An Efficacy and Safety Study in Children 6 to Less Than 18 Years of Age With Hypertension
- Conditions
- Hypertension
- Interventions
- Drug: Azilsartan Medoxomil High-dose (40 mg)Drug: Azilsartan Medoxomil Medium-dose (20 mg)
- Registration Number
- NCT02235909
- Lead Sponsor
- Arbor Pharmaceuticals, Inc.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 377
-
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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Double-blind: Azilsartan Medoxomil - Low dose Azilsartan Medoxomil Low-dose 6-week, double-blind (DB), randomized, treatment phase (DB Phase): Azilsartan medoxomil low-dose (AZM-L), 10 mg once daily. Double blind phase: Losartan 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. Withdrawal Phase: Azilsartan medoxomil low-dose (AZM-L) Azilsartan Medoxomil Low-dose 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. Withdrawal Phase: Placebo to match azilsartan medoxomil low dose (AZM-L) Losartan 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 Open Label Phase: Azilsartan Medoxomil Azilsartan Medoxomil Low-dose 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) Withdrawal Phase: Losartan 50 mg Losartan Withdrawal Phase, subjects will be randomized (1:1) to continue taking their previously assigned active treatment or to be switched to placebo. Withdrawal Phase: Placebo to Losartan Placebo for 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. Double-blind: Azilsartan Medoxomil - Medium dose Azilsartan Medoxomil Low-dose 6-week, double-blind (DB), randomized, treatment phase (DB Phase), Azilsartan medoxomil Medium-dose (AZM-M), 20 mg once daily at Week 2. Double-blind: Azilsartan Medoxomil - Medium dose Placebo for Losartan 6-week, double-blind (DB), randomized, treatment phase (DB Phase), Azilsartan medoxomil Medium-dose (AZM-M), 20 mg once daily at Week 2. Double-blind: Azilsartan Medoxomil - Medium dose Azilsartan Medoxomil Medium-dose (20 mg) 6-week, double-blind (DB), randomized, treatment phase (DB Phase), Azilsartan medoxomil Medium-dose (AZM-M), 20 mg once daily at Week 2. Double-blind: Azilsartan Medoxomil - High dose (AZM-H) Azilsartan Medoxomil High-dose (40 mg) 6-week, double-blind (DB), randomized, treatment phase (DB Phase): Azilsartan medoxomil High-dose (AZM-H), 40 mg AZM-M Withdrawal: Azilsartan Medoxomil - Medium dose Azilsartan Medoxomil Low-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. Withdrawal: Azilsartan Medoxomil - Medium dose Azilsartan Medoxomil Medium-dose (20 mg) 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. Withdrawal: Azilsartan Medoxomil - High dose Azilsartan Medoxomil High-dose (40 mg) 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. Withdrawal Phase: Placebo to match azilsartan medoxomil medium dose (AZM-M) Placebo for Azilsartan Medoxomil 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 Withdrawal Phase: Placebo to match azilsartan medoxomil high dose (AZM-H) Placebo for Azilsartan Medoxomil 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
- Primary Outcome Measures
Name Time Method Change in Seated Diastolic Blood Pressure Between AZM and Placebo From Week 6/Final Visit of DB Phase to Week 8/Final Visit of Withdrawal Phase 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
- Secondary Outcome Measures
Name Time Method 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 Trough Seated Systolic Blood Pressure from Week 6 of the Double-Blind Phase to Week 8 of the Withdrawal Phase Between AZM and Placebo, analysis of study subjects randomized to receiving placebo at Week 6 of treatment versus those who remained on treatment
Change in Mean Arterial Pressure From Week 6 of the Double-Blind Phase to Week 8 of the Withdrawal Phase Change in Mean Arterial Pressure from Week 6 of the Double-Blind Phase to Week 8 of the Withdrawal Phase Between AZM and Placebo, analysis of study subjects randomized to receiving placebo at Week 6 of treatment versus those who remained on treatment
Trial Locations
- Locations (69)
Fundação José Luiz Egydio Setúbal
🇧🇷São Paulo, Brazil
Pioneer Clinical Research
🇺🇸North Miami, Florida, United States
Georgia Clinical Research
🇺🇸Snellville, Georgia, United States
Zoe Center for Pediatrics
🇺🇸Thomaston, Georgia, United States
David M. Headley, MD PA
🇺🇸Port Gibson, Mississippi, United States
Mount Sinai PRIME
🇺🇸Lake Success, New York, United States
Memphis and Shelby County Pediatric Group
🇺🇸Memphis, Tennessee, United States
Mid-Columbia Research
🇺🇸Richland, Washington, United States
Hospital São Lucas da PUCRS
🇧🇷Porto Alegre, Brazil
Fundacion Oftalmologica de Santander - FOSCAL
🇨🇴Bucaramanga, Colombia
Fundacion Valle del Lili
🇨🇴Cali, Colombia
Hospital Samaritano
🇧🇷São Paulo, Brazil
Eurolatino Pesquisas Médicas Ltda.
🇧🇷Uberlândia, Brazil
SHATPPD-Ruse EOOD
🇧🇬Ruse, Bulgaria
Hospital Pablo Tobón Uribe
🇨🇴Medellin, Colombia
Szegedi Tud.Egyetem Szent-Gyorgyi Albert Klin. Kozp.
🇭🇺Szeged, Hungary
Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
🇮🇹Milano, Italy
Prehospital Med Kft.
🇭🇺Miskolc, Hungary
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
SPZOZ Uniwersytecki Dzieciecy Szpital Kliniczny im. L. Zamenhofa
🇵🇱Bialystok, Poland
Centro de Investigacion Clinica Chapultepec S.A. de C.V.
🇲🇽Morelia, Mexico
Uniwersytecki Szpital Dziecięcy w Krakowie
🇵🇱Krakow, Poland
NZOZ TRI-medica
🇵🇱Lodz, Poland
Praktyka Lekarzy Rodzinnych R.Jadach, M.Domanski NZOZ
🇵🇱Wroclaw, Poland
Soweto Clinical Trial Centre
🇿🇦Soweto, Gauteng, South Africa
Clinical Projects Research SA (PTY) LTD
🇿🇦Worcester, Western Cape, South Africa
CRISMO Bertha Gxowa Research Centre
🇿🇦Germiston, South Africa
Erciyes University Medical Faculty
🇹🇷Kayseri, 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
Celal Bayar University Medical Faculty
🇹🇷Manisa, Turkey
USPC of ES EO&T Transplantation of MHU
🇺🇦Kyiv, Ukraine
Regional Children CH Cardiology Department Kharkiv NMU
🇺🇦Kharkiv, Ukraine
SI National Research Center of Radiation Medicine of NAMSU
🇺🇦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
Advanced Research Center, INC
🇺🇸Anaheim, California, United States
Direct Helpers Research Center
🇺🇸Hialeah, Florida, United States
Texas Children's Heart Center
🇺🇸Houston, Texas, United States
LCS Clinical Research Unit
🇿🇦Johannesburg, Gauteng, South Africa
Groote Schuur Hospital E13 Renal Unit
🇿🇦Cape Town, Western Cape, South Africa
Netcare St. Anne's Hospital
🇿🇦Pietermaritzburg, KwaZulu-Natal, South Africa
Institucion Prestadora de Servicios de Salud de la Universidad de Antioquia "IPS UNIVERSITARIA"
🇨🇴Medellin, Colombia
Hospital Italiano
🇦🇷Ciudad Autonoma, Buenos Aires, Argentina
Hospital de Niños
🇦🇷Ciudad Autonoma, Buenos Aires, Argentina
Principal SMO Kft.
🇭🇺Baja, Hungary
Ospedale Pediatrico Giovanni XXIII
🇮🇹Bari, Italy
Ericksen Research & Development, LLC
🇺🇸Clinton, Utah, United States
Clinica de Nefrologia, Urologia y Enf. Cardiovasculares S A
🇦🇷Santa Fe, Argentina
Clínica Nefrokids Ltda
🇧🇷Curitiba, Brazil
Fundacion Hospitalaria San Vicente de Paul
🇨🇴Medellin, Colombia
Szent Lukacs Korhaz Dombovar
🇭🇺Dombovar, Hungary
Svabhegy Plusz Gyermekegeszsegugyi Kozpont
🇭🇺Budapest, Hungary
Instituto de Cardiologia do Rio Grande do Sul
🇧🇷Porto Alegre, Brazil
CMI Chernivtsi City Children Clinical Hospital
🇺🇦Chernivtsi, Ukraine
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
University of Louisville
🇺🇸Louisville, Kentucky, United States
Medical University of South Carolina (MUSC)
🇺🇸Charleston, South Carolina, United States
Southeast Texas Clinical Research Center
🇺🇸Beaumont, Texas, United States