A Comparative Single-Dose Pharmacokinetic (PK) and Safety Study of Azilsartan Medoxomil in Children With Hypertension and in Healthy Adults
Condition: Hypertension
MeSH terms: Hypertension
Intervention: Azilsartan medoxomil (TAK-491); Azilsartan medoxomil (TAK-491); Azilsartan medoxomil (TAK-491); Azilsartan medoxomil (TAK-491)
Intervention description: Azilsartan medoxomil 80 mg, tablets, orally, one day only; Azilsartan medoxomil 20 mg to 60 mg (based on participant weight), tablets, orally, one day only; Azilsartan medoxomil 20 mg to 60 mg (based on participant weight), tablets, orally, one day only; Azilsartan medoxomil 0.66 mg/kg participant body weight, granules, reconstituted orally, one day only
Intervention MeSH terms: Azilsartan medoxomil
Phase: Phase 1
Study type: Interventional
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: All
Minimum age: 1 Year
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Pediatrics; Blood Pressure, High; Drug Therapy

Summary:

      The purpose of this study was to assess the pharmacokinetics (PK) and safety of a single dose
      of azilsartan medoxomil in children with hypertension, and comparative PK in healthy adults.
    

Eligibility criteria:

        Inclusion Criteria:

        For Pediatric Participants:

        Must have a diagnosis of hypertension (SBP and/or DBP ≥95th percentile for
        age/gender/height).

          -  For Cohorts 1 and 2 only, is within the weight range of 20 kg (44 pounds) to 100 kg
             (220 pounds), inclusive, at Screening.

          -  For Cohort 3 only, weighs at least 8.0 kg (17.6 pounds) at Screening.

          -  Participants 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 Participants:

          -  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 Participants:

          -  Females of child bearing potential who are sexually active, as well as sexually active
             male participants, 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 Participants:

          -  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 participants:

          -  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 participant unsuitable for the study.

          -  Has taken or requires the use of any medications, supplements, or food products within
             the stated time periods, including:

               -  Pediatric participants 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 participants 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 participants only.

               -  Alcohol-containing products.

               -  Products that contain caffeine or xanthine-related compounds.

               -  Foods or beverages containing grapefruit juice or Seville-type oranges.