, was life threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability or incapacity, led to a congenital anomaly/birth defect or was an important medical event that may have required intervention to prevent any of items above.
- Percentage of Participants at Final Visit Who Achieve Target Systolic Blood Pressure <130 mm Hg [ Time Frame: Week 52 ]Systolic blood pressure is the arithmetic mean of the 3 serial sitting systolic blood pressure measurements. Percentage of participants who achieve a sitting clinic systolic blood pressure response defined as less than 130 mm Hg at Week 52.
- Percentage of Participants at Final Visit Who Achieved Target Diastolic Blood Pressure <80 mm Hg [ Time Frame: Week 52 ]Diastolic blood pressure is the arithmetic mean of the 3 serial sitting diastolic blood pressure measurements. Percentage of participants at Week 52 who achieved a sitting clinic diastolic blood pressure response, defined as less than 80 mm Hg.
- Percentage of Participants at Final Visit Who Achieved Both a Clinic Systolic and Diastolic Blood Pressure Response [ Time Frame: Week 52 ]Systolic/diastolic blood pressure is the arithmetic mean of the 3 serial sitting systolic/diastolic blood pressure measurements. Percentage of participants who achieved both a sitting clinic systolic and diastolic blood pressure response, defined as systolic blood pressure less than 130 mm Hg and diastolic blood pressure less than 80 mm Hg at Week 52.
|Study Start Date:||March 2011|
|Study Completion Date:||October 2012|
|Primary Completion Date:||October 2012 (Final data collection date for primary outcome measure)|
Experimental: Azilsartan Medoxomil + Chlorthalidone
United States and Europe: Azilsartan medoxomil 20 mg plus chlorthalidone 12.5 mg fixed dose combination tablets, titrated up to azilsartan medoxomil 40 mg plus chlorthalidone 25 mg orally, once daily for up to 52 weeks.
Drug: Azilsartan medoxomil and chlorthalidone
Fixed-dose combination tablets.
Other Name: TAK-491CLD
Active Comparator: Olmesartan Medoxomil + Hydrochlorothiazide
United States: Olmesartan medoxomil 20 mg plus hydrochlorothiazide 12.5 mg fixed dose combination tablets, titrated up to olmesartan medoxomil 40 mg plus hydrochlorothiazide 25 mg orally, once daily for up to 52 weeks. Europe: Olmesartan medoxomil 20 mg plus hydrochlorothiazide 12.5 mg fixed dose combination tablets, titrated up to olmesartan medoxomil 20 mg plus hydrochlorothiazide 25 mg orally, once daily for up to 52 weeks.
Drug: Olmesartan medoxomil and hydrochlorothiazide
Fixed-dose combination tablets.
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-like diuretic agent, and 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 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01309828
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|Study Director:||Medical Director, Clinical Science||Takeda|