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

NCT01078376 | Terminated Phase 1 Results DMC

• 3 other identifiers: TAK-491_1092009-013165-25U1111-1113-4416
• Study Type: interventional
• Target: 29
• Locations: 2 countries
• Sites: 8

Brief 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.

Conditions

Hypertension

Keywords

Pediatrics; Blood Pressure, High; Drug Therapy

Outcome Measures

Primary Outcomes (17)

• Area Under the Plasma Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC[0-tlqc]) for TAK-536

  AUC(0-tlqc) is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration (AUC\[0-tlqc\]).

  Day 1

• 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.

  AUC(0-tlqc) is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration (AUC\[0-tlqc\]).

  Day 1

• Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC[0-inf]) for TAK-536

  Area under the plasma concentration-time curve from time 0 to infinity, calculated as AUC(0-inf)=AUC(0-tlqc) + Clast/λz.

  Day 1

• Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC[0-inf]) for TAK-536 Metabolite M-II

  Area under the plasma concentration-time curve from time 0 to infinity, calculated as AUC(0-inf)=AUC(0-tlqc) + Clast/λz.

  Day 1

• Maximum Observed Plasma Concentration (Cmax) for TAK-536

  Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.

  Day 1

• Maximum Observed Plasma Concentration (Cmax) for TAK-536 Metabolite M-II

  Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.

  Day 1

• Time to Reach Cmax (Tmax) for TAK-536

  Tmax: Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax, as observed on Day 1.

  Day 1

• Time to Reach Cmax (Tmax) for TAK-536 Metabolite M-II

  Tmax: Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax, as observed on Day 1.

  Day 1

• Terminal Elimination Half-life (T1/2) for TAK-536

  Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma.

  Day 1

• Terminal Elimination Half-life (T1/2) for TAK-536 Metabolite M-II

  Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma.

  Day 1

• Apparent Oral Clearance (CL/F) for TAK-536

  CL/F is apparent clearance of the drug from the plasma, expressed in L/hr.

  Day 1

• 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)

  Day 1

• 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)

  Day 1

• 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)

  Fe=\[Ae(0-24)/dose\]×100 (molecular weight adjusted for metabolites.

  Day 1

• 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)

  Fe=\[Ae(0-24)/dose\]×100 (molecular weight adjusted for metabolites.

  Day 1

• Renal Clearance (CLr) From 0 to 24 Hours Postdose (for Cohorts 1 and 2 Urine Pharmacokinetic Endpoint for TAK-536)

  Renal clearance, calculated as CLr=Ae(0-24)/AUC(0-24).

  Day 1

• Renal Clearance (CLr) From 0 to 24 Hours Postdose (for Cohorts 1 and 2 Urine Pharmacokinetic Endpoint for TAK-536 Metabolite M-II)

  Renal clearance, calculated as CLr=Ae(0-24)/AUC(0-24).

  Day 1

Study Arms (4)

Cohort 1: Healthy Adults (18 years to 45 years old)

EXPERIMENTAL

Azilsartan medoxomil 80 mg, tablets, orally, one day only

Drug: Azilsartan medoxomil (TAK-491)

Cohort 1: Adolescents (≥12 to <17 years old)

EXPERIMENTAL

Azilsartan medoxomil 20 mg to 60 mg (based on participant weight), tablets, orally, one day only

Drug: Azilsartan medoxomil (TAK-491)

Cohort 2: Children (≥6 to <12 years old)

EXPERIMENTAL

Azilsartan medoxomil 20 mg to 60 mg (based on participant weight), tablets, orally, one day only

Drug: Azilsartan medoxomil (TAK-491)

Cohort 3: Children (≥1 to <6 years old)

EXPERIMENTAL

Azilsartan medoxomil 0.66 mg/kg participant body weight, granules, reconstituted orally, one day only

Drug: Azilsartan medoxomil (TAK-491)

Interventions

Azilsartan medoxomil (TAK-491) DRUG

Azilsartan medoxomil 80 mg, tablets, orally, one day only

Also known as: TAK-491

Cohort 1: Healthy Adults (18 years to 45 years old)

Eligibility Criteria

• Age: 1 Year - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Takeda: lead

Study Sites (8)

Unknown Facility

Little Rock, Arkansas, United States

Location

Unknown Facility

Atlanta, Georgia, United States

Location

Unknown Facility

Louisville, Kentucky, United States

Location

Unknown Facility

Toledo, Ohio, United States

Location

Unknown Facility

Birmingham, England, United Kingdom

Location

Unknown Facility

Bristol, England, United Kingdom

Location

Unknown Facility

London, England, United Kingdom

Location

Unknown Facility

Manchester, England, United Kingdom

Location

MeSH Terms

Conditions

Hypertension

Interventions

azilsartan medoxomil

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Limitations and Caveats

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.

Results Point of Contact

• Title: Medical Director, Clinical Science
• Organization: Takeda

clinicaltrialregistry@tpna.com

800-778-2860

Study Officials

• Medical Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2010
• First Posted: March 2, 2010
• Study Start: May 1, 2010
• Primary Completion: July 1, 2013
• Study Completion: September 1, 2013
• Last Updated: July 25, 2014
• Results First Posted: July 25, 2014

Record last verified: 2014-06

Locations

US (4); GB (4)