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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 377
- 试验地点
- 69
- 主要终点
- Change in Seated Diastolic Blood Pressure Between AZM and Placebo
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Double-blind masking in the Double Blind Phase and Withdrawal Phase.
入排标准
- 年龄范围
- 6 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Double-blind: Azilsartan Medoxomil - Low dose
6-week, double-blind (DB), randomized, treatment phase (DB Phase): Azilsartan medoxomil low-dose (AZM-L), 10 mg once daily.
干预措施: Azilsartan Medoxomil Low-dose (Drug)
Double blind phase: 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.
干预措施: Losartan (Drug)
Withdrawal Phase: Azilsartan medoxomil low-dose (AZM-L)
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.
干预措施: Azilsartan Medoxomil Low-dose (Drug)
Withdrawal Phase: Placebo to match azilsartan medoxomil low dose (AZM-L)
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
干预措施: Losartan (Drug)
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)
干预措施: Azilsartan Medoxomil Low-dose (Drug)
Withdrawal Phase: Losartan 50 mg
Withdrawal Phase, subjects will be randomized (1:1) to continue taking their previously assigned active treatment or to be switched to placebo.
干预措施: Losartan (Drug)
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.
干预措施: Placebo for Losartan (Drug)
Double-blind: Azilsartan Medoxomil - Medium dose
6-week, double-blind (DB), randomized, treatment phase (DB Phase), Azilsartan medoxomil Medium-dose (AZM-M), 20 mg once daily at Week 2.
干预措施: Azilsartan Medoxomil Low-dose (Drug)
Double-blind: Azilsartan Medoxomil - Medium dose
6-week, double-blind (DB), randomized, treatment phase (DB Phase), Azilsartan medoxomil Medium-dose (AZM-M), 20 mg once daily at Week 2.
干预措施: Placebo for Losartan (Drug)
Double-blind: Azilsartan Medoxomil - Medium dose
6-week, double-blind (DB), randomized, treatment phase (DB Phase), Azilsartan medoxomil Medium-dose (AZM-M), 20 mg once daily at Week 2.
干预措施: Azilsartan Medoxomil Medium-dose (20 mg) (Drug)
Double-blind: Azilsartan Medoxomil - High dose (AZM-H)
6-week, double-blind (DB), randomized, treatment phase (DB Phase): Azilsartan medoxomil High-dose (AZM-H), 40 mg AZM-M
干预措施: Azilsartan Medoxomil High-dose (40 mg) (Drug)
Withdrawal: Azilsartan Medoxomil - Medium 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.
干预措施: Azilsartan Medoxomil Low-dose (Drug)
Withdrawal: Azilsartan Medoxomil - Medium 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.
干预措施: Azilsartan Medoxomil Medium-dose (20 mg) (Drug)
Withdrawal: Azilsartan Medoxomil - High dose
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.
干预措施: Azilsartan Medoxomil High-dose (40 mg) (Drug)
Withdrawal Phase: Placebo to match azilsartan medoxomil medium dose (AZM-M)
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
干预措施: Placebo for Azilsartan Medoxomil (Drug)
Withdrawal Phase: Placebo to match azilsartan medoxomil high dose (AZM-H)
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
干预措施: Placebo for Azilsartan Medoxomil (Drug)
结局指标
主要结局
Change in Seated Diastolic Blood Pressure Between AZM and Placebo
时间窗: 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
次要结局
- 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 Mean Arterial Pressure(From Week 6 of the Double-Blind Phase to Week 8 of the Withdrawal Phase)