Clinical trial NCT02079805: 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
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Essential Hypertension Complicated by Type 2 Diabetes Mellitus
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2014-03-06
Enrollment: 33
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility 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.

Primary outcomes:
measure: Change in Insulin Resistance Index (HOMA-R) From Baseline at the End of the Treatment Period (Week 12)
timeFrame: Baseline and Week 12
Secondary outcomes:
measure: Change in Fasting Blood Glucose From Baseline at the End of the Treatment Period (Week 12)
timeFrame: Baseline and Week 12
measure: Change in Fasting Insulin From Baseline at the End of the Treatment Period (Week 12)
timeFrame: Baseline and Week 12
measure: Change in Glycosylated Hemoglobin (HbA1c) From Baseline at the End of the Treatment Period (Week 12)
timeFrame: Baseline and Week 12
measure: Change in Homeostasis Model Assessment of Beta Cell Function (HOMA-β) From Baseline at the End of the Treatment Period (Week 12)
timeFrame: Baseline and Week 12
measure: Change in 1,5-anhydroglucitol (1,5-AG) From Baseline at the End of the Treatment Period (Week 12)
timeFrame: Baseline and Week 12
measure: Number of Participants With Treatment-Emergent Adverse Events
timeFrame: Up to Week 12
Other outcomes:
Locations:
city: Kyoto-Shi
country: Japan
state: Kyoto
Study officials:
affiliation: Takeda
name: General Manager
role: STUDY_DIRECTOR
References:
citation: Naruse M, Koike Y, Kamei N, Sakamoto R, Yambe Y, Arimitsu M. Effects of azilsartan compared with telmisartan on insulin resistance in patients with essential hypertension and type 2 diabetes mellitus: An open-label, randomized clinical trial. PLoS One. 2019 Apr 3;14(4):e0214727. doi: 10.1371/journal.pone.0214727. eCollection 2019.