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

NCT02235909 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: AR14.001
• Study Type: interventional
• Target: 377
• Locations: 12 countries
• Sites: 69

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.

Conditions

Hypertension

Keywords

Pediatric Hypertension; High Blood Pressure; Hypertension; Pediatric; Primary Hypertension; Secondary Hypertension

Outcome Measures

Primary Outcomes (1)

• Change in Seated Diastolic Blood Pressure Between AZM and Placebo

  Change in Seated Diastolic Blood Pressure from Week 6/Final visit of DB Phase to Week 8/Final Visit of the Withdrawal Phase, analysis of study subjects randomized to receiving placebo at Week 6 of treatment versus those who remained on treatment

  From Week 6/Final Visit of DB Phase to Week 8/Final Visit of Withdrawal Phase

Secondary Outcomes (2)

• Change in Trough Seated Systolic Blood Pressure

  From Week 6/Final Visit of the Double-Blind Phase to Week 8/Final Visit of the Withdrawal Phase

• Change in Mean Arterial Pressure

  From Week 6 of the Double-Blind Phase to Week 8 of the Withdrawal Phase

Study Arms (13)

Double-blind: Azilsartan Medoxomil - Low dose

EXPERIMENTAL

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

Drug: Azilsartan Medoxomil Low-dose

Double blind phase: Losartan

ACTIVE COMPARATOR

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.

Drug: Losartan

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

ACTIVE COMPARATOR

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.

Drug: Azilsartan Medoxomil Low-dose

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

PLACEBO COMPARATOR

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

Drug: Losartan

Open Label Phase: Azilsartan Medoxomil

EXPERIMENTAL

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)

Drug: Azilsartan Medoxomil Low-dose

Withdrawal Phase: Losartan 50 mg

ACTIVE COMPARATOR

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

Drug: Losartan

Withdrawal Phase: Placebo to Losartan

PLACEBO COMPARATOR

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.

Drug: Placebo for Losartan

Double-blind: Azilsartan Medoxomil - Medium dose

EXPERIMENTAL

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

Drug: Azilsartan Medoxomil Low-dose; Drug: Placebo for Losartan; Drug: Azilsartan Medoxomil Medium-dose (20 mg)

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

EXPERIMENTAL

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

Drug: Azilsartan Medoxomil High-dose (40 mg)

Withdrawal: Azilsartan Medoxomil - Medium dose

EXPERIMENTAL

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.

Drug: Azilsartan Medoxomil Low-dose; Drug: Azilsartan Medoxomil Medium-dose (20 mg)

Withdrawal: Azilsartan Medoxomil - High dose

EXPERIMENTAL

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.

Drug: Azilsartan Medoxomil High-dose (40 mg)

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

EXPERIMENTAL

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

Drug: Placebo for Azilsartan Medoxomil

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

EXPERIMENTAL

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

Drug: Placebo for Azilsartan Medoxomil

Interventions

Azilsartan Medoxomil Low-dose DRUG

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

Also known as: AR14, AZM-L

Double-blind: Azilsartan Medoxomil - Low dose; Double-blind: Azilsartan Medoxomil - Medium dose; Open Label Phase: Azilsartan Medoxomil; Withdrawal Phase: Azilsartan medoxomil low-dose (AZM-L); Withdrawal: Azilsartan Medoxomil - Medium dose

Losartan DRUG

Also known as: Cozaar

Double blind phase: Losartan; Withdrawal Phase: Losartan 50 mg; Withdrawal Phase: Placebo to match azilsartan medoxomil low dose (AZM-L)

Placebo for Azilsartan Medoxomil DRUG

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

Placebo for Losartan DRUG

Double-blind: Azilsartan Medoxomil - Medium dose; Withdrawal Phase: Placebo to Losartan

Azilsartan Medoxomil Medium-dose (20 mg) DRUG

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

Also known as: AR14, AZM-M

Double-blind: Azilsartan Medoxomil - Medium dose; Withdrawal: Azilsartan Medoxomil - Medium dose

Azilsartan Medoxomil High-dose (40 mg) DRUG

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

Also known as: AR14, AZM-H

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

Eligibility Criteria

• Age: 6 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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
• 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)
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Arbor Pharmaceuticals, Inc.: lead

Study Sites (69)

Advanced Research Center, INC

Anaheim, California, 92805, United States

Location

Direct Helpers Research Center

Hialeah, Florida, 33012, United States

Location

JDH Medical Group LLC

Miami, Florida, 33125, United States

Location

University of Miami/Jackson Memorial Hospital

Miami, Florida, 33136, United States

Location

Medical Research Center of Miami II, Inc.

Miami, Florida, 33144, United States

Location

Pioneer Clinical Research

North Miami, Florida, 33162, United States

Location

Georgia Clinical Research

Snellville, Georgia, 30078, United States

Location

Zoe Center for Pediatrics

Thomaston, Georgia, 30286, United States

Location

University of Louisville

Louisville, Kentucky, 40202, United States

Location

David M. Headley, MD PA

Port Gibson, Mississippi, 39150, United States

Location

Mount Sinai PRIME

Lake Success, New York, 10029, United States

Location

Medical University of South Carolina (MUSC)

Charleston, South Carolina, 29425, United States

Location

Memphis and Shelby County Pediatric Group

Memphis, Tennessee, 38116, United States

Location

Southeast Texas Clinical Research Center

Beaumont, Texas, 77701, United States

Location

Texas Children's Heart Center

Houston, Texas, 77030, United States

Location

Ericksen Research & Development, LLC

Clinton, Utah, 84015, United States

Location

Mid-Columbia Research

Richland, Washington, 99352, United States

Location

Hospital Italiano

Ciudad Autonoma, Buenos Aires, 1181, Argentina

Location

Hospital de Niños

Ciudad Autonoma, Buenos Aires, C1425EFD, Argentina

Location

Clinica de Nefrologia, Urologia y Enf. Cardiovasculares S A

Santa Fe, S3000EPV, Argentina

Location

Clínica Nefrokids Ltda

Curitiba, 80240-060, Brazil

Location

Hospital São Lucas da PUCRS

Porto Alegre, 90610-000, Brazil

Location

Instituto de Cardiologia do Rio Grande do Sul

Porto Alegre, 90620-001, Brazil

Location

Fundação José Luiz Egydio Setúbal

São Paulo, 01227-200, Brazil

Location

Hospital Samaritano

São Paulo, 01232-010, Brazil

Location

Eurolatino Pesquisas Médicas Ltda.

Uberlândia, 38411-186, Brazil

Location

SHATPPD-Ruse EOOD

Rousse, 7002, Bulgaria

Location

Fundacion Oftalmologica de Santander - FOSCAL

Bucaramanga, Colombia

Location

Fundacion Valle del Lili

Cali, Colombia

Location

Fundacion Hospitalaria San Vicente de Paul

Medellín, Colombia

Location

Hospital Pablo Tobón Uribe

Medellín, Colombia

Location

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

Medellín, Colombia

Location

Principal SMO Kft.

Baja, 6500, Hungary

Location

Svabhegy Plusz Gyermekegeszsegugyi Kozpont

Budapest, 1037, Hungary

Location

Szent Lukacs Korhaz Dombovar

Dombóvár, 7200, Hungary

Location

Prehospital Med Kft.

Miskolc, 3526, Hungary

Location

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

Szeged, 6720, Hungary

Location

Ospedale Pediatrico Giovanni XXIII

Bari, 70125, Italy

Location

Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

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

Palermo, Italy

Location

Instituto de Investigaciones Aplicadas a la Neurociencia A.C.

Durango, 34000, Mexico

Location

Hospital General de Mexico

Mexico City, Mexico

Location

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

Monterrey, 6400, Mexico

Location

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

Morelia, 58260, Mexico

Location

SPZOZ Uniwersytecki Dzieciecy Szpital Kliniczny im. L. Zamenhofa

Bialystok, 15-274, Poland

Location

Uniwersytecki Szpital Dziecięcy w Krakowie

Krakow, 30-663, Poland

Location

NZOZ TRI-medica

Lodz, 93-338, Poland

Location

Praktyka Lekarzy Rodzinnych R.Jadach, M.Domanski NZOZ

Wroclaw, 50-072, Poland

Location

LCS Clinical Research Unit

Johannesburg, Gauteng, 2021, South Africa

Location

Soweto Clinical Trial Centre

Soweto, Gauteng, 1818, South Africa

Location

Netcare St. Anne's Hospital

Pietermaritzburg, KwaZulu-Natal, 3201, South Africa

Location

Groote Schuur Hospital E13 Renal Unit

Cape Town, Western Cape, 7925, South Africa

Location

Clinical Projects Research SA (PTY) LTD

Worcester, Western Cape, 6850, South Africa

Location

CRISMO Bertha Gxowa Research Centre

Germiston, South Africa

Location

Cukurova University Medical Faculty

Adana, 01330, Turkey (Türkiye)

Location

Gazi University Medical Faculty

Ankara, 06500, Turkey (Türkiye)

Location

Istanbul University Istanbul Medical Faculty

Istanbul, 34093, Turkey (Türkiye)

Location

Dokuz Eylul University Medicine Faculty

Izmir, 35100, Turkey (Türkiye)

Location

Erciyes University Medical Faculty

Kayseri, 38039, Turkey (Türkiye)

Location

Celal Bayar University Medical Faculty

Manisa, 45040, Turkey (Türkiye)

Location

CMI Chernivtsi City Children Clinical Hospital

Chernivtsi, Ukraine

Location

Regional Children CH Cardiology Department Kharkiv NMU

Kharkiv, Ukraine

Location

SI National Research Center of Radiation Medicine of NAMSU

Kyiv, Ukraine

Location

USPC of ES EO&T Transplantation of MHU

Kyiv, Ukraine

Location

HSEI of Ukraine UMSA

Poltava, Ukraine

Location

SSU Division MU Ch of pediatrics

Sumy, Ukraine

Location

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

Vinnytsia, Ukraine

Location

CI Zaporizhzhia City Multibranch Children Hospital #5

Zaporizhzhia, Ukraine

Location

CI Zaporizhzhia Regional Clinical Children Hospital of ZRC

Zaporizhzhia, Ukraine

Location

MeSH Terms

Conditions

Hypertension; Essential Hypertension

Interventions

azilsartan medoxomil; Losartan

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles

Results Point of Contact

• Title: David Sequeira
• Organization: Azurity Pharmaceuticals, Inc.

david.sequeira@azurity.com

(913) 389-7961

Study Officials

• Steve Caras, MD

  Arbor Pharmaceuticals, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double-blind masking in the Double Blind Phase and Withdrawal Phase.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: There are 3 phases in this study. Double-blind, withdrawal phase, and open-label phase.

Study Record Dates

• First Submitted: September 8, 2014
• First Posted: September 10, 2014
• Study Start: March 30, 2015
• Primary Completion: November 11, 2019
• Study Completion: November 11, 2019
• Last Updated: February 25, 2025
• Results First Posted: February 25, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

BR (6); TU (6); PL (4); IT (3); BU (1); ME (4); US (17); ZA (6); AR (3); HU (5); CO (5); UA (9)