Trial Outcomes & Findings for International Multicenter, Observational, Non-Interventional Prospective Study of Azilsartan Medoxomil in Participants With Arterial Hypertension Who Are Overweight or Obese in the Russian Federation and The Republic of Kazakhstan (NCT NCT02756819)

NCT ID: NCT02756819

Last Updated: 2019-11-20

Results Overview

The change in clinic sitting SBP measured at Month 6 relative to baseline.

• Recruitment status: COMPLETED
• Target enrollment: 1945 participants
• Primary outcome timeframe: Baseline and Month 6
• Results posted on: 2019-11-20

Participant Flow

Participants took part at 65 sites in the study in Russian Federation and the Republic of Kazakhstan from 18-Jul-2016 to 08-May-2018.

Participants with a diagnosis of hypertension and who were obese, prescribed azilsartan medoxomil in accordance with local summary of product characteristics (SmPC) were enrolled in this observational study.

Participant milestones

Measure	Azilsartan Medoxomil Overweight or obese participants with hypertension who received azilsartan medoxomil tablets, orally, as prescribed by physician according to local SmPC were observed for approximately 6 months.
Overall Study STARTED	1945
Overall Study Per-protocol Set (PPS)	1724
Overall Study Safety Analysis Set (SAS)	1934
Overall Study COMPLETED	1893
Overall Study NOT COMPLETED	52

Reasons for withdrawal

Measure	Azilsartan Medoxomil Overweight or obese participants with hypertension who received azilsartan medoxomil tablets, orally, as prescribed by physician according to local SmPC were observed for approximately 6 months.
Overall Study Lost for observation	23
Overall Study Patient's unwillingness	16
Overall Study Insufficient efficacy	2
Overall Study Adverse Event	2
Overall Study Reason not Specified	9

Baseline Characteristics

Number analyzed is the number of participants with data available for analysis at the given timepoint.

Baseline characteristics by cohort

Measure	Azilsartan Medoxomil n=1945 Participants Overweight or obese participants with hypertension who received azilsartan medoxomil tablets, orally, as prescribed by physician according to local SmPC were observed for approximately 6 months.
Age, Continuous	55.2 years STANDARD_DEVIATION 11.9 • n=1944 Participants • Number analyzed is the number of participants with data available for analysis at the given timepoint.
Sex: Female, Male Female	1103 Participants n=1945 Participants
Sex: Female, Male Male	842 Participants n=1945 Participants
Race/Ethnicity, Customized European	1787 Participants n=1945 Participants
Race/Ethnicity, Customized Asian	158 Participants n=1945 Participants
Region of Enrollment Russia	1759 Participants n=1945 Participants
Region of Enrollment Kazakhstan	186 Participants n=1945 Participants

PRIMARY outcome

Timeframe: Baseline and Month 6

Population: Full analysis set (FAS) included all participants who were enrolled and received azilsartan medoxomil (Edarbi®) therapy. Number analyzed is the number of participants with data available for analysis at the given timepoint.

The change in clinic sitting SBP measured at Month 6 relative to baseline.

Outcome measures

Measure	Azilsartan Medoxomil n=1945 Participants Overweight or obese participants with hypertension who received azilsartan medoxomil tablets, orally, as prescribed by physician according to local SmPC were observed for approximately 6 months.
Change From Baseline in Clinic Systolic Blood Pressure (SBP) at Month 6 Change from baseline at Month 6	-30.5 mmHg Standard Deviation 13.4
Change From Baseline in Clinic Systolic Blood Pressure (SBP) at Month 6 Baseline	156.8 mmHg Standard Deviation 11.8

SECONDARY outcome

Timeframe: Baseline and Month 6

Population: FAS included all participants who were enrolled and received azilsartan medoxomil (Edarbi®) therapy. Number analyzed is the number of participants with data available for analysis at the given timepoint.

The change in clinic sitting DBP measured at Month 6 relative to baseline.

Outcome measures

Measure	Azilsartan Medoxomil n=1945 Participants Overweight or obese participants with hypertension who received azilsartan medoxomil tablets, orally, as prescribed by physician according to local SmPC were observed for approximately 6 months.
Change From Baseline in Clinic Diastolic Blood Pressure (DBP) at Month 6	-14 mmHg Standard Deviation 9.4

SECONDARY outcome

Timeframe: Month 6

Population: Participants from FAS, all participants who were enrolled and received azilsartan medoxomil (Edarbi®) therapy with data available for analysis at the given time point.

Response was defined as a decrease of SBP ≥20 mm Hg or a decrease of DBP ≥10 mm Hg.

Outcome measures

Measure	Azilsartan Medoxomil n=1890 Participants Overweight or obese participants with hypertension who received azilsartan medoxomil tablets, orally, as prescribed by physician according to local SmPC were observed for approximately 6 months.
Percentage of Participants With Response at Month 6	92.6 percentage of participants Interval 91.3 to 93.7

SECONDARY outcome

Timeframe: Month 6

Population: Participants from FAS, all participants who were enrolled and received azilsartan medoxomil (Edarbi®) therapy with data available for analysis at the given time point.

Outcome measures

Measure	Azilsartan Medoxomil n=1890 Participants Overweight or obese participants with hypertension who received azilsartan medoxomil tablets, orally, as prescribed by physician according to local SmPC were observed for approximately 6 months.
Percentage of Participants Who Achieved Target Blood Pressure (BP) SBP<140 mm Hg and DBP<90 mm Hg	86.4 percentage of participants Interval 84.8 to 87.9

SECONDARY outcome

Timeframe: Baseline and Month 6

Population: FAS included all participants who were enrolled and received azilsartan medoxomil (Edarbi®) therapy. Number analyzed is the number of participants with data available for analysis at the given timepoint.

The change in clinic sitting SBP measured at Month 6 relative to baseline. Subgroups included overweight, obesity I (basic metabolic rate [BMI] 30-34.9), class II (BMI 35-39.9) and class III (BMI ≥ 40), impaired glucose tolerance, normal glucose metabolism, diabetes mellitus (Yes/No), metabolic syndrome, neither diabetes mellitus (DM) nor metabolic syndrome.

Outcome measures

Measure	Azilsartan Medoxomil n=1945 Participants Overweight or obese participants with hypertension who received azilsartan medoxomil tablets, orally, as prescribed by physician according to local SmPC were observed for approximately 6 months.
Change From Baseline in Clinic Systolic Blood Pressure (SBP) in Subgroups of Participants at Month 6 Change at Week 6, BMI (Obesity class II)	-31.5 mmHg Standard Deviation 12.5
Change From Baseline in Clinic Systolic Blood Pressure (SBP) in Subgroups of Participants at Month 6 Change at Week 6, Overweight	-30.2 mmHg Standard Deviation 13.6
Change From Baseline in Clinic Systolic Blood Pressure (SBP) in Subgroups of Participants at Month 6 Change at Week 6, BMI (Obesity class I)	-30.6 mmHg Standard Deviation 13.2
Change From Baseline in Clinic Systolic Blood Pressure (SBP) in Subgroups of Participants at Month 6 Change at Week 6, BMI (Obesity class III)	-27.1 mmHg Standard Deviation 15.8
Change From Baseline in Clinic Systolic Blood Pressure (SBP) in Subgroups of Participants at Month 6 Change at Week 6, Normal glucose metabolism	-30.5 mmHg Standard Deviation 13.3
Change From Baseline in Clinic Systolic Blood Pressure (SBP) in Subgroups of Participants at Month 6 Change at Week 6, Impaired glucose tolerance	-30.1 mmHg Standard Deviation 13.2
Change From Baseline in Clinic Systolic Blood Pressure (SBP) in Subgroups of Participants at Month 6 Change at Week 6, Diabetes Mellitus (No)	-30.6 mmHg Standard Deviation 13.3
Change From Baseline in Clinic Systolic Blood Pressure (SBP) in Subgroups of Participants at Month 6 Change at Week 6, Diabetes Mellitus (Yes)	-30.5 mmHg Standard Deviation 13.7
Change From Baseline in Clinic Systolic Blood Pressure (SBP) in Subgroups of Participants at Month 6 Change at Week 6,Neither DM nor Metabolic Syndrome	-29.4 mmHg Standard Deviation 13.6
Change From Baseline in Clinic Systolic Blood Pressure (SBP) in Subgroups of Participants at Month 6 Change at Week 6, Metabolic syndrome	-31.2 mmHg Standard Deviation 13.1

SECONDARY outcome

Timeframe: Baseline and Month 6

Population: FAS included all participants who were enrolled and received azilsartan medoxomil (Edarbi®) therapy. Number analyzed is the number of participants with data available for analysis at the given timepoint.

The change in clinic sitting DBP measured at Month 6 relative to baseline. Subgroups included overweight, obesity I (basic metabolic rate [BMI] 30-34.9), class II (BMI 35-39.9) and class III (BMI ≥ 40), impaired glucose tolerance, normal glucose metabolism, diabetes mellitus (Yes/No), metabolic syndrome, neither diabetes mellitus nor metabolic syndrome.

Outcome measures

Measure	Azilsartan Medoxomil n=1945 Participants Overweight or obese participants with hypertension who received azilsartan medoxomil tablets, orally, as prescribed by physician according to local SmPC were observed for approximately 6 months.
Change From Baseline in Clinic Diastolic Blood Pressure (DBP) in Subgroups of Participants at Month 6 Change at Week 6, BMI (Obesity class II)	-14.3 percentage of participants Standard Deviation 9.4
Change From Baseline in Clinic Diastolic Blood Pressure (DBP) in Subgroups of Participants at Month 6 Change at Week 6, BMI (Obesity class III)	-12.6 percentage of participants Standard Deviation 11
Change From Baseline in Clinic Diastolic Blood Pressure (DBP) in Subgroups of Participants at Month 6 Change at Week 6, Normal glucose metabolism	-14 percentage of participants Standard Deviation 9.4
Change From Baseline in Clinic Diastolic Blood Pressure (DBP) in Subgroups of Participants at Month 6 Change at Week 6, Diabetes Mellitus (No)	-13.9 percentage of participants Standard Deviation 9.2
Change From Baseline in Clinic Diastolic Blood Pressure (DBP) in Subgroups of Participants at Month 6 Change at Week 6, Diabetes Mellitus (Yes)	-13.7 percentage of participants Standard Deviation 10.6
Change From Baseline in Clinic Diastolic Blood Pressure (DBP) in Subgroups of Participants at Month 6 Change at Week 6, Overweight	-13.9 percentage of participants Standard Deviation 9.5
Change From Baseline in Clinic Diastolic Blood Pressure (DBP) in Subgroups of Participants at Month 6 Change at Week 6, BMI (Obesity class I)	-14 percentage of participants Standard Deviation 9.3
Change From Baseline in Clinic Diastolic Blood Pressure (DBP) in Subgroups of Participants at Month 6 Change at Week 6, Impaired glucose tolerance	-14.2 percentage of participants Standard Deviation 8.6
Change From Baseline in Clinic Diastolic Blood Pressure (DBP) in Subgroups of Participants at Month 6 Change at Week 6,Neither DM nor metabolic syndrome	-13.4 percentage of participants Standard Deviation 9.5
Change From Baseline in Clinic Diastolic Blood Pressure (DBP) in Subgroups of Participants at Month 6 Change at Week 6, Metabolic syndrome	-14.4 percentage of participants Standard Deviation 9.1

SECONDARY outcome

Timeframe: Month 6

Population: FAS included all participants who were enrolled and received azilsartan medoxomil (Edarbi®) therapy. Number analyzed is the number of participants with data available for analysis at the given timepoint.

Target BP was SBP<140 mm Hg and DBP<90 mm Hg. Subgroups included BMI, overweight, Obesity I (BMI 30-34.9), class II (BMI 35-39.9) and class III (BMI ≥ 40), impaired glucose tolerance (Yes/No), metabolic syndrome (Yes/No) and diabetes mellitus (Yes/No).

Outcome measures

Measure	Azilsartan Medoxomil n=1945 Participants Overweight or obese participants with hypertension who received azilsartan medoxomil tablets, orally, as prescribed by physician according to local SmPC were observed for approximately 6 months.
Percentage of Participants Who Achieved Target Blood Pressure (BP) in Subgroups of Participants at Month 6 Impaired glucose tolerance	80.5 percentage of participants Interval 74.4 to 85.7
Percentage of Participants Who Achieved Target Blood Pressure (BP) in Subgroups of Participants at Month 6 Neither diabetes mellitus nor metabolic syndrome	88.4 percentage of participants Interval 85.8 to 90.7
Percentage of Participants Who Achieved Target Blood Pressure (BP) in Subgroups of Participants at Month 6 BMI (Overweight)	89.8 percentage of participants Interval 87.1 to 92.1
Percentage of Participants Who Achieved Target Blood Pressure (BP) in Subgroups of Participants at Month 6 BMI (Obesity Class I)	86.7 percentage of participants Interval 84.3 to 88.9
Percentage of Participants Who Achieved Target Blood Pressure (BP) in Subgroups of Participants at Month 6 BMI (Obesity Class II)	82.5 percentage of participants Interval 77.9 to 86.5
Percentage of Participants Who Achieved Target Blood Pressure (BP) in Subgroups of Participants at Month 6 BMI (Obesity Class III)	74.2 percentage of participants Interval 64.1 to 82.7
Percentage of Participants Who Achieved Target Blood Pressure (BP) in Subgroups of Participants at Month 6 Normal glucose metabolism	88 percentage of participants Interval 86.2 to 89.6
Percentage of Participants Who Achieved Target Blood Pressure (BP) in Subgroups of Participants at Month 6 Diabetes Mellitus (No)	86.4 percentage of participants Interval 84.6 to 88.1
Percentage of Participants Who Achieved Target Blood Pressure (BP) in Subgroups of Participants at Month 6 Diabetes Mellitus (Yes)	81.7 percentage of participants Interval 76.1 to 86.5
Percentage of Participants Who Achieved Target Blood Pressure (BP) in Subgroups of Participants at Month 6 Metabolic syndrome	86.1 percentage of participants Interval 83.7 to 88.2

Adverse Events

Azilsartan Medoxomil

Serious events: 6 serious events

Other events: 39 other events

Deaths: 0 deaths

Serious adverse events

Measure	Azilsartan Medoxomil n=1934 participants at risk Overweight or obese participants with hypertension who received azilsartan medoxomil tablets, orally, as prescribed by physician according to local SmPC were observed for approximately 6 months.
Skin and subcutaneous tissue disorders Angioedema	0.05% 1/1934 • Baseline up to Month 6 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. Safety population included all participants who received at least one dose of study treatment and had any follow-up data.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.05% 1/1934 • Baseline up to Month 6 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. Safety population included all participants who received at least one dose of study treatment and had any follow-up data.
Ear and labyrinth disorders Deafness neurosensory	0.05% 1/1934 • Baseline up to Month 6 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. Safety population included all participants who received at least one dose of study treatment and had any follow-up data.
Injury, poisoning and procedural complications Skull fracture	0.05% 1/1934 • Baseline up to Month 6 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. Safety population included all participants who received at least one dose of study treatment and had any follow-up data.
Gastrointestinal disorders Pancreatitis	0.05% 1/1934 • Baseline up to Month 6 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. Safety population included all participants who received at least one dose of study treatment and had any follow-up data.
Vascular disorders Hypertension	0.05% 1/1934 • Baseline up to Month 6 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. Safety population included all participants who received at least one dose of study treatment and had any follow-up data.

Other adverse events

Measure	Azilsartan Medoxomil n=1934 participants at risk Overweight or obese participants with hypertension who received azilsartan medoxomil tablets, orally, as prescribed by physician according to local SmPC were observed for approximately 6 months.
Vascular disorders Hypotension	0.72% 14/1934 • Baseline up to Month 6 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. Safety population included all participants who received at least one dose of study treatment and had any follow-up data.
Vascular disorders Hypertension	0.21% 4/1934 • Baseline up to Month 6 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. Safety population included all participants who received at least one dose of study treatment and had any follow-up data.
Nervous system disorders Dizziness	0.10% 2/1934 • Baseline up to Month 6 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. Safety population included all participants who received at least one dose of study treatment and had any follow-up data.
Metabolism and nutrition disorders Dyslipidaemia	0.10% 2/1934 • Baseline up to Month 6 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. Safety population included all participants who received at least one dose of study treatment and had any follow-up data.
Cardiac disorders Left ventricular hypertrophy	0.10% 2/1934 • Baseline up to Month 6 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. Safety population included all participants who received at least one dose of study treatment and had any follow-up data.
Metabolism and nutrition disorders Hyperglycaemia	0.05% 1/1934 • Baseline up to Month 6 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. Safety population included all participants who received at least one dose of study treatment and had any follow-up data.
Cardiac disorders Palpitations	0.05% 1/1934 • Baseline up to Month 6 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. Safety population included all participants who received at least one dose of study treatment and had any follow-up data.
Investigations Blood cholesterol increased	0.05% 1/1934 • Baseline up to Month 6 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. Safety population included all participants who received at least one dose of study treatment and had any follow-up data.
Investigations Blood pressure decreased	0.10% 2/1934 • Baseline up to Month 6 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. Safety population included all participants who received at least one dose of study treatment and had any follow-up data.
Gastrointestinal disorders Nausea	0.05% 1/1934 • Baseline up to Month 6 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. Safety population included all participants who received at least one dose of study treatment and had any follow-up data.
Gastrointestinal disorders Pancreatitis	0.05% 1/1934 • Baseline up to Month 6 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. Safety population included all participants who received at least one dose of study treatment and had any follow-up data.
Infections and infestations Tracheitis	0.05% 1/1934 • Baseline up to Month 6 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. Safety population included all participants who received at least one dose of study treatment and had any follow-up data.
Infections and infestations Upper respiratory tract infection	0.05% 1/1934 • Baseline up to Month 6 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. Safety population included all participants who received at least one dose of study treatment and had any follow-up data.
General disorders Asthenia	0.05% 1/1934 • Baseline up to Month 6 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. Safety population included all participants who received at least one dose of study treatment and had any follow-up data.
Nervous system disorders Headache	0.10% 2/1934 • Baseline up to Month 6 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. Safety population included all participants who received at least one dose of study treatment and had any follow-up data.
Metabolism and nutrition disorders Hypercholesterolaemia	0.05% 1/1934 • Baseline up to Month 6 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. Safety population included all participants who received at least one dose of study treatment and had any follow-up data.
General disorders Drug effect increased	0.05% 1/1934 • Baseline up to Month 6 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. Safety population included all participants who received at least one dose of study treatment and had any follow-up data.
General disorders Drug ineffective	0.05% 1/1934 • Baseline up to Month 6 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. Safety population included all participants who received at least one dose of study treatment and had any follow-up data.

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: trialdisclosures@takeda.com

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