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

NCT ID: NCT02235909

Last Updated: 2025-02-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 377 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-03-30
• Study Completion Date: 2019-11-11

Brief Summary

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.

Detailed 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.

Conditions

Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Double-blind: Azilsartan Medoxomil - Low dose

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

Group Type: EXPERIMENTAL

Azilsartan Medoxomil Low-dose

Intervention Type: DRUG

Azilsartan medoxomil low-dose (AZM-L) 10 mg

Double blind phase: Losartan

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.

Group Type: ACTIVE_COMPARATOR

Losartan

Intervention Type: DRUG

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

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.

Group Type: ACTIVE_COMPARATOR

Azilsartan Medoxomil Low-dose

Intervention Type: DRUG

Azilsartan medoxomil low-dose (AZM-L) 10 mg

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

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

Group Type: PLACEBO_COMPARATOR

Losartan

Intervention Type: DRUG

Open Label Phase: Azilsartan Medoxomil

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)

Group Type: EXPERIMENTAL

Azilsartan Medoxomil Low-dose

Intervention Type: DRUG

Azilsartan medoxomil low-dose (AZM-L) 10 mg

Withdrawal Phase: Losartan 50 mg

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

Group Type: ACTIVE_COMPARATOR

Losartan

Intervention Type: DRUG

Withdrawal Phase: Placebo to Losartan

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.

Group Type: PLACEBO_COMPARATOR

Placebo for Losartan

Intervention Type: DRUG

Double-blind: Azilsartan Medoxomil - Medium dose

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

Group Type: EXPERIMENTAL

Azilsartan Medoxomil Low-dose

Intervention Type: DRUG

Azilsartan medoxomil low-dose (AZM-L) 10 mg

Placebo for Losartan

Intervention Type: DRUG

Azilsartan Medoxomil Medium-dose (20 mg)

Intervention Type: DRUG

Azilsartan medoxomil medium-dose (AZM-M) 20 mg

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

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

Group Type: EXPERIMENTAL

Azilsartan Medoxomil High-dose (40 mg)

Intervention Type: DRUG

Azilsartan medoxomil high-dose (AZM-L) 40 mg

Withdrawal: Azilsartan Medoxomil - Medium dose

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.

Group Type: EXPERIMENTAL

Azilsartan Medoxomil Low-dose

Intervention Type: DRUG

Azilsartan medoxomil low-dose (AZM-L) 10 mg

Azilsartan Medoxomil Medium-dose (20 mg)

Intervention Type: DRUG

Azilsartan medoxomil medium-dose (AZM-M) 20 mg

Withdrawal: Azilsartan Medoxomil - High dose

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.

Group Type: EXPERIMENTAL

Azilsartan Medoxomil High-dose (40 mg)

Intervention Type: DRUG

Azilsartan medoxomil high-dose (AZM-L) 40 mg

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

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

Group Type: EXPERIMENTAL

Placebo for Azilsartan Medoxomil

Intervention Type: DRUG

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

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

Group Type: EXPERIMENTAL

Placebo for Azilsartan Medoxomil

Intervention Type: DRUG

Interventions

Azilsartan Medoxomil Low-dose

Azilsartan medoxomil low-dose (AZM-L) 10 mg

Intervention Type: DRUG

Losartan

Intervention Type: DRUG

Placebo for Azilsartan Medoxomil

Intervention Type: DRUG

Placebo for Losartan

Intervention Type: DRUG

Azilsartan Medoxomil Medium-dose (20 mg)

Azilsartan medoxomil medium-dose (AZM-M) 20 mg

Intervention Type: DRUG

Azilsartan Medoxomil High-dose (40 mg)

Azilsartan medoxomil high-dose (AZM-L) 40 mg

Intervention Type: DRUG

Other Intervention Names

AR14; AZM-L; Cozaar; AR14; AZM-M; AR14; AZM-H

Eligibility Criteria

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

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Arbor Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Steve Caras, MD

Role: STUDY_DIRECTOR

Arbor Pharmaceuticals, LLC

Locations

Advanced Research Center, INC

Anaheim, California, United States

Direct Helpers Research Center

Hialeah, Florida, United States

JDH Medical Group LLC

Miami, Florida, United States

University of Miami/Jackson Memorial Hospital

Miami, Florida, United States

Medical Research Center of Miami II, Inc.

Miami, Florida, United States

Pioneer Clinical Research

North Miami, Florida, United States

Georgia Clinical Research

Snellville, Georgia, United States

Zoe Center for Pediatrics

Thomaston, Georgia, United States

University of Louisville

Louisville, Kentucky, United States

David M. Headley, MD PA

Port Gibson, Mississippi, United States

Mount Sinai PRIME

Lake Success, New York, United States

Medical University of South Carolina (MUSC)

Charleston, South Carolina, United States

Memphis and Shelby County Pediatric Group

Memphis, Tennessee, United States

Southeast Texas Clinical Research Center

Beaumont, Texas, United States

Texas Children's Heart Center

Houston, Texas, United States

Ericksen Research & Development, LLC

Clinton, Utah, United States

Mid-Columbia Research

Richland, Washington, United States

Hospital Italiano

Ciudad Autonoma, Buenos Aires, Argentina

Hospital de Niños

Ciudad Autonoma, Buenos Aires, Argentina

Clinica de Nefrologia, Urologia y Enf. Cardiovasculares S A

Santa Fe, , Argentina

Clínica Nefrokids Ltda

Curitiba, , Brazil

Hospital São Lucas da PUCRS

Porto Alegre, , Brazil

Instituto de Cardiologia do Rio Grande do Sul

Porto Alegre, , Brazil

Fundação José Luiz Egydio Setúbal

São Paulo, , Brazil

Hospital Samaritano

São Paulo, , Brazil

Eurolatino Pesquisas Médicas Ltda.

Uberlândia, , Brazil

SHATPPD-Ruse EOOD

Rousse, , Bulgaria

Fundacion Oftalmologica de Santander - FOSCAL

Bucaramanga, , Colombia

Fundacion Valle del Lili

Cali, , Colombia

Fundacion Hospitalaria San Vicente de Paul

Medellín, , Colombia

Hospital Pablo Tobón Uribe

Medellín, , Colombia

Institucion Prestadora de Servicios de Salud de la Universidad de Antioquia "IPS UNIVERSITARIA"

Medellín, , Colombia

Principal SMO Kft.

Baja, , Hungary

Svabhegy Plusz Gyermekegeszsegugyi Kozpont

Budapest, , Hungary

Szent Lukacs Korhaz Dombovar

Dombóvár, , Hungary

Prehospital Med Kft.

Miskolc, , Hungary

Szegedi Tud.Egyetem Szent-Gyorgyi Albert Klin. Kozp.

Szeged, , Hungary

Ospedale Pediatrico Giovanni XXIII

Bari, , Italy

Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico

Milan, , Italy

A.R.N.A.S. Ospedale Civico e Benfratelli, G. Cristina e M.Ascoli

Palermo, , Italy

Instituto de Investigaciones Aplicadas a la Neurociencia A.C.

Durango, , Mexico

Hospital General de Mexico

Mexico City, , Mexico

Accelerium S. de R.L. de C.V.

Monterrey, , Mexico

Centro de Investigacion Clinica Chapultepec S.A. de C.V.

Morelia, , Mexico

SPZOZ Uniwersytecki Dzieciecy Szpital Kliniczny im. L. Zamenhofa

Bialystok, , Poland

Uniwersytecki Szpital Dziecięcy w Krakowie

Krakow, , Poland

NZOZ TRI-medica

Lodz, , Poland

Praktyka Lekarzy Rodzinnych R.Jadach, M.Domanski NZOZ

Wroclaw, , Poland

LCS Clinical Research Unit

Johannesburg, Gauteng, South Africa

Soweto Clinical Trial Centre

Soweto, Gauteng, South Africa

Netcare St. Anne's Hospital

Pietermaritzburg, KwaZulu-Natal, South Africa

Groote Schuur Hospital E13 Renal Unit

Cape Town, Western Cape, South Africa

Clinical Projects Research SA (PTY) LTD

Worcester, Western Cape, South Africa

CRISMO Bertha Gxowa Research Centre

Germiston, , South Africa

Cukurova University Medical Faculty

Adana, , Turkey (Türkiye)

Gazi University Medical Faculty

Ankara, , Turkey (Türkiye)

Istanbul University Istanbul Medical Faculty

Istanbul, , Turkey (Türkiye)

Dokuz Eylul University Medicine Faculty

Izmir, , Turkey (Türkiye)

Erciyes University Medical Faculty

Kayseri, , Turkey (Türkiye)

Celal Bayar University Medical Faculty

Manisa, , Turkey (Türkiye)

CMI Chernivtsi City Children Clinical Hospital

Chernivtsi, , Ukraine

Regional Children CH Cardiology Department Kharkiv NMU

Kharkiv, , Ukraine

SI National Research Center of Radiation Medicine of NAMSU

Kyiv, , Ukraine

USPC of ES EO&T Transplantation of MHU

Kyiv, , Ukraine

HSEI of Ukraine UMSA

Poltava, , Ukraine

SSU Division MU Ch of pediatrics

Sumy, , Ukraine

Vynnitsa Regional Children CH pediatric department № 1 M.I. Pyrogov NMU

Vinnytsia, , Ukraine

CI Zaporizhzhia City Multibranch Children Hospital #5

Zaporizhzhia, , Ukraine

CI Zaporizhzhia Regional Clinical Children Hospital of ZRC

Zaporizhzhia, , Ukraine

Countries

United States; Argentina; Brazil; Bulgaria; Colombia; Hungary; Italy; Mexico; Poland; South Africa; Turkey (Türkiye); Ukraine

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

AR14.001

Identifier Type: -

Identifier Source: org_study_id