Efficacy and Safety of Azilsartan Medoxomil Used in Combination With Metformin in Participants With Hypertension and Diabetes
Condition: Hypertension; Diabetes
MeSH terms: Hypertension; Diabetes Mellitus
Intervention: Placebo; Azilsartan medoxomil; Azilsartan medoxomil
Intervention MeSH terms: Azilsartan medoxomil
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 105.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Drug Therapy; Hypertension and Diabetes

Summary:

      The purpose of this study was to evaluate the antihypertensive and antiglycemic effects, as
      well as the safety and tolerability of TAK-491 (azilsartan medoxomil), once daily (QD), in
      stage 1 hypertensive, type 2 diabetes mellitus (T2DM) participants whose glycemic control was
      inadequate on metformin alone.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Was male or female and ≥18 years.

          2. Had type 2 diabetes mellitus with HbA1c of ≥7.5 to ≤9.5% at Screening.

          3. Was treated with metformin alone (no treatment with any antidiabetic agents other than
             metformin within the 3 months prior to Screening) and was experiencing inadequate
             glycemic control. The participant should have received metformin monotherapy for ≥8
             weeks prior to Screening at a stable dose ≥1500 mg). Participants with a maximum
             tolerated dose (MTD) that was documented to be less than 1500 mg of metformin could
             also be enrolled if this dose had been stable for 8 weeks prior to Screening.

          4. Was treated with antihypertensive therapy and had a mean, trough, sitting clinic
             systolic blood pressure (SBP) ≥135 and < 160 mm Hg on Day -1 (after washout of prior
             antihypertensive therapy) or the participant had not received antihypertensive
             treatment within 28 days before Screening and had a mean sitting clinic SBP ≥135 and <
             160 mm Hg at the Screening Visit and on Day -1.

          5. Had clinical laboratory evaluations (including clinical chemistry, hematology, and
             complete urinalysis) within the reference range for the testing laboratory or results
             that were deemed not clinically significant in this participant population for
             inclusion in this study, by the investigator.

        Exclusion Criteria:

          1. Had a mean, trough, sitting clinic diastolic blood pressure (DBP) ≥ 100 mm Hg at Day
             -1.

          2. Had type 1 or poorly controlled type 2 diabetes mellitus (HbA1c >9.5%) at Screening.

          3. Was taking or expected to take an excluded medication.

          4. Had a history of myocardial infarction, heart failure, unstable angina, coronary
             artery bypass graft, percutaneous coronary intervention, hypertensive encephalopathy,
             cerebrovascular accident, or transient ischemic attack.

          5. Had clinically significant cardiac conduction defects (for example, 3rd degree
             atrioventricular block, left bundle branch block, sick sinus syndrome, atrial
             fibrillation).

          6. Had hemodynamically significant left ventricular outflow obstruction due to aortic
             valvular disease.

          7. Had secondary hypertension of any etiology (e.g., renovascular disease,
             pheochromocytoma, Cushing's syndrome).

          8. Had renal dysfunction defined as estimated glomerular filtration rate (eGFR) <60
             mL/min/1.73 m2 at Screening.

          9. Had albuminuria defined as >200 mg/g at Screening.

         10. Had known or suspected unilateral or bilateral renal artery stenosis.

         11. Had unexplained microhematuria ≥3 RBCs/HPF or macrohematuria at Screening and
             confirmed on repeat testing.

         12. Treatment with antidiabetic agents (sulfonylureas, glucagon-like peptide-1 (GLP-1)
             analogues, dipeptidyl peptidase-4 (DPP-4) inhibitors, glinides, thiazolidinediones
             (TZDs), and/or insulin) other than metformin during the 3 months prior to Screening.

         13. Had hyperkalemia as defined by central laboratory normal reference range at Screening.