Trastuzumab deruxtecan in patients with human epidermal growth factor receptor 2-expressing salivary gland carcinoma: a pooled analysis of two phase I studies.

Background: HER2-expressing salivary gland carcinoma (SGC) is associated with poor prognosis. Trastuzumab deruxtecan (T-DXd, DS-8201) has shown evidence of antitumor activity for several HER2-expressing solid tumors in multiple studies. This study aimed to present the efficacy and safety of T-DXd in patients with HER2-expressing SGC from a pooled analysis.

The renoprotective effect of esaxerenone independent of blood pressure lowering: a post hoc mediation analysis of the ESAX-DN trial.

Angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) are recommended as first-line drugs for hypertension with diabetic nephropathy owing to their renoprotective effect; however, their effect beyond lowering blood pressure (BP) has not been confirmed. Recent studies have shown that aldosterone plays a key role in causing renal injury; therefore, it is likely that mineralocorticoid receptor (MR) blockers inhibit aldosterone-induced renal damage in different ways from ACE inhibitors and ARBs. Therefore, we investigated the mechanism of the effect of an MR blocker on reducing the urinary albumin-to-creatinine ratio (UACR) using data from a randomized, double-blind, placebo-controlled phase 3 study (ESAX-DN) of a new nonsteroidal MR blocker, esaxerenone.

Reduction in the magnitude of serum potassium elevation in combination therapy with esaxerenone (CS-3150) and sodium-glucose cotransporter 2 inhibitor in patients with diabetic kidney disease: Subanalysis of two phase III studies.

Aims/introduction: We evaluated the effect of co-administration of esaxerenone and a sodium-glucose cotransporter 2 (SGLT2) inhibitor on the magnitude of serum potassium elevation in Japanese patients with diabetic kidney disease.

Materials And Methods: We carried out a prespecified subanalysis of data from two phase III studies: a multicenter, randomized, double-blind, placebo-controlled trial in patients with type 2 diabetes and microalbuminuria (J308); and a multicenter, single-arm, open-label trial in patients with type 2 diabetes and macroalbuminuria (J309). Changes in serum potassium levels during the studies and other measures were evaluated according to SGLT2 inhibitor use.

Effect of esaxerenone on nocturnal blood pressure and natriuretic peptide in different dipping phenotypes.

There are limited data on the nighttime blood pressure (BP)-lowering effect of esaxerenone and its effect on N-terminal pro b-type natriuretic peptide (NT-proBNP), a predictor of cardiovascular risk, according to different dipping patterns of nocturnal BP. This was a post hoc analysis of a multicenter, open-label, long-term phase 3 study of esaxerenone, a new highly selective mineralocorticoid receptor blocker, in patients with essential hypertension. Patients were classified by dipping pattern (extreme dippers, dippers, non-dippers, risers).

Effect of wearing diapers on toddler's gait.

Gait maturation in infants develops gradually through several phases. However, external factors such as childrearing practices, especially the wearing of diapers, may affect an infant's motor development. This study investigated the influence of different bulk stresses on the gait of toddlers wearing a disposable diaper.

Pharmacokinetics, Safety, and Efficacy of Trastuzumab Deruxtecan with Concomitant Ritonavir or Itraconazole in Patients with HER2-Expressing Advanced Solid Tumors.

Purpose: To evaluate drug-drug interactions between the human epidermal growth factor receptor 2 (HER2)-targeted antibody-drug conjugate trastuzumab deruxtecan (T-DXd; DS-8201a) and the OATP1B/CYP3A inhibitor ritonavir or the strong CYP3A inhibitor itraconazole.

Patients And Methods: Patients with HER2-expressing advanced solid tumors were enrolled in this phase I, open-label, single-sequence crossover study (NCT03383692) and received i.v.

Effects of Repeated Oral Administration of Esaxerenone on the Pharmacokinetics of Midazolam in Healthy Japanese Males.

Background And Objective: Esaxerenone showed the potential to inhibit and induce activity against cytochrome P450 (CYP) 3A in in vitro studies. We investigated whether repeated administration of 5 mg/day esaxerenone for 14 days influences the pharmacokinetics of midazolam, a sensitive CYP3A substrate, in healthy Japanese males.

Methods: This single-centre, open-label, single-sequence study had two administration periods: period 1: single oral dose of 2 mg midazolam (day 0); period 2: repeated oral doses of 5 mg/day esaxerenone for 14 days, with a single oral dose of 2 mg midazolam on day 14.

Efficacy and safety of esaxerenone (CS-3150) in Japanese patients with type 2 diabetes and macroalbuminuria: a multicenter, single-arm, open-label phase III study.

Background: Esaxerenone has potential renoprotective effects and reduces the urinary albumin-to-creatinine ratio (UACR) in patients with diabetic kidney disease and overt nephropathy. We investigated the efficacy and safety of esaxerenone in Japanese patients with type 2 diabetes (T2D) and macroalbuminuria (UACR ≥ 300 mg/g creatinine).

Methods: We conducted a multicenter, single-arm, open-label phase III study in 56 patients with T2D and UACR ≥ 300 mg/g creatinine with estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.

Trastuzumab deruxtecan (DS-8201) in patients with HER2-expressing metastatic colorectal cancer (DESTINY-CRC01): a multicentre, open-label, phase 2 trial.

Background: HER2 amplification has been identified in 2-3% of patients with colorectal cancer, although there are currently no approved HER2-targeted therapies for colorectal cancer. We aimed to study the antitumour activity and safety of trastuzumab deruxtecan (an antibody-drug conjugate of humanised anti-HER2 antibody with topoisomerase I inhibitor payloads) in patients with HER2-expressing metastatic colorectal cancer.

Methods: DESTINY-CRC01 is an open-label, phase 2 study that recruited patients from 25 clinics and hospitals in Italy, Japan, Spain, the UK, and the USA.

Antihypertensive effects and safety of esaxerenone in patients with moderate kidney dysfunction.

Renin-angiotensin system inhibitors are recommended for treating hypertension with chronic kidney disease. The addition of a mineralocorticoid receptor blocker may be one option to achieve target blood pressure. We investigated the efficacy and safety of esaxerenone, a mineralocorticoid receptor blocker, in Japanese hypertensive patients with moderate kidney dysfunction.

Esaxerenone (CS-3150) in Patients with Type 2 Diabetes and Microalbuminuria (ESAX-DN): Phase 3 Randomized Controlled Clinical Trial.

Background And Objectives: Diabetic kidney disease is an important complication of type 2 diabetes. In a phase 2b study, adding esaxerenone to renin-angiotensin system inhibitors dose dependently reduced the urinary albumin-to-creatinine ratio in patients with type 2 diabetes and microalbuminuria. This 52-week phase 3 study further investigated the effects of esaxerenone on the urinary albumin-to-creatinine ratio in this patient group.

Efficacy and safety of esaxerenone (CS-3150), a newly available nonsteroidal mineralocorticoid receptor blocker, in hypertensive patients with primary aldosteronism.

Mineralocorticoid receptor (MR) blockers are very beneficial for patients with hypertension and primary aldosteronism (PA). We investigated the efficacy and safety of a newly available nonsteroidal MR blocker, esaxerenone, in Japanese patients with hypertension and PA. A multicenter, open-label study was conducted in Japan between October 2016 and July 2017.

Double-Blind Randomized Phase 3 Study Comparing Esaxerenone (CS-3150) and Eplerenone in Patients With Essential Hypertension (ESAX-HTN Study).

Mineralocorticoid receptors (MRs) are implicated in the pathology of hypertension. MR blockers are recommended for the treatment of salt-sensitive or resistant hypertension. However, use of currently available MR blockers is limited by adverse events.

Long-term phase 3 study of esaxerenone as mono or combination therapy with other antihypertensive drugs in patients with essential hypertension.

This study investigated the long-term antihypertensive effects of esaxerenone, a novel nonsteroidal mineralocorticoid receptor blocker, alone or in combination with a calcium channel blocker (CCB) or a renin-angiotensin system (RAS) inhibitor, in Japanese patients with essential hypertension. Patients were treated with esaxerenone starting at 2.5 mg/day increasing to 5 mg/day if required to achieve blood pressure (BP) targets as a monotherapy or with a CCB or RAS inhibitor.

Efficacy and Safety of Esaxerenone (CS-3150) for the Treatment of Type 2 Diabetes with Microalbuminuria: A Randomized, Double-Blind, Placebo-Controlled, Phase II Trial.

Background And Objectives: The progression of kidney disease in some patients with type 2 diabetes mellitus may not be adequately suppressed by renin-angiotensin system inhibitors. Esaxerenone (CS-3150) is a nonsteroidal mineralocorticoid receptor blocker that has shown kidney protective effects in preclinical studies, and it is a potential add-on therapy to treat diabetic kidney disease. This phase 2 study evaluated the efficacy and safety of esaxerenone in Japanese patients with type 2 diabetes mellitus and microalbuminuria.

Efficacy and safety of dosage-escalation of low-dosage esaxerenone added to a RAS inhibitor in hypertensive patients with type 2 diabetes and albuminuria: a single-arm, open-label study.

The stimulation of mineralocorticoid receptors is linked to the development of hypertension and cardiovascular or renal damage in patients with diabetes, and the blockade of these receptors may be an effective treatment option. This open-label study with a 12-week treatment period assessed the antihypertensive (primary) and antialbuminuric (secondary) efficacy and safety of esaxerenone as an add-on therapy to a renin-angiotensin system inhibitor in hypertensive patients with type 2 diabetes and albuminuria (urinary albumin-creatinine ratio 30 to <1000 mg/g•Cr). Esaxerenone was administered over 12 weeks at a starting dosage of 1.

Efficacy and safety of esaxerenone (CS-3150) for the treatment of essential hypertension: a phase 2 randomized, placebo-controlled, double-blind study.

This was a phase 2, multicenter, randomized, double-blind, placebo-controlled, open-label comparator study to investigate the efficacy and safety of esaxerenone (CS-3150), a novel non-steroidal mineralocorticoid receptor blocker, in Japanese patients with essential hypertension. Eligible patients (n = 426) received esaxerenone (1.25, 2.

Morning Home Blood Pressure and Cardiovascular Events in Japanese Hypertensive Patients.

SPRINT (Systolic Blood Pressure Intervention Trial) demonstrated the benefit of achieving strict blood pressure control with a lower target blood pressure level in high-risk patients with hypertension. The aim of this post hoc analysis was to investigate the relationship between the 2-year average on-treatment home blood pressure and cardiovascular disease risk in subgroups stratified by risk status using data from the HONEST study (Home Blood Pressure Measurement With Olmesartan Naive Patients to Establish Standard Target Blood Pressure). Participants in the HONEST study (n=21 591) were stratified according to risk level as follows: SPRINT population (n=5823)-patients (≥50 years of age) without diabetes mellitus or prior stroke, with SPRINT-defined cardiovascular risk and systolic blood pressure (SBP) of ≥130 mm Hg; SPRINT-excluded high-risk population (n=5481)-patients with diabetes mellitus or prior stroke; and non-SPRINT low-risk population-all other patients in the HONEST study (n=10 287).

Home blood pressure and cardiovascular outcomes in very elderly patients receiving antihypertensive drug therapy: a subgroup analysis of Home blood pressure measurement with Olmesartan Naive patients to Establish Standard Target blood pressure (HONEST) study.

The appropriate target blood pressure (BP) in elderly patients with hypertension remains uncertain. We investigated the relationship between morning home systolic blood pressure (MHSBP) during follow-up and cardiovascular (CV) risk in outpatients receiving olmesartan-based treatment aged <75 years (n = 16799) and ≥75 years (n = 4792) in the HONEST study. In the follow-up period (mean 2.

Increased cardiovascular risk of treated white coat and masked hypertension in patients with diabetes and chronic kidney disease: the HONEST Study.

The prognostic implications of treated white coat hypertension (WCH) and masked hypertension (MH) in patients with diabetes mellitus (DM) or chronic kidney disease (CKD) are not well documented. Using data from the HONEST study (n=21 591), we investigated the relationships between morning home systolic blood pressure (MHSBP) or clinic systolic blood pressure (CSBP) and cardiovascular (CV) risk in hypertensive patients with and without DM or CKD receiving olmesartan-based antihypertensive therapy. The study included 4426 DM patients and 4346 CKD patients at baseline who had 101 and 87 major CV events, respectively, during the follow-up.