Handley Alison, Lloyd Eric, Roberts Andrew, Barger Bruce
a Takeda Pharmaceuticals International, Inc. , Deerfield , IL , USA and.
b Takeda Development Center Americas, Inc. , Deerfield , IL , USA .
Clin Exp Hypertens. 2016;38(2):180-8. doi: 10.3109/10641963.2015.1081213. Epub 2016 Jan 28.
This 56-week phase 3, open-label, treat-to-target study, involving 2 consecutive, non-randomized cohorts, evaluated the safety and tolerability of azilsartan medoxomil (AZL-M) in essential hypertension (mean baseline blood pressure [BP] 152/100 mmHg). All subjects (n = 669) initiated AZL-M 40 mg QD, force-titrated to 80 mg QD at week 4, if tolerated. From week 8, subjects could receive additional medications, starting with chlorthalidone (CLD) 25 mg QD (Cohort 1) or hydrochlorothiazide (HCTZ) 12.5-25 mg QD (Cohort 2), if required, to reach BP targets. Adverse events (AEs) were reported in 75.9% of subjects overall in the two cohorts (73.8% Cohort 1, 78.5% Cohort 2). The most common AEs were dizziness (14.3%), headache (9.9%) and fatigue (7.2%). Transient serum creatinine elevations were more frequent with add-on CLD. Clinic systolic/diastolic BP (observed cases at week 56) decreased by 25.2/18.4 mmHg (Cohort 1) and 24.2/17.9 mmHg (Cohort 2). These results demonstrate that AZL-M is well tolerated over the long term and provides stable BP improvements when used in a treat-to-target BP approach with thiazide-type diuretics.
这项为期56周的3期开放标签、达标治疗研究涉及2个连续的非随机队列，评估了阿齐沙坦美索米酯（AZL-M）在原发性高血压（平均基线血压[BP]152/100 mmHg）中的安全性和耐受性。所有受试者（n = 669）开始服用40 mg QD的AZL-M，若耐受则在第4周强制滴定至80 mg QD。从第8周开始，如有需要，受试者可加用其他药物，队列1从25 mg QD的氯噻酮（CLD）开始，队列2从12.5 - 25 mg QD的氢氯噻嗪（HCTZ）开始，以达到血压目标。两个队列中总体75.9%的受试者报告了不良事件（AE）（队列1为73.8%，队列2为78.5%）。最常见的AE是头晕（14.3%）、头痛（9.9%）和疲劳（7.2%）。加用CLD时短暂性血清肌酐升高更常见。临床收缩压/舒张压（第56周观察病例）在队列1中降低了25.2/18.4 mmHg，在队列2中降低了24.2/17.9 mmHg。这些结果表明，AZL-M长期耐受性良好，在与噻嗪类利尿剂联合用于达标治疗血压的方法中可稳定改善血压。
