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

Phase 1

Conditions: MedDRA version: 18.1 Level: PT Classification code 10039834 Term: Secondary hypertension System Organ Class: 10047065 - Vascular disorders
primary or secondary hypertension
MedDRA version: 18.1 Level: LLT Classification code 10036695 Term: Primary hypertension System Organ Class: 10047065 - Vascular disorders
Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Registration Number: EUCTR2014-000674-18-HU

Lead Sponsor: Arbor Pharmaceuticals, LLC.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 260

Inclusion Criteria

* The subject has hypertension (primary or secondary) defined as clinic seDBP =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.
a) If currently treated: The subject has a documented historical diagnosis of hypertension AND a post-washout clinic seDBP meeting the above criteria on Day -1 (or Day 1 for subjects not participating in ABPM).
b) If currently untreated: The subject has elevated seDBP meeting the above criteria on 3 separate occasions before Randomization, including on Day -1 (or Day 1 for subjects not participating in ABPM).
* 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 phase must have begun at least 30 days prior to Screening/Visit 1.
* Subjects may be renal transplant patients if time post-transplant has been greater than 6 months prior to Screening, with stable graft function (and eGFR =30 mL/min/1.73 m2) for at least 6 months, stable use of immunosuppressive therapy for at least 30 days prior to Screening, and documented evidence that there is no transplant renal artery stenosis.
* The subject is untreated, or willing, and in the opinion of their treating physician, can safely be withdrawn from previous antihypertensive medications for a maximum of 4 weeks (if a washout extension is required) prior to randomization.
Are the trial subjects under 18? yes
Number of subjects for this age range: 260
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

*The subject has a clinic seSBP greater than 15 mm Hg and/or seDBP 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 (eg, 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 1.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the antihypertensive effect of AZM compared with placebo after a randomized, double-blind, withdrawal (Withdrawal Phase).;<br> Secondary Objective: To evaluate the antihypertensive effect of AZM compared with losartan during double-blind treatment (Double-Blind Phase).<br><br> To evaluate the safety and tolerability of AZM relative to placebo and losartan during double-blind treatment, and of AZM during a long-term, open label (OL) extension (OL Phase).<br> ;Primary end point(s): Change from Week 6/Final Visit of the double blind (DB) Phase to Week 8/Final Visit of the Withdrawal Phase in trough clinic seated diastolic blood pressure (seDBP) between AZM and placebo.;Timepoint(s) of evaluation of this end point: Week 8

Secondary Outcome Measures

Name	Time	Method
<br> Secondary end point(s): * Change from Week 6/Final Visit of the DB Phase to Week 8/Final Visit of the Withdrawal Phase in trough clinic seated systolic blood pressure (seSBP) and mean arterial pressure (MAP) between AZM and placebo.<br> * Change from Baseline in trough clinic seDBP, seSBP, and MAP at Week 6/Final Visit for AZM and losartan.<br> * Percentage of subjects who achieve target BP (seDBP, seSBP, both) at Week 8/Final Visit of the Withdrawal Phase, with the target defined as <90th percentile for age, gender, and height<br><br> Safety Endpoints for this study are:<br> AEs, physical examination, laboratory tests, 12-lead ECG findings, vital signs, and anthropometric (height, weight, and body mass index z-scores) measurements.<br> ;Timepoint(s) of evaluation of this end point: Week 6 and week 8, respectively - as described in secondary end-points

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