Azilsartan Medoxomil in the Treatment of Essential Hypertension and Type 2 Diabetes in Asia

Phase 4

Completed

• Conditions: Type 2 Diabetes Mellitus; Essential Hypertension
• Interventions: Drug: Azilsartan Medoxomil

• Registration Number: NCT02517866
• Lead Sponsor: Takeda

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of azilsartan medoxomil (AZM) in Asian adult participants with both essential hypertension and type 2 diabetes.

Detailed Description

The drug being tested in this study is called azilsartan medoxomil. Azilsartan medoxomil is being tested to treat people who have essential hypertension and type 2 diabetes mellitus (T2DM). This study will look at the blood pressure of people who take azilsartan medoxomil in addition to standard care for T2DM.

The study will enroll approximately 380 patients. All participants will receive azilsartan medoxomil 40 mg tablets to be administered orally, once a day, for 12 weeks. If a participant's blood pressure (BP) has not reached BP goal of \<140/85 mmHg at week 6, azilsartan medoxomil dose will be up-titrated to 80 mg daily.

All participants will be asked to take one tablet at the same time each day throughout the study.

This multi-center trial will be conducted in Asia. The overall time to participate in this study is 14 weeks. Participants will make multiple visits to the clinic, and will be contacted by 14 days after last dose of study drug for a follow-up assessment.

Study Timeline

• Study First Submitted: 2015-06-24
• Study Start: 2015-07-13
• Study First Submitted QC: 2015-08-06
• Study First Posted: 2015-08-07
• Primary Completion: 2016-11-15
• Study Completion: 2016-11-25
• Results First Submitted: 2017-10-04
• Status Verified: 2018-10
• Results First Submitted QC: 2018-10-29
• Last Update Submitted: 2018-10-29
• Results First Posted: 2019-03-01
• Last Update Posted: 2019-03-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 380

Inclusion Criteria

1. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
2. The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
3. Has type 2 diabetes mellitus (T2DM) with essential hypertension.
4. T2DM participants are either treated by stable life style intervention or by oral antidiabetic drugs (OADs) that are stable, including no dose adjustment within 12 weeks before baseline.
5. Is male or female and aged 18 to 75 years, inclusive.
6. Uncontrolled hypertension (systolic blood pressure ≥140 mmHg to <180 mmHg, or diastolic blood pressure ≥85 mmHg and <110 mmHg at screening and baseline.
7. Has screening glycosylated hemoglobin (HbA1C) <9.5%.
8. Female participants must be either of non-childbearing potential, ie, surgically sterilized (defined as having undergone hysterectomy and/or bilateral oophorectomy and/or bilateral salpingectomy; tubal ligation alone is not considered sufficient) or one year after the last menstrual period; or, if of childbearing potential and participant is sexually active with a nonsterilized male partner, must agree to use routinely adequate contraception from signing of informed consent throughout the duration of study.

Exclusion Criteria

1. Has systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg despite concurrent treatment with three antihypertensive medications from different classes at adequate doses including a diuretic.
2. Has type 1 or poorly controlled type 2 diabetes mellitus, defined as HbA1c ≥9.5% at screening.
3. Is treated with OADs has not been on stable treatment including no dose change of their OADs for at least 12 weeks prior to baseline.
4. Has been previously treated with azilsartan medoxomil (AZM) or azilsartan.
5. Has secondary hypertension of any etiology (eg, renovascular disease, pheochromocytoma, Cushing's syndrome).
6. Has congestive heart failure (New York Heart Association class III or IV), clinically relevant cardiac arrhythmias (as determined by the investigator's clinical judgment on a participant-by-participant basis), severe obstructive coronary artery disease.
7. Has participated in a clinical trial including interventional and observational studies, or received any investigational compound currently or 30 days prior to screening.
8. Has severe renal impairment (based on estimated glomerular filtration rate [GFR] <30 mL/min/1.73m^2) at Screening.
9. Has hyperkalemia defined as serum potassium >5.0 mEq/L.
10. Has an alanine aminotransferase (ALT) level of greater than 2.5 times the upper limit of normal, active liver disease, or jaundice at screening.
11. Has any clinically relevant disease (eg malignancy, neurological, hepatic abnormalities) and/or significant abnormal laboratory findings (past or present), which, in the opinion of the investigator, may put the participant at risk because of participation in the study.
12. Is taking prohibited medications including lithium and aliskiren (refer to Edarbi® product insert).
13. Has known hypersensitivity to any excipients or angiotensin converting enzyme inhibitor (ACEIs)/ angiotensin receptor blockers (ARBs).
14. Has prior angioedema due to an ACE inhibitor or ARB.
15. Breast feeding or pregnant women or women who are intending to become pregnant before, during or within 1 month after participating in the study; or intending to donate ova during such time period, or refusal to submit to a urine test to rule out pregnancy prior to enrolment and at end of study.
16. Have a history of alcohol abuse, drug abuse or illegal drug addiction within the 6 months prior to signing the informed consent.
17. Is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Azilsartan medoxomil	Azilsartan Medoxomil	Azilsartan medoxomil 40 mg, tablets, orally, once, daily, for 12 weeks. Azilsartan medoxomil dose may be increased to 80 mg once daily if blood pressure has not reach BP goal of \<140/85 mmHg at Week 6.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Blood Pressure (BP) <140/85 mmHg (Systolic BP <140 mmHg and Diastolic BP <85 mmHg) by Clinic-Measured Sitting BP at Week 12	Week 12	Three serial BP measurements were determined while the participant was seated, with a sphygmomanometer.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Systolic Blood Pressure (SBP) <140 mmHg at Week 12	Week 12	Three serial BP measurements were determined while the participant was seated, with a sphygmomanometer.
Percentage of "Treatment-Naïve" Participants Reaching BP <140/85 mmHg	Up to Week 12	Treatment-naïve participants are defined as participants who have not received anti-hypertensive treatment for at least four weeks prior to screening. At each visit 3 serial BP measurements were determined while the participant was seated, with a sphygmomanometer.
Percentage of Participants Treated With Thiazides Before Baseline Reaching BP <130/80 mmHg	Weeks 6 and 12	At each visit 3 serial BP measurements were determined while the participant was seated, with a sphygmomanometer.
Change From Baseline in DBP at Week 12	Baseline and Week 12	At each visit 3 serial BP measurements were determined while the participant was seated, with a sphygmomanometer. Change from Baseline was estimated using an ANCOVA model with fixed effects, country, BHT and baseline SBP (or DBP) included as a covariate. A negative change from baseline indicates improvement.
Percentage of Participants Treated With Calcium Channel Blocker (CCB) Before Baseline Reaching BP<140/85 mmHg	Weeks 6 and 12	At each visit three serial BP measurements were determined while the participant was seated, with a sphygmomanometer.
Percentage of Participants Treated With Angiotensin Converting Enzyme (ACE) Inhibitors or Other Angiotensin Receptor Blockers (ARBs) Before Baseline Reaching BP <140/85 mmHg	Weeks 6 and 12	At each visit 3 serial BP measurements were determined while the participant was seated, with a sphygmomanometer.
Percentage of Participants Treated With Thiazides Before Baseline Reaching BP <140/85 mmHg	Weeks 6 and 12	At each visit three serial BP measurements were determined while the participant was seated, with a sphygmomanometer.
Percentage of Participants Treated With ACE Inhibitors or Other ARBs Before Baseline Reaching BP <130/80 mmHg	Weeks 6 and 12	At each visit 3 serial BP measurements were determined while the participant was seated, with a sphygmomanometer.
Change From Baseline in DBP at Week 12 in "Treatment-Naïve" Participants	Baseline and Week 12	At each visit 3 serial BP measurements were determined while the participant was seated, with a sphygmomanometer. Change from Baseline was estimated using an ANCOVA model with fixed effects, country, BHT and baseline SBP (or DBP) included as a covariate. A negative change from baseline indicates improvement.
Percentage of "Treatment-Naïve" Participants Reaching BP <130/80 mmHg	Up to Week 12	Treatment-naïve participants are defined as participants who have not received anti-hypertensive treatment for at least four weeks prior to screening. At each visit 3 serial BP measurements were determined while the participant was seated, with a sphygmomanometer.
Percentage of Participants Treated With CCB Before Baseline Reaching BP <130/80 mmHg	Weeks 6 and 12	At each visit 3 serial BP measurements were determined while the participant was seated, with a sphygmomanometer.
Percentage of Participants With DBP <80 mmHg at Week 12	Week 12	Three serial BP measurements were determined while the participant was seated, with a sphygmomanometer.
Change From Baseline in Trough Sitting SBP at Week 12	Baseline and Week 12	At each visit 3 serial BP measurements were determined while the participant was seated, with a sphygmomanometer. Change from Baseline was estimated using an ANCOVA model with fixed effects, country, baseline hypertension therapy (BHT) and baseline SBP (or DBP) included as a covariate. A negative change from baseline indicates improvement.
Change From Baseline in Trough Sitting SBP at Week 12 in "Treatment-Naïve" Participants	Baseline and Week 12	At each visit 3 serial BP measurements were determined while the participant was seated, with a sphygmomanometer. Change from Baseline was estimated using an ANCOVA model with fixed effects, country, baseline hypertension therapy (BHT) and baseline SBP (or DBP) included as a covariate. A negative change from baseline indicates improvement.
Percentage of Participants With Diastolic Blood Pressure (DBP) <85 mmHg at Week 12	Week 12	Three serial BP measurements were determined while the participant was seated, with a sphygmomanometer.
Percentage of Participants With DBP <90 mmHg at Week 12	Week 12	Three serial BP measurements were determined while the participant was seated, with a sphygmomanometer.
Percentage of Participants With BP <130/80 mmHg at Week 12	Week 12	Three serial BP measurements were determined while the participant was seated, with a sphygmomanometer.
Percentage of Participants With SBP <130 mmHg at Week 12	Week 12	Three serial BP measurements were determined while the participant was seated, with a sphygmomanometer.
Percentage of Participants With BP <140/90 mmHg at Week 12	Week 12	Three serial BP measurements were determined while the participant was seated, with a sphygmomanometer.