Essential Hypertension Complicated by Type 2 Diabetes MellitusPhase 4NCT02079805

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

A Phase 4 study testing Azilsartan and Telmisartan in people with Essential Hypertension Complicated by Type 2 Diabetes Mellitus, run by Takeda at 1 site in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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 Read more about this study

Who is it for?: Ages 20 years and older
Conditions the study is for: Essential Hypertension Complicated by Type 2 Diabetes Mellitus
What is being tested?: Azilsartan and Telmisartan
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 33 participants
Where: 1 siteJapan
Study dates: Jun 2014to Apr 2016
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 20 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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)

Show all 31Show fewer

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.

Trial locations and contacts

1 site in 1 country.

Japan1 site

Study site
Kyoto, Kyoto

Other trials in Japan

About this study

Read the 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.

Conditions: Essential Hypertension Complicated by Type 2 Diabetes Mellitus
Being tested: Azilsartan, Telmisartan

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AzilsartanDrug
Also called Azilva Tablets
Azilsartan tablets
TelmisartanDrug
Also called Micardis Tablets
Telmisartan tablets

Study groups in NCT02079805
Study group	Role	What they receive
Azilsartan 20 mg	Experimental	Participants will receive azilsartan 20 mg once daily in the morning before or after breakfast. Receives: Drug: Azilsartan
Telmisartan 40 mg	Active comparator	Participants will receive telmisartan 40 mg once daily in the morning before or after breakfast. Receives: Drug: Telmisartan

What is being measured

The primary outcome is the main question the study is designed to answer.

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).
Measured: Baseline and Week 12

Secondary outcomes (6)

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.
Measured: 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.
Measured: 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.
Measured: 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}.
Measured: 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.
Measured: Baseline and Week 12
Number of Participants With Treatment-Emergent Adverse Events
Measured: Up to Week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 2014Apr 2016

First posted6 Mar 2014 (estimated)
Study startJun 2014
Primary completionApr 2016
Study completionApr 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Essential Hypertension Complicated by Type 2 Diabetes MellitusStudies of the same condition, open and under way.
More trials run by TakedaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 33 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02079805
Sponsor's protocol ID: 279/NRP-001
Other IDs: U1111-1151-7168, AZI-P4-004, JapicCTI-142461
Status last verified: Apr 2017
First submitted: 4 Mar 2014
Last updated: 2 Aug 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

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.
PubMed 30943275

Study at a glance

From the registry record, last updated by the sponsor on 2 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT02079805
Acronym / sponsor ID: 279/NRP-001
Conditions: Essential Hypertension Complicated by Type 2 Diabetes Mellitus
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 33 participants (actual)
Lead sponsor: TakedaIndustry (pharma, biotech, devices)
Study start: Jun 2014
Primary completion: Apr 2016 (actual)
Study completion: Apr 2016 (actual)
First posted: 6 Mar 2014 (estimated)
Results: Posted 2 Aug 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Azilsartan 20 mg	Experimental	Drug: AzilsartanParticipants will receive azilsartan 20 mg once daily in the morning before or after breakfast.
Telmisartan 40 mg	Active comparator	Drug: TelmisartanParticipants will receive telmisartan 40 mg once daily in the morning before or after breakfast.

Who may qualify

Ages: 20 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

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)

Key exclusion criteria (31 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
AzilsartanAlso: Azilva TabletsAzilsartan tablets	Drug	Azilsartan 20 mg
TelmisartanAlso: Micardis TabletsTelmisartan tablets	Drug	Telmisartan 40 mg

Primary outcome

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).

6 secondary outcomes

Change in Fasting Blood Glucose From Baseline at the End of the Treatment Period (Week 12)
Time frame: Baseline and Week 12
Change in Fasting Insulin From Baseline at the End of the Treatment Period (Week 12)
Time frame: Baseline and Week 12
Change in Glycosylated Hemoglobin (HbA1c) From Baseline at the End of the Treatment Period (Week 12)
Time frame: 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)
Time frame: Baseline and Week 12
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
Number of Participants With Treatment-Emergent Adverse Events
Time frame: Up to Week 12

Results and safety

Results posted to the registry on 2 Aug 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Telmisartan 40 mg	16	16
Azilsartan 20 mg	17	15

Primary outcome: Change in Insulin Resistance Index (HOMA-R) From Baseline at the End of the Treatment Period (Week 12)

Time frame: Baseline and Week 12. Mean (Standard Deviation). Unit: HOMA-R Score

Measure	Telmisartan 40 mg n = 16	Azilsartan 20 mg n = 16
Value	-0.23 (0.928)	0.22 (2.449)

Telmisartan 40 mg vs Azilsartan 20 mg: Mean Difference (Final Values): 0.44 (95% CI -0.89 to 1.78)

Population analysed: The full analysis set was defined as the participants who received at least 1 dose of the study drug for the treatment period.

6 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to Week 12. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Telmisartan 40 mg	0 of 16 (0%)	8 of 16 (50%)	Not reported
Azilsartan 20 mg	0 of 17 (0%)	6 of 17 (35.3%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 2 Aug 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 30943275Naruse 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.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

General Manager study director

Takeda

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Azilsartan and Telmisartan in people with Essential Hypertension Complicated by Type 2 Diabetes Mellitus, run by Takeda at 1 site in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Aug 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Insulin Resistance Index (HOMA-R) From Baseline at the End of the Treatment Period (Week 12) (time frame: Baseline and Week 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02079805, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Aug 2017.