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

Sponsor

Arbor Pharmaceuticals, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT02235909

Collaborator

(none)

215

Enrollment

Locations

Arms

69.3

Actual Duration (Months)

3.1

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hypertension	Drug: Azilsartan Medoxomil Drug: Losartan Drug: Placebo for Azilsartan Medoxomil Drug: Placebo for Losartan Drug: antihypertension medication	Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

215 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

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

Masking:

Triple (Participant, Care Provider, Investigator)

Masking Description:

Double-blind masking in the Double Blind Phase and Withdrawal Phase.

Primary Purpose:

Treatment

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

Actual Study Start Date :

Dec 19, 2014

Actual Primary Completion Date :

Nov 27, 2019

Actual Study Completion Date :

Sep 27, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Double blind phase: Azilsartan Medoxomil Double blind phase; Randomized 1:1:1:1. Once a day dosing. Azilsartan medoxomil at 10 mg, or 20 mg, or 40 mg force-titrated to 80 mg	Drug: Azilsartan Medoxomil Other Names: AZM AR14
Active Comparator: Double blind phase: Losartan 25 or 50 mg Double blind phase: Double blind phase; Randomized 1:1:1:1. Once a day dosing	Drug: Losartan Other Names: Cozaar
Active Comparator: Withdrawal Phase: Azilsartan medoxomil dose taken in Double blind phase Experimental 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: Azilsartan Medoxomil Other Names: AZM AR14
Placebo Comparator: Withdrawal Phase: Placebo to match azilsartan medoxomil 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 Azilsartan Medoxomil Other Names: sugar pill
Experimental: 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)	Drug: Azilsartan Medoxomil Other Names: AZM AR14
Other: Open Label Phase: "Other" Additional antihypertension medication, as needed. Name and dose as determined by PI	Drug: Azilsartan Medoxomil Other Names: AZM AR14 Drug: antihypertension medication If add-on therapy is needed, the type of medication (eg a calcium channel blocker, such as amlodipine, a diuretic, such as hydrochlorothiazide, or a beta-blocker such as metoprolol) added will be determined per the investigator's clinical judgment.". These are not predefined.
Active Comparator: Withdrawal Phase: Losartan 25 or 50 mg Withdrawal Phase, subjects will be randomized (1:1) to continue taking their previously assigned active treatment or to be switched to placebo.	Drug: Losartan Other Names: Cozaar
Placebo Comparator: 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.	Drug: Placebo for Losartan Other Names: sugar pill

Outcome Measures

Primary Outcome Measures

Change in Blood Pressure [Double-Blind and Withdrawal Phase]
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

Secondary Outcome Measures

Change in blood Pressure relative to the comparator [Double Blind and Withdrawal Phase]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Years to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

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

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Advanced Research Center, INC	Anaheim	California	United States	92805
2	Direct Helpers Research Center	Hialeah	Florida	United States	33012
3	JDH Medical Group LLC	Miami	Florida	United States	33125
4	University of Miami/Jackson Memorial Hospital	Miami	Florida	United States	33136
5	Medical Research Center of Miami II, Inc.	Miami	Florida	United States	33144
6	Pioneer Clinical Research	North Miami	Florida	United States	33162
7	Georgia Clinical Research	Snellville	Georgia	United States	30078
8	Zoe Center for Pediatrics	Thomaston	Georgia	United States	30286
9	University of Louisville	Louisville	Kentucky	United States	40202
10	David M. Headley, MD PA	Port Gibson	Mississippi	United States	39150
11	Mount Sinai PRIME	Lake Success	New York	United States	10029
12	Medical University of South Carolina (MUSC)	Charleston	South Carolina	United States	29425
13	Memphis and Shelby County Pediatric Group	Memphis	Tennessee	United States	38116
14	Southeast Texas Clinical Research Center	Beaumont	Texas	United States	77701
15	Texas Children's Heart Center	Houston	Texas	United States	77030
16	Ericksen Research & Development, LLC	Clinton	Utah	United States	84015
17	Mid-Columbia Research	Richland	Washington	United States	99352
18	Hospital Italiano	Ciudad Autonoma	Buenos Aires	Argentina	1181
19	Hospital de Niños	Ciudad Autonoma	Buenos Aires	Argentina	C1425EFD
20	Clinica de Nefrologia, Urologia y Enf. Cardiovasculares S A	Santa Fe		Argentina	S3000EPV
21	Clínica Nefrokids Ltda	Curitiba		Brazil	80240-060
22	Hospital São Lucas da PUCRS	Porto Alegre		Brazil	90610-000
23	Instituto de Cardiologia do Rio Grande do Sul	Porto Alegre		Brazil	90620-001
24	Fundação José Luiz Egydio Setúbal	São Paulo		Brazil	01227-200
25	Hospital Samaritano	São Paulo		Brazil	01232-010
26	Eurolatino Pesquisas Médicas Ltda.	Uberlândia		Brazil	38411-186
27	SHATPPD-Ruse EOOD	Ruse		Bulgaria	7002
28	Fundacion Oftalmologica de Santander - FOSCAL	Bucaramanga		Colombia
29	Fundacion Valle del Lili	Cali		Colombia
30	Fundacion Hospitalaria San Vicente de Paul	Medellin		Colombia
31	Hospital Pablo Tobón Uribe	Medellin		Colombia
32	Institucion Prestadora de Servicios de Salud de la Universidad de Antioquia "IPS UNIVERSITARIA"	Medellin		Colombia
33	Principal SMO Kft.	Baja		Hungary	6500
34	Svabhegy Plusz Gyermekegeszsegugyi Kozpont	Budapest		Hungary	1037
35	Szent Lukacs Korhaz Dombovar	Dombovar		Hungary	7200
36	Prehospital Med Kft.	Miskolc		Hungary	3526
37	Szegedi Tud.Egyetem Szent-Gyorgyi Albert Klin. Kozp.	Szeged		Hungary	6720
38	Ospedale Pediatrico Giovanni XXIII	Bari		Italy	70125
39	Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico	Milano		Italy	20122
40	A.R.N.A.S. Ospedale Civico e Benfratelli, G. Cristina e M.Ascoli	Palermo		Italy
41	Instituto de Investigaciones Aplicadas a la Neurociencia A.C.	Durango		Mexico	34000
42	Hospital General de Mexico	Mexico City		Mexico
43	Accelerium S. de R.L. de C.V.	Monterrey		Mexico	6400
44	Centro de Investigacion Clinica Chapultepec S.A. de C.V.	Morelia		Mexico	58260
45	SPZOZ Uniwersytecki Dzieciecy Szpital Kliniczny im. L. Zamenhofa	Bialystok		Poland	15-274
46	Uniwersytecki Szpital Dziecięcy w Krakowie	Krakow		Poland	30-663
47	NZOZ TRI-medica	Lodz		Poland	93-338
48	Praktyka Lekarzy Rodzinnych R.Jadach, M.Domanski NZOZ	Wroclaw		Poland	50-072
49	LCS Clinical Research Unit	Johannesburg	Gauteng	South Africa	2021
50	Soweto Clinical Trial Centre	Soweto	Gauteng	South Africa	1818
51	Netcare St. Anne's Hospital	Pietermaritzburg	KwaZulu-Natal	South Africa	3201
52	Groote Schuur Hospital E13 Renal Unit	Cape Town	Western Cape	South Africa	7925
53	Clinical Projects Research SA (PTY) LTD	Worcester	Western Cape	South Africa	6850
54	CRISMO Bertha Gxowa Research Centre	Germiston		South Africa
55	Cukurova University Medical Faculty	Adana		Turkey	01330
56	Gazi University Medical Faculty	Ankara		Turkey	06500
57	Istanbul University Istanbul Medical Faculty	Istanbul		Turkey	34093
58	Dokuz Eylul University Medicine Faculty	Izmir		Turkey	35100
59	Erciyes University Medical Faculty	Kayseri		Turkey	38039
60	Celal Bayar University Medical Faculty	Manisa		Turkey	45040
61	CMI Chernivtsi City Children Clinical Hospital	Chernivtsi		Ukraine
62	Regional Children CH Cardiology Department Kharkiv NMU	Kharkiv		Ukraine
63	SI National Research Center of Radiation Medicine of NAMSU	Kyiv		Ukraine
64	USPC of ES EO&T Transplantation of MHU	Kyiv		Ukraine
65	HSEI of Ukraine UMSA	Poltava		Ukraine
66	SSU Division MU Ch of pediatrics	Sumy		Ukraine
67	Vynnitsa Regional Children CH pediatric department № 1 M.I. Pyrogov NMU	Vinnytsia		Ukraine
68	CI Zaporizhzhia City Multibranch Children Hospital #5	Zaporizhzhia		Ukraine
69	CI Zaporizhzhia Regional Clinical Children Hospital of ZRC	Zaporizhzhia		Ukraine