tak-491 and Hypertension

Azilsartan medoxomil (AZM) is the newest representative in the class of angiotensin receptor blockers. Azilsartan medoxomil in combination with the older diuretic chlorthalidone (CLD) in fixed-doses of AZM/CLD 40/12.5 mg and 40/25 mg has been approved by the FDA for use in patients with essential hypertension. We sought to evaluate the safety and tolerability of AZL-M alone and in combination with CLD.. We conducted a search in PubMed using the keywords 'azilsartan', 'azilsartan medoxomil', 'chlorthalidone, 'safety', 'tolerability' in order to find scientific studies evaluating the safety of these drugs. We included studies reporting side effects of these drugs, alone or in combination, in comparison to placebo or other antihypertensive medications. For our systematic review, we followed the PRISMA guidelines.. Azilsartan medoxomil is a potent antihypertensive medicine with an acceptable safety profile. The most commonly reported adverse events are dizziness, headache, fatigue, upper respiratory tract infection and urinary tract infection. Chlorthalidone is more potent and has a considerably longer duration of action than the most commonly prescribed diuretic hydrochlorothiazide. Safety and tolerability between these two drugs are similar except higher serum uric acid and lower potassium levels with chlorthalidone.. The combination of azilsartan medoxomil with chlorthalidone has been shown to be effective in lowering blood pressure with an acceptable safety and tolerability profile. This fixeddose combination is an attractive treatment option for hypertension management.

Topics: Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Benzimidazoles; Blood Pressure; Chlorthalidone; Drug Therapy, Combination; Humans; Hypertension; Oxadiazoles; Treatment Outcome; Uric Acid

Angiotensin-receptor blockers are often considered insufficiently efficacious in reducing blood pressure. However, newer angiotensin-receptor blockers may be more effective than the older ones. A network meta-analysis was performed to compare the efficacy of various angiotensin-receptor blockers in reducing office and ambulatory blood pressure in hypertensive patients. Relevant literature was searched from English and Chinese databases for randomized controlled trials involving angiotensin-receptor blockers in hypertension. Efficacy variables included systolic and diastolic blood pressure either in the office or on ambulatory blood pressure monitoring. Absolute blood pressure reductions at 6-12 weeks of treatment and their credible intervals were reported. A total of 34 publications provided adequate data for analysis (n = 14 859). In 28 studies on office systolic blood pressure (n = 12 731), against the common comparator valsartan 80 mg, the differences in systolic blood pressure were in favor of azilsartan medoxomil (20-80 mg), irbesartan (300 mg), olmesartan (20-40 mg), telmisartan (80 mg), and valsartan (160-320 mg), but not candesartan (8-16 mg), losartan (50-100 mg), irbesartan (150 mg), olmesartan (10 mg), and telmisartan (40 mg). The ranking plot shows that azilsartan medoxomil 80 mg had a possibility of 99% being the best in the class. Similar results were observed for office diastolic blood pressure and from 13 studies for 24-hour ambulatory systolic and diastolic blood pressure. In conclusion, angiotensin-receptor blockers had different blood pressure lowering efficacy. The newest angiotensin-receptor blocker azilsartan medoxomil at the dose of 80 mg seemed to be most efficacious in reducing both systolic and diastolic blood pressure in the office and on ambulatory measurement.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Angiotensins; Antihypertensive Agents; Benzimidazoles; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Humans; Hypertension; Network Meta-Analysis; Olmesartan Medoxomil; Oxadiazoles; Tetrazoles

Azilsartan is used for treatment of the high blood pressure (hypertension). Reducing high blood pressure enables avoid strokes, heart attacks and problems of kidneys. Azilsartan comes under the name angiotensin receptor blocker (ARBs) as a class of drugs. It acts by relaxing blood vessels to make it easier for blood to flow. Azilsartan Medoxomil's a comprehensive profile containing the description, formulae, Elemental Analysis, Uses and application. Furthermore, methods and schemes are outlined for the preparation of the drug substance. The physical properties of the medication include constant of ionization, solubility, X-ray powder diffraction pattern, differential scanning calorimetry, thermal conduct and spectroscopic studies are investigated. The methods employed in bulk medicines and/or in pharmaceutical formulations to analyze the drug substance include spectrophotometric, electrochemical and the chromatographic methods. Other studies on this drug substance include drug stability, Pharmaceutical Applications, Mechanism of Action, Pharmacodynamics, and a Dosing Information are reviewed. At the end of this profile, there are more than sixty references were listed.

Topics: Angiotensin Receptor Antagonists; Antihypertensive Agents; Benzimidazoles; Blood Pressure; Drug Stability; Humans; Hypertension; Oxadiazoles

The goal of this study was to review recent clinical studies of azilsartan medoxomil (AZL-M) and chlorthalidone (CLD), a combined angiotensin receptor blocker and thiazide-like diuretic, and its role in recently published guidelines. This review explores the role of AZL-M/CLD in treating patients with hypertension.. A systematic review of literature published from 1990 to 2018 was performed by using the following key words: Edarbyclor, azilsartan, chlorthalidone, pharmacokinetic, and hypertension. Available English-language data from reviews, abstracts, presentations, and clinical trials regarding the use of AZL-M/CLD therapy specifically detailing effects of lowering blood pressure (BP) and outcomes on cardiovascular disease in humans and rats were reviewed.. One study compared a single-pill combination of AZL-M/CLD with co-administration of AZL-M and hydrochlorothiazide and found a greater reduction in clinic systolic BP with AZL-M/CLD (-35.1 mm Hg vs -29.5 mm Hg) than for AZL-M and hydrochlorothiazide. Another study of 153 patients with chronic kidney disease who received AZL-M/CLD or other single-pill combination agents found that AZL-M/CLD was more effective in lowering BP, achieving superior adherence. According to new guidelines, an increase in the prevalence of resistant hypertension can occur as a result of trying to lower target BP.. A powerful and effective medication that can increase patient compliance is essential to reduce the incidence of resistant hypertension. AZL-M/CLD is a powerful and safe antihypertensive medication that has been thoroughly studied in patients with hypertension.

Topics: Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Benzimidazoles; Chlorthalidone; Drug Combinations; Humans; Hypertension; Oxadiazoles

Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Antihypertensive Agents; Benzimidazoles; Blood Pressure; Clinical Trials as Topic; Humans; Hypertension; Oxadiazoles; Renin-Angiotensin System; Signal Transduction; Treatment Outcome

Arterial hypertension (AH) is one of the most common cardiovascular disease. Angiotensin II (AT II), the hormone of renin-angiotensin-aldosterone system, realizes its negative effects through AT 1 receptors - application point of angiotensin receptor blockers (ARB). Due to different dissociation AT 1 receptors properties some ARBs are more effective than others. Multiply multicenter randomized and observational studies approve the effectiveness and safety of azilsartan medoxomil in patients with AH 1-2 grade. Several preclinical studies have shown the additional properties of azilsartan, including increase of insulin sensitivity, cardio- and nephron protection in obesity. In our clinical case we showed the positive influence of azilsartan medoxomil on clinic and ambulatory blood pressure, 24-hour aortic stiffness parameters, longitudinal left ventricular strain in patient with AH and obesity.

Topics: Adult; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Benzimidazoles; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Humans; Hypertension; Male; Obesity; Oxadiazoles

Azilsartan medoxomil (AZL) is the most recently approved angiotensin receptor blocker (ARB) for treating patients with hypertension. A fixed-dose combination product with AZL and the thiazide-like diuretic chlorthalidone (CLD) is now available to treat individuals who require additional blood pressure lowering. For this review, a literature search was conducted using MEDLINE and the keywords and MeSH terms azilsartan, azilsartan medoxomil, chlorthalidone, thiazide, blood pressure and hypertension. References for retrieved articles were also scanned for relevant citations. No language restrictions were used. AZL is structurally related to candesartan and has been shown to provide more potent angiotensin receptor antagonism versus other ARBs. CLD is a thiazide-like diuretic with a longer half-life and greater blood pressure lowering efficacy than hydrochlorothiazide. The combination of AZL plus CLD has superior efficacy to other ARBs alone or in combination with hydrochlorothiazide based on extensive evaluation in clinical trials. This superior efficacy is not offset by a large imbalance in clinically important adverse events.

Topics: Angiotensin II Type 1 Receptor Blockers; Benzimidazoles; Blood Pressure; Chlorthalidone; Diuretics; Drug Therapy, Combination; Humans; Hypertension; Oxadiazoles; Randomized Controlled Trials as Topic; Treatment Outcome

Azilsartan medoxomil is a newly approved angiotensin-receptor blocker for the management of hypertension. It is a prodrug that is quickly hydrolyzed to the active moiety azilsartan, a potent and highly selective angiotensin-receptor blocker with estimated bioavailability of ∼ 60%. This new agent induces a potent and long-lasting antihypertensive effect. The effective therapeutic antihypertensive dosages of azilsartan medoxomil in humans vary from 40 to 80 mg/day.. The authors review the results of clinical trials published in journals indexed in Medline, Scopus and Google Scholar. Primarily the authors discuss articles that analyze the safety and efficacy of azilsartan in lowering blood pressure.. Clinical trials have demonstrated that azilsartan is superior to other angiotensin-receptor blockers in lowering blood pressure. However, the clinical blood pressure trials of azilsartan published to date have been mainly conducted in patients without serious comorbidities and it is not clear if azilsartan has advantages over other angiotensin-receptor blockers in the treatment of these types of hypertensive patients. In addition, it remains to be determined whether the specific pharmacologic and pharmacokinetic characteristics of azilsartan will have a clinically significant impact on long-term cardiovascular outcomes.

Topics: Angiotensin Receptor Antagonists; Antihypertensive Agents; Benzimidazoles; Blood Pressure; Drug Evaluation; Drug Interactions; Humans; Hypertension; Oxadiazoles; Randomized Controlled Trials as Topic; Treatment Outcome

Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Benzimidazoles; Chlorthalidone; Clinical Trials as Topic; Drug Combinations; Humans; Hypertension; Oxadiazoles

Appropriate control of blood pressure (BP) in hypertensive patients still represents the major therapeutic goal in the treatment of hypertension. Despite the growing attention and wide range of antihypertensive agents available in the clinical scenario, the target of BP below the advised thresholds of 140/90 mmHg is, unfortunately, often unreached. For this reason, the search for new antihypertensive agents is still ongoing. Azilsartan medoxomil, a new angiotensin receptor blocker that has been recently introduced in the clinical arena, represents the eighth angiotensin receptor blocker currently available for BP control. The aim of this paper is to describe the efficacy and safety profile of this new compound, reviewing available data obtained from both pre-clinical and clinical studies.

Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Antihypertensive Agents; Benzimidazoles; Blood Pressure; Drug Interactions; Evidence-Based Medicine; Humans; Hypertension; Oxadiazoles; Renin-Angiotensin System; Risk Assessment; Treatment Outcome

Azilsartan medoxomil (Edarbi®; Ipreziv™) is an orally administered angiotensin II receptor type 1 antagonist (blocker) used in the treatment of adults with essential hypertension. This article reviews data on the clinical efficacy and tolerability of azilsartan medoxomil in adults with essential hypertension and provides a summary of its pharmacological properties. Azilsartan medoxomil is a prodrug that undergoes rapid hydrolysis in the gastrointestinal tract after oral administration to the bioactive moiety azilsartan, before systemic absorption. Azilsartan medoxomil produces antihypertensive effects by selectively blocking the binding of angiotensin II to the angiotensin type 1 (AT(1)) receptor, thereby antagonizing the pressor response activity of angiotensin II. In vitro, azilsartan produced greater and more sustained AT(1) receptor binding/blockade activity than several comparator angiotensin II receptor antagonists. Azilsartan medoxomil reduces blood pressure (BP) in hypertensive adults. In addition, the drug has been shown to have pleiotropic effects (i.e. effects beyond AT(1) receptor blockade). In adults with essential hypertension, azilsartan medoxomil 20, 40 or 80 mg effectively reduced BP over a 24-hour period with once-daily administration in three major, randomized, controlled trials in which the primary endpoints were changes from baseline in 24-hour mean systolic BP (SBP) at week 6 (two trials) or week 24, assessed by ambulatory BP monitoring (ABPM). In the two 6-week trials, azilsartan medoxomil showed dose-dependent efficacy over all evaluated dosages and was more effective than placebo in lowering SBP. At the maximum approved dosage of 80 mg once daily, azilsartan medoxomil was significantly more effective than maximum dosages of olmesartan medoxomil (40 mg once daily) or valsartan (320 mg once daily), based on primary endpoint assessments. Mean reductions in clinic measurements of SBP and diastolic BP (DBP) measurements were also generally greater with azilsartan medoxomil 80 mg once daily than with the comparator drugs in these 6-week studies. Over a longer treatment period of 24 weeks, azilsartan medoxomil showed sustained BP-lowering efficacy, with the reduction in 24-hour mean SBP at week 24 significantly greater with azilsartan medoxomil 40 or 80 mg once daily than with valsartan 320 mg once daily. Mean reductions from baseline in mean clinic SBP and DBP as well as DBP by ABPM were also significantly greater with azilsartan medoxo

Topics: Antihypertensive Agents; Benzimidazoles; Humans; Hypertension; Oxadiazoles

The use of angiotensin receptor blockers (ARBs) represents a favorable approach for the control of blood pressure in patients with hypertension. Azilsartan medoxomil, a prodrug that undergoes rapid hydrolysis to its active moiety azilsartan, is an angiotensin AT(1) receptor antagonist with promising antihypertensive activity and a good safety profile. The agent has been evaluated as monotherapy and in combination with amlodipine or chlorthalidone in phase III trials in patients with essential hypertension. In 2011, azilsartan medoxomil was approved in the U.S. for the treatment of hypertension.

Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Antihypertensive Agents; Benzimidazoles; Blood Pressure; Drug Therapy, Combination; Humans; Hypertension; Oxadiazoles; Prodrugs; Treatment Outcome

Azilsartan medoxomil is an angiotensin receptor blocker, approved on February 25, 2011 by the US Food and Drug Administration (FDA) for hypertension management.. The purpose of this study was to review the pharmacology, pharmacokinetics, efficacy, safety profile, and role of azilsartan for hypertension management.. Peer-reviewed clinical trials, review articles, and relevant treatment guidelines were identified from MEDLINE and Current Contents (both 1966 to August 31, 2011) using the search terms azilsartan, TAK-491, TAK-536, pharmacology, pharmacokinetics, pharmacodynamics, pharmacoeconomics, and cost-effectiveness. The FDA Web site and manufacturer prescribing information were also reviewed to identify other relevant information.. Compared with olmesartan 40 mg daily, azilsartan 80 mg reduced mean systolic blood pressure (SBP) by an additional 2.1 mm Hg (P = 0.038), whereas azilsartan 40 mg was noninferior to olmesartan 40 mg. Azilsartan 40 mg or 80 mg added to chlorthalidone 25 mg daily significantly reduced SBP to a greater extent than did chlorthalidone alone (P < 0.05), but there was no difference between azilsartan 40 mg and 80 mg (40 mg: -31.72 mm Hg; 80 mg: -31.3 mm Hg [P > 0.05]). When coadministered with amlodipine 5 mg daily, both azilsartan 40 mg and 80 mg + amlodipine decreased SBP significantly more than amlodipine alone (amlodipine: -13.6 mm Hg; with azilsartan 40 mg: -24.79 mm Hg; with azilsartan 80 mg: -24.51 mm Hg [P < 0.05]). Compared with ramipril 10 mg daily, both azilsartan 40 mg and 80 mg resulted in significantly (P < 0.001) greater reductions in mean SBP (-20.63 and -21.24 mm Hg, respectively; ramipril: -12.22 mm Hg). The most common adverse events reported were dizziness (4%), dyslipidemia (3.3%), and diarrhea (2%).. At the recommended dose of 80 mg once daily, azilsartan is reported to be an efficacious BP-lowering agent. With once-daily dosing and a favorable side-effect profile, azilsartan is an attractive option for the treatment of hypertension. There is a lack of data supporting the use of azilsartan for improvement in cardiovascular outcomes; therefore, azilsartan is not approved for indications other than the treatment of hypertension.

Topics: Angiotensin Receptor Antagonists; Antihypertensive Agents; Benzimidazoles; Clinical Trials as Topic; Cost-Benefit Analysis; Humans; Hypertension; Oxadiazoles

To evaluate the efficacy, safety, and clinical role of azilsartan medoxomil, an angiotensin II receptor blocker (ARB) that recently gained Food and Drug Administration approval for lowering of blood pressure (BP) in patients with hypertension.. A systematic review of the literature was performed through August 2011 using MEDLINE, Web of Science, and International Pharmaceutical Abstracts and the key words and MeSH terms azilsartan, azilsartan medoxomil, TAK-491, TAK-536, and Edarbi. Abstracts presented in the last 2 years from the annual meetings of appropriate medical societies were reviewed in addition to a search of clinicaltrials.gov.. Studies eligible for inclusion were in vitro or in vivo evaluations of azilsartan medoxomil, with no restrictions on patient population or indication. Data related to the patient populations and outcomes of interest were extracted from each publication.. Three trials are available in full publication form with others available only as abstracts. Azilsartan medoxomil 40 mg and 80 mg daily significantly improves both systolic and diastolic BP from baseline compared with placebo, and the 80-mg dose has greater efficacy than other ARBs, including olmesartan 40 mg daily and valsartan 320 mg daily. Improvements in both 24-hour BP using ambulatory monitoring and clinic monitoring have been seen with azilsartan medoxomil as well as a higher proportion of patients reaching the goal level. Additional information shows added BP lowering when azilsartan medoxomil is combined with chlorthalidone. Adverse events are similar with azilsartan medoxomil versus other ARBs and include headache, dizziness, urinary tract infections, and fatigue.. Azilsartan medoxomil is a safe and effective ARB with a unique pharmacologic profile versus other agents, including slowed angiotensin II type 1 receptor dissociation rates and improved receptor specificity. Studies have shown azilsartan medoxomil 80 mg once daily to reduce BP to a greater extent than valsartan and olmesartan, with similar safety and tolerability.

Topics: Angiotensin Receptor Antagonists; Antihypertensive Agents; Benzimidazoles; Blood Pressure; Clinical Trials as Topic; Humans; Hypertension; Oxadiazoles; United States; United States Food and Drug Administration

Azilsartan medoxomil (AZL-M) is a potent angiotensin II receptor blocker that decreases blood pressure in a dose-dependent manner. It is a prodrug that is not detected in blood after its oral administration because of its rapid hydrolysis to the active moiety, azilsartan (AZL). AZL undergoes further metabolism to the major metabolite, M-II, and minor metabolites. The objective of this study was to determine the effect of mild to moderate hepatic impairment on the pharmacokinetics of AZL and its major metabolite. This was a single-center, open-label, phase 1 parallel-group study that examined the single-dose (day 1) and multiple-dose (days 4-8) - 40 mg - pharmacokinetics of AZL and M-II in 16 subjects with mild and moderate hepatic impairment by Child-Pugh classification (n = 8 per group) and subjects (n = 16) matched based on age, sex, race, weight, and smoking status. Mild or moderate hepatic impairment did not cause clinically meaningful increases in exposure to AZL and M-II. Mild or moderate hepatic impairment had no clinically meaningful effect on the plasma protein binding of AZL and M-II. Single and multiple doses of AZL-M 40 mg were well tolerated in all subject groups. Based on the pharmacokinetic and tolerability findings, no dose adjustment of AZL-M is required for subjects with mild and moderate hepatic impairment.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Antihypertensive Agents; Benzimidazoles; Blood Pressure; Chemical and Drug Induced Liver Injury; Female; Humans; Hypertension; Male; Middle Aged; Oxadiazoles

Azilsartan medoxomil (AZL-M), an angiotensin II receptor blocker, has been developed in fixed-dose combinations (FDCs) with chlorthalidone (CTD).. We compared FDCs of AZL-M/CTD 20/12.5 mg once daily titrated to 40/25 mg if needed or AZL-M/CTD 40/12.5 mg once daily titrated to 80/25 mg if needed with an olmesartan medoxomil (OLM)-hydrochlorothiazide (HCTZ) 20/12.5 mg FDC once daily titrated to 40/25 mg if needed in a randomized, double-blind, 8-week study of 1085 participants with clinic SBP 160-190 mmHg and DBP 119 mmHg or less. Titration to higher doses occurred at week 4 if BP was at least 140/90 mmHg (≥130/80 mmHg if diabetes or chronic kidney disease). The primary endpoint was change from baseline in clinic SBP; 24-h ambulatory BP monitoring was also measured.. Greater reductions in clinic SBP from a baseline of 165 mmHg were observed (P < 0.001) in both AZL-M/CTD arms (-37.6 and -38.2 mmHg) versus OLM/HCTZ (-31.5 mmHg), despite greater dose titration in the OLM/HCTZ group. At 8 weeks, both AZL-M/CTD FDCs reduced 24-h SBP more than OLM/HCTZ (-26.4 and -27.9 versus -20.7 mmHg; both P < 0.001), and higher proportions in both AZL-M/CTD groups achieved target BP compared with the OLM/HCTZ group (69.4 and 68.9 versus 54.7%, both P < 0.001). Adverse events leading to drug discontinuation occurred in 6.2, 9.5, and 3.1% with the AZL-M/CTD lower and higher doses, and OLM/HCTZ, respectively.. This large, titration-to-target BP study demonstrated AZL-M/CTD FDCs to have superior antihypertensive efficacy compared with the maximum approved dose of OLM/HCTZ.

Topics: Aged; Antihypertensive Agents; Benzimidazoles; Blood Pressure; Chlorthalidone; Diuretics; Double-Blind Method; Drug Combinations; Female; Humans; Hydrochlorothiazide; Hypertension; Imidazoles; Male; Middle Aged; Oxadiazoles; Tetrazoles

An open-label, long-term study evaluated safety and tolerability of azilsartan medoxomil/chlorthalidone (AZL-M/CLD) vs olmesartan/hydrochlorothiazide (OLM/HCTZ) in hypertensive participants with stage 3 chronic kidney disease. Initial therapy was AZL-M/CLD 20/12.5 mg (n = 77) or OLM/HCTZ 20/12.5 mg (n = 76), but could be up-titrated (AZL-M/CLD to 40/25 mg; OLM/HCTZ to 40/25 mg [US] or 20/25 mg [Europe]) with other agents added during weeks 4-52. Primary endpoint was proportion of participants with ≥ 1 adverse event (AE) through week 52. Baseline demographics were similar. AEs did not differ between groups (88.3%, AZL-M/CLD vs 76.3%, OLM/HCTZ; P = .058). AZL-M/CLD showed greater systolic BP reductions after initial dosing (P = .037) but not during long-term follow-up (P = .588). A greater proportion of participants up-titrated to the highest dose with OLM/HCTZ (48.7%) vs AZL-M/CLD (29.9%) (P = .021) and were taking additional antihypertensive medications (26.3% vs 16.9%). Both AZL-M/CLD and OLM/HCTZ showed similar efficacy and tolerability.

Topics: Aged; Benzimidazoles; Chlorthalidone; Drug Therapy, Combination; Female; Humans; Hydrochlorothiazide; Hypertension; Male; Middle Aged; Olmesartan Medoxomil; Oxadiazoles; Renal Insufficiency, Chronic; Treatment Outcome

Two post hoc analyses in self-identified black and white patients with hypertension evaluated the angiotensin II receptor blocker azilsartan medoxomil (AZL-M) and the fixed-dose combination of AZL-M with chlorthalidone (AZL-M/CLD) versus the ARB olmesartan (OLM) and the OLM fixed-dose combination with hydrochlorothiazide (OLM/HCTZ). One analysis pooled 1,610 patients from two 6-week randomized controlled trials to compare once daily AZL-M 40 mg, AZL-M 80 mg, OLM 40 mg, and placebo. The second analysis included 1,020 patients from a 12-week randomized controlled trial to compare once daily AZL-M/CLD 40/25 mg, AZL-M/CLD 80/25 mg, and OLM/HCTZ 40/25 mg. Efficacy end points were 24-hour mean ambulatory and clinic systolic and diastolic blood pressure (SPB/DBP) and the percentage of patients achieving clinic SBP/DBP targets. Treatment with AZL-M 80 mg lowered mean clinic SBP by 12.5 mm Hg (p <0.01 vs OLM), treatment with AZL-M/CLD 40 mg/25 mg lowered mean ambulatory SBP by 31.0 mm Hg and mean clinic SBP by 39.3 mm Hg (both p <0.05 vs OLM/HCTZ), and treatment with AZL-M/CLD 80 mg/25 mg lowered mean ambulatory SBP by 34.4 mm Hg (p <0.01 vs OLM/HCTZ) and mean clinic SBP by 39.2 mm Hg (p <0.05 vs OLM/HCTZ). Target BP goals were achieved more frequently with AZL-M versus OLM and with AZL-M/CLD versus OLM/HCTZ. In conclusion, in both black and white patients, BP was lowered more effectively with AZL-M versus OLM and with AZL-M/CLD versus OLM/HCTZ. The AZL-M/CLD 40 mg/25 mg combination resulted in a statistically significant reduction in BP in both black and white patients.

Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Benzimidazoles; Black or African American; Chlorthalidone; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Hydrochlorothiazide; Hypertension; Imidazoles; Male; Middle Aged; Oxadiazoles; Tetrazoles; United States; White People

The efficacy and safety of azilsartan medoxomil (AZL-M) were evaluated in African-American patients with hypertension in a 6-week, double-blind, randomized, placebo-controlled trial, for which the primary end point was change from baseline in 24-hour mean systolic blood pressure (BP). There were 413 patients, with a mean age of 52 years, 57% women, and baseline 24-hour BP of 146/91 mm Hg. Treatment differences in 24-hour systolic BP between AZL-M 40 mg and placebo (-5.0 mm Hg; 95% confidence interval, -8.0 to -2.0) and AZL-M 80 mg and placebo (-7.8 mm Hg; 95% confidence interval, -10.7 to -4.9) were significant (P≤.001 vs placebo for both comparisons). Changes in the clinic BPs were similar to the ambulatory BP results. Incidence rates of adverse events were comparable among the treatment groups, including those of a serious nature. In African-American patients with hypertension, AZL-M significantly reduced ambulatory and clinic BPs in a dose-dependent manner and was well tolerated.

Topics: Adult; Angiotensin Receptor Antagonists; Antihypertensive Agents; Benzimidazoles; Black or African American; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Double-Blind Method; Female; Humans; Hypertension; Male; Middle Aged; Oxadiazoles; Treatment Outcome; United States

In this phase 2, multicenter, parallel-group, double-blind, dose-ranging study, hypertensive adults (n=449) were randomized to receive one of five doses of a capsule formulation of azilsartan medoxomil (AZL-M; 5, 10, 20, 40, 80 mg), olmesartan medoxomil (OLM) 20 mg, or placebo once daily. The primary endpoint was change in trough clinic diastolic blood pressure (DBP) at week 8. AZL-M provided rapid statistically and clinically significant reductions in DBP and systolic blood pressure (SBP) vs placebo at all doses except 5 mg. Placebo-subtracted changes were greatest with the 40 mg dose (DBP, -5.7 mm Hg; SBP, -12.3 mm Hg). Clinic changes with AZL-M (all doses) were statistically indistinguishable vs OLM, although there were greater reductions with AZL-M 40 mg using 24-hour ambulatory blood pressure. Adverse event frequency was similar in the AZL-M and placebo groups. Based on these and other findings, subsequent trials investigated the commercial AZL-M tablet in the dose range of 20 to 80 mg/d.

Topics: Adult; Aged; Angiotensin II Type 1 Receptor Blockers; Benzimidazoles; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Diastole; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Hypertension; Imidazoles; Male; Middle Aged; Oxadiazoles; Tetrazoles; Treatment Outcome

Population pharmacokinetic and exposure-response models for azilsartan medoxomil (AZL-M) and chlorthalidone (CLD) were developed using data from an 8-week placebo-controlled phase 3, factorial study of 20, 40, and 80 mg AZL-M every day (QD) and 12.5 and 25 mg CLD QD in fixed-dose combination (FDC) in subjects with moderate to severe essential hypertension. A 2-compartment model with first-order absorption and elimination was developed to describe pharmacokinetics. An Emax model for exposure-response analysis evaluated AZL-M/CLD effects on ambulatory systolic blood pressure (SBP). Estimated oral clearance and apparent volume of distribution (central compartment) were 1.47 L/h and 3.98 L for AZL, and 4.13 L/h and 62.1 L for CLD. Age as a covariate had the largest effect on AZL and CLD exposure (±20% change). Predicted maximal SBP responses (Emax ) were -15.6 and -23.9 mm Hg for AZL and CLD. Subgroup analysis identified statistically significant Emax differences for black vs nonblack subjects, whereby the reduced AZL response in black subjects was offset by greater response to CLD. The estimated Emax for AZL and CLD was generally greater in subjects with higher baseline BP. In conclusion, no dose adjustments to AZL-M or CLD are warranted based on identified covariates, and antihypertensive efficacy of AZL-M/CLD combination therapy is comparable in black and nonblack subjects.

Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Benzimidazoles; Chlorthalidone; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hypertension; Male; Middle Aged; Oxadiazoles; Treatment Outcome

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.

Topics: Adult; Aged; Benzimidazoles; Chlorthalidone; Cohort Studies; Dizziness; Drug Therapy, Combination; Essential Hypertension; Fatigue; Female; Headache; Humans; Hydrochlorothiazide; Hypertension; Male; Middle Aged; Oxadiazoles; Sodium Chloride Symporter Inhibitors; Treatment Outcome

Increased abdominal obesity is associated with increased cardiovascular risk, especially in African American women. The adipocyte is documented to produce a number of inflammatory factors including the hormone aldosterone. There are very few data documenting aldosterone production from adipocytes of postmenopausal women as well as data demonstrating the effects of angiotensin receptor blockade (ARB) on its production in predominately African American women. The authors hypothesize that increased central adipocyte mass in obese postmenopausal women contributes to increased production of aldosterone that is suppressed with the ARB azilsartan medoxomil. The authors tested this hypothesis in a double-blind, placebo-controlled pilot study of 34 hypertensive postmenopausal women (mean age 57.5±7.5 years), 91% of whom were African American. Patients had a mean 24-hour ambulatory systolic blood pressure of 127±13 mm Hg off any blocker of the renin-angiotensin system but while taking other antihypertensive medications. The authors further validated aldosterone production in a nested cohort of women using fat cells from a fat pad biopsy. Azilsartan reduced 24-hour urinary aldosterone by 47.3% from baseline (P=.03), with between-groups differences in urine aldosterone of -5.3±52.3% placebo vs -47.3±32.9% azilsartan (P=.07) at 6 months. An adrenal cell line treated with adipocyte-conditioned media from subcutaneous abdominal adipocytes of postmenopausal women (n=3) showed an increase in aldosterone production blocked by an ARB (1948±1297 pg/mL fat alone vs 894±438 pg/mL fat + ARB; P=.022). The authors conclude that aldosterone is produced from subcutaneous adipocytes of obese postmenopausal women. Moreover, use of an ARB significantly reduces aldosterone production within 6 months of use in these women as well as in cells exposed to their adipocytes.

Topics: Adipocytes; Aged; Aldosterone; Benzimidazoles; Black or African American; Cell Line; Culture Media, Conditioned; Double-Blind Method; Female; Humans; Hypertension; Middle Aged; Obesity, Abdominal; Oxadiazoles; Pilot Projects; Postmenopause

A phase 3, 26-week, open-label, titrate-to-target study (n=418) assessed the safety of azilsartan medoxomil (AZL-M) alone and with chlorthalidone (CLD), followed by a 6-week, double-blind, placebo-controlled reversal phase with change in clinic diastolic blood pressure (DBP) as the primary endpoint. Target blood pressure (BP) was <140/90 mm Hg (<130/80 mm Hg with diabetes/chronic kidney disease). AZL-M was initiated at 40 mg once a day (QD), force-titrated to 80 mg at week 4. CLD 25 mg QD could be added (weeks 8-22), if required, to reach target, followed by additional antihypertensives from week 12. At the end of the open-label phase, mean change in systolic BP (SBP)/DBP from baseline was -23/-16 mm Hg. The most common adverse events, irrespective of treatment, were dizziness (8.9%) and headache (7.2%). Serious AEs were reported in eight patients (1.9%). Consecutive creatinine elevations ≥50% with values exceeding the upper limit of normal (ULN) were reported in nine (2.2%) patients. All returned to below the 50% threshold; most also returned to below the ULN after drug discontinuation. Mean DBP was maintained through the reversal phase in patients receiving AZL-M, but increased with placebo (difference: -7.8 mm Hg, 95% confidence interval, -9.8 to -5.8; P<.001). AZL-M alone or with CLD showed good long-term safety and stable BP improvements in a titrate-to-target approach. BP improvements caused by AZL-M therapy were safely reversible upon AZL-M withdrawal.

Topics: Adult; Angiotensin Receptor Antagonists; Antihypertensive Agents; Benzimidazoles; Blood Pressure; Chlorthalidone; Diuretics; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Drug Tolerance; Female; Follow-Up Studies; Humans; Hypertension; Longitudinal Studies; Male; Mass Screening; Middle Aged; Oxadiazoles; Treatment Outcome

The aim of the study was to measure the effects on blood pressure (BP) of the angiotensin receptor blocker azilsartan medoxomil, in 40 and 80 mg doses, combined with 5 mg of the calcium channel blocker amlodipine and to compare these effects with placebo plus amlodipine 5 mg.. This was a randomized, controlled, double-blind study of 6 weeks' duration in 566 patients with stage 2 hypertension. The primary endpoint was 24-h systolic BP by ambulatory monitoring.. The mean age of the participants was 58 years; men and women were equally represented, and baseline 24-h BP (153-154/93 mmHg) and clinic BP (165-166/94-95 mmHg) were similar across the three treatment groups. After 6 weeks, 24-h BP decreased by 25/15 mmHg in both the azilsartan medoxomil/amlodipine 40/5 and 80/5 mg groups. These reductions were each greater than the 14/8 mmHg decrease with placebo plus amlodipine 5 mg (P≤0.001 for both comparisons). All treatments were well tolerated, and adverse events did not increase with the azilsartan medoxomil doses. Edema or fluid retention was less common in both combination groups (2.6 and 2.7%) than with placebo plus amlodipine (7.6%).. Coadministration of azilsartan medoxomil with amlodipine was well tolerated and led to meaningful additional BP reductions compared with placebo plus amlodipine.

Topics: Aged; Amlodipine; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Benzimidazoles; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Calcium Channel Blockers; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hypertension; Male; Middle Aged; Oxadiazoles

Drug therapy often fails to control hypertension. Azilsartan medoxomil (AZL-M) is a newly developed angiotensin II receptor blocker with high efficacy and good tolerability. This double-blind, controlled, randomised trial compared its antihypertensive efficacy and safety vs the angiotensin-converting enzyme inhibitor ramipril (RAM) in patients with clinic systolic blood pressure (SBP) 150-180 mm Hg. Patients were randomised (n=884) to 20 mg AZL-M or 2.5 mg RAM once daily for 2 weeks, then force-titrated to 40 or 80 mg AZL-M or 10 mg RAM for 22 weeks. The primary endpoint was change in trough, seated, clinic SBP. Mean patient age was 57±11 years, 52.4% were male, 99.5% were Caucasian. Mean baseline BP was 161.1±7.9/94.9±9.0 mm Hg. Clinic SBP decreased by 20.6±0.95 and 21.2±0.95 mm Hg with AZL-M 40 and 80 mg vs12.2±0.95 mm Hg with RAM (P<0.001 for both AZL-M doses). Adverse events leading to discontinuation were less frequent with AZL-M 40 and 80 mg (2.4% and 3.1%, respectively) than with RAM (4.8%). These data demonstrated that treatment of stage 1-2 hypertension with AZL-M was more effective than RAM and better tolerated.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Double-Blind Method; Female; Humans; Hypertension; Male; Middle Aged; Oxadiazoles; Ramipril

This study compared the efficacy and safety of fixed-dose combinations (FDCs) of the angiotensin II receptor blocker azilsartan medoxomil (AZL-M) and the thiazide-like diuretic chlorthalidone (CLD) with the individual monotherapies in a double-blind factorial study. A total of 1714 patients with clinic systolic blood pressure (SBP) 160 mm Hg to 190 mm Hg inclusive were randomized to AZL-M 0 mg, 20 mg, 40 mg, or 80 mg and/or chlorthalidone 0 mg, 12.5 mg, or 25 mg. The primary efficacy end point was change from baseline to 8 weeks in trough (hour 22-24) SBP by ambulatory blood pressure (BP) monitoring (ABPM). Patients' mean age was 57 years; 47% were men and 20% were black. Baseline trough BP was approximately 165/95 mm Hg and 151/91 mm Hg by clinic and ABPM measurements, respectively. For the pooled AZL-M/CLD 40/25-mg and 80/25-mg FDC groups, SBP reduction by ABPM at trough was 28.9 mm Hg and exceeded AZL-M 80 mg and CLD 25 mg monotherapies by 13.8 mm Hg and 13 mm Hg, respectively (P<.001 for both comparisons). Discontinuation rates and elevations in serum creatinine were dose-dependent and occurred more often in the AZL-M/CLD groups. In patients with stage 2 hypertension, treatment with the combination of AZL-M and CLD resulted in substantially greater SBP reduction compared with either agent alone.

Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Benzimidazoles; Black People; Blood Pressure; Chlorthalidone; Diuretics; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hypertension; Male; Middle Aged; Oxadiazoles; Treatment Outcome; White People

Azilsartan medoxomil, an effective, long-acting angiotensin II receptor blocker, is a new treatment for hypertension that is also being developed in fixed-dose combinations with chlorthalidone, a potent, long-acting thiazide-like diuretic. We compared once-daily fixed-dose combinations of azilsartan medoxomil/chlorthalidone force titrated to a high dose of either 40/25 mg or 80/25 mg with a fixed-dose combination of the angiotensin II receptor blocker olmesartan medoxomil plus the thiazide diuretic hydrochlorothiazide force titrated to 40/25 mg. The design was a randomized, 3-arm, double-blind, 12-week study of 1071 participants with baseline clinic systolic blood pressure 160 to 190 mm Hg and diastolic blood pressure ≤119 mm Hg. Patients had a mean age of 57 years; 59% were men, 73% were white, and 22% were black. At baseline, mean clinic blood pressure was 165/96 mm Hg and 24-hour mean blood pressure was 150/88 mm Hg. Changes in clinic (primary end point) and ambulatory systolic blood pressures at week 12 were significantly greater in both azilsartan medoxomil/chlorthalidone arms than in the olmesartan/hydrochlorothiazide arm (P<0.001). Changes in clinic systolic blood pressure (mean±SE) were -42.5±0.8, -44.0±0.8, and -37.1±0.8 mm Hg, respectively. Changes in 24-hour ambulatory systolic blood pressure were -33.9±0.8, -36.3±0.8, and -27.5±0.8 mm Hg, respectively. Adverse events leading to permanent drug discontinuation occurred in 7.9%, 14.5%, and 7.1% of the groups given azilsartan medoxomil/chlorthalidone 40/25 mg, azilsartan medoxomil/chlorthalidone 80/25 mg, and olmesartan/hydrochlorothiazide 40/25 mg, respectively. This large, forced-titration study has demonstrated superior antihypertensive efficacy of azilsartan medoxomil/chlorthalidone fixed-dose combinations compared with the maximum approved dose of olmesartan/hydrochlorothiazide.

Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Benzimidazoles; Black People; Blood Pressure; Chlorthalidone; Diuretics; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hydrochlorothiazide; Hypertension; Imidazoles; Male; Middle Aged; Oxadiazoles; Severity of Illness Index; Tetrazoles; Treatment Outcome; White People

Chlorthalidone has proven efficacy to reduce cardiovascular morbidity and mortality, yet it is infrequently used in practice. This study provides a direct comparison of chlorthalidone with hydrochlorothiazide, each combined with the angiotensin receptor blocker azilsartan medoxomil, on blood pressure reduction and control rates.. This is a randomized, double-blind, titrate-to-target blood pressure trial comparing the single-pill combination of azilsartan medoxomil and chlorthalidone versus co-administration of azilsartan medoxomil and hydrochlorothiazide in participants with stage 2 primary hypertension. After 2 weeks of treatment with azilsartan medoxomil 40 mg alone, all participants also received 12.5 mg of diuretic for 4 weeks (up to week 6) and were titrated to 25 mg for another 4 weeks (up to week 10) if they failed to achieve target blood pressure. The primary end point was change in clinic systolic blood pressure. Target blood pressure was defined as clinic blood pressure <140/90 mm Hg for participants without diabetes or chronic kidney disease or <130/80 mm Hg for participants with diabetes or chronic kidney disease.. The mean age of the 609 participants was 56.4 years, and the mean baseline clinic blood pressure was 164.6/95.4 mm Hg. The primary end point analysis at week 6 demonstrated a greater reduction of clinic systolic blood pressure for the chlorthalidone (-35.1 mm Hg) versus hydrochlorothiazide combination (-29.5 mm Hg) (mean difference, -5.6 mm Hg; 95% confidence interval, -8.3 to -2.9; P <.001). The mean difference in 24-hour ambulatory systolic blood pressure at week 6 was -5.8 mm Hg (95% confidence interval, -8.4 to -3.2; P <.001), favoring the azilsartan medoxomil/chlorthalidone group. The percentage of participants achieving target clinic blood pressure at week 6 was greater for the chlorthalidone versus hydrochlorothiazide combination (64.1% vs 45.9%, P <.001). Drug discontinuations due to adverse events were not statistically significantly different between groups (9.3% vs 7.3%, P = .38), and hypokalemia was uncommon in both groups.. Chlorthalidone combined with azilsartan medoxomil provides better blood pressure reduction and a higher likelihood of achieving blood pressure control than hydrochlorothiazide combined with azilsartan medoxomil. This benefit occurred without a difference in safety measurements.

Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Benzimidazoles; Blood Pressure Monitoring, Ambulatory; Chlorthalidone; Creatinine; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Female; Humans; Hydrochlorothiazide; Hypertension; Male; Middle Aged; Oxadiazoles; Potassium; Systole

The current study assesses the antihypertensive efficacy and safety of the investigational angiotensin receptor blocker (ARB), azilsartan medoxomil (AZL-M), compared with placebo and the ARB olmesartan medoxomil (OLM-M). This randomized, double-blind, placebo-controlled, multicenter study assessed change from baseline in mean 24-hour ambulatory systolic blood pressure (SBP) following 6 weeks of treatment. Patients with primary hypertension (n=1275) and baseline 24-hour mean ambulatory systolic pressure ≥ 130 mm Hg and ≤ 170 mm Hg were studied; 142 received placebo and the remainder received 20 mg, 40 mg, or 80 mg AZL-M or 40 mg OLM-M. Mean age of participants was 58 ± 11 years, baseline mean 24-hour SBP was 146 mm Hg. Dose-dependent reductions in 24-hour mean SBP at study end occurred in all AZL-M groups. Reduction in 24-hour mean SBP was greater with AZL-M 80 mg than OLM-M 40 mg by 2.1 mm Hg (95% confidence interval, -4.0 to -0.1; P=.038), while AZL-M 40 mg was noninferior to OLM-M 40 mg. The side effect profiles of both ARBs were similar to placebo. AZL-M is well tolerated and more efficacious at its maximal dose than the highest dose of OLM-M.

Topics: Aged; Angiotensin Receptor Antagonists; Argentina; Benzimidazoles; Blood Pressure; Blood Pressure Determination; Blood Pressure Monitoring, Ambulatory; Double-Blind Method; Female; Humans; Hypertension; Imidazoles; Male; Mexico; Middle Aged; Oxadiazoles; Peru; Racial Groups; Tetrazoles; Treatment Outcome; United States

Azilsartan medoxomil is an angiotensin receptor blocker (ARB) being developed for hypertension treatment. To compare this ARB with others in the class, we studied the effects of 2 doses of azilsartan medoxomil, with valsartan 320 mg and olmesartan medoxomil (olmesartan) 40 mg, in a randomized, double-blind, placebo-controlled trial using ambulatory blood pressure (BP) monitoring and clinic BP measurements. The primary efficacy end point was the change from baseline in 24-hour mean systolic BP. Hierarchical analysis testing for superiority over placebo was followed by noninferiority analysis and then superiority testing of azilsartan medoxomil (80 mg and then 40 mg) versus the comparator ARBs. For 1291 randomized patients, mean age was 56 years, 54% were men, and baseline 24-hour mean systolic BP was 145 mm Hg. Azilsartan medoxomil at 80 mg had superior efficacy to both valsartan at 320 mg and olmesartan at 40 mg: placebo-adjusted 24-hour systolic BP was lowered (-14.3 mm Hg) more than 320 mg of valsartan (-10.0 mm Hg; P<0.001) and 40 mg of olmesartan (-11.7 mm Hg; P=0.009). Azilsartan medoxomil at 40 mg was noninferior to 40 mg of olmesartan (difference: -1.4 mm Hg [95% CI: -3.3 to 0.5]). For clinic systolic BP, both doses of azilsartan medoxomil were superior to the comparator ARBs. Safety and tolerability were similar among the placebo and 4 active treatments. These data demonstrate that azilsartan medoxomil at its maximal dose has superior efficacy to both olmesartan and valsartan at their maximal, approved doses without increasing adverse events. Azilsartan medoxomil could provide higher rates of hypertension control within the ARB class.

Topics: Adult; Aged; Analysis of Variance; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Benzimidazoles; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Double-Blind Method; Female; Humans; Hypertension; Imidazoles; Male; Middle Aged; Oxadiazoles; Tetrazoles; Treatment Outcome; Valine; Valsartan

Azilsartan medoxomil (AZL) is an anti-hypertensive drug, and its numerous FDCs are used for the treatment of hypertension. Numerous chromatographic methods have been reported for the estimation of FDCs of AZL, but analysts have to establish a separate chromatographic condition for the analysis of each FDC of AZL. No reverse-phase high-pressure liquid chromatography (RP-HPLC) method has been reported yet that can be used for synchronous estimation of multiple FDCs of AZL.. Hence, the RP-HPLC-PDA method has been developed for synchronous estimation of multiple FDCs of AZL to save time, cost, and solvent for the analysis.. The RP-HPLC-PDA method has been developed by the implementation of the analytical quality by design (AQbD) approach based on chemometric and DoE as per the upcoming International Council for Harmonization (ICH) Q14 guideline.. The method was applied for synchronous estimation of multiple FDCs of AZL, and the assay results were found in compliance with the labeled claim of the FDCs.. The developed method requires less time, cost, and organic solvent for analysis of the said pharmaceutical dosage forms compared to published chromatographic methods. Hence, the developed method is green and multipurpose for the estimation of multiple FDCs of AZL.. Development and validation of RP-HPLC method for synchronous estimation of multiple FDCs of AZL using chemometric (principal component analysis and PLS) and design of experiments (DoE). Applications of the method for synchronous estimation of multiple FDCs of AZL.

Topics: Angiotensin II Type 1 Receptor Blockers; Chemometrics; Chromatography, High Pressure Liquid; Humans; Hypertension; Oxadiazoles

To assess the influence of the therapy of arterial hypertension with azilsartan medoxomil on the renal function in overweight or obese patients with concomitant metabolic disorders.. An international multicenter observational nonintervention prospective study included 1945 patients, taking azilsartan medoxomil in accordance with approved prescribing information. The observation period reached 6 months.. In patients with an initial glomerular filtration rate (GFR)60 ml/min/1.73 m2 or 60 ml/min/1.73 m2 mean change in systolic blood pressure after 6 months of therapy reached -32.511.1 and -30.413.6 mmHg, correspondingly, while the change in diastolic blood pressure was -13.78.8 and -14.29.4 mmHg, respectively. No decrease in renal function was observed. Moreover, in patients with an initial GFR60 ml/min/1.73 m2 GFR increased significantly (p0.001).. Azilsartan medoxomil, prescribed as monotherapy or in free combinations, provided an effective control of blood pressure in patients with arterial hypertension with both normal or moderately reduced and initially significantly reduced renal function. High efficacy and acceptability of the drug was associated with a beneficial effect on renal function, which allows to consider azilsartan medoxomil as the drug of choice for the treatment of hypertension in patients with concomitant metabolic disorders.. Цель. Оценить влияние антигипертензивной терапии азилсартана медоксомилом на динамику функционального состояния почек у пациентов с избыточной массой тела или ожирением и сопутствующими метаболическими нарушениями. Материалы и методы. Оценено состояние функции почек у 1945 пациентов, включенных в международное многоцентровое наблюдательное неинтервенционное проспективное исследование с применением азилсартана медоксомила в соответствии с утвержденной инструкцией по использованию препарата. Период наблюдения составил 6 мес. Результаты. Выделены 2 группы пациентов в зависимости от исходной скорости клубочковой фильтрации (СКФ): 1-я группа с СКФ60 мл/мин/1,73 м2 и 2-я с СКФ60 мл/мин/1,73 м2. В обеих группах пациентов среднее изменение систолического артериального давления через 6 мес терапии достигло -32,511,1 и -30,413,6 мм рт. ст. соответственно, а изменение диастолического артериального давления -13,78,8 и -14,29,4 мм рт. ст. соответственно. В результате исследования не отмечено ухудшения функции почек на фоне терапии азилсартана медоксомилом. Более того, у пациентов с исходной СКФ60 мл/мин/1,73 м2 установлено статистически значимое увеличение СКФ по сравнению с исходными показателями (p0,001). Заключение. Азилсартана медоксомил как в режиме монотерапии, так и в свободных комбинациях с другими антигипертензивными препаратами обеспечивает эффективный контроль артериального давления у пациентов с артериальной гипертонией и метаболическими нарушениями как при нормальной или умеренно сниженной, так и при исходно значительно сниженной функции почек. Высокая эффективность и хорошая переносимость препарата сочетаются с нефропротективным действием, что позволяет рассматривать азилсартана медоксомил как препарат выбора для терапии артериальной гипертонии у пациентов с сопутствующими метаболическими нарушениями и сниженной функцией почек.

Topics: Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Blood Pressure; Humans; Hypertension; Kidney; Metabolic Diseases; Obesity; Overweight; Prospective Studies; Tetrazoles; Treatment Outcome

Control of arterial hypertension in obese or overweight patients is complicated since obesity directly contributes to increased blood pressure, requiring new, highly effective antihypertensive drugs. This study evaluates the efficacy of azilsartan medoxomil in real clinical practice.. An international multicenter observational non-interventional prospective study of azilsartan medoxomil was conducted in 64 clinical centers in the Russian Federation and 5 centers in the Republic of Kazakhstan. This study included 1945 obese or overweight patients with arterial hypertension. Azilsartan medoxomil was prescribed in accordance with the approved instruction for use. The decision to prescribe the drug, dose adjustment and monitoring target BP achievement belonged to the attending physicians according to their routine clinical practice. The observation period took about 6 months.. The average duration of taking the medicine was 26.1 ± 4 weeks. By the fourth visit, the use of azilsartan medoxomil either in a monotherapy regimen or in free combinations resulted in a pronounced decrease in systolic and diastolic blood pressure by 30.5 ± 13.4 and 14 ± 9.4 mmHg, respectively (. Over the study time of 1945 patients, significant changes in blood pressure levels over time were noted, and a high frequency of response to the azilsartan therapy was observed. Adverse events related to the study drug were of mild or moderate intensity and did not require discontinuation of therapy. Thus, azilsartan medoxomil demonstrated a good safety profile and provided effective blood pressure control for overweight or obese patients with hypertension in real clinical practice.

Topics: Antihypertensive Agents; Benzimidazoles; Blood Pressure; Humans; Hypertension; Internationality; Male; Middle Aged; Obesity; Oxadiazoles; Prospective Studies

Hypertension is one of the most common chronic diseases and an increasingly public-health challenge worldwide. Previous meta-analyses evaluated the effects of azilsartan medoxomil compared to placebo or other antihypertensive drugs in patients with hypertension. However, it is still unclear which dose of azilsartan is optimal. This study will perform a network meta-analysis to assess the efficacy and safety of different doses of azilsartan medoxomil in patients with hypertension.. PubMed, EMBASE.com, the Cochrane library, Scopus, and Web of Science were searched from inception to May 2019. Randomized controlled trials reporting efficacy and safety of different doses of azilsartan medoxomil on hypertension will be included if they compared 1 dose of azilsartan medoxomil with another dose of azilsartan medoxomil or with a placebo. Risk of bias of the included trials will be evaluated according to the Cochrane Handbook 5.1.0. NMA will be performed in a Bayesian hierarchical framework using WinBUGS 14.. The results will be submitted to a peer-reviewed journal for publication.. This study will summarize all the available data to provide reliable evidence of the value of different doses of azilsartan medoxomil for the treatment of hypertension.. CRD42019136882.

Topics: Angiotensin II Type 1 Receptor Blockers; Benzimidazoles; Humans; Hypertension; Network Meta-Analysis; Oxadiazoles

To evaluate azilsartan medoxomil (AZM) (Edarbi. This is a retrospective cohort study among patients receiving AZM in the primary-care setting in Germany. Prescription patterns - including patient demographics, off-label use, use in specific populations, concomitant use of other antihypertensive drugs, and drugs potentially causing interactions with AZM - were analyzed in two periods (01/2012 - 12/2013 and 01/2014 - 11/2016) using the primary-care physician panel of German IMS. In total, 852 of 1,159 (74%) and 696 of 811 (86%) patients met the inclusion criteria for both periods, respectively. Approximately 25% of patients were aged ≥ 75 years; 1 patient was < 18 years old; ~ 50% were females. AZM was prescribed for the approved indication of essential hypertension in 83% and 68% of patients in the first and second period, while indication was missing in 12% and 26% of patients, respectively. AZM was coprescribed on the same day with other antihypertensive drugs in 23% (first period) and 37% (second period) of patients. Drugs that might cause an interaction with AZM were coprescribed on the same day in 3% of patients in both periods; overlapping prescription periods were detected in 14% (first period) and 8% (second period) of patients. Coprescription of AZM with angiotensin-converting enzyme (ACE) inhibitors (2%) or aliskiren (< 1%) on the same day was rare in both periods. Overlapping prescription periods with AZM decreased from 20 to 6% for ACE inhibitors and from 8 to 1% for aliskiren.. Findings from this real-world evidence study demonstrate that AZM was generally utilized for approved indication and in accordance with the summary of product characteristics recommendations.
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Topics: Adolescent; Adult; Aged; Antihypertensive Agents; Benzimidazoles; Female; Germany; Humans; Hypertension; Male; Middle Aged; Oxadiazoles; Practice Patterns, Physicians'; Retrospective Studies; Young Adult

Topics: Antihypertensive Agents; Benzimidazoles; Chlorthalidone; Humans; Hydrochlorothiazide; Hypertension; Olmesartan Medoxomil; Oxadiazoles

Topics: Antihypertensive Agents; Benzimidazoles; Chlorthalidone; Humans; Hydrochlorothiazide; Hypertension; Imidazoles; Olmesartan Medoxomil; Oxadiazoles; Renal Insufficiency, Chronic; Tetrazoles

To study effects of a fixed azilsartan medoxomil/chlorthalidone combination (Edarbi Clo) on clinical, ambulatory and central blood pressure (BP) in patients with uncontrolled arterial hypertension (AH)).. Patients (n=25) with uncontrolled AH were given fixed azilsartan medoxomil/chlorthalidone combination (40 / 12.5 mg / day) for 4 weeks. After 4 weeks, in patients who did not achieve target BP levels the dose was increased up to 40 / 25 mg / day. Duration of the study was 12 weeks.. After 12 weeks of treatment 88 % of patients achieved target clinical BP (.

Topics: Antihypertensive Agents; Benzimidazoles; Blood Pressure; Chlorthalidone; Drug Therapy, Combination; Humans; Hypertension; Oxadiazoles; Tetrazoles; Treatment Outcome

A pharmacokinetic-pharmacodynamic (PK-PD) model was developed to describe the time course of blood pressure following oral administration of azilsartan medoxomil (AZM) and/or chlorthalidone (CLT) in spontaneously hypertensive (SH) rats. The drug concentration and pharmacological effects, including systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and tail-cuff manometry, respectively. Sequential PK-PD analysis was performed, wherein the plasma concentration-time data was modeled by one compartmental analysis. Subsequently PD parameters were calculated to describe the time-concentration-response relationship using indirect response (IDR) PK-PD model. The combination of AZ and CLT had greater BP lowering effect compared to AZ or CLT alone, despite of no pharmacokinetic interaction between two drugs. These findings suggest synergistic antihypertensive pharmacodynamic interaction between AZ and CLT noncompetitively, which was simulated by inhibitory function of AZ and stimulatory function of CLT after concomitant administration of the two drugs. The present model was able to capture the turnover of blood pressure adequately at different time points at two different dose levels. The current PK-PD model was successfully utilized in the simulation of PD effect at a dose combination of 0.5 and 2.5 mg/kg for AZ and CLT, respectively. The developed preclinical PK-PD model may provide guidance in the optimization of dose ratio of individual drugs in the combined pharmacotherapy of AZ and CLT at clinical situations.

Topics: Administration, Oral; Angiotensin II Type 1 Receptor Blockers; Animals; Antihypertensive Agents; Benzimidazoles; Blood Pressure; Chlorthalidone; Chromatography, Liquid; Computer Simulation; Disease Models, Animal; Drug Monitoring; Drug Synergism; Drug Therapy, Combination; Hypertension; Models, Biological; Oxadiazoles; Rats, Inbred SHR; Sodium Chloride Symporter Inhibitors; Tandem Mass Spectrometry

This open-label, multicenter, single-dose study characterized the pharmacokinetics and short-term safety of azilsartan medoxomil (AZL-M) in hypertensive pediatric subjects (12-16 years [cohort 1a; n = 9]; 6-11 years [cohort 2; n = 8]; 4-5 years [cohort 3; n = 3]).. Model-based simulations were performed to guide dosing, especially in 1-5-year olds, who were difficult to enroll. AZL-M was dosed according to body weight (20-60-mg tablet, cohorts 1a and 2; 0.66 mg/kg granule suspension, cohort 3). In cohort 1, gender-matched healthy adults (cohort 1b; n = 9) received AZL-M 80 mg.. Exposure to AZL (active moiety of AZL-M), measured by dose-/body weight-normalized C max and AUC0-∞, was ∼15-30 % lower in pediatric subjects versus adults. In simulations, exposure with 0.66 mg/kg AZL-M in pediatric subjects weighing 8-25 kg approximated to AZL-M 40 mg (typical starting dose) in adults. The simulations suggest that 25-50-kg subjects require half the adult dose (10-40 mg), whereas 50-100-kg subjects can use the same dosing as adults. Adverse events were mild in intensity, apart from one moderate event (migraine).. This dosing strategy should be safe in pediatric patients, as AZL exposure would not exceed that seen in adults with the highest approved AZL-M dose (80 mg).

Topics: Adolescent; Adult; Antihypertensive Agents; Area Under Curve; Benzimidazoles; Child; Child, Preschool; Female; Healthy Volunteers; Humans; Hypertension; Male; Oxadiazoles

To describe the efficacy and safety profile of the new angiotensin receptor blocker (ARB), "Azilsartan Medoxomil", reviewing data available from both clinical and pre-clinical studies.. We completed a review of the English literature from PubMed using the keywords- azilsartan medoxomil, angiotensin receptor blockers (ARB), angiotensin converting enzyme inhibitors (ACEi) and hypertension.. Many clinical trials have been conducted comparing the efficacy of azilsartan with other ARB's and also with the ACEi ramipril. The trials have shown azilsartan to be more effective in reducing the mean 24-hour systolic blood pressure compared to its counterparts.. Azilsartan is a recently approved ARB and appears to be more efficacious in reducing blood pressure (BP) than the other ARBs with a similar safety and tolerability profile. Azilsartan's very high affinity to and slow dissociation from the angiotensin 1 receptor (AT1R) along with its inverse agonistic properties make it a very good candidate for clinical effects beyond simple BP control, potentially counteracting cardiac hypertrophy, cardiac fibrosis and insulin resistance, together with improved reno-protection and atherosclerotic plaque stabilization.

Topics: Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Benzimidazoles; Blood Pressure; Chlorthalidone; Clinical Trials as Topic; Drug Combinations; Drug Interactions; Humans; Hypertension; Oxadiazoles; Treatment Outcome; United States; United States Food and Drug Administration

Determination of the effectiveness and safety of different dosing regimens during the day (in the morning or at bedtime) combination therapy including azilsartan medoxomil in patients with essential hypertension and metabolic syndrome (MS).. The study included 60 patients with uncontrolled hypertension and MS (age median - 59 (54-65) years). Patients were randomized in two groups: group 1 (n=30) received azilsartan medoxomil 40 mg/day, and indapamide retard 1,5 mg/day in the morning; group 2 (n=30)- azilsartan medoxomoil 40 mg at bedtime and indapamide retard 1,5 mg in the morning. All patients at baseline, and after 4 and 12weeks assessed levels of office blood pressure (BP), heart rate (HR); at baseline and after 12 weeks was conducted ambulatory BPmonitoring (ABPM). Evaluated the main indicators of circadian blood pressure profile, as well as the central aortic pressure (CAP) and the rigidity of the vascular wall: systolic, diastolic, and mean arterial pressure in the aorta, aortic augmentation index, pulse wave velocity in the aorta, the augmentation index. Study results were processed using the program Statistica 6.1 by methods nonparametric statistics.. Regardless of the regimen used azilsartan destination as part of combination therapy after 4 weeks showed a significant (p<0.05) reduction in SBP and DBP. After 12 weeks of observation target blood pressure was recorded 27 (90%) patients of group 1 and 29 (96.7%)- group2. As a result of ABPM after 12 weeks of treatment in both groups showed a statistically significant (p<0.05) improvement in all parameters investigated. However, positive changes such indicators as an index time of hypertension in the day and night hours, SBP, DBP, and BP variability during the night, the morning rise of systolic as well as the speed of morning rise in SBP and DBP were more pronounced in the appointment azilsartan medoxomil at bedtime compared to morning reception. The use of both treatment regimens provided significant (p<0.05) increase frequency registration profile dippear and reduction - non-dipper. Importantly, irrespective of the time of taking the drugs in both groups occurred significant (p <0.05), and a comparable improvement in rigidity and CAP vascular wall.. When combined with essential hypertension and MS azilsartana use of combination drug therapy provided achievement of the target values of blood pressure in the majority of patients, a significant improvement in the main indicators of ABPM, CAP, and the rigidity of the vascular wall, as well as the normalization of daily profile of blood pressure in the majority of patients, regardless of dosing regimen during the day. However, the combination of indapamide retard morning - azilsartan medoxomil at bedtime accompanied by a significantly greater positive changes most ABPM parameters, especially at night.

Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Arterial Pressure; Benzimidazoles; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Drug Chronotherapy; Drug Therapy, Combination; Female; Humans; Hypertension; Indapamide; Male; Metabolic Syndrome; Middle Aged; Oxadiazoles; Pulse Wave Analysis; Random Allocation

For patients with newly diagnosed hypertension, angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) are usually the first-line therapies. There is, however, no real-life data regarding the relative clinical effectiveness and tolerability of either drug class. The prospective registry, Treatment With Azilsartan Compared to ACE Inhibitors in Antihypertensive Therapy (EARLY), was conducted to evaluate the effectiveness of the ARB azilsartan medoxomil (AZL-M) vs ACE inhibitors in real-world patients. Of the 1153 patients with newly diagnosed hypertension who were included in the registry, 789 were prescribed AZL-M and 364 were prescribed an ACE inhibitor. After multivariate adjustment, AZL-M was found to provide superior blood pressure reduction and better target blood pressure (<140/90 mm Hg) achievement. The proportion of patients with adverse events was not statistically different between groups. The authors conclude that in newly diagnosed hypertensive patients, AZL-M provides superior blood pressure control with a similar safety profile compared with ACE inhibitors.

Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Blood Pressure; Blood Pressure Determination; Female; Follow-Up Studies; Humans; Hypertension; Male; Middle Aged; Oxadiazoles; Prospective Studies; Ramipril; Registries

Patient characteristics and blood pressure-related outcomes in randomized clinical trials (RCTs) differ from clinical practice because of stringent selection criteria. The present study aimed to explore the relationship between clinical trials and clinical practice. We analyzed data from patients enrolled in the "Treatment with Azilsartan Compared to ACE-Inhibitors in Anti-Hypertensive Therapy" (EARLY) registry comparing blood pressure (BP) effects of the angiotensin receptor blocker (ARB) azilsartan medoxomil (AZL-M) with the angiotensin-converting enzyme (ACE) inhibitor ramipril between patients who met the eligibility criteria of a previous RCT and those who did not.. Patients with primary arterial hypertension were consecutively enrolled from primary care offices in Germany into the EARLY registry in a 7:3 ratio for treatment with AZL-M or an ACE inhibitor, provided that they met the following criteria at baseline: 1) no antihypertensive treatment prior to inclusion or a non-renin-angiotensin system (RAS) based monotherapy; 2) initiation of treatment with either AZL-M or an ACE inhibitor alone. Analyses were performed to evaluate BP effects for patients in the EARLY registry who met the selection criteria of a prior RCT (RCT+) versus those who did not (RCT-).. Out of 3,698 patients considered, 1,644 complied with the RCT criteria (RCT+) while 2,054 did not (RCT-). RCT- patients (55.5%) displayed a higher risk profile in terms of age and comorbidities, and a wider spectrum of BP values at baseline, as highlighted by the grades of hypertension and mean BP values. The proportion of patients who achieved target blood pressure control in the RCT+ group was significantly higher for AZL-M versus ramipril (64.1 versus 56.1%; P<0.01), in accordance with the result of the clinical trial. In the RCT- AZL-M group, the proportion of patients who met BP targets was lower (58.1%) than in the RCT+ AZL-M group (64.1%), whereas the proportion of patients with target BP values in the RCT- ramipril and the RCT+ ramipril groups was similar (57.7 versus 56.1%). Thus, in contrast to results for the RCT+ group, in the RCT- group, the target BP attainment rate for AZL-M was not significantly superior to that for ramipril. However, the tolerability profile of AZL-M and ramipril was comparable in both populations. At the 12-month follow-up, death and stroke rates were low (≤0.5%) and adverse events did not differ between the AZL-M and ramipril groups, irrespective of RCT eligibility.. These data confirm that the EARLY population comprised a broader spectrum of hypertensive patients than RCTs, and the differences in patient characteristics were accompanied by disparate rates of blood pressure goal attainment. Overall, the validity of the RCT was demonstrated and confirmed in clinical practice with a broader range of patients with various comorbidities.

Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Arterial Pressure; Benzimidazoles; Comorbidity; Female; Germany; Humans; Hypertension; Male; Middle Aged; Oxadiazoles; Patient Selection; Practice Guidelines as Topic; Primary Health Care; Prospective Studies; Ramipril; Randomized Controlled Trials as Topic; Registries; Renin-Angiotensin System; Research Design; Risk Factors; Treatment Outcome

Angiotensin II type 1 receptor blockers (ARBs) are widely used in treating hypertension. In the present study, we tested the hypothesis that a novel ARB, azilsartan medoxomil (AZL-M) will prevent renal and cardiovascular injury in the spontaneously hypertensive obese rat (SHROB), a model of cardiometabolic syndrome.. Male SHROB were treated with vehicle or AZL-M orally for 56 days. Vehicle treated normotensive Wistar-Kyoto (WKY) rats served as controls. The effects of AZL-M on kidney injury, vascular endothelial and heart functions, lipid profile, and glucose tolerance were assessed.. AZL-M demonstrated anti-hypertensive effects along with markedly improved vascular endothelial function in SHROB. In these rats, AZL-M demonstrates strong kidney protective effects with lower albuminuria and nephrinuria along with reduced tubular cast formation and glomerular injury. AZL-M treatment also improved left ventricular heart function, attenuated development of left ventricular hypertrophy, and reduced cardiac fibrosis in SHROB.. Overall, these findings demonstrate kidney and heart protective effects of AZL-M in SHROB, and these effects were associated with its ability to lower blood pressure and improve endothelial function.

Topics: Animals; Antihypertensive Agents; Benzimidazoles; Blood Glucose; Body Weight; Cholesterol; Disease Models, Animal; Heart; Hypertension; Hypertrophy, Left Ventricular; In Vitro Techniques; Insulin; Kidney; Male; Mesenteric Arteries; Myocardium; Obesity; Oxadiazoles; Protective Agents; Rats, Inbred WKY; Triglycerides; Vasodilation

Topics: Animals; Antihypertensive Agents; Benzimidazoles; Hypertension; Male; Obesity; Oxadiazoles; Protective Agents

To evaluate the efficacy, safety, and clinical utility of the combination product azilsartan medoxomil/chlorthalidone for the treatment of hypertension.. Articles indexed in PubMed through December 2012 were identified using the MeSH terms azilsartan and chlorthalidone, Edarbyclor, TAK-490, and Edarbi. Additional information was gathered from references cited in the identified publications, the package insert, and from a review of the ClinicalTrials.gov registry.. English-language articles, including clinical trials and reviews involving azilsartan medoxomil/chlorthalidone or each component individually for the treatment of hypertension were reviewed.. The antihypertensive combination tablet azilsartan medoxomil/chlorthalidone is the first to combine an inhibitor of the renin-angiotensin-aldosterone system with chlorthalidone, a thiazide-type diuretic. In 4 randomized controlled trials (3 published to date), azilsartan medoxomil/chlorthalidone 40 mg/12.5 mg and 40 mg/25 mg reduced blood pressure (BP) significantly more than comparators did, including an approximately 5-mm Hg greater BP reduction than olmesartan medoxomil/hydrochlorothiazide 40 mg/25 mg and azilsartan medoxomil/hydrochlorothiazide. Reductions in 24-hour ambulatory BP and clinic BP were observed, and a greater proportion of patients achieved BP targets while receiving azilsartan medoxomil/chlorthalidone. Azilsartan medoxomil/chlorthalidone was generally well tolerated, with minor, transient increases in serum creatinine and without a significant effect on potassium homeostasis. No studies have directly examined cardiovascular morbidity and mortality benefits associated with this combination.. The combination of azilsartan medoxomil/chlorthalidone has demonstrated safety and efficacy in lowering BP in hypertensive patients to a greater degree than olmesartan medoxomil/hydrochlorothiazide and azilsartan medoxomil/hydrochlorothiazide. As a fixed-dose combination tablet, it offers several clinical advantages.

Topics: Antihypertensive Agents; Benzimidazoles; Chlorthalidone; Drug Combinations; Drug Interactions; Humans; Hypertension; Oxadiazoles; Randomized Controlled Trials as Topic

Topics: Angiotensin II Type 1 Receptor Blockers; Benzimidazoles; Drug Approval; Humans; Hypertension; Oxadiazoles; Receptor, Angiotensin, Type 1; United States

The angiotensin receptor blocker (ARB) azilsartan medoxomil (Edarbi-Takeda) was recently approved by the FDA for oral treatment of hypertension, either alone or combined with other drugs. It is the eighth ARB approved for this indication.

Topics: Angiotensin Receptor Antagonists; Benzimidazoles; Blood Pressure; Humans; Hypertension; Oxadiazoles; Randomized Controlled Trials as Topic; Receptor, Angiotensin, Type 1

The pharmacological profile of a novel angiotensin II type 1 receptor blocker, azilsartan medoxomil, was compared with that of the potent angiotensin II receptor blocker olmesartan medoxomil. Azilsartan, the active metabolite of azilsartan medoxomil, inhibited the binding of [(125)I]-Sar(1)-I1e(8)-angiotensin II to angiotensin II type 1 receptors. Azilsartan medoxomil inhibited angiotensin II-induced pressor responses in rats, and its inhibitory effects lasted 24h after oral administration. The inhibitory effects of olmesartan medoxomil disappeared within 24h. ID(50) values were 0.12 and 0.55 mg/kg for azilsartan medoxomil and olmesartan medoxomil, respectively. In conscious spontaneously hypertensive rats (SHRs), oral administration of 0.1-1mg/kg azilsartan medoxomil significantly reduced blood pressure at all doses even 24h after dosing. Oral administration of 0.1-3mg/kg olmesartan medoxomil also reduced blood pressure; however, only the two highest doses significantly reduced blood pressure 24h after dosing. ED(25) values were 0.41 and 1.3mg/kg for azilsartan medoxomil and olmesartan medoxomil, respectively. In renal hypertensive dogs, oral administration of 0.1-1mg/kg azilsartan medoxomil reduced blood pressure more potently and persistently than that of 0.3-3mg/kg olmesartan medoxomil. In a 2-week study in SHRs, azilsartan medoxomil showed more stable antihypertensive effects than olmesartan medoxomil and improved the glucose infusion rate, an indicator of insulin sensitivity, more potently (≥ 10 times) than olmesartan medoxomil. Azilsartan medoxomil also exerted more potent antiproteinuric effects than olmesartan medoxomil in Wistar fatty rats. These results suggest that azilsartan medoxomil is a potent angiotensin II receptor blocker that has an attractive pharmacological profile as an antihypertensive agent.

Topics: Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Animals; Antihypertensive Agents; Benzimidazoles; Blood Glucose; Blood Pressure; CHO Cells; Cricetinae; Cricetulus; Dogs; Hypertension; Hypertension, Renal; Imidazoles; Insulin; Male; Olmesartan Medoxomil; Oxadiazoles; Protective Agents; Proteinuria; Rats; Rats, Inbred SHR; Rats, Sprague-Dawley; Tetrazoles