A Comparative Single-Dose Pharmacokinetic (PK) and Safety Study of Azilsartan Medoxomil in Children With Hypertension and in Healthy Adults

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: June 26, 2014
Last verified: June 2014
Results First Received: June 26, 2014  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Pharmacokinetics Study;   Intervention Model: Parallel Assignment;   Masking: Open Label
Condition: Hypertension
Intervention: Drug: Azilsartan medoxomil (TAK-491)

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants took part in the study at 6 sites in the United States and 3 sites in the United Kingdom from 10 May 2010 to 10 July 2013.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Children between the ages of 1 to 16 years (including up to their 17th birthday) with hypertension and gender-matched healthy adults aged 18 to 45 years, inclusive, were enrolled in 1 of 3 cohorts.

Reporting Groups
  Description
Cohort 1: Healthy Adults Azilsartan medoxomil 80 mg, tablets, orally, one day only
Cohort 1: Adolescents (≥12 to <17 Years Old) 40-60 mg Azilsartan medoxomil 40-60 mg, tablets, orally, one day only. Dose regimen was based on body weight. Participants 40 to < 80 kg received a 40 mg dose and participants 80 to 100 kg received a 60 mg dose.
Cohort 2: Children (≥6 to <12 Years Old) 20-60 mg Azilsartan medoxomil 20-60 mg, tablets, orally, one day only. Dose regimen was based on body weight. Participants 20 to < 40 kg received a 20 mg dose, participants 40 to < 80 kg received a 40 mg dose and participants 80 to 100 kg received a 60 mg dose.
Cohort 3: Children (≥1 to <6 Years Old) Azilsartan medoxomil 0.66 mg/kg participant body weight, granules, reconstituted orally, one day only

Participant Flow:   Overall Study
    Cohort 1: Healthy Adults     Cohort 1: Adolescents (≥12 to <17 Years Old) 40-60 mg     Cohort 2: Children (≥6 to <12 Years Old) 20-60 mg     Cohort 3: Children (≥1 to <6 Years Old)  
STARTED     9     9     8     3  
COMPLETED     9     9     8     3  
NOT COMPLETED     0     0     0     0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Cohort 1: Healthy Adults Azilsartan medoxomil 80 mg, tablets, orally, one day only
Cohort 1: Adolescents (≥12 to <17 Years Old) 40-60 mg Azilsartan medoxomil 40-60 mg, tablets, orally, one day only. Dose regimen was based on body weight. Participants 40 to < 80 kg received a 40 mg dose and participants 80 to 100 kg received a 60 mg dose.
Cohort 2: Children (≥6 to <12 Years Old) 20-60 mg Azilsartan medoxomil 20-60 mg, tablets, orally, one day only. Dose regimen was based on body weight. Participants 20 to < 40 kg received a 20 mg dose, participants 40 to < 80 kg received a 40 mg dose and participants 80 to 100 kg received a 60 mg dose.
Cohort 3: Children (≥1 to <6 Years Old) Azilsartan medoxomil 0.66 mg/kg participant body weight, granules, reconstituted orally, one day only
Total Total of all reporting groups

Baseline Measures
    Cohort 1: Healthy Adults     Cohort 1: Adolescents (≥12 to <17 Years Old) 40-60 mg     Cohort 2: Children (≥6 to <12 Years Old) 20-60 mg     Cohort 3: Children (≥1 to <6 Years Old)     Total  
Number of Participants  
[units: participants]
  9     9     8     3     29  
Age  
[units: years]
Mean ± Standard Deviation
  28.3  ± 7.78     14.2  ± 1.64     9.1  ± 2.10     4.7  ± 0.58     16.2  ± 9.81  
Gender  
[units: participants]
         
Female     2     2     5     2     11  
Male     7     7     3     1     18  
Race/Ethnicity, Customized  
[units: participants]
         
Hispanic or Latino     4     0     1     0     5  
Not Hispanic or Latino     5     7     5     3     20  
Not Reported     0     2     2     0     4  
Race/Ethnicity, Customized  
[units: participants]
         
Asian     0     0     1     0     1  
Black or African American     1     2     2     2     7  
White     8     7     5     1     21  
Height  
[units: cm]
Mean ± Standard Deviation
  172.6  ± 9.70     163.1  ± 11.72     138.6  ± 12.74     107.7  ± 11.06     153.6  ± 23.45  
Weight  
[units: kg]
Mean ± Standard Deviation
  74.64  ± 11.207     71.71  ± 15.512     48.50  ± 22.523     18.30  ± 4.026     60.69  ± 23.859  
Body Mass Index (BMI)  
[units: kg/m^2]
Mean ± Standard Deviation
  25.06  ± 3.345     27.22  ± 6.611     24.29  ± 8.327     15.67  ± 0.551     24.54  ± 6.625  



  Outcome Measures
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1.  Primary:   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 ]

2.  Primary:   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 ]

3.  Primary:   Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC[0-inf]) for TAK-536   [ Time Frame: Day 1 ]

4.  Primary:   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 ]

5.  Primary:   Maximum Observed Plasma Concentration (Cmax) for TAK-536   [ Time Frame: Day 1 ]

6.  Primary:   Maximum Observed Plasma Concentration (Cmax) for TAK-536 Metabolite M-II   [ Time Frame: Day 1 ]

7.  Primary:   Time to Reach Cmax (Tmax) for TAK-536   [ Time Frame: Day 1 ]

8.  Primary:   Time to Reach Cmax (Tmax) for TAK-536 Metabolite M-II   [ Time Frame: Day 1 ]

9.  Primary:   Terminal Elimination Half-life (T1/2) for TAK-536   [ Time Frame: Day 1 ]

10.  Primary:   Terminal Elimination Half-life (T1/2) for TAK-536 Metabolite M-II   [ Time Frame: Day 1 ]

11.  Primary:   Apparent Oral Clearance (CL/F) for TAK-536   [ Time Frame: Day 1 ]

12.  Primary:   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 ]

13.  Primary:   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 ]

14.  Primary:   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 ]

15.  Primary:   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 ]

16.  Primary:   Renal Clearance (CLr) From 0 to 24 Hours Postdose (for Cohorts 1 and 2 Urine Pharmacokinetic Endpoint for TAK-536)   [ Time Frame: Day 1 ]

17.  Primary:   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 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
The study was discontinued without complete enrollment of Cohort 3. Therefore, PK modeling will be used to determine the appropriate doses in children 1 to <6 years of age, in lieu of completing Cohort 3.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Medical Director, Clinical Science
Organization: Takeda
phone: 800-778-2860
e-mail: clinicaltrialregistry@tpna.com


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
Results First Received: June 26, 2014
Last Updated: June 26, 2014
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency