An Efficacy and Safety Study in Children 6 to Less Than 18 Years of Age With Hypertension

Arbor Pharmaceuticals

Status and phase

Completed

Phase 3

Conditions

Hypertension

Treatments

Drug: Placebo for Azilsartan Medoxomil

Drug: Azilsartan Medoxomil High-dose (40 mg)

Drug: Placebo for Losartan

Drug: Azilsartan Medoxomil Medium-dose (20 mg)

Drug: Azilsartan Medoxomil Low-dose

Drug: Losartan

Study type

Interventional

Funder types

Industry

Identifiers

NCT02235909

AR14.001

Details and patient eligibility

About

The purpose of the study is to evaluate the efficacy and safety of the study drug relative to an active comparator losartan which is in the same class of drug and is approved for use in the pediatric population aged 6 years and older. Approximately 260 subjects will participate in a 6-week, double-blind, randomized, treatment phase, followed by a 2-week, double-blind, randomized, placebo-controlled withdrawal phase. A 44-week, open-label extension in which all subjects will receive azilsartan and other antihypertensive medications (if needed). Blood pressure will be assessed throughout the study.

Full description

The purpose of the study is to evaluate the efficacy and safety of the study drug relative to an active comparator losartan which the same class of drug and is approved for use in the pediatric population aged 6 years and older. Approximately 260 subjects will participate in a 6-week, double-blind, randomized, treatment phase, followed by a 2-week, double-blind, randomized, placebo-controlled withdrawal phase. This study also includes a 44-week, open-label extension Phase in which all subjects will receive azilsartan and other antihypertensive medications (if needed) in order to reach an optimal blood pressure. Blood pressure will be assessed in the clinic throughout the study, and subjects may also participate in a 24-hour ambulatory blood pressure monitoring procedure at baseline, at the end of the double-blind Phase and at the end of the open-label Phase.

Enrollment

377 patients

Sex

All

Ages

6 to 18 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

The subject has hypertension (primary or secondary) defined as clinic Seated Diastolic BP ≥95th percentile (by age, gender, and height) or ≥90th percentile (by age, gender, height) if chronic renal disease, diabetes, heart failure or hypertensive target organ damage is present
1. If currently treated: The subject has a documented historical diagnosis of hypertension AND a post-washout clinic Seated Diastolic BP meeting the above criteria on Day -1 (or Day 1 for subjects not participating in Ambulatory Blood Pressure Monitoring)
2. If currently untreated: The subject has elevated Seated Diastolic BP meeting the above criteria on 3 separate occasions before Randomization, including on Day -1 (or Day 1 for subjects not participating in Ambulatory Blood Pressure Monitoring)
The subject is male or female and aged 6 to <18 years at Baseline and weighs at least 25 kg
The subject agrees to continue their previously implemented nonpharmacological life style modifications if begun prior to Screening. Note: For subjects participating in a weight loss program, the weight maintenance

Exclusion criteria

The subject has a clinic Seated Diastolic BP greater than 15 mm Hg and/or Seated Diastolic BP greater than 10 mm Hg above the 99th percentile for age, gender, and height as confirmed by the average (arithmetic mean) of 3 serial clinic seated BP measurements at Screening/Visit 1
The subject has a diagnosis of malignant or accelerated hypertension
The subject is currently treated with more than 2 antihypertensive agents
The subject or parent/legal guardian is not willing for the subject's previous antihypertensive medications to be stopped
The subject has participated in the intensive, active weight-loss phase of a weight-loss program within 30 days prior to Screening/Visit 1
The subject has any of the following: severe renal impairment (eGFR <30 mL/min/1.73 m2 by the Schwartz formula); is currently undergoing dialysis treatment; renovascular disease affecting both kidneys or a solitary kidney; severe nephrotic syndrome not in remission; or serum albumin <2.5 g/dL
The subject has a history or clinical manifestations of severe cardiovascular, hepato-biliary, gastrointestinal, endocrine-metabolic (e.g., hyperthyroidism, Cushing's syndrome), hematologic, immunologic, genito-urinary, or psychiatric disease, cancer, and/or any conditions that would interfere with the health status of the subject through study participation, or would jeopardize study integrity in the opinion of the investigator
The subject is suffering from uncorrected coarctation of the aorta, or hemodynamically significant left ventricular outflow tract obstruction due to eg, aortic valvular disease, or is likely to undergo a procedure known to affect blood pressure (eg, repair of arterial anomalies) during the course of the study
The subject is poorly controlled diabetic defined as having a glycosylated hemoglobin value >8.5% at Screening/Visit 1
The subject has hyperkalemia as defined by the central laboratory's normal reference range or any pertinent electrolyte disorders at Screening/Visit

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Triple Blind

377 participants in 13 patient groups, including a placebo group

Double-blind: Azilsartan Medoxomil - Low dose

Experimental group

Description:

6-week, double-blind (DB), randomized, treatment phase (DB Phase): Azilsartan medoxomil low-dose (AZM-L), 10 mg once daily.

Treatment:

Drug: Azilsartan Medoxomil Low-dose

Double blind phase: Losartan

Active Comparator group

Description:

6-week, double-blind (DB), randomized, treatment phase (DB Phase): Starting at Losartan 25/50 and force titrated to 50/100 mg daily at Week 2.

Treatment:

Drug: Losartan

Withdrawal Phase: Azilsartan medoxomil low-dose (AZM-L)

Active Comparator group

Description:

Experimental Arm in the Withdrawal Phase, subjects will be randomized (1:1) to continue taking their previously assigned active treatment (AZM-L) that was taken in Double blind OR to be switched to placebo.

Treatment:

Drug: Azilsartan Medoxomil Low-dose

Withdrawal Phase: Placebo to match azilsartan medoxomil low dose (AZM-L)

Placebo Comparator group

Description:

Placebo Arm in the Withdrawal Phase for subjects who were on AZM-L in double blind then randomized (1:1) to placebo for withdrawal phase

Treatment:

Drug: Losartan

Open Label Phase: Azilsartan Medoxomil

Experimental group

Description:

Azilsartan Medoxomil 10 mg which can be titrated to higher dose(s) (up to 40 mg for subjects \<50 kg or up to 80 mg for subjects ≥50 kg)

Treatment:

Drug: Azilsartan Medoxomil Low-dose

Withdrawal Phase: Losartan 50 mg

Active Comparator group

Description:

Withdrawal Phase, subjects will be randomized (1:1) to continue taking their previously assigned active treatment or to be switched to placebo.

Treatment:

Drug: Losartan

Withdrawal Phase: Placebo to Losartan

Placebo Comparator group

Description:

Placebo Arm In the Withdrawal Phase, subjects will be randomized (1:1) to continue taking their previously assigned active treatment or to be switched to placebo.

Treatment:

Drug: Placebo for Losartan

Double-blind: Azilsartan Medoxomil - Medium dose

Experimental group

Description:

6-week, double-blind (DB), randomized, treatment phase (DB Phase), Azilsartan medoxomil Medium-dose (AZM-M), 20 mg once daily at Week 2.

Treatment:

Drug: Azilsartan Medoxomil Low-dose

Drug: Azilsartan Medoxomil Medium-dose (20 mg)

Drug: Placebo for Losartan

Double-blind: Azilsartan Medoxomil - High dose (AZM-H)

Experimental group

Description:

6-week, double-blind (DB), randomized, treatment phase (DB Phase): Azilsartan medoxomil High-dose (AZM-H), 40 mg AZM-M

Treatment:

Drug: Azilsartan Medoxomil High-dose (40 mg)

Withdrawal: Azilsartan Medoxomil - Medium dose

Experimental group

Description:

Experimental Arm in the Withdrawal Phase, subjects will be randomized (1:1) to continue taking their previously assigned active treatment (AZM-M) that was taken in Double blind OR to be switched to placebo.

Treatment:

Drug: Azilsartan Medoxomil Low-dose

Drug: Azilsartan Medoxomil Medium-dose (20 mg)

Withdrawal: Azilsartan Medoxomil - High dose

Experimental group

Description:

Experimental Arm in the Withdrawal Phase, subjects will be randomized (1:1) to continue taking their previously assigned active treatment (AZM-H) that was taken in double blind OR to be switched to placebo.

Treatment:

Drug: Azilsartan Medoxomil High-dose (40 mg)

Withdrawal Phase: Placebo to match azilsartan medoxomil medium dose (AZM-M)

Experimental group

Description:

Placebo arm in the Withdrawal Phase for subjects who were on AZM-M in double blind then randomized (1:1) to matching placebo for withdrawal phase

Treatment:

Drug: Placebo for Azilsartan Medoxomil

Withdrawal Phase: Placebo to match azilsartan medoxomil high dose (AZM-H)

Experimental group

Description:

Placebo arm in the Withdrawal Phase for subjects who were on AZM-H in Double blind then randomized (1:1) to matching placebo for withdrawal phase