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

Hypertension Clinical Trial

Official title:

A Randomized, Double-Blind, Efficacy and Safety Study of AR 14 (AZILSARTAN MEDOXOMIL) Treatment and Withdrawal, Followed by an Open-Label Extension, in Children 6 to Less Than 18 Years of Age With Hypertension

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02235909
• Other study ID #: AR14.001
• Status: Completed
• Phase: Phase 3
• Start date: December 19, 2014
• Est. completion date: September 27, 2020

Study information

• Verified date: February 2023
• Source: Arbor Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 215
• Est. completion date: September 27, 2020
• Est. primary completion date: November 27, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypertension

Intervention

Drug:
• Azilsartan Medoxomil Low-dose

• Losartan

• Placebo for Azilsartan Medoxomil

• Placebo for Losartan

• antihypertension medication - Add-on Therapy
add-on therapy (e.g., a calcium channel blocker, such as amlodipine, a diuretic, such as hydrochlorothiazide, or a beta-blocker such as metoprolol) per PI's clinical judgment.
• Azilsartan Medoxomil Medium-dose

• Azilsartan Medoxomil High-dose

Locations

Country	Name	City	State
Argentina	Hospital de Niños	Ciudad Autonoma	Buenos Aires
Argentina	Hospital Italiano	Ciudad Autonoma	Buenos Aires
Argentina	Clinica de Nefrologia, Urologia y Enf. Cardiovasculares S A	Santa Fe
Brazil	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
Bulgaria	SHATPPD-Ruse EOOD	Ruse
Colombia	Fundacion Oftalmologica de Santander - FOSCAL	Bucaramanga
Colombia	Fundacion Valle del Lili	Cali
Colombia	Fundacion Hospitalaria San Vicente de Paul	Medellin
Colombia	Hospital Pablo Tobón Uribe	Medellin
Colombia	Institucion Prestadora de Servicios de Salud de la Universidad de Antioquia "IPS UNIVERSITARIA"	Medellin
Hungary	Principal SMO Kft.	Baja
Hungary	Svabhegy Plusz Gyermekegeszsegugyi Kozpont	Budapest
Hungary	Szent Lukacs Korhaz Dombovar	Dombovar
Hungary	Prehospital Med Kft.	Miskolc
Hungary	Szegedi Tud.Egyetem Szent-Gyorgyi Albert Klin. Kozp.	Szeged
Italy	Ospedale Pediatrico Giovanni XXIII	Bari
Italy	Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico	Milano
Italy	A.R.N.A.S. Ospedale Civico e Benfratelli, G. Cristina e M.Ascoli	Palermo
Mexico	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
Poland	SPZOZ Uniwersytecki Dzieciecy Szpital Kliniczny im. L. Zamenhofa	Bialystok
Poland	Uniwersytecki Szpital Dzieciecy w Krakowie	Krakow
Poland	NZOZ TRI-medica	Lodz
Poland	Praktyka Lekarzy Rodzinnych R.Jadach, M.Domanski NZOZ	Wroclaw
South Africa	Groote Schuur Hospital E13 Renal Unit	Cape Town	Western Cape
South Africa	CRISMO Bertha Gxowa Research Centre	Germiston
South Africa	LCS Clinical Research Unit	Johannesburg	Gauteng
South Africa	Netcare St. Anne's Hospital	Pietermaritzburg	KwaZulu-Natal
South Africa	Soweto Clinical Trial Centre	Soweto	Gauteng
South Africa	Clinical Projects Research SA (PTY) LTD	Worcester	Western Cape
Turkey	Cukurova University Medical Faculty	Adana
Turkey	Gazi University Medical Faculty	Ankara
Turkey	Istanbul University Istanbul Medical Faculty	Istanbul
Turkey	Dokuz Eylul University Medicine Faculty	Izmir
Turkey	Erciyes University Medical Faculty	Kayseri
Turkey	Celal Bayar University Medical Faculty	Manisa
Ukraine	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
United States	Advanced Research Center, INC	Anaheim	California
United States	Southeast Texas Clinical Research Center	Beaumont	Texas
United States	Medical University of South Carolina (MUSC)	Charleston	South Carolina
United States	Ericksen Research & Development, LLC	Clinton	Utah
United States	Direct Helpers Research Center	Hialeah	Florida
United States	Texas Children's Heart Center	Houston	Texas
United States	Mount Sinai PRIME	Lake Success	New York
United States	University of Louisville	Louisville	Kentucky
United States	Memphis and Shelby County Pediatric Group	Memphis	Tennessee
United States	JDH Medical Group LLC	Miami	Florida
United States	Medical Research Center of Miami II, Inc.	Miami	Florida
United States	University of Miami/Jackson Memorial Hospital	Miami	Florida
United States	Pioneer Clinical Research	North Miami	Florida
United States	David M. Headley, MD PA	Port Gibson	Mississippi
United States	Mid-Columbia Research	Richland	Washington
United States	Georgia Clinical Research	Snellville	Georgia
United States	Zoe Center for Pediatrics	Thomaston	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
Arbor Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Bulgaria,  Colombia,  Hungary,  Italy,  Mexico,  Poland,  South Africa,  Turkey,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Blood Pressure	Change from Week 6/Final Visit of the double-blindPhase to Week 8/Final Visit of the WD Phase in trough clinic seated diastolic blood pressure between azilsartan medoxomil and placebo	Double-Blind and Withdrawal Phase
Secondary	Change in blood Pressure relative to the comparator	Change from Week 6/Final Visit of the double-blind Phase to Week 8/Final Visit of the withdrawal phase in trough clinic seated systolic blood pressure and mean arterial pressure (MAP) between azilsartan medoxomil and placebo.	Double Blind and Withdrawal Phase