Safety and Tolerability of Azilsartan Medoxomil Plus Chlorthalidone Compared to Olmesartan Medoxomil Plus Hydrochlorothiazide in Participants With Essential Hypertension

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00996281
• Collaborator: (none)
• Enrollment: 837
• Locations: 26
• Arms: 2
• Duration (Months): 25
• Patients Per Site: 32.2
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the safety and tolerability of azilsartan medoxomil plus chlorthalidone, once daily (QD), versus olmesartan medoxomil-hydrochlorothiazide in adults with essential hypertension.

Condition or Disease	Intervention/Treatment	Phase
Essential Hypertension	Drug: Azilsartan medoxomil and chlorthalidone; Drug: Olmesartan medoxomil and hydrochlorothiazide	Phase 3

Detailed Description

High Blood Pressure (Hypertension) is the most common cause of preventable death in developed nations. Uncontrolled hypertension greatly increases the risk of heart disease, brain disease, and kidney failure. As the population ages, the incidence of hypertension will continue to increase if effective preventive measures are not implemented. Despite the availability of antihypertensive agents, hypertension is not adequately controlled; only about one in three patients successfully keep blood pressure normal.

Treatment for high blood pressure includes thiazides or thiazide-like diuretics, either alone or as part of combination treatment. Chlorthalidone is a commercially available, orally administered thiazide-type diuretic agent.

TAK-491 (azilsartan) is an angiotensin II receptor blocker being evaluated by Takeda to treat patients with high blood pressure (essential hypertension).

This study will compare the safety and tolerability of azilsartan medoxomil plus chlorthalidone (TAK-491CLD) fixed-dose combination to olmesartan medoxomil-hydrochlorothiazide fixed-dose combination.

Initially patients will undergo a Screening Visit to confirm that they are eligible to participate in the study. All participants will receive the study drug for up to 52 weeks. The dose of the study drug may be gradually increased throughout the study so that a target blood pressure value can be reached for each participant.

Throughout the treatment period of the study, participants will be required to visit the research site for 11 visits. At these study visits participants will be required to undergo certain study procedures including physical examinations, vital sign measurements (blood pressure, heart rate, weight and height), electrocardiograms (monitoring of the heart), and blood and urine samples taken for clinical laboratory tests.

Study Design

• Study Type: Interventional
• Actual Enrollment: 837 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Open-Label, Randomized, Long-Term Comparison of the Safety and Tolerability of the TAK-491 Plus Chlorthalidone Fixed-Dose Combination vs. Olmesartan Medoxomil-Hydrochlorothiazide Fixed-Dose Combination in Subjects With Essential Hypertension
• Study Start Date: Oct 1, 2009
• Actual Primary Completion Date: Nov 1, 2011
• Actual Study Completion Date: Nov 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Azilsartan Medoxomil and Chlorthalidone Azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablet, orally, once daily for up to 52 weeks. For participants who did not achieve target blood pressure by Week 4, titration to a maximum dose of azilsartan medoxomil 80 mg and chlorthalidone 25 mg.	Drug: Azilsartan medoxomil and chlorthalidone; Combination tablet.; Other Names: TAK-491CLD
Active Comparator: Olmesartan Medoxomil and Hydrochlorothiazide QD Participants in the United States: Olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg combination tablet, orally, once daily for up to 52 weeks. For participants who did not achieve target blood pressure by Week 4, titration to a maximum dose of Olmesartan medoxomil 40 mg and hydrochlorothiazide 25 mg. Participants in Europe: Olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg combination tablet, orally, once daily for up to 52 weeks. For participants who did not achieve target blood pressure by Week 4, titration to a maximum dose of Olmesartan medoxomil 20 mg and hydrochlorothiazide 25 mg.	Drug: Olmesartan medoxomil and hydrochlorothiazide; Combination tablet.; Other Names: Benicar HCT® Olmetec Plus®

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With at Least 1 Adverse Event [From Week 0 (Day 1) to Week 52.]

   An adverse event is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product without regard to causality.

Secondary Outcome Measures

1. Percentage of Participants With Serum Creatinine Elevations Greater Than 50% From Baseline and Greater Than the Upper Limit of Normal (ULN) [Baseline and Week 52]

   Serum creatinine was measured at every visit and evaluated as a laboratory parameter of special interest. The percentage of participants with creatinine increase ≥50% from Baseline and greater than ULN was summarized: - At any visit (includes transient and persistent elevations). - At the Final Visit (includes persistent elevations and participants whose first elevation may have been at the Final Visit). - At least 2 consecutive visits (includes only persistent elevations).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Is treated with antihypertensive therapy and has a post-washout mean sitting clinic systolic blood pressure greater than or equal to 160 and less than or equal to 190 mm Hg on Day, or has not received antihypertensive treatment within 14 days prior to Screening and has a mean sitting clinic systolic blood pressure greater than or equal to 160 and less than or equal to 190 mm Hg at the Screening Visit and on Day 1.

• Females of childbearing potential who are sexually active agree to routinely use adequate contraception, and can neither be pregnant nor lactating from before study participation to Screening to 30 days after the last study drug dose.

• Has clinical laboratory test results within the reference range for the testing laboratory or the investigator does not consider the results to be clinically significant.

• Is willing to discontinue current antihypertensive medications up to 3 weeks before enrollment.

Exclusion Criteria:

• Has a mean clinic diastolic blood pressure (sitting, trough) greater than 119 mm Hg on Day 1.

• Has secondary hypertension of any etiology (eg, renovascular disease, pheochromocytoma, Cushing's syndrome).

• Has a recent history (within the last 6 months) of myocardial infarction, heart failure, unstable angina, coronary artery bypass graft, percutaneous coronary intervention, hypertensive encephalopathy, cerebrovascular accident or transient ischemic attack.

• Has clinically significant cardiac conduction defects (ie, third-degree atrioventricular block, sick sinus syndrome).

• Has hemodynamically significant left ventricular outflow obstruction due to aortic valvular disease.

• Has severe renal dysfunction or disease.

• Has known or suspected unilateral or bilateral renal artery stenosis.

• Has a history of cancer that has not been in remission for at least 5 years prior to the first dose of study drug.

• Has poorly-controlled type 1 or 2 diabetes mellitus at Screening.

• Has hypokalemia or hyperkalemia at Screening.

• Has an alanine aminotransferase or aspartate aminotransferase level of greater than 2.5 times the upper limit of normal, active liver disease, or jaundice at Screening.

• Has any other known serious disease or condition that would compromise safety, might affect life expectancy, or make it difficult to successfully manage and follow according to the protocol.

• Has known hypersensitivity to angiotensin II receptor blockers or thiazide-type diuretics or other sulfonamide-derived compounds.

• Has been randomized/enrolled in a previous azilsartan or azilsartan medoxomil plus chlorthalidone study.

• Currently is participating in another investigational study or has received any investigational compound within 30 days prior to Screening.

• Has a history of drug abuse or a history of alcohol abuse within the past 2 years.

• Is taking or expected to take any excluded medication, including:

• Antihypertensive medications must be discontinued completely by Day -14, except antihypertensive medications used in the open-label treatment period in accordance with the titration-to-target blood pressure titration.

• Angiotensin II receptor blockers or thiazide-type diuretics other than study medication.

• Over-the-counter products not permitted by investigator.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Graz	Styria	Austria
2		Karlsruhe	Baden-Wurttemberg	Germany
3		Hannover	Lower Saxony	Germany
4		Kiel-Kronshagen	Schleswig-Holstein	Germany
5		Breda	North Brabant	Netherlands
6		Eindhoven	North Brabant	Netherlands
7		Amsterdam	North Holland	Netherlands
8		Velp	Rheden	Netherlands
9		Leiderdorp	South Holland	Netherlands
10		Zoetermeer	South Holland	Netherlands
11		Rotterdam	Zuid-Holland	Netherlands
12		Groningen		Netherlands
13		Bydgoszcz	Kuyavian-Pomeranian	Poland
14		Skierniewice	L0dz	Poland
15		Zgierz	L0dz	Poland
16		Gdansk	Pomeranian	Poland
17		Gdynia	Pomeranian	Poland
18		Sopot	Pomeranian	Poland
19		Mikolow	Silesian	Poland
20		Avon	England	United Kingdom
21		Bolton	England	United Kingdom
22		Chorley	England	United Kingdom
23		Inverness	England	United Kingdom
24		Liverpool	England	United Kingdom
25		Surrey	England	United Kingdom
26		Warwickshire	England	United Kingdom

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Executive Medical Director, Clinical Science, Takeda

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT00996281
• Other Study ID Numbers: TAK-491CLD_308; 2008-008260-28; U1111-1111-7891
• First Posted: Oct 16, 2009
• Last Update Posted: Nov 12, 2012
• Last Verified: Oct 1, 2012

• Keywords provided by Takeda: Hypertensive; Blood Pressure, High; Cardiovascular disease; Vascular Disease; Drug Therapy
• Additional relevant MeSH terms: Hypertension; Essential Hypertension; Hydrochlorothiazide; Olmesartan; Olmesartan Medoxomil; Chlorthalidone; Azilsartan medoxomil

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 79 investigative sites in the United States, Netherlands, Poland, the United Kingdom and Germany from 27 October 2009 to 17 November 2011.
Pre-assignment Detail	Participants with a diagnosis of essential hypertension were randomized to receive open-label treatment with either Azilsartan Medoxomil and Chlorthalidone or Olmesartan Medoxomil and Hydrochlorothiazide for up to 52 weeks.

Arm/Group Title	Azilsartan Medoxomil and Chlorthalidone	Olmesartan Medoxomil and Hydrochlorothiazide
Arm/Group Description	Azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablet, orally, once daily for up to 52 weeks. For participants who did not achieve target blood pressure by Week 4, titration to a maximum dose of azilsartan medoxomil 80 mg and chlorthalidone 25 mg. Additional antihypertensive agents could be added as needed to achieve blood pressure control.	Participants in the United States: Olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg combination tablet, orally, once daily for up to 52 weeks. For participants who did not achieve target blood pressure by Week 4, titration to a maximum dose of Olmesartan medoxomil 40 mg and hydrochlorothiazide 25 mg. Participants in Europe: Olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg combination tablet, orally, once daily for up to 52 weeks. For participants who did not achieve target blood pressure by Week 4, titration to a maximum dose of Olmesartan medoxomil 20 mg and hydrochlorothiazide 25 mg. Additional antihypertensive agents could be added as needed to achieve blood pressure control.
Period Title: Overall Study
STARTED	418	419
COMPLETED	287	330
NOT COMPLETED	131	89

Baseline Characteristics

Arm/Group Title	Azilsartan Medoxomil and Chlorthalidone	Olmesartan Medoxomil and Hydrochlorothiazide	Total
Arm/Group Description	Azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablet, orally, once daily for up to 52 weeks. For participants who did not achieve target blood pressure by Week 4, titration to a maximum dose of azilsartan medoxomil 80 mg and chlorthalidone 25 mg. Additional antihypertensive agents could be added as needed to achieve blood pressure control.	Participants in the United States: Olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg combination tablet, orally, once daily for up to 52 weeks. For participants who did not achieve target blood pressure by Week 4, titration to a maximum dose of Olmesartan medoxomil 40 mg and hydrochlorothiazide 25 mg. Participants in Europe: Olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg combination tablet, orally, once daily for up to 52 weeks. For participants who did not achieve target blood pressure by Week 4, titration to a maximum dose of Olmesartan medoxomil 20 mg and hydrochlorothiazide 25 mg. Additional antihypertensive agents could be added as needed to achieve blood pressure control.	Total of all reporting groups
Overall Participants	418	419	837
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.5 (10.79)	57.6 (10.80)	58.1 (10.80)
Age, Customized (participants) [Number]
<45 years	46 11%	48 11.5%	94 11.2%
45 to 64 years	251 60%	259 61.8%	510 60.9%
65 to 74 years	94 22.5%	93 22.2%	187 22.3%
≥75 years	27 6.5%	19 4.5%	46 5.5%
Sex: Female, Male (Count of Participants)
Female	192 45.9%	173 41.3%	365 43.6%
Male	226 54.1%	246 58.7%	472 56.4%
Race/Ethnicity, Customized (participants) [Number]
Hispanic or Latino	40 9.6%	41 9.8%	81 9.7%
Non-Hispanic or Latino	209 50%	205 48.9%	414 49.5%
Not collected	169 40.4%	172 41.1%	341 40.7%
Missing	0 0%	1 0.2%	1 0.1%
Race/Ethnicity, Customized (participants) [Number]
American Indian or Alaska Native	4 1%	5 1.2%	9 1.1%
Asian	4 1%	7 1.7%	11 1.3%
Black or African American	72 17.2%	74 17.7%	146 17.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
White	341 81.6%	336 80.2%	677 80.9%
Multiracial	3 0.7%	3 0.7%	6 0.7%
Region of Enrollment (participants) [Number]
Poland	52 12.4%	54 12.9%	106 12.7%
United States	249 59.6%	247 58.9%	496 59.3%
Netherlands	56 13.4%	58 13.8%	114 13.6%
Germany	22 5.3%	21 5%	43 5.1%
United Kingdom	39 9.3%	39 9.3%	78 9.3%
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	169.9 (10.2)	169.6 (10.1)	169.8 (10.1)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	91.00 (21.025)	92.00 (21.727)	91.50 (21.373)
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	31.4 (6.21)	31.9 (6.63)	31.7 (6.42)
Smoking history (participants) [Number]
Never smoked	214 51.2%	205 48.9%	419 50.1%
Current smoker	82 19.6%	78 18.6%	160 19.1%
Ex-smoker	122 29.2%	136 32.5%	258 30.8%
Diabetes Status (participants) [Number]
Yes	64 15.3%	59 14.1%	123 14.7%
No	354 84.7%	360 85.9%	714 85.3%
Estimated glomerular filtration rate (participants) [Number]
Moderate impairment: ≥30 and <60 ml/min/1.73 m^2	54 12.9%	43 10.3%	97 11.6%
Mild impairment: ≥60 and <90 ml/min/1.73 m^2	275 65.8%	265 63.2%	540 64.5%
Normal: ≥90 ml/min/1.73 m^2	87 20.8%	110 26.3%	197 23.5%
Missing	2 0.5%	1 0.2%	3 0.4%
Chronic Kidney Disease (CKD) status (participants) [Number]
Yes	59 14.1%	51 12.2%	110 13.1%
No	359 85.9%	368 87.8%	727 86.9%
Systolic blood pressure (participants) [Number]
≥140 - < 160 mmHg	1 0.2%	1 0.2%	2 0.2%
≥160 - < 180 mmHg	382 91.4%	385 91.9%	767 91.6%
≥180 mm Hg	35 8.4%	33 7.9%	68 8.1%
Diastolic blood pressure (participants) [Number]
< 90 mmHg	107 25.6%	103 24.6%	210 25.1%
≥90 mmHg	311 74.4%	316 75.4%	627 74.9%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With at Least 1 Adverse Event
Description	An adverse event is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product without regard to causality.
Time Frame	From Week 0 (Day 1) to Week 52.

Outcome Measure Data

Analysis Population Description

Safety analysis set: All participants who received at least 1 dose of study medication.

Arm/Group Title	Azilsartan Medoxomil and Chlorthalidone	Olmesartan Medoxomil and Hydrochlorothiazide
Arm/Group Description	Azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablet, orally, once daily for up to 52 weeks. For participants who did not achieve target blood pressure by Week 4, titration to a maximum dose of azilsartan medoxomil 80 mg and chlorthalidone 25 mg. Additional antihypertensive agents could be added as needed to achieve blood pressure control.	Participants in the United States: Olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg combination tablet, orally, once daily for up to 52 weeks. For participants who did not achieve target blood pressure by Week 4, titration to a maximum dose of Olmesartan medoxomil 40 mg and hydrochlorothiazide 25 mg. Participants in Europe: Olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg combination tablet, orally, once daily for up to 52 weeks. For participants who did not achieve target blood pressure by Week 4, titration to a maximum dose of Olmesartan medoxomil 20 mg and hydrochlorothiazide 25 mg. Additional antihypertensive agents could be added as needed to achieve blood pressure control.
Measure Participants	418	419
Number [percentage of participants]	78.5 18.8%	76.4 18.2%

2. Secondary Outcome

Title	Percentage of Participants With Serum Creatinine Elevations Greater Than 50% From Baseline and Greater Than the Upper Limit of Normal (ULN)
Description	Serum creatinine was measured at every visit and evaluated as a laboratory parameter of special interest. The percentage of participants with creatinine increase ≥50% from Baseline and greater than ULN was summarized: - At any visit (includes transient and persistent elevations). - At the Final Visit (includes persistent elevations and participants whose first elevation may have been at the Final Visit). - At least 2 consecutive visits (includes only persistent elevations).
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

Safety analysis set.

Arm/Group Title	Azilsartan Medoxomil and Chlorthalidone	Olmesartan Medoxomil and Hydrochlorothiazide
Arm/Group Description	Azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablet, orally, once daily for up to 52 weeks. For participants who did not achieve target blood pressure by Week 4, titration to a maximum dose of azilsartan medoxomil 80 mg and chlorthalidone 25 mg. Additional antihypertensive agents could be added as needed to achieve blood pressure control.	Participants in the United States: Olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg combination tablet, orally, once daily for up to 52 weeks. For participants who did not achieve target blood pressure by Week 4, titration to a maximum dose of Olmesartan medoxomil 40 mg and hydrochlorothiazide 25 mg. Participants in Europe: Olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg combination tablet, orally, once daily for up to 52 weeks. For participants who did not achieve target blood pressure by Week 4, titration to a maximum dose of Olmesartan medoxomil 20 mg and hydrochlorothiazide 25 mg. Additional antihypertensive agents could be added as needed to achieve blood pressure control.
Measure Participants	418	419
At any postbaseline visit	14.2 3.4%	5.8 1.4%
at the Final Visit	5.9 1.4%	1.0 0.2%
≥2 consecutive elevations	5.1 1.2%	1.2 0.3%

Adverse Events

Time Frame	Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of study drug.
Adverse Event Reporting Description	At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Arm/Group Title	Azilsartan Medoxomil and Chlorthalidone		Olmesartan Medoxomil and Hydrochlorothiazide
Arm/Group Description	Azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablet, orally, once daily for up to 52 weeks. For participants who did not achieve target blood pressure by Week 4, titration to a maximum dose of azilsartan medoxomil 80 mg and chlorthalidone 25 mg. Additional antihypertensive agents could be added as needed to achieve blood pressure control.		Participants in the United States: Olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg combination tablet, orally, once daily for up to 52 weeks. For participants who did not achieve target blood pressure by Week 4, titration to a maximum dose of Olmesartan medoxomil 40 mg and hydrochlorothiazide 25 mg. Participants in Europe: Olmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg combination tablet, orally, once daily for up to 52 weeks. For participants who did not achieve target blood pressure by Week 4, titration to a maximum dose of Olmesartan medoxomil 20 mg and hydrochlorothiazide 25 mg. Additional antihypertensive agents could be added as needed to achieve blood pressure control.
All Cause Mortality
	Azilsartan Medoxomil and Chlorthalidone		Olmesartan Medoxomil and Hydrochlorothiazide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Azilsartan Medoxomil and Chlorthalidone		Olmesartan Medoxomil and Hydrochlorothiazide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/418 (5.7%)		26/419 (6.2%)
Cardiac disorders
Angina pectoris	0/418 (0%)		2/419 (0.5%)
Atrial fibrillation	1/418 (0.2%)		1/419 (0.2%)
Cardiac arrest	1/418 (0.2%)		0/419 (0%)
Cardiogenic shock	1/418 (0.2%)		0/419 (0%)
Coronary artery disease	0/418 (0%)		1/419 (0.2%)
Mitral valve incompetence	1/418 (0.2%)		0/419 (0%)
Myocardial infarction	0/418 (0%)		1/419 (0.2%)
Congenital, familial and genetic disorders
Hydrocele	1/418 (0.2%)		0/419 (0%)
Ear and labyrinth disorders
Vertigo	0/418 (0%)		1/419 (0.2%)
Gastrointestinal disorders
Colitis ulcerative	1/418 (0.2%)		0/419 (0%)
Gastritis	0/418 (0%)		1/419 (0.2%)
Hemorrhoid	0/418 (0%)		1/419 (0.2%)
Pancreatitis acute	1/418 (0.2%)		0/419 (0%)
Rectal hemorrhage	0/418 (0%)		1/419 (0.2%)
General disorders
Non-cardiac chest pain	1/418 (0.2%)		2/419 (0.5%)
Drowning	1/418 (0.2%)		0/419 (0%)
Hepatobiliary disorders
Biliary colic	1/418 (0.2%)		0/419 (0%)
Cholelitiasis	1/418 (0.2%)		0/419 (0%)
Infections and infestations
Pneumonia	0/418 (0%)		2/419 (0.5%)
Septic shock	2/418 (0.5%)		0/419 (0%)
Bronchitis	1/418 (0.2%)		0/419 (0%)
Bronchopneumonia	1/418 (0.2%)		0/419 (0%)
Cellulitis	0/418 (0%)		1/419 (0.2%)
Diverticulitis	0/418 (0%)		1/419 (0.2%)
Endocarditis	1/418 (0.2%)		0/419 (0%)
Postoperative wound infection	1/418 (0.2%)		0/419 (0%)
Rectal abscess	0/418 (0%)		1/419 (0.2%)
Sepsis	1/418 (0.2%)		0/419 (0%)
Urinary tract infection	1/418 (0.2%)		0/419 (0%)
Injury, poisoning and procedural complications
Road traffic accident	1/418 (0.2%)		2/419 (0.5%)
Clavicle fracture	0/418 (0%)		1/419 (0.2%)
Contusion	1/418 (0.2%)		0/419 (0%)
Femur fracture	0/418 (0%)		1/419 (0.2%)
Fibula fracture	0/418 (0%)		1/419 (0.2%)
Gun shot wound	0/418 (0%)		1/419 (0.2%)
Head injury	1/418 (0.2%)		0/419 (0%)
Hip fracture	0/418 (0%)		1/419 (0.2%)
Joint dislocation	1/418 (0.2%)		0/419 (0%)
Rib fracture	0/418 (0%)		1/419 (0.2%)
Skeletal injury	1/418 (0.2%)		0/419 (0%)
Tibia fracture	0/418 (0%)		1/419 (0.2%)
Wound secretion	1/418 (0.2%)		0/419 (0%)
Investigations
Blood creatinine increased	0/418 (0%)		2/419 (0.5%)
Musculoskeletal and connective tissue disorders
Back pain	1/418 (0.2%)		1/419 (0.2%)
Intervertebral disc protrusion	2/418 (0.5%)		0/419 (0%)
Osteoarthritis	1/418 (0.2%)		1/419 (0.2%)
Lumbar spinal stenosis	1/418 (0.2%)		0/419 (0%)
Pseudarthrosis	1/418 (0.2%)		0/419 (0%)
Vertebral foraminal stenosis	1/418 (0.2%)		0/419 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder transitional cell carcinoma	0/418 (0%)		1/419 (0.2%)
Breast cancer	1/418 (0.2%)		0/419 (0%)
Breast cancer stage II	0/418 (0%)		1/419 (0.2%)
Malignant melanoma	1/418 (0.2%)		0/419 (0%)
Prostate cancer	1/418 (0.2%)		0/419 (0%)
Renal cancer	1/418 (0.2%)		0/419 (0%)
Nervous system disorders
Syncope	2/418 (0.5%)		0/419 (0%)
Loss of consciousness	1/418 (0.2%)		0/419 (0%)
Presyncope	0/418 (0%)		1/419 (0.2%)
Radicular syndrome	1/418 (0.2%)		0/419 (0%)
Transient ischaemic attack	0/418 (0%)		1/419 (0.2%)
Psychiatric disorders
Major depression	1/418 (0.2%)		0/419 (0%)
Renal and urinary disorders
Renal failure acute	0/418 (0%)		1/419 (0.2%)
Reproductive system and breast disorders
Rectocele	1/418 (0.2%)		0/419 (0%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	1/418 (0.2%)		1/419 (0.2%)
Pulmonary embolism	2/418 (0.5%)		0/419 (0%)
Bronchitis chronic	0/418 (0%)		1/419 (0.2%)
Interstitial lung disease	0/418 (0%)		1/419 (0.2%)
Pulmonary mass	0/418 (0%)		1/419 (0.2%)
Respiratory failure	0/418 (0%)		1/419 (0.2%)
Vascular disorders
Arteriosclerosis	0/418 (0%)		1/419 (0.2%)
Orthostatic hypotension	1/418 (0.2%)		0/419 (0%)
Other (Not Including Serious) Adverse Events
	Azilsartan Medoxomil and Chlorthalidone		Olmesartan Medoxomil and Hydrochlorothiazide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	217/418 (51.9%)		183/419 (43.7%)
Gastrointestinal disorders
Diarrhoea	20/418 (4.8%)		21/419 (5%)
Nausea	20/418 (4.8%)		21/419 (5%)
General disorders
Fatigue	21/418 (5%)		17/419 (4.1%)
Infections and infestations
Nasopharyngitis	51/418 (12.2%)		48/419 (11.5%)
Upper respiratory tract infection	20/418 (4.8%)		27/419 (6.4%)
Investigations
Blood creatinine increased	90/418 (21.5%)		35/419 (8.4%)
Nervous system disorders
Dizziness	68/418 (16.3%)		53/419 (12.6%)
Headache	31/418 (7.4%)		46/419 (11%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.