Azilsartan Medoxomil Study in Hypertensive Children

Within the past 10 years, the incidence of high blood pressure (hypertension) in children
and adolescents has increased all over the world. This increase is connected in part to a
growing number of people who are overweight and do not eat right or exercise enough.

This study will look at a new and untested blood pressure medicine called TAK-491
(azilsartan medoxomil) to see how it works in children who have hypertension. Azilsartan
medoxomil is a prodrug that converts into TAK-536 (azilsartan), another untested blood
pressure medicine. Adults who do not have hypertension will also take part in this study to
provide a comparison.

To be eligible to take part in this study, children must be between the ages of 6 months and
16 years old, and will have to stop taking their current antihypertensive medication for one
day prior to the start of this study. Each child will be given one dose of azilsartan
medoxomil, followed by a number of blood tests and assessments within 24 hours after taking
azilsartan medoxomil to see how the medication is working.

This study will take place in approximately 10 sites in the UK and USA. A total of
approximately 24 children with hypertension and approximately 8 adults without hypertension.

This study will last about 43 days. This includes a 28 day screening period, a 2 day
treatment phase and a follow up period. Each person taking part in this study may be
requested to remain in a hospital for one overnight stay during the course of the study.
Each participant will also be contacted by telephone 6 days and 15 days after taking
azilsartan medoxomil.

Inclusion Criteria:

For Pediatric Subjects:

- Must have a diagnosis of hypertension.

- For Cohorts 1 and 2 only, is within the weight range of 44 pounds to 220 pounds,
inclusive, at Screening.

- For Cohort 3 only, weighs at least 8.0 kg (17.6 pounds) at Screening.

- Subjects greater than or equal to 6 years of age must have the ability to swallow a
tablet of the size 6.0 millimeter diameter and 3.5 millimeter thickness.

- Has no known history of hepatitis B, hepatitis C, and human immunodeficiency virus.

- For Cohort 3 only, may be renal transplant patient if all other inclusion and none of
the exclusion criteria are met, along with additional criteria.

- Must have been at a constant weight, or expected weight gain for that particular age,
for 30 days with no change to the dose of their diuretic drugs.

For Healthy Adult Subjects:

- Weighs at least 50 kilograms (110 pounds) and has a screening body mass index between
18 and 32 kilograms/m2, inclusive.

- Is in good health as determined by the physician

- Has a negative test result for hepatitis B surface antigen and antibody to hepatitis
C virus, and has no known history of human immunodeficiency virus.

- Must have a negative urine test result for selected substances of abuse .

- Has a diastolic blood pressure between 60 and 90 mm Hg, inclusive, and a systolic
blood pressure between 100 and 140 mm Hg, inclusive.

For All Subjects:

- Females of child bearing potential who are sexually active, as well as sexually
active male subjects, agree to routinely use adequate contraception from Screening
until 30 days after receiving the last dose of study medication.

- Has clinical laboratory results within the reference range for the testing laboratory
unless the results are deemed not clinically significant by the investigator.

Exclusion Criteria:

For Pediatric Subjects:

- Is currently treated with more than 2 antihypertensive agents.

- Has sitting trough clinic systolic blood pressure greater than 15 mm Hg or diastolic
blood pressure greater than 10 mm Hg above the 99th percentile for age, gender, and
height at Check-in .

- Has renovascular disease affecting both kidneys or a solitary kidney, dialysis
treatment, severe nephrotic syndrome and not in remission.

- For Cohort 1 and 2 only, a previous renal transplant.

- Has a creatinine clearance less than 30 mL/min/1.73 m2.

For all subjects:

- Has previously received azilsartan or azilsartan medoxomil.

- Has a known hypersensitivity or allergy to any angiotensin type II receptor blockers
or to any of the excipients in the azilsartan medoxomil formulation to be taken.

- Has a history or clinical manifestations of severe cardiovascular disease,
psychiatric disease, and any conditions that would interfere with gastrointestinal
absorption.

- Has hemodynamically significant left ventricular outflow obstruction due to aortic
valvular disease, cardiomyopathy, or uncorrected coarctation of the aorta.

- Has been diagnosed with malignant or accelerated hypertension.

- Has severe hepatic impairment.

- Has a serum albumin less than 2.5 g/dL.

- Has a glycosylated hemoglobin value greater than 8.5%.

- Has alanine aminotransferase, aspartate aminotransferase greater than 2 times the
upper limit of normal, or total bilirubin greater than 1.5 times the upper limit of
normal, active liver disease, or jaundice.

- Has hyperkalemia as defined by the laboratory normal reference range or any pertinent
electrolyte disorders.

- Is participating in another investigational study or has taken an investigational
drug within 30 days prior to Check-in .

- Has a history of drug abuse or a history of alcohol abuse within 1 year prior to
study Check-in.

- Has a history of abdominal surgery or thoracic or nonperipheral vascular surgery
within 6 months prior to study Check-in .

- Has a history of cancer, other than basal cell carcinoma or stage I squamous cell
carcinoma of the skin that has not been in remission for at least 5 years prior to
study Check-in .

- Has taken any cytotoxic drugs within 12 months prior to study Check-in .

- Has a history or presence of a clinically significant abnormal 12-lead
electrocardiogram as determined by the investigator or sponsor/designee.

- Has poor peripheral venous access.

- Has any other condition or prior therapy that, in the opinion of the investigator,
would make the subject unsuitable for the study.

- Has taken or requires the use of any medications, supplements, or food products
within the stated time periods, including:

- Pediatric subjects taking angiotensin-converting enzyme inhibitors and other
angiotensin II receptor blockers will be required to withhold these medications
from the morning of Day -1 until the 24 hour pharmacokinetic sample is completed
on Day 2.

- Only pediatric subjects will be allowed to take medications for primary renal or
urologic conditions or hypertension as long as they have been on a stable dose
of their medication for at least 30 days prior to Check-in (Day -1) and those
medications are not potent cytochrome P-450 inhibitors or inducers.

- Nutraceuticals including herbal or dietary preparations such as ginseng, kava
kava, and ginkgo biloba.

- Over-the-counter medications.

- Vitamin supplements except for pediatric subjects only.

- Alcohol-containing products.

- Products that contain caffeine or xanthine-related compounds.

- Foods or beverages containing grapefruit juice or Seville-type oranges.