Trial Outcomes & Findings for Long-Term Safety of Azilsartan Medoxomil and Chlorthalidone Compared to Olmesartan Medoxomil and Hydrochlorothiazide in Participants With Hypertension and Kidney Disease (NCT NCT01309828)

Last Updated: 2013-12-13

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

153 participants

Primary outcome timeframe

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).

Results posted on

2013-12-13

Participant Flow

Participants took part in the study at 46 investigative sites in the United States, Germany, Latvia, Lithuania, Poland, Slovakia, and the Ukraine from 02 March 2011 to 11 October 2012.

Participants with high blood pressure and moderate renal impairment were enrolled in 1 of 2 once-daily (QD) treatment groups.

Participant milestones

Participant milestones
Measure	Azilsartan Medoxomil + Chlorthalidone United States and Europe: Azilsartan medoxomil 20 mg plus chlorthalidone 12.5 mg fixed dose combination tablets (TAK-491CLD), titrated up to azilsartan medoxomil 40 mg plus chlorthalidone 25 mg orally, once daily for up to 52 weeks.	Olmesartan Medoxomil + Hydrochlorothiazide United States: Olmesartan medoxomil 20 mg plus hydrochlorothiazide 12.5 mg fixed dose combination tablets (OLM/HCTZ), 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.
Overall Study STARTED	77	76
Overall Study COMPLETED	61	60
Overall Study NOT COMPLETED	16	16

Reasons for withdrawal

Reasons for withdrawal
Measure	Azilsartan Medoxomil + Chlorthalidone United States and Europe: Azilsartan medoxomil 20 mg plus chlorthalidone 12.5 mg fixed dose combination tablets (TAK-491CLD), titrated up to azilsartan medoxomil 40 mg plus chlorthalidone 25 mg orally, once daily for up to 52 weeks.	Olmesartan Medoxomil + Hydrochlorothiazide United States: Olmesartan medoxomil 20 mg plus hydrochlorothiazide 12.5 mg fixed dose combination tablets (OLM/HCTZ), 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.
Overall Study Adverse Event	10	11
Overall Study Voluntary Withdrawal	5	4
Overall Study Major Protocol Deviation	0	1
Overall Study Other	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Azilsartan Medoxomil + Chlorthalidone n=77 Participants United States and Europe: Azilsartan medoxomil 20 mg plus chlorthalidone 12.5 mg fixed dose combination tablets (TAK-491CLD), titrated up to azilsartan medoxomil 40 mg plus chlorthalidone 25 mg orally, once daily for up to 52 weeks.	Olmesartan Medoxomil + Hydrochlorothiazide n=76 Participants United States: Olmesartan medoxomil 20 mg plus hydrochlorothiazide 12.5 mg fixed dose combination tablets (OLM/HCTZ), 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.	Total n=153 Participants Total of all reporting groups
Age Continuous	67.9 years STANDARD_DEVIATION 8.24 • n=5 Participants	68.9 years STANDARD_DEVIATION 9.10 • n=7 Participants	68.4 years STANDARD_DEVIATION 8.66 • n=5 Participants
Age, Customized <45 years	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Age, Customized ≥45 to <65 years	21 participants n=5 Participants	18 participants n=7 Participants	39 participants n=5 Participants
Age, Customized ≥65 to <75 years	38 participants n=5 Participants	39 participants n=7 Participants	77 participants n=5 Participants
Age, Customized ≥75 years	18 participants n=5 Participants	18 participants n=7 Participants	36 participants n=5 Participants
Sex: Female, Male Female	45 Participants n=5 Participants	31 Participants n=7 Participants	76 Participants n=5 Participants
Sex: Female, Male Male	32 Participants n=5 Participants	45 Participants n=7 Participants	77 Participants n=5 Participants
Race/Ethnicity, Customized White	57 participants n=5 Participants	62 participants n=7 Participants	119 participants n=5 Participants
Race/Ethnicity, Customized Black or African American	18 participants n=5 Participants	12 participants n=7 Participants	30 participants n=5 Participants
Race/Ethnicity, Customized Asian	2 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants
Region of Enrollment Germany	10 participants n=5 Participants	9 participants n=7 Participants	19 participants n=5 Participants
Region of Enrollment Latvia	4 participants n=5 Participants	5 participants n=7 Participants	9 participants n=5 Participants
Region of Enrollment Lithuania	5 participants n=5 Participants	2 participants n=7 Participants	7 participants n=5 Participants
Region of Enrollment Poland	7 participants n=5 Participants	6 participants n=7 Participants	13 participants n=5 Participants
Region of Enrollment Slovakia	6 participants n=5 Participants	6 participants n=7 Participants	12 participants n=5 Participants
Region of Enrollment Ukraine	6 participants n=5 Participants	11 participants n=7 Participants	17 participants n=5 Participants
Region of Enrollment United States	39 participants n=5 Participants	37 participants n=7 Participants	76 participants n=5 Participants
Weight	83.54 kg STANDARD_DEVIATION 17.894 • n=5 Participants	90.14 kg STANDARD_DEVIATION 21.587 • n=7 Participants	86.82 kg STANDARD_DEVIATION 20.025 • n=5 Participants
Height	165.7 cm STANDARD_DEVIATION 9.65 • n=5 Participants	168.7 cm STANDARD_DEVIATION 9.48 • n=7 Participants	167.2 cm STANDARD_DEVIATION 9.65 • n=5 Participants
Body Mass Index (BMI)	30.44 kg/m^2 STANDARD_DEVIATION 6.226 • n=5 Participants	31.57 kg/m^2 STANDARD_DEVIATION 6.524 • n=7 Participants	31.00 kg/m^2 STANDARD_DEVIATION 6.380 • n=5 Participants
Smoking Classification Never Smoked	46 participants n=5 Participants	40 participants n=7 Participants	86 participants n=5 Participants
Smoking Classification Current Smoker	11 participants n=5 Participants	11 participants n=7 Participants	22 participants n=5 Participants
Smoking Classification Ex-smoker	20 participants n=5 Participants	25 participants n=7 Participants	45 participants n=5 Participants
Diabetes Status Yes	33 participants n=5 Participants	32 participants n=7 Participants	65 participants n=5 Participants
Diabetes Status No	44 participants n=5 Participants	44 participants n=7 Participants	88 participants n=5 Participants
Estimated glomerular filtration rate (eGFR)	48.25 mL/min/1.73 m^2 STANDARD_DEVIATION 10.205 • n=5 Participants	47.73 mL/min/1.73 m^2 STANDARD_DEVIATION 8.761 • n=7 Participants	47.99 mL/min/1.73 m^2 STANDARD_DEVIATION 9.487 • n=5 Participants
Baseline estimated glomerular filtration rate (eGFR) category ≥45 and <60 mL/min/1.73 m^2	40 participants n=5 Participants	39 participants n=7 Participants	79 participants n=5 Participants
Baseline estimated glomerular filtration rate (eGFR) category ≥30 and <45 mL/min/1.73 m^2	31 participants n=5 Participants	33 participants n=7 Participants	64 participants n=5 Participants
Baseline estimated glomerular filtration rate (eGFR) category ≥60 mL/min/1.73 m^2	6 participants n=5 Participants	4 participants n=7 Participants	10 participants n=5 Participants
Systolic blood pressure	151.1 mm Hg STANDARD_DEVIATION 10.30 • n=5 Participants	149.0 mm Hg STANDARD_DEVIATION 7.80 • n=7 Participants	150.1 mm Hg STANDARD_DEVIATION 9.18 • n=5 Participants
Diastolic blood pressure	84.8 mm Hg STANDARD_DEVIATION 10.31 • n=5 Participants	84.7 mm Hg STANDARD_DEVIATION 9.68 • n=7 Participants	84.7 mm Hg STANDARD_DEVIATION 9.97 • n=5 Participants
Systolic blood pressure categories <140 mm Hg	11 participants n=5 Participants	10 participants n=7 Participants	21 participants n=5 Participants
Systolic blood pressure categories ≥140 to <160 mm Hg	60 participants n=5 Participants	64 participants n=7 Participants	124 participants n=5 Participants
Systolic blood pressure categories ≥160 to <180 mm Hg	5 participants n=5 Participants	2 participants n=7 Participants	7 participants n=5 Participants
Systolic blood pressure categories ≥180 mm Hg	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Diastolic blood pressure categories <90 mm Hg	52 participants n=5 Participants	50 participants n=7 Participants	102 participants n=5 Participants
Diastolic blood pressure categories ≥90 mm Hg	25 participants n=5 Participants	26 participants n=7 Participants	51 participants n=5 Participants

PRIMARY outcome

Timeframe: 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).

Population: Safety analysis set - All participants who received at least 1 dose of open-label study drug.

Outcome measures

Outcome measures
Measure	Azilsartan Medoxomil + Chlorthalidone n=77 Participants United States and Europe: Azilsartan medoxomil 20 mg plus chlorthalidone 12.5 mg fixed dose combination tablets (TAK-491CLD), titrated up to azilsartan medoxomil 40 mg plus chlorthalidone 25 mg orally, once daily for up to 52 weeks.	Olmesartan Medoxomil + Hydrochlorothiazide n=76 Participants United States: Olmesartan medoxomil 20 mg plus hydrochlorothiazide 12.5 mg fixed dose combination tablets (OLM/HCTZ), 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.
Number of Participants With at Least 1 Adverse Event (AE) Adverse Events	68 participants	58 participants
Number of Participants With at Least 1 Adverse Event (AE) Adverse Events Leading to Discontinuation	17 participants	15 participants
Number of Participants With at Least 1 Adverse Event (AE) Serious Adverse Events	8 participants	9 participants
Number of Participants With at Least 1 Adverse Event (AE) Serious Adverse Events Leading to Discontinuation	5 participants	4 participants
Number of Participants With at Least 1 Adverse Event (AE) Death	0 participants	1 participants

SECONDARY outcome

Timeframe: Week 52

Population: Full analysis set participants (all randomized participants who received at least 1 dose of open-label study drug) with both Baseline and a post-baseline value; last observation carried forward was used.

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.

Outcome measures

Outcome measures
Measure	Azilsartan Medoxomil + Chlorthalidone n=75 Participants United States and Europe: Azilsartan medoxomil 20 mg plus chlorthalidone 12.5 mg fixed dose combination tablets (TAK-491CLD), titrated up to azilsartan medoxomil 40 mg plus chlorthalidone 25 mg orally, once daily for up to 52 weeks.	Olmesartan Medoxomil + Hydrochlorothiazide n=74 Participants United States: Olmesartan medoxomil 20 mg plus hydrochlorothiazide 12.5 mg fixed dose combination tablets (OLM/HCTZ), 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.
Percentage of Participants at Final Visit Who Achieve Target Systolic Blood Pressure <130 mm Hg	69.3 percentage of participants Interval 57.6 to 79.5	78.4 percentage of participants Interval 67.3 to 87.1

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Azilsartan Medoxomil + Chlorthalidone n=75 Participants United States and Europe: Azilsartan medoxomil 20 mg plus chlorthalidone 12.5 mg fixed dose combination tablets (TAK-491CLD), titrated up to azilsartan medoxomil 40 mg plus chlorthalidone 25 mg orally, once daily for up to 52 weeks.	Olmesartan Medoxomil + Hydrochlorothiazide n=74 Participants United States: Olmesartan medoxomil 20 mg plus hydrochlorothiazide 12.5 mg fixed dose combination tablets (OLM/HCTZ), 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.
Percentage of Participants at Final Visit Who Achieved Target Diastolic Blood Pressure <80 mm Hg	80.0 percentage of participants Interval 69.2 to 88.4	87.8 percentage of participants Interval 78.2 to 94.3

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Azilsartan Medoxomil + Chlorthalidone n=75 Participants United States and Europe: Azilsartan medoxomil 20 mg plus chlorthalidone 12.5 mg fixed dose combination tablets (TAK-491CLD), titrated up to azilsartan medoxomil 40 mg plus chlorthalidone 25 mg orally, once daily for up to 52 weeks.	Olmesartan Medoxomil + Hydrochlorothiazide n=74 Participants United States: Olmesartan medoxomil 20 mg plus hydrochlorothiazide 12.5 mg fixed dose combination tablets (OLM/HCTZ), 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.
Percentage of Participants at Final Visit Who Achieved Both a Clinic Systolic and Diastolic Blood Pressure Response	58.7 percentage of participants Interval 46.7 to 69.9	73.0 percentage of participants Interval 61.4 to 82.6

Adverse Events

Azilsartan Medoxomil + Chlorthalidone

Serious events: 8 serious events

Other events: 52 other events

Deaths: 0 deaths

Olmesartan Medoxomil + Hydrochlorothiazide

Serious events: 9 serious events

Other events: 41 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Azilsartan Medoxomil + Chlorthalidone n=77 participants at risk United States and Europe: Azilsartan medoxomil 20 mg plus chlorthalidone 12.5 mg fixed dose combination tablets (TAK-491CLD), titrated up to azilsartan medoxomil 40 mg plus chlorthalidone 25 mg orally, once daily for up to 52 weeks.	Olmesartan Medoxomil + Hydrochlorothiazide n=76 participants at risk United States: Olmesartan medoxomil 20 mg plus hydrochlorothiazide 12.5 mg fixed dose combination tablets (OLM/HCTZ), 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.
Gastrointestinal disorders Diarrhoea	1.3% 1/77 • 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). 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.	5.3% 4/76 • 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). 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.
General disorders Asthenia	3.9% 3/77 • 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). 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.	5.3% 4/76 • 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). 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.
Infections and infestations Bronchitis	5.2% 4/77 • 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). 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.	3.9% 3/76 • 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). 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.
Infections and infestations Pharygitis	0.00% 0/77 • 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). 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.	5.3% 4/76 • 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). 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.
Investigations Blood creatinine increased	44.2% 34/77 • 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). 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.	38.2% 29/76 • 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). 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.
Metabolism and nutrition disorders Hyperuricaemia	3.9% 3/77 • 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). 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.	5.3% 4/76 • 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). 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.
Metabolism and nutrition disorders Hypokalaemia	5.2% 4/77 • 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). 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.	3.9% 3/76 • 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). 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.
Nervous system disorders Dizziness	7.8% 6/77 • 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). 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.	6.6% 5/76 • 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). 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.
Nervous system disorders Headache	10.4% 8/77 • 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). 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.	2.6% 2/76 • 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). 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.
Vascular disorders Hypotension	5.2% 4/77 • 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). 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.	3.9% 3/76 • 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). 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.

Additional Information

Medical Director, Clinical Science

Takeda

Phone: 800-778-2860

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	Azilsartan Medoxomil + Chlorthalidone n=77 participants at risk United States and Europe: Azilsartan medoxomil 20 mg plus chlorthalidone 12.5 mg fixed dose combination tablets (TAK-491CLD), titrated up to azilsartan medoxomil 40 mg plus chlorthalidone 25 mg orally, once daily for up to 52 weeks.	Olmesartan Medoxomil + Hydrochlorothiazide n=76 participants at risk United States: Olmesartan medoxomil 20 mg plus hydrochlorothiazide 12.5 mg fixed dose combination tablets (OLM/HCTZ), 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.
Cardiac disorders Angina unstable	2.6% 2/77 • 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). 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.	1.3% 1/76 • 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). 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.
Cardiac disorders Coronary artery disease	2.6% 2/77 • 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). 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.	1.3% 1/76 • 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). 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.
Cardiac disorders Angina pectoris	0.00% 0/77 • 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). 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.	2.6% 2/76 • 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). 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.
Cardiac disorders Atrial tachycardia	0.00% 0/77 • 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). 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.	1.3% 1/76 • 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). 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.
Cardiac disorders Bradycardia	0.00% 0/77 • 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). 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.	1.3% 1/76 • 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). 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.
Gastrointestinal disorders Vomiting	0.00% 0/77 • 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). 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.	1.3% 1/76 • 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). 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.
General disorders Device malfunction	1.3% 1/77 • 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). 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.	0.00% 0/76 • 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). 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.
Infections and infestations Gastroenteritis salmonella	1.3% 1/77 • 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). 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.	0.00% 0/76 • 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). 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.
Injury, poisoning and procedural complications Concussion	0.00% 0/77 • 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). 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.	1.3% 1/76 • 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). 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.
Injury, poisoning and procedural complications Hip fracture	0.00% 0/77 • 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). 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.	1.3% 1/76 • 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). 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.
Metabolism and nutrition disorders Diabetes mellitus	0.00% 0/77 • 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). 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.	1.3% 1/76 • 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). 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pituitary tumour recurrent	0.00% 0/77 • 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). 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.	1.3% 1/76 • 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). 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.
Nervous system disorders Cervicobrachial syndrome	1.3% 1/77 • 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). 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.	0.00% 0/76 • 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). 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.
Nervous system disorders Hypoglycaemic coma	1.3% 1/77 • 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). 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.	0.00% 0/76 • 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). 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.
Renal and urinary disorders Renal failure acute	1.3% 1/77 • 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). 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.	0.00% 0/76 • 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). 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.
Respiratory, thoracic and mediastinal disorders Pulmonary artery thrombosis	0.00% 0/77 • 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). 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.	1.3% 1/76 • 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). 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.