Dataset Information

Safety and tolerability of azilsartan medoxomil in subjects with essential hypertension: a one-year, phase 3, open-label study.

ABSTRACT: 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.

SUBMITTER: Handley A

PROVIDER: S-EPMC4819839 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Safety and tolerability of azilsartan medoxomil in subjects with essential hypertension: a one-year, phase 3, open-label study.

Handley Alison A Lloyd Eric E Roberts Andrew A Barger Bruce B

Clinical and experimental hypertension (New York, N.Y. : 1993) 20160128 2

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 ...[more]

PMID: 26817604

Similar Datasets

Project description:BackgroundAzilsartan medoxomil (AZL-M), an angiotensin II receptor blocker, has a well-characterized efficacy and safety profile in patients with hypertension. AZL-M is approved for use in over 40 countries globally; however, it is not yet approved in China. Therefore, a phase 3 registration study to assess the efficacy (antihypertensive effect), safety, and tolerability of AZL-M compared with valsartan in Chinese patients with essential hypertension was undertaken.MethodsThis multicenter, double-blind, randomized, 8-week phase 3 study compared AZL-M with valsartan in Chinese patients aged ≥18 years with essential hypertension. Endpoints included change from baseline to week 8 in trough sitting clinic systolic blood pressure (scSBP) and ambulatory blood pressure monitoring parameters.ResultsOverall, 612 patients (mean age, 57.1 years; 57.5% male) were randomized to AZL-M 80 mg (n = 209), AZL-M 40 mg (n = 199), or valsartan 160 mg (n = 204). Baseline mean scSBP was similar in all groups (157.9-158.5 mm Hg). The mean reduction in trough scSBP from baseline to week 8 was significantly greater with AZL-M 80 mg than with valsartan (-24.2 vs -20.6 mm Hg; P = .010), and noninferior with AZL-M 40 mg versus valsartan (-22.5 vs -20.6 mm Hg; P = .184). Mean reduction in 24-hour mean systolic blood pressure (n = 257) was significantly greater with both AZL-M 80 mg (-17.0 mm Hg; P < .001) and AZL-M 40 mg (-14.7 mm Hg; P = .014) than with valsartan (-9.4 mm Hg). Treatment-emergent adverse events had similar incidence (52.8%-56.5%) across the treatment groups and were generally mild or moderate. Dizziness was the most frequent treatment-related treatment-emergent adverse events (AZL-M 80 mg, 1.9%; AZL-M 40 mg, 1.5%; valsartan, 1.0%). The safety and tolerability of AZL-M were comparable with valsartan.ConclusionsAZL-M was noninferior to valsartan at the 40-mg dose and superior to valsartan at the 80-mg dose in reducing trough scSBP, and showed acceptable safety-consistent with the AZL-M safety profile in other populations-in Chinese adults with hypertension.Trial registration numberNCT02480764.

Project description:BackgroundBased on non-clinical data, it is expected that azilsartan, an angiotensin II receptor blocker, will help improve insulin resistance in addition to its hypotensive action. The present study is aimed to explore the effect of azilsartan compared to telmisartan on insulin sensitivity in hypertensive patients in the clinical setting.MethodsThis multicenter, randomized, open-label, parallel-group exploratory study was conducted in Japan. We randomized adult patients (≥20 years old) with grade I or II essential hypertension and coexisting type 2 diabetes (1:1) to receive either oral azilsartan (20 mg/day;17 patients) or telmisartan (40 mg/day;16 patients) for 12 weeks. The primary endpoint was the change in the homeostasis model assessment ratio of insulin resistance (HOMA-R) from the baseline at the end of the treatment period. We also evaluated its safety and efficacy on other diabetes-related variables and blood pressure.FindingsThe mean changes in HOMA-R at the end of treatment were 0.22 (95% CI, -1.09-1.52) in the azilsartan group and -0.23 (95% CI, -0.72-0.27) in the telmisartan group. We found no clinically remarkable changes between the groups in diabetes-related variables such as fasting blood glucose, fasting insulin, HbA1c (NGSP), HOMA-β, or 1,5-anhydroglucitol. Reductions in clinic systolic and diastolic blood pressure were observed at week 4 and the reduced levels were maintained throughout the treatment period in both groups. No serious treatment-emergent adverse events (TEAEs) were observed. Only one drug-related TEAE (mild decrease in blood pressure) was reported in one patient in the azilsartan group.ConclusionNeither azilsartan nor telmisartan had any clinically remarkable effects on insulin resistance parameters when administered for 12 weeks to patients with grade I or II essential hypertension and coexisting type 2 diabetes mellitus. Azilsartan (20 mg/day) and telmisartan (40 mg/day) exerted comparable antihypertensive effects.Trial registrationClinicalTrials.gov NCT02079805.

Dataset Information

Safety and tolerability of azilsartan medoxomil in subjects with essential hypertension: a one-year, phase 3, open-label study.

Publications

Safety and tolerability of azilsartan medoxomil in subjects with essential hypertension: a one-year, phase 3, open-label study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets