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

• Sponsor: Takeda (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01078376
• Collaborator: (none)
• Enrollment: 29
• Locations: 8
• Arms: 4
• Duration (Months): 40
• Patients Per Site: 3.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hypertension	Drug: Azilsartan medoxomil (TAK-491); Drug: Azilsartan medoxomil (TAK-491); Drug: Azilsartan medoxomil (TAK-491); Drug: Azilsartan medoxomil (TAK-491)	Phase 1

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. In younger children though, high blood pressure is a common consequence of underlying diseases, such as renal diseases.

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), a blood pressure lowering medicine that had not been tested in children.

To be eligible to take part in this study, children with a diagnosis of hypertension (primary or secondary) must have been between the ages of 1 year and 16 years old (up to their 17th birthday). 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. Adults who do not have hypertension also took part in this study to provide comparison.

This study took place in 9 sites in the UK and USA. A total of 20 children with hypertension and 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 participant 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 (participants 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 29 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (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
• Study Start Date: May 1, 2010
• Actual Primary Completion Date: Jul 1, 2013
• Actual Study Completion Date: Sep 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1: Healthy Adults (18 years to 45 years old) Azilsartan medoxomil 80 mg, tablets, orally, one day only	Drug: Azilsartan medoxomil (TAK-491); Azilsartan medoxomil 80 mg, tablets, orally, one day only; Other Names: TAK-491
Experimental: Cohort 1: Adolescents (≥12 to <17 years old) Azilsartan medoxomil 20 mg to 60 mg (based on participant weight), tablets, orally, one day only	Drug: Azilsartan medoxomil (TAK-491); Azilsartan medoxomil 20 mg to 60 mg (based on participant weight), tablets, orally, one day only; Other Names: TAK-491
Experimental: Cohort 2: Children (≥6 to <12 years old) Azilsartan medoxomil 20 mg to 60 mg (based on participant weight), tablets, orally, one day only	Drug: Azilsartan medoxomil (TAK-491); Azilsartan medoxomil 20 mg to 60 mg (based on participant weight), tablets, orally, one day only; Other Names: TAK-491
Experimental: Cohort 3: Children (≥1 to <6 years old) Azilsartan medoxomil 0.66 mg/kg participant body weight, granules, reconstituted orally, one day only	Drug: Azilsartan medoxomil (TAK-491); Azilsartan medoxomil 0.66 mg/kg participant body weight, granules, reconstituted orally, one day only; Other Names: TAK-491

Outcome Measures

Primary Outcome Measures

1. Area Under the Plasma Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC[0-tlqc]) for TAK-536 [Day 1]

   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]).

2. 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. [Day 1]

   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]).

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

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

4. Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC[0-inf]) for TAK-536 Metabolite M-II [Day 1]

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

12. 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]

13. 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]

14. 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) [Day 1]

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

15. 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) [Day 1]

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

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

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

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

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Year to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Little Rock	Arkansas	United States
2		Atlanta	Georgia	United States
3		Louisville	Kentucky	United States
4		Toledo	Ohio	United States
5		Birmingham	England	United Kingdom
6		Bristol	England	United Kingdom
7		London	England	United Kingdom
8		Manchester	England	United Kingdom

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Medical Director, Takeda

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT01078376
• Other Study ID Numbers: TAK-491_109; 2009-013165-25; U1111-1113-4416
• First Posted: Mar 2, 2010
• Last Update Posted: Jul 25, 2014
• Last Verified: Jun 1, 2014

• Keywords provided by Takeda: Pediatrics; Blood Pressure, High; Drug Therapy
• Additional relevant MeSH terms: Hypertension; Azilsartan medoxomil

Study Results

Participant Flow

Recruitment Details	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 Detail	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.

Arm/Group Title	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)
Arm/Group Description	Azilsartan medoxomil 80 mg, tablets, orally, one day only	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.	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.	Azilsartan medoxomil 0.66 mg/kg participant body weight, granules, reconstituted orally, one day only
Period Title: Overall Study
STARTED	9	9	8	3
COMPLETED	9	9	8	3
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	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
Arm/Group Description	Azilsartan medoxomil 80 mg, tablets, orally, one day only	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.	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.	Azilsartan medoxomil 0.66 mg/kg participant body weight, granules, reconstituted orally, one day only	Total of all reporting groups
Overall Participants	9	9	8	3	29
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	28.3 (7.78)	14.2 (1.64)	9.1 (2.10)	4.7 (0.58)	16.2 (9.81)
Sex: Female, Male (Count of Participants)
Female	2 22.2%	2 22.2%	5 62.5%	2 66.7%	11 37.9%
Male	7 77.8%	7 77.8%	3 37.5%	1 33.3%	18 62.1%
Race/Ethnicity, Customized (participants) [Number]
Hispanic or Latino	4 44.4%	0 0%	1 12.5%	0 0%	5 17.2%
Not Hispanic or Latino	5 55.6%	7 77.8%	5 62.5%	3 100%	20 69%
Not Reported	0 0%	2 22.2%	2 25%	0 0%	4 13.8%
Race/Ethnicity, Customized (participants) [Number]
Asian	0 0%	0 0%	1 12.5%	0 0%	1 3.4%
Black or African American	1 11.1%	2 22.2%	2 25%	2 66.7%	7 24.1%
White	8 88.9%	7 77.8%	5 62.5%	1 33.3%	21 72.4%
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	172.6 (9.70)	163.1 (11.72)	138.6 (12.74)	107.7 (11.06)	153.6 (23.45)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	74.64 (11.207)	71.71 (15.512)	48.50 (22.523)	18.30 (4.026)	60.69 (23.859)
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	25.06 (3.345)	27.22 (6.611)	24.29 (8.327)	15.67 (0.551)	24.54 (6.625)

Outcome Measures

1. Primary Outcome

Title	Area Under the Plasma Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC[0-tlqc]) for TAK-536
Description	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]).
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Set; Results are presented by individual dose for Cohorts 1 and 2.

Arm/Group Title	Cohort 1: Healthy Adults	Cohort 1: Adolescents (≥12 to <17 Years Old) 60 mg	Cohort 1: Adolescents (≥12 to <17 Years Old) 40 mg	Cohort 2: Children (≥6 to <12 Years Old) 60 mg	Cohort 2: Children (≥6 to <12 Years Old) 40 mg	Cohort 2: Children (≥6 to <12 Years Old) 20 mg	Cohort 3: Children (≥1 to <6 Years Old)
Arm/Group Description	Azilsartan medoxomil 80 mg, tablets, orally, one day only	Azilsartan medoxomil 60 mg, tablets, orally, one day only	Azilsartan medoxomil 40 mg, tablets, orally, one day only	Azilsartan medoxomil 60 mg, tablets, orally, one day only	Azilsartan medoxomil 40 mg, tablets, orally, one day only	Azilsartan medoxomil 20 mg, tablets, orally, one day only	Azilsartan medoxomil 0.66 mg/kg participant body weight, granules, reconstituted orally, one day only
Measure Participants	9	2	6	1	4	3	3
Mean (Standard Deviation) [ng.hr/mL]	40613 (9609.6)	23889 (5383.8)	17423 (3559.7)	16056 (NA)	22556 (5792.6)	18691 (5489.9)	16963 (4948.4)

2. Primary Outcome

Title	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.
Description	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]).
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Set; Results are presented by individual dose for Cohorts 1 and 2.

Arm/Group Title	Cohort 1: Healthy Adults	Cohort 1: Adolescents (≥12 to <17 Years Old) 60 mg	Cohort 1: Adolescents (≥12 to <17 Years Old) 40 mg	Cohort 2: Children (≥6 to <12 Years Old) 60 mg	Cohort 2: Children (≥6 to <12 Years Old) 40 mg	Cohort 2: Children (≥6 to <12 Years Old) 20 mg	Cohort 3: Children (≥1 to <6 Years Old)
Arm/Group Description	Azilsartan medoxomil 80 mg, tablets, orally, one day only	Azilsartan medoxomil 60 mg, tablets, orally, one day only	Azilsartan medoxomil 40 mg, tablets, orally, one day only	Azilsartan medoxomil 60 mg, tablets, orally, one day only	Azilsartan medoxomil 40 mg, tablets, orally, one day only	Azilsartan medoxomil 20 mg, tablets, orally, one day only	Azilsartan medoxomil 0.66 mg/kg participant body weight, granules, reconstituted orally, one day only
Measure Participants	9	2	6	1	4	3	3
Mean (Standard Deviation) [ng.hr/mL]	11563 (3106.5)	7409 (78.6)	7428 (2120.7)	7392 (NA)	7929 (3502.6)	9130 (1338.3)	7285 (3626.0)

3. Primary Outcome

Title	Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC[0-inf]) for TAK-536
Description	Area under the plasma concentration-time curve from time 0 to infinity, calculated as AUC(0-inf)=AUC(0-tlqc) + Clast/λz.
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Set; Results are presented by individual dose for Cohorts 1 and 2.

Arm/Group Title	Cohort 1: Healthy Adults	Cohort 1: Adolescents (≥12 to <17 Years Old) 60 mg	Cohort 1: Adolescents (≥12 to <17 Years Old) 40 mg	Cohort 2: Children (≥6 to <12 Years Old) 60 mg	Cohort 2: Children (≥6 to <12 Years Old) 40 mg	Cohort 2: Children (≥6 to <12 Years Old) 20 mg	Cohort 3: Children (≥1 to <6 Years Old)
Arm/Group Description	Azilsartan medoxomil 80 mg, tablets, orally, one day only	Azilsartan medoxomil 60 mg, tablets, orally, one day only	Azilsartan medoxomil 40 mg, tablets, orally, one day only	Azilsartan medoxomil 60 mg, tablets, orally, one day only	Azilsartan medoxomil 40 mg, tablets, orally, one day only	Azilsartan medoxomil 20 mg, tablets, orally, one day only	Azilsartan medoxomil 0.66 mg/kg participant body weight, granules, reconstituted orally, one day only
Measure Participants	9	2	6	1	4	3	3
Mean (Standard Deviation) [ng.hr/mL]	44820 (11680.7)	26411 (6703.1)	18686 (3720.4)	16563 (NA)	23792 (6157.0)	19543 (6181.1)	17771 (5263.1)

4. Primary Outcome

Title	Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC[0-inf]) for TAK-536 Metabolite M-II
Description	Area under the plasma concentration-time curve from time 0 to infinity, calculated as AUC(0-inf)=AUC(0-tlqc) + Clast/λz.
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Set; Results are presented by individual dose for Cohorts 1 and 2.

Arm/Group Title	Cohort 1: Healthy Adults	Cohort 1: Adolescents (≥12 to <17 Years Old) 60 mg	Cohort 1: Adolescents (≥12 to <17 Years Old) 40 mg	Cohort 2: Children (≥6 to <12 Years Old) 60 mg	Cohort 2: Children (≥6 to <12 Years Old) 40 mg	Cohort 2: Children (≥6 to <12 Years Old) 20 mg	Cohort 3: Children (≥1 to <6 Years Old)
Arm/Group Description	Azilsartan medoxomil 80 mg, tablets, orally, one day only	Azilsartan medoxomil 60 mg, tablets, orally, one day only	Azilsartan medoxomil 40 mg, tablets, orally, one day only	Azilsartan medoxomil 60 mg, tablets, orally, one day only	Azilsartan medoxomil 40 mg, tablets, orally, one day only	Azilsartan medoxomil 20 mg, tablets, orally, one day only	Azilsartan medoxomil 0.66 mg/kg participant body weight, granules, reconstituted orally, one day only
Measure Participants	9	2	6	1	4	3	3
Mean (Standard Deviation) [ng.hr/mL]	19188 (6766.0)	10596 (1168.8)	12532 (3905.3)	8961 (NA)	11387 (5440.7)	14230 (3419.6)	9477 (4659.6)

5. Primary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) for TAK-536
Description	Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Set; Results are presented by individual dose for Cohorts 1 and 2.

Arm/Group Title	Cohort 1: Healthy Adults	Cohort 1: Adolescents (≥12 to <17 Years Old) 60 mg	Cohort 1: Adolescents (≥12 to <17 Years Old) 40 mg	Cohort 2: Children (≥6 to <12 Years Old) 60 mg	Cohort 2: Children (≥6 to <12 Years Old) 40 mg	Cohort 2: Children (≥6 to <12 Years Old) 20 mg	Cohort 3: Children (≥1 to <6 Years Old)
Arm/Group Description	Azilsartan medoxomil 80 mg, tablets, orally, one day only	Azilsartan medoxomil 60 mg, tablets, orally, one day only	Azilsartan medoxomil 40 mg, tablets, orally, one day only	Azilsartan medoxomil 60 mg, tablets, orally, one day only	Azilsartan medoxomil 40 mg, tablets, orally, one day only	Azilsartan medoxomil 20 mg, tablets, orally, one day only	Azilsartan medoxomil 0.66 mg/kg participant body weight, granules, reconstituted orally, one day only
Measure Participants	9	2	6	1	4	3	3
Mean (Standard Deviation) [ng/mL]	5699 (1346.1)	3245 (106.1)	2512 (701.6)	2810 (NA)	3858 (1363.0)	2960 (364.3)	3320 (656.0)

6. Primary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) for TAK-536 Metabolite M-II
Description	Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Set; Results are presented by individual dose for Cohorts 1 and 2.

Arm/Group Title	Cohort 1: Healthy Adults	Cohort 1: Adolescents (≥12 to <17 Years Old) 60 mg	Cohort 1: Adolescents (≥12 to <17 Years Old) 40 mg	Cohort 2: Children (≥6 to <12 Years Old) 60 mg	Cohort 2: Children (≥6 to <12 Years Old) 40 mg	Cohort 2: Children (≥6 to <12 Years Old) 20 mg	Cohort 3: Children (≥1 to <6 Years Old)
Arm/Group Description	Azilsartan medoxomil 80 mg, tablets, orally, one day only	Azilsartan medoxomil 60 mg, tablets, orally, one day only	Azilsartan medoxomil 40 mg, tablets, orally, one day only	Azilsartan medoxomil 60 mg, tablets, orally, one day only	Azilsartan medoxomil 40 mg, tablets, orally, one day only	Azilsartan medoxomil 20 mg, tablets, orally, one day only	Azilsartan medoxomil 0.66 mg/kg participant body weight, granules, reconstituted orally, one day only
Measure Participants	9	2	6	1	4	3	3
Mean (Standard Deviation) [ng/mL]	736 (241.6)	480 (74.2)	535 (200.2)	514 (NA)	561 (211.7)	561 (40.3)	488 (212.2)

7. Primary Outcome

Title	Time to Reach Cmax (Tmax) for TAK-536
Description	Tmax: Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax, as observed on Day 1.
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Set; Results are presented by individual dose for Cohorts 1 and 2.

Arm/Group Title	Cohort 1: Healthy Adults	Cohort 1: Adolescents (≥12 to <17 Years Old) 60 mg	Cohort 1: Adolescents (≥12 to <17 Years Old) 40 mg	Cohort 2: Children (≥6 to <12 Years Old) 60 mg	Cohort 2: Children (≥6 to <12 Years Old) 40 mg	Cohort 2: Children (≥6 to <12 Years Old) 20 mg	Cohort 3: Children (≥1 to <6 Years Old)
Arm/Group Description	Azilsartan medoxomil 80 mg, tablets, orally, one day only	Azilsartan medoxomil 60 mg, tablets, orally, one day only	Azilsartan medoxomil 40 mg, tablets, orally, one day only	Azilsartan medoxomil 60 mg, tablets, orally, one day only	Azilsartan medoxomil 40 mg, tablets, orally, one day only	Azilsartan medoxomil 20 mg, tablets, orally, one day only	Azilsartan medoxomil 0.66 mg/kg participant body weight, granules, reconstituted orally, one day only
Measure Participants	9	2	6	1	4	3	3
Median (Full Range) [hr]	2.00 (0.8819)	2.01 (0.0118)	2.00 (0.4082)	2.00 (NA)	2.00 (2.2043)	2.00 (0.0096)	1.00 (0.0000)

8. Primary Outcome

Title	Time to Reach Cmax (Tmax) for TAK-536 Metabolite M-II
Description	Tmax: Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax, as observed on Day 1.
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Set; Results are presented by individual dose for Cohorts 1 and 2.

Arm/Group Title	Cohort 1: Healthy Adults	Cohort 1: Adolescents (≥12 to <17 Years Old) 60 mg	Cohort 1: Adolescents (≥12 to <17 Years Old) 40 mg	Cohort 2: Children (≥6 to <12 Years Old) 60 mg	Cohort 2: Children (≥6 to <12 Years Old) 40 mg	Cohort 2: Children (≥6 to <12 Years Old) 20 mg	Cohort 3: Children (≥1 to <6 Years Old)
Arm/Group Description	Azilsartan medoxomil 80 mg, tablets, orally, one day only	Azilsartan medoxomil 60 mg, tablets, orally, one day only	Azilsartan medoxomil 40 mg, tablets, orally, one day only	Azilsartan medoxomil 60 mg, tablets, orally, one day only	Azilsartan medoxomil 40 mg, tablets, orally, one day only	Azilsartan medoxomil 20 mg, tablets, orally, one day only	Azilsartan medoxomil 0.66 mg/kg participant body weight, granules, reconstituted orally, one day only
Measure Participants	9	2	6	1	4	3	3
Median (Full Range) [hr]	6.00 (1.4227)	5.00 (1.4142)	6.00 (0.8256)	6.00 (NA)	4.03 (1.9890)	4.00 (2.3094)	6.0 (0.0000)

9. Primary Outcome

Title	Terminal Elimination Half-life (T1/2) for TAK-536
Description	Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma.
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Set; Results are presented by individual dose for Cohorts 1 and 2.

Arm/Group Title	Cohort 1: Healthy Adults	Cohort 1: Adolescents (≥12 to <17 Years Old) 60 mg	Cohort 1: Adolescents (≥12 to <17 Years Old) 40 mg	Cohort 2: Children (≥6 to <12 Years Old) 60 mg	Cohort 2: Children (≥6 to <12 Years Old) 40 mg	Cohort 2: Children (≥6 to <12 Years Old) 20 mg	Cohort 3: Children (≥1 to <6 Years Old)
Arm/Group Description	Azilsartan medoxomil 80 mg, tablets, orally, one day only	Azilsartan medoxomil 60 mg, tablets, orally, one day only	Azilsartan medoxomil 40 mg, tablets, orally, one day only	Azilsartan medoxomil 60 mg, tablets, orally, one day only	Azilsartan medoxomil 40 mg, tablets, orally, one day only	Azilsartan medoxomil 20 mg, tablets, orally, one day only	Azilsartan medoxomil 0.66 mg/kg participant body weight, granules, reconstituted orally, one day only
Measure Participants	9	2	6	1	4	3	3
Mean (Standard Deviation) [hr]	7.35 (1.083)	7.74 (0.621)	5.76 (1.158)	5.07 (NA)	5.75 (0.760)	5.37 (0.922)	4.59 (1.627)

10. Primary Outcome

Title	Terminal Elimination Half-life (T1/2) for TAK-536 Metabolite M-II
Description	Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma.
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Set; Results are presented by individual dose for Cohorts 1 and 2.

Arm/Group Title	Cohort 1: Healthy Adults	Cohort 1: Adolescents (≥12 to <17 Years Old) 60 mg	Cohort 1: Adolescents (≥12 to <17 Years Old) 40 mg	Cohort 2: Children (≥6 to <12 Years Old) 60 mg	Cohort 2: Children (≥6 to <12 Years Old) 40 mg	Cohort 2: Children (≥6 to <12 Years Old) 20 mg	Cohort 3: Children (≥1 to <6 Years Old)
Arm/Group Description	Azilsartan medoxomil 80 mg, tablets, orally, one day only	Azilsartan medoxomil 60 mg, tablets, orally, one day only	Azilsartan medoxomil 40 mg, tablets, orally, one day only	Azilsartan medoxomil 60 mg, tablets, orally, one day only	Azilsartan medoxomil 40 mg, tablets, orally, one day only	Azilsartan medoxomil 20 mg, tablets, orally, one day only	Azilsartan medoxomil 0.66 mg/kg participant body weight, granules, reconstituted orally, one day only
Measure Participants	9	2	6	1	4	3	3
Mean (Standard Deviation) [hr]	16.60 (6.870)	12.78 (2.915)	14.00 (2.414)	8.50 (NA)	11.56 (3.314)	13.97 (2.983)	10.35 (2.770)

11. Primary Outcome

Title	Apparent Oral Clearance (CL/F) for TAK-536
Description	CL/F is apparent clearance of the drug from the plasma, expressed in L/hr.
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Set; Results are presented by individual dose for Cohorts 1 and 2.

Arm/Group Title	Cohort 1: Healthy Adults	Cohort 1: Adolescents (≥12 to <17 Years Old) 60 mg	Cohort 1: Adolescents (≥12 to <17 Years Old) 40 mg	Cohort 2: Children (≥6 to <12 Years Old) 60 mg	Cohort 2: Children (≥6 to <12 Years Old) 40 mg	Cohort 2: Children (≥6 to <12 Years Old) 20 mg	Cohort 3: Children (≥1 to <6 Years Old)
Arm/Group Description	Azilsartan medoxomil 80 mg, tablets, orally, one day only	Azilsartan medoxomil 60 mg, tablets, orally, one day only	Azilsartan medoxomil 40 mg, tablets, orally, one day only	Azilsartan medoxomil 60 mg, tablets, orally, one day only	Azilsartan medoxomil 40 mg, tablets, orally, one day only	Azilsartan medoxomil 20 mg, tablets, orally, one day only	Azilsartan medoxomil 0.66 mg/kg participant body weight, granules, reconstituted orally, one day only
Measure Participants	9	2	6	1	4	3	3
Mean (Standard Deviation) [L/hr]	1.52 (0.414)	1.88 (0.477)	1.78 (0.411)	2.90 (NA)	1.43 (0.427)	0.87 (0.232)	0.54 (0.134)

12. Primary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Set; Results are presented by individual dose for Cohorts 1 and 2.

Arm/Group Title	Cohort 1: Healthy Adults	Cohort 1: Adolescents (≥12 to <17 Years Old) 60 mg	Cohort 1: Adolescents (≥12 to <17 Years Old) 40 mg	Cohort 2: Children (≥6 to <12 Years Old) 60 mg	Cohort 2: Children (≥6 to <12 Years Old) 40 mg	Cohort 2: Children (≥6 to <12 Years Old) 20 mg
Arm/Group Description	Azilsartan medoxomil 80 mg, tablets, orally, one day only	Azilsartan medoxomil 60 mg, tablets, orally, one day only	Azilsartan medoxomil 40 mg, tablets, orally, one day only	Azilsartan medoxomil 60 mg, tablets, orally, one day only	Azilsartan medoxomil 40 mg, tablets, orally, one day only	Azilsartan medoxomil 20 mg, tablets, orally, one day only
Measure Participants	9	3	6	1	4	3
Mean (Standard Deviation) [mg]	10.65 (4.673)	4.56 (1.029)	2.89 (0.936)	4.59 (NA)	3.63 (2.125)	1.27 (0.580)

13. Primary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Set; Results are presented by individual dose for Cohorts 1 and 2.

Arm/Group Title	Cohort 1: Healthy Adults	Cohort 1: Adolescents (≥12 to <17 Years Old) 60 mg	Cohort 1: Adolescents (≥12 to <17 Years Old) 40 mg	Cohort 2: Children (≥6 to <12 Years Old) 60 mg	Cohort 2: Children (≥6 to <12 Years Old) 40 mg	Cohort 2: Children (≥6 to <12 Years Old) 20 mg
Arm/Group Description	Azilsartan medoxomil 80 mg, tablets, orally, one day only	Azilsartan medoxomil 60 mg, tablets, orally, one day only	Azilsartan medoxomil 40 mg, tablets, orally, one day only	Azilsartan medoxomil 60 mg, tablets, orally, one day only	Azilsartan medoxomil 40 mg, tablets, orally, one day only	Azilsartan medoxomil 20 mg, tablets, orally, one day only
Measure Participants	9	3	6	1	4	3
Mean (Standard Deviation) [mg]	6.60 (5.149)	2.93 (0.582)	2.73 (1.528)	4.43 (NA)	2.77 (1.197)	1.48 (0.284)

14. Primary Outcome

Title	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)
Description	Fe=[Ae(0-24)/dose]×100 (molecular weight adjusted for metabolites.
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Set; Results are presented by individual dose for Cohorts 1 and 2.

Arm/Group Title	Cohort 1: Healthy Adults	Cohort 1: Adolescents (≥12 to <17 Years Old) 60 mg	Cohort 1: Adolescents (≥12 to <17 Years Old) 40 mg	Cohort 2: Children (≥6 to <12 Years Old) 60 mg	Cohort 2: Children (≥6 to <12 Years Old) 40 mg	Cohort 2: Children (≥6 to <12 Years Old) 20 mg
Arm/Group Description	Azilsartan medoxomil 80 mg, tablets, orally, one day only	Azilsartan medoxomil 60 mg, tablets, orally, one day only	Azilsartan medoxomil 40 mg, tablets, orally, one day only	Azilsartan medoxomil 60 mg, tablets, orally, one day only	Azilsartan medoxomil 40 mg, tablets, orally, one day only	Azilsartan medoxomil 20 mg, tablets, orally, one day only
Measure Participants	9	3	6	1	4	3
Mean (Standard Deviation) [percent]	16.65 (7.302)	9.50 (2.144)	9.04 (2.925)	9.57 (NA)	11.36 (6.639)	7.94 (3.622)

15. Primary Outcome

Title	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)
Description	Fe=[Ae(0-24)/dose]×100 (molecular weight adjusted for metabolites.
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Set; Results are presented by individual dose for Cohorts 1 and 2.

Arm/Group Title	Cohort 1: Healthy Adults	Cohort 1: Adolescents (≥12 to <17 Years Old) 60 mg	Cohort 1: Adolescents (≥12 to <17 Years Old) 40 mg	Cohort 2: Children (≥6 to <12 Years Old) 60 mg	Cohort 2: Children (≥6 to <12 Years Old) 40 mg	Cohort 2: Children (≥6 to <12 Years Old) 20 mg
Arm/Group Description	Azilsartan medoxomil 80 mg, tablets, orally, one day only	Azilsartan medoxomil 60 mg, tablets, orally, one day only	Azilsartan medoxomil 40 mg, tablets, orally, one day only	Azilsartan medoxomil 60 mg, tablets, orally, one day only	Azilsartan medoxomil 40 mg, tablets, orally, one day only	Azilsartan medoxomil 20 mg, tablets, orally, one day only
Measure Participants	9	3	6	1	4	3
Mean (Standard Deviation) [percent]	11.01 (8.581)	6.55 (1.293)	9.11 (5.094)	9.85 (NA)	9.22 (3.991)	9.89 (1.896)

16. Primary Outcome

Title	Renal Clearance (CLr) From 0 to 24 Hours Postdose (for Cohorts 1 and 2 Urine Pharmacokinetic Endpoint for TAK-536)
Description	Renal clearance, calculated as CLr=Ae(0-24)/AUC(0-24).
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Set; Results are presented by individual dose for Cohorts 1 and 2.

Arm/Group Title	Cohort 1: Healthy Adults	Cohort 1: Adolescents (≥12 to <17 Years Old) 60 mg	Cohort 1: Adolescents (≥12 to <17 Years Old) 40 mg	Cohort 2: Children (≥6 to <12 Years Old) 60 mg	Cohort 2: Children (≥6 to <12 Years Old) 40 mg	Cohort 2: Children (≥6 to <12 Years Old) 20 mg
Arm/Group Description	Azilsartan medoxomil 80 mg, tablets, orally, one day only	Azilsartan medoxomil 60 mg, tablets, orally, one day only	Azilsartan medoxomil 40 mg, tablets, orally, one day only	Azilsartan medoxomil 60 mg, tablets, orally, one day only	Azilsartan medoxomil 40 mg, tablets, orally, one day only	Azilsartan medoxomil 20 mg, tablets, orally, one day only
Measure Participants	9	2	6	1	4	3
Mean (Standard Deviation) [L/hr]	0.28 (0.130)	0.22 (0.051)	0.17 (0.077)	0.29 (NA)	0.15 (0.069)	0.07 (0.011)

17. Primary Outcome

Title	Renal Clearance (CLr) From 0 to 24 Hours Postdose (for Cohorts 1 and 2 Urine Pharmacokinetic Endpoint for TAK-536 Metabolite M-II)
Description	Renal clearance, calculated as CLr=Ae(0-24)/AUC(0-24).
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Set; Results are presented by individual dose for Cohorts 1 and 2.

Arm/Group Title	Cohort 1: Healthy Adults	Cohort 1: Adolescents (≥12 to <17 Years Old) 60 mg	Cohort 1: Adolescents (≥12 to <17 Years Old) 40 mg	Cohort 2: Children (≥6 to <12 Years Old) 60 mg	Cohort 2: Children (≥6 to <12 Years Old) 40 mg	Cohort 2: Children (≥6 to <12 Years Old) 20 mg
Arm/Group Description	Azilsartan medoxomil 80 mg, tablets, orally, one day only	Azilsartan medoxomil 60 mg, tablets, orally, one day only	Azilsartan medoxomil 40 mg, tablets, orally, one day only	Azilsartan medoxomil 60 mg, tablets, orally, one day only	Azilsartan medoxomil 40 mg, tablets, orally, one day only	Azilsartan medoxomil 20 mg, tablets, orally, one day only
Measure Participants	9	2	6	1	4	3
Mean (Standard Deviation) [L/hr]	0.55 (0.309)	0.37 (0.084)	0.34 (0.146)	0.60 (NA)	0.36 (0.099)	0.16 (0.022)

Adverse Events

Time Frame	A treatment-emergent adverse event (TEAE) had an onset occurring after the first dose of study medication and within 14 days after the last dose of study medication or, if an SAE, within 30 days after last dose of study medication.
Adverse Event Reporting Description	At each visit the investigator assessed whether any subjective adverse events have occurred and had to document any occurrence of adverse events and clinically significant abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Arm/Group Title	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)
Arm/Group Description	Azilsartan medoxomil 80 mg, tablets, orally, one day only		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.		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.		Azilsartan medoxomil 0.66 mg/kg participant body weight, granules, reconstituted orally, one day only
All Cause Mortality
	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)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	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)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/9 (0%)		0/8 (0%)		0/3 (0%)
Other (Not Including Serious) Adverse Events
	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)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/9 (22.2%)		5/9 (55.6%)		3/8 (37.5%)		0/3 (0%)
Cardiac disorders
Sinus bradycardia	1/9 (11.1%)		0/9 (0%)		0/8 (0%)		0/3 (0%)
Gastrointestinal disorders
Abdominal discomfort	0/9 (0%)		2/9 (22.2%)		0/8 (0%)		0/3 (0%)
General disorders
Infusion site pain	0/9 (0%)		0/9 (0%)		1/8 (12.5%)		0/3 (0%)
Infections and infestations
Infected bites	1/9 (11.1%)		0/9 (0%)		0/8 (0%)		0/3 (0%)
Sinusitis	0/9 (0%)		0/9 (0%)		1/8 (12.5%)		0/3 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/9 (0%)		0/9 (0%)		1/8 (12.5%)		0/3 (0%)
Nervous system disorders
Headache	0/9 (0%)		2/9 (22.2%)		1/8 (12.5%)		0/3 (0%)
Dizziness	0/9 (0%)		1/9 (11.1%)		0/8 (0%)		0/3 (0%)
Migraine	0/9 (0%)		1/9 (11.1%)		0/8 (0%)		0/3 (0%)
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	0/9 (0%)		0/9 (0%)		1/8 (12.5%)		0/3 (0%)
Vascular disorders
Haematoma	0/9 (0%)		1/9 (11.1%)		0/8 (0%)		0/3 (0%)

Limitations/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.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

No publication related to study results will be made without Sponsor's prior written approval. Any proposed publication or presentation will be submitted to Sponsor for review 60 days in advance of publication. Institution will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for an additional 60 days to preserve intellectual property.