Clinical trial NCT02235909: An Efficacy and Safety Study in Children 6 to Less Than 18 Years of Age With Hypertension
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypertension
Keywords: Pediatric Hypertension
High Blood Pressure
Hypertension
Pediatric
Primary Hypertension
Secondary Hypertension
Lead sponsor: Arbor Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2014-09-10
Enrollment: 377
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: There are 3 phases in this study. Double-blind, withdrawal phase, and open-label phase.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change in Seated Diastolic Blood Pressure Between AZM and Placebo
timeFrame: From Week 6/Final Visit of DB Phase to Week 8/Final Visit of Withdrawal Phase
Secondary outcomes:
measure: Change in Trough Seated Systolic Blood Pressure
timeFrame: From Week 6/Final Visit of the Double-Blind Phase to Week 8/Final Visit of the Withdrawal Phase
measure: Change in Mean Arterial Pressure
timeFrame: From Week 6 of the Double-Blind Phase to Week 8 of the Withdrawal Phase
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Advanced Research Center, INC
state: California
city: Hialeah
country: United States
facility: Direct Helpers Research Center
state: Florida
city: Miami
country: United States
facility: JDH Medical Group LLC
state: Florida
city: Miami
country: United States
facility: University of Miami/Jackson Memorial Hospital
state: Florida
city: Miami
country: United States
facility: Medical Research Center of Miami II, Inc.
state: Florida
city: North Miami
country: United States
facility: Pioneer Clinical Research
state: Florida
city: Snellville
country: United States
facility: Georgia Clinical Research
state: Georgia
city: Thomaston
country: United States
facility: Zoe Center for Pediatrics
state: Georgia
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Port Gibson
country: United States
facility: David M. Headley, MD PA
state: Mississippi
city: Lake Success
country: United States
facility: Mount Sinai PRIME
state: New York
city: Charleston
country: United States
facility: Medical University of South Carolina (MUSC)
state: South Carolina
city: Memphis
country: United States
facility: Memphis and Shelby County Pediatric Group
state: Tennessee
city: Beaumont
country: United States
facility: Southeast Texas Clinical Research Center
state: Texas
city: Houston
country: United States
facility: Texas Children's Heart Center
state: Texas
city: Clinton
country: United States
facility: Ericksen Research & Development, LLC
state: Utah
city: Richland
country: United States
facility: Mid-Columbia Research
state: Washington
city: Ciudad Autonoma
country: Argentina
facility: Hospital Italiano
state: Buenos Aires
city: Ciudad Autonoma
country: Argentina
facility: Hospital de Niños
state: Buenos Aires
city: Santa Fe
country: Argentina
facility: Clinica de Nefrologia, Urologia y Enf. Cardiovasculares S A
city: Curitiba
country: Brazil
facility: Clínica Nefrokids Ltda
city: Porto Alegre
country: Brazil
facility: Hospital São Lucas da PUCRS
city: Porto Alegre
country: Brazil
facility: Instituto de Cardiologia do Rio Grande do Sul
city: São Paulo
country: Brazil
facility: Fundação José Luiz Egydio Setúbal
city: São Paulo
country: Brazil
facility: Hospital Samaritano
city: Uberlândia
country: Brazil
facility: Eurolatino Pesquisas Médicas Ltda.
city: Ruse
country: Bulgaria
facility: SHATPPD-Ruse EOOD
city: Bucaramanga
country: Colombia
facility: Fundacion Oftalmologica de Santander - FOSCAL
city: Cali
country: Colombia
facility: Fundacion Valle del Lili
city: Medellin
country: Colombia
facility: Fundacion Hospitalaria San Vicente de Paul
city: Medellin
country: Colombia
facility: Hospital Pablo Tobón Uribe
city: Medellin
country: Colombia
facility: Institucion Prestadora de Servicios de Salud de la Universidad de Antioquia "IPS UNIVERSITARIA"
city: Baja
country: Hungary
facility: Principal SMO Kft.
city: Budapest
country: Hungary
facility: Svabhegy Plusz Gyermekegeszsegugyi Kozpont
city: Dombovar
country: Hungary
facility: Szent Lukacs Korhaz Dombovar
city: Miskolc
country: Hungary
facility: Prehospital Med Kft.
city: Szeged
country: Hungary
facility: Szegedi Tud.Egyetem Szent-Gyorgyi Albert Klin. Kozp.
city: Bari
country: Italy
facility: Ospedale Pediatrico Giovanni XXIII
city: Milano
country: Italy
facility: Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
city: Palermo
country: Italy
facility: A.R.N.A.S. Ospedale Civico e Benfratelli, G. Cristina e M.Ascoli
city: Durango
country: Mexico
facility: Instituto de Investigaciones Aplicadas a la Neurociencia A.C.
city: Mexico City
country: Mexico
facility: Hospital General de Mexico
city: Monterrey
country: Mexico
facility: Accelerium S. de R.L. de C.V.
city: Morelia
country: Mexico
facility: Centro de Investigacion Clinica Chapultepec S.A. de C.V.
city: Bialystok
country: Poland
facility: SPZOZ Uniwersytecki Dzieciecy Szpital Kliniczny im. L. Zamenhofa
city: Krakow
country: Poland
facility: Uniwersytecki Szpital Dziecięcy w Krakowie
city: Lodz
country: Poland
facility: NZOZ TRI-medica
city: Wroclaw
country: Poland
facility: Praktyka Lekarzy Rodzinnych R.Jadach, M.Domanski NZOZ
city: Johannesburg
country: South Africa
facility: LCS Clinical Research Unit
state: Gauteng
city: Soweto
country: South Africa
facility: Soweto Clinical Trial Centre
state: Gauteng
city: Pietermaritzburg
country: South Africa
facility: Netcare St. Anne's Hospital
state: KwaZulu-Natal
city: Cape Town
country: South Africa
facility: Groote Schuur Hospital E13 Renal Unit
state: Western Cape
city: Worcester
country: South Africa
facility: Clinical Projects Research SA (PTY) LTD
state: Western Cape
city: Germiston
country: South Africa
facility: CRISMO Bertha Gxowa Research Centre
city: Adana
country: Turkey
facility: Cukurova University Medical Faculty
city: Ankara
country: Turkey
facility: Gazi University Medical Faculty
city: Istanbul
country: Turkey
facility: Istanbul University Istanbul Medical Faculty
city: Izmir
country: Turkey
facility: Dokuz Eylul University Medicine Faculty
city: Kayseri
country: Turkey
facility: Erciyes University Medical Faculty
city: Manisa
country: Turkey
facility: Celal Bayar University Medical Faculty
city: Chernivtsi
country: Ukraine
facility: CMI Chernivtsi City Children Clinical Hospital
city: Kharkiv
country: Ukraine
facility: Regional Children CH Cardiology Department Kharkiv NMU
city: Kyiv
country: Ukraine
facility: SI National Research Center of Radiation Medicine of NAMSU
city: Kyiv
country: Ukraine
facility: USPC of ES EO&T Transplantation of MHU
city: Poltava
country: Ukraine
facility: HSEI of Ukraine UMSA
city: Sumy
country: Ukraine
facility: SSU Division MU Ch of pediatrics
city: Vinnytsia
country: Ukraine
facility: Vynnitsa Regional Children CH pediatric department № 1 M.I. Pyrogov NMU
city: Zaporizhzhia
country: Ukraine
facility: CI Zaporizhzhia City Multibranch Children Hospital #5
city: Zaporizhzhia
country: Ukraine
facility: CI Zaporizhzhia Regional Clinical Children Hospital of ZRC
Study officials:
affiliation: Arbor Pharmaceuticals, LLC
name: Steve Caras, MD
role: STUDY_DIRECTOR
References: