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 Description

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Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Essential Hypertension Complicated by Type 2 Diabetes Mellitus	Drug: Azilsartan; Drug: Telmisartan	Phase 4

Detailed Description:

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	33 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	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 Start Date :	June 2014
Actual Primary Completion Date :	April 2016
Actual Study Completion Date :	April 2016

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Azilsartan 20 mg; Participants will receive azilsartan 20 mg once daily in the morning before or after breakfast.	Drug: Azilsartan; Azilsartan tablets; Other Name: Azilva Tablets
Active Comparator: Telmisartan 40 mg; Participants will receive telmisartan 40 mg once daily in the morning before or after breakfast.	Drug: Telmisartan; Telmisartan tablets; Other Name: Micardis Tablets

Outcome Measures

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Primary Outcome Measures :

1. Change in Insulin Resistance Index (HOMA-R) From Baseline at the End of the Treatment Period (Week 12) [ Time Frame: Baseline and 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).

Secondary Outcome Measures :

1. Change in Fasting Blood Glucose From Baseline at the End of the Treatment Period (Week 12) [ Time Frame: Baseline and Week 12 ]
   Change from baseline in fasting blood glucose values collected at week 12 or final visit relative to baseline was reported.
2. Change in Fasting Insulin From Baseline at the End of the Treatment Period (Week 12) [ Time Frame: Baseline and Week 12 ]
   Change from baseline in fasting insulin values collected at week 12 or final visit relative to baseline was reported.
3. Change in Glycosylated Hemoglobin (HbA1c) From Baseline at the End of the Treatment Period (Week 12) [ Time Frame: Baseline and 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.
4. Change in Homeostasis Model Assessment of Beta Cell Function (HOMA-β) From Baseline at the End of the Treatment Period (Week 12) [ Time Frame: Baseline and 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}.
5. Change in 1,5-anhydroglucitol (1,5-AG) From Baseline at the End of the Treatment Period (Week 12) [ Time Frame: Baseline and Week 12 ]
   Change from baseline in 1,5-G concentration collected at week 12 or final visit relative to baseline was reported.
6. Number of Participants With Treatment-Emergent Adverse Events [ Time Frame: Up to Week 12 ]

Eligibility Criteria

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Ages Eligible for Study:	20 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

1. 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.
2. 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).
3. Type 2 diabetes mellitus
4. 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
5. 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)
6. Age ≥ 20 years at the time of consent
7. Outpatients
8. Capable of providing written consent before participation in this study.

Exclusion Criteria:

1. Grade III essential hypertension (i.e., sitting systolic blood pressure 180 mmHg or sitting diastolic blood pressure ≥ 110 mmHg), secondary hypertension, or malignant hypertension.
2. 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
3. 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.
4. Use of RAS inhibitors or thiazolidines within 3 months before the start of the treatment period
5. Type 1 diabetes mellitus
6. Fasting blood glucose of < 180 mg/dL and HOMA-R of ≤ 1.6 at the start of the treatment period (Week 0)

7. 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
8. Change of antidiabetic medication (including dosage change) within 3 months before the start of the treatment period

9. 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)

10. 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

11. 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
12. Have severe ketosis, diabetic coma or precoma, severe infection, or serious trauma
13. Clinically evident renal disorder (e.g., eGFR <30 mL/min/1.73 m2)
14. Markedly low bile secretion or severe hepatic disorder
15. History of hypersensitivity or allergy to azilsartan or telmisartan or to both.
16. Presence of hyperkalemia (potassium level ≥ 5.5 mEq/L on laboratory testing)
17. Currently participating in any other clinical study.
18. Pregnant women, women with possible pregnancy, or breast-feeding women.
19. Other participants who are inappropriate for participation in this study in the opinion of the principal investigator or investigator.

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

Japan
Kyoto-Shi, Kyoto, Japan

Sponsors and Collaborators

Takeda

Investigators

Study Director:	General Manager	Takeda

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Takeda
ClinicalTrials.gov Identifier:	NCT02079805 History of Changes
Other Study ID Numbers:	279/NRP-001; U1111-1151-7168 ( Registry Identifier: UTN (WHO) ); AZI-P4-004 ( Other Identifier: Takeda ); JapicCTI-142461 ( Registry Identifier: JapicCTI )
First Posted:	March 6, 2014
Results First Posted:	August 2, 2017
Last Update Posted:	August 2, 2017
Last Verified:	April 2017

Additional relevant MeSH terms:

Diabetes Mellitus; Hypertension; Diabetes Mellitus, Type 2; Insulin Resistance; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Vascular Diseases	Cardiovascular Diseases; Hyperinsulinism; Telmisartan; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Molecular Mechanisms of Pharmacological Action