A Study to Explore the Effects of Azilsartan Compared to Telmisartan on Insulin Resistance of Patients With Essential Hypertension on Type 2 Diabetes Mellitus by HOMA-R

Study Overview
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Brief Summary
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Multicenter, randomized, open-label, parallel-group exploratory study to explore the effects of azilsartan (Azirva), compared with telmisartan, on insulin resistance in participants with essential hypertension complicated by type 2 diabetes mellitus

Detailed Description
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The primary objective of the present study is to explore the effects of azilsartan 20 mg, compared with telmisartan 40 mg, once daily orally for 12 weeks on insulin resistance in participants with essential hypertension complicated by type 2 diabetes mellitus.

Official Title
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A Study to Explore the Effects of Azilsartan Compared to Telmisartan on Insulin Resistance of Patients With Essential Hypertension on Type 2 Diabetes Mellitus by HOMA-R

Conditions
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Essential Hypertension Complicated by Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Azilsartan
* Drug: Telmisartan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The participant was given the diagnosis of grade I or II essential hypertension and was judged by the principal investigator or investigator that they can be appropriately treated with azilsartan 20 mg and telmisartan 40 mg. Sitting systolic blood pressure of ≥ 130 mmHg and < 180 mmHg or sitting diastolic blood pressure of ≥ 80 mmHg and < 110 mmHg at the start of the treatment period (Week 0) Sitting blood pressure will be measured until 2 consecutive stable measurements are obtained (i.e., the difference between 2 measurements: diastolic blood pressure of <5 mmHg and systolic blood pressure of < 10 mmHg) after resting in a sitting position for at least 5 minutes. The average value of the last 2 measurements will be recorded (the first the decimal place is rounded off). Type 2 diabetes mellitus HbA1c (NGSP (National Glycohemoglobin Standardization Program) value) of < 8.4% during 3 months before informed consent, with a ≤ 0.3% change in HbA1c (peak minus nadir) during 3 months before informed consent No change in diet/exercise therapy during the 3 months before the informed consent in a participant who has been on diet/exercise therapy and instructed to improve life style (e.g., diet and exercise) Age ≥ 20 years at the time of consent Outpatients Capable of providing written consent before participation in this study. Exclusion Criteria: Grade III essential hypertension (i.e., sitting systolic blood pressure 180 mmHg or sitting diastolic blood pressure ≥ 110 mmHg), secondary hypertension, or malignant hypertension. Grade II essential hypertension (i.e., sitting systolic blood pressure ≥ 160 mmHg or sitting diastolic blood pressure ≥ 100 mmHg) for which antihypertensive drug(s) are used Use of oral antihypertensive medication within 2 weeks before the start of the treatment period Participants who are on any antihypertensive agent at the time of informed consent can be enrolled in the study only after 2-week washout following informed consent. Use of RAS inhibitors or thiazolidines within 3 months before the start of the treatment period Type 1 diabetes mellitus Fasting blood glucose of < 180 mg/dL and HOMA-R of ≤ 1.6 at the start of the treatment period (Week 0) Receiving or requiring any of the following at the time of informed consent: Insulin, glucagon-like peptide-1 (GLP-1) receptor agonists, or other parenteral hypoglycemic agents Combination therapy with 3 or more oral hypoglycemic agents Change of antidiabetic medication (including dosage change) within 3 months before the start of the treatment period Having diagnosed/treated any of the following cardiovascular diseases within 3 months before the start of the treatment period: Cardiac disease/condition: myocardial infarction, coronary revascularization procedure Cerebrovascular disease: cerebral infarction, cerebral haemorrhage, transient ischaemic attack Advanced hypertensive retinopathy (retinal bleeding or oozing, papilloedema) Having diagnosed/treated for any of the following cardiovascular diseases more than 3 months before the start of the treatment period, and is now still in unstable condition. Cardiac disease/condition: myocardial infarction, coronary revascularization procedure Cerebrovascular disease: cerebral infarction, cerebral haemorrhage, transient ischaemic attack Past or current history of any of the following cardiovascular diseases. Cardiac valve stenosis Angina pectoris requiring medication Congestive cardiac failure requiring medication Arrhythmia requiring medication (e.g., paroxysmal atrial fibrillation, severe bradycardia, torsade de pointes, and ventricular fibrillation) Arteriosclerosis obliterans with intermittent claudication or other symptoms Have severe ketosis, diabetic coma or precoma, severe infection, or serious trauma Clinically evident renal disorder (e.g., eGFR <30 mL/min/1.73 m2) Markedly low bile secretion or severe hepatic disorder History of hypersensitivity or allergy to azilsartan or telmisartan or to both. Presence of hyperkalemia (potassium level ≥ 5.5 mEq/L on laboratory testing) Currently participating in any other clinical study. Pregnant women, women with possible pregnancy, or breast-feeding women. Other participants who are inappropriate for participation in this study in the opinion of the principal investigator or investigator.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Azilsartan 20 mg<br>Participants will receive azilsartan 20 mg once daily in the morning before or after breakfast. | Drug: Azilsartan<br>* Azilsartan tablets<br>* Other names: Azilva Tablets;|
| Active Comparator: Telmisartan 40 mg<br>Participants will receive telmisartan 40 mg once daily in the morning before or after breakfast. | Drug: Telmisartan<br>* Telmisartan tablets<br>* Other names: Micardis Tablets;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Insulin Resistance Index (HOMA-R) From Baseline at the End of the Treatment Period (Week 12) | Change from the start of the treatment period (baseline) at the end of the treatment period (Week 12) was reported. Insulin Resistance Index (HOMA-R) measures insulin resistance, calculated by fasting insulin (μU/mL) multiplied by fasting glucose (mg/dL), and divided by a constant (405). | Baseline and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Fasting Blood Glucose From Baseline at the End of the Treatment Period (Week 12) | Change from baseline in fasting blood glucose values collected at week 12 or final visit relative to baseline was reported. | Baseline and Week 12 | 
| Change in Fasting Insulin From Baseline at the End of the Treatment Period (Week 12) | Change from baseline in fasting insulin values collected at week 12 or final visit relative to baseline was reported. | Baseline and Week 12 | 
| Change in Glycosylated Hemoglobin (HbA1c) From Baseline at the End of the Treatment Period (Week 12) | Change from baseline in the values of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 12 or final visit relative to baseline was reported. | Baseline and Week 12 | 
| Change in Homeostasis Model Assessment of Beta Cell Function (HOMA-β) From Baseline at the End of the Treatment Period (Week 12) | Change from baseline in HOMA-β collected at week 12 or final visit relative to baseline was reported. Homeostasis model assessment of beta cell function measures as following; HOMA-β = fasting insulin (μU/mL) ×360/{fasting glucose (mg/dL) - 63}. | Baseline and Week 12 | 
| Change in 1,5-anhydroglucitol (1,5-AG) From Baseline at the End of the Treatment Period (Week 12) | Change from baseline in 1,5-G concentration collected at week 12 or final visit relative to baseline was reported. | Baseline and Week 12 | 
| Number of Participants With Treatment-Emergent Adverse Events |  | Up to Week 12 |