Azilsartan Medoxomil Study in Hypertensive Children

This study has been terminated.
(Business Decision (see below))
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT01078376
First received: February 26, 2010
Last updated: October 23, 2013
Last verified: October 2013
  Purpose

The purpose of this study is to assess the pharmacokinetics and safety of azilsartan medoxomil in pediatric subjects who have hypertension and healthy adult subjects.


Condition Intervention Phase
Hypertension
Drug: Azilsartan medoxomil (TAK-491)
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: A Comparative Single-Dose Pharmacokinetic and Safety Study of TAK-491 Between Infants, Children, and Adolescents With Hypertension and Healthy Adults

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • Area under the plasma concentration-time curve from time 0 to time of last quantifiable concentration (AUC[0-tlqc]) for TAK-536 [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • Area under the plasma concentration-time curve from time 0 to time of last quantifiable concentration (AUC[0-tlqc]) for TAK-536 metabolite M-II. [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • Area under the plasma concentration-time curve from time 0 to infinity (AUC[0-inf]) for TAK-536 [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • Area under the plasma concentration-time curve from time 0 to infinity (AUC[0-inf]) for TAK-536 metabolite M-II [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • Maximum observed plasma concentration (Cmax) for TAK-536 [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • Maximum observed plasma concentration (Cmax) for TAK-536 metabolite M-II [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • Time to reach Cmax (Tmax) for TAK-536 [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • Time to reach Cmax (Tmax) for TAK-536 metabolite M-II [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • Terminal elimination half-life (T1/2) for TAK-536 [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • Terminal elimination half-life (T1/2) for TAK-536 metabolite M-II [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • Apparent oral clearance (CL/F) (TAK-536 only, assuming complete conversion from TAK-491 to TAK-536) [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • Total amount of drug excreted in urine from time 0 to 24 hours postdose (Ae[0-t]) (for Cohorts 1 and 2 urine pharmacokinetic endpoint for TAK-536) [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • Total amount of drug excreted in urine from time 0 to 24 hours postdose (Ae[0-t]) (for Cohorts 1 and 2 urine pharmacokinetic endpoint for TAK-536 metabolite M-II) [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • Fraction of unchanged drug excreted in urine from 0 to 24 hours postdose (Fe%) (for Cohorts 1 and 2 urine pharmacokinetic endpoint for TAK-536) [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • Fraction of unchanged drug excreted in urine from 0 to 24 hours postdose (Fe%) (for Cohorts 1 and 2 urine pharmacokinetic endpoint for TAK-536 metabolite M-II) [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • Renal clearance (CLr) from 0 to 24 hours postdose (for Cohorts 1 and 2 urine pharmacokinetic endpoint for TAK-536) [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • Renal clearance (CLr) from 0 to 24 hours postdose (for Cohorts 1 and 2 urine pharmacokinetic endpoint for TAK-536 metabolite M-II) [ Time Frame: Day 1 ] [ Designated as safety issue: No ]

Enrollment: 29
Study Start Date: May 2010
Study Completion Date: September 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1: Pediatrics (12 yrs to 16 yrs old) Drug: Azilsartan medoxomil (TAK-491)
Azilsartan medoxomil 20 mg to 60 mg (based on subject weight), tablets, orally, one day only
Other Name: TAK-491
Experimental: Cohort 1: Adults (18 years to 45 years old) Drug: Azilsartan medoxomil (TAK-491)
Azilsartan medoxomil 80 mg, tablets, orally, one day only
Other Name: TAK-491
Experimental: Cohort 2: Pediatrics (6 years to 11 years old) Drug: Azilsartan medoxomil (TAK-491)
Azilsartan medoxomil 20 mg to 60 mg (based on subject weight), tablets, orally, one day only
Other Name: TAK-491
Experimental: Cohort 3: Pediatrics (6 months to 5 years old) Drug: Azilsartan medoxomil (TAK-491)
Azilsartan medoxomil 0.66 mg/kg subject body weight, granules, reconstituted orally, one day only
Other Name: TAK-491

Detailed Description:

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 looked at a 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 also took part in this study to provide a comparison.

To be eligible to take part in this study, children must have been between the ages of 1 year and 16 years old, and had to stop taking their current antihypertensive medication for one day prior to the start of this study. Each child was 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 took place in approximately 10 sites in the UK and USA. A total of approximately 20 children with hypertension and approximately 9 adults without hypertension participated in this study.

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

Takeda has decided to close Cohort 3 (subjects between 1 and 6 years of age with hypertension) enrollment early and end this study with the agreement of both the US Food and Drug Administration (FDA) and the Pediatric Committee (PDCO) at the European Medicines Agency. Requests to the FDA and PDCO were submitted to close the study without completion of enrollment in Cohort 3 due to difficulty enrolling this particular patient population. Takeda proposed an alternative option to collect PK data in this age subset by utilizing PK modeling to determine the appropriate doses in children 1-5 years of age in lieu of completing Cohort 3. The FDA and PDCO agreed with this approach

  Eligibility

Ages Eligible for Study:   1 Year to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01078376

Locations
United States, Arkansas
Little Rock, Arkansas, United States
United States, Georgia
Atlanta, Georgia, United States
United States, Kentucky
Louisville, Kentucky, United States
United States, Ohio
Toledo, Ohio, United States
United Kingdom
Birmingham, England, United Kingdom
Bristol, England, United Kingdom
London, England, United Kingdom
Manchester, England, United Kingdom
Sponsors and Collaborators
Takeda
Investigators
Study Director: Medical Director Takeda
  More Information

Additional Information:
No publications provided

Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT01078376     History of Changes
Other Study ID Numbers: TAK-491_109, 2009-013165-25, U1111-1113-4416
Study First Received: February 26, 2010
Last Updated: October 23, 2013
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Takeda:
Pediatrics
Blood Pressure, High
Drug Therapy

Additional relevant MeSH terms:
Hypertension
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on July 20, 2014