Balcinrenone plus dapagliflozin in patients with heart failure and chronic kidney disease: Results from the phase 2b MIRACLE trial.

Aims: Many patients with heart failure (HF) have chronic kidney disease (CKD) and may not tolerate mineralocorticoid receptor antagonists. We investigated the efficacy and safety of the novel mineralocorticoid receptor modulator balcinrenone in combination with dapagliflozin in a phase 2b study.

Methods And Results: From January 2021 to October 2023, we randomized 133 adults with symptomatic HF, ejection fraction <60%, estimated glomerular filtration rate (eGFR) ≥30 to ≤60 ml/min/1.

Ticagrelor in Patients with Stable Coronary Disease and Diabetes.

Background: Patients with stable coronary artery disease and diabetes mellitus who have not had a myocardial infarction or stroke are at high risk for cardiovascular events. Whether adding ticagrelor to aspirin improves outcomes in this population is unclear.

Methods: In this randomized, double-blind trial, we assigned patients who were 50 years of age or older and who had stable coronary artery disease and type 2 diabetes mellitus to receive either ticagrelor plus aspirin or placebo plus aspirin.

Ticagrelor versus placebo for the reduction of vaso-occlusive crises in pediatric sickle cell disease: Rationale and design of a randomized, double-blind, parallel-group, multicenter phase 3 study (HESTIA3).

Background: An unmet need for therapies exists to reduce sickle cell disease (SCD) complications in pediatric patients. Activated platelets contribute to the formation of cellular aggregates during sickling and vaso-occlusive crises (VOCs). Ticagrelor is an oral, direct-acting, and reversible adenosine diphosphate P2Y receptor antagonist that inhibits platelet activation and aggregation.

YINGLONG: A Multicenter, Prospective, Non-Interventional Study Evaluating the Safety and Tolerability of Ticagrelor in Chinese Patients with Acute Coronary Syndrome.

Introduction: Ticagrelor is an oral, reversible, direct-acting P2Y receptor inhibitor approved for the prevention of cardiovascular events in acute coronary syndrome (ACS). In China, drug intensive monitoring regulations for new drugs require additional safety data post-approval.

Methods: YINGLONG, a single-arm, phase-IV, 1-year, non-interventional study, described the safety of ticagrelor 90 mg twice daily in Chinese patients (≥ 18 years) with ACS treated with ≥ 1 dose of ticagrelor.

Ticagrelor does not impact patient-reported pain in young adults with sickle cell disease: a multicentre, randomised phase IIb study.

Ticagrelor is an antiplatelet agent for adults with coronary artery disease. The inhibition of platelet activation may decrease the frequency of vaso-occlusion crisis (VOC) in sickle cell disease (SCD). The HESTIA2 study (NCT02482298) randomised 87 adults with SCD (aged 18-30 years) 1:1:1 to twice-daily ticagrelor 10, 45 mg or placebo for 12 weeks.

Safety and Incidence of Cardiovascular Events in Chinese Patients with Acute Coronary Syndrome Treated with Ticagrelor: the 12-Month, Phase IV, Multicenter, Single-Arm DAYU Study.

Purpose: Ticagrelor is an orally administered, reversibly binding, direct-acting P2Y receptor antagonist previously evaluated in several phase III trials. This phase IV, multicenter, single-arm trial assessed the safety and incidence of cardiovascular (CV) events with ticagrelor in Chinese patients experiencing an acute coronary syndrome (ACS).

Methods: Patients hospitalized with an ACS received ticagrelor (180 mg loading dose, 90 mg twice daily thereafter) plus low-dose aspirin (75-100 mg/day) for up to 12 months.

Visceral Fat and Novel Biomarkers of Cardiovascular Disease in Patients With Addison's Disease: A Case-Control Study.

Context: Patients with Addison's disease (AD) have increased cardiovascular mortality.

Objective: To study visceral fat and conventional and exploratory cardiovascular risk factors in patients with AD.

Design: A cross-sectional, single-center, case-control study.

Effect of Food Intake on the Pharmacodynamics of Tenapanor: A Phase 1 Study.

Tenapanor (RDX5791/AZD1722) is a minimally systemic small-molecule inhibitor of the sodium/hydrogen exchanger NHE3. Tenapanor acts in the gut to reduce absorption of sodium and phosphate. This phase 1 open-label, 3-way crossover study (NCT02226783) evaluated the effect of food on the pharmacodynamics of tenapanor.

Effect of Tenapanor on Serum Phosphate in Patients Receiving Hemodialysis.

Hyperphosphatemia is common among patients with CKD stage 5D and is associated with morbidity and mortality. Current guidelines recommend lowering serum phosphate concentrations toward normal. Tenapanor is a minimally absorbed small molecule inhibitor of the sodium/hydrogen exchanger isoform 3 that functions in the gut to reduce sodium and phosphate absorption.

Preclinical and Healthy Volunteer Studies of Potential Drug-Drug Interactions Between Tenapanor and Phosphate Binders.

Tenapanor (RDX5791, AZD1722), a first-in-class small molecule with minimal systemic availability, is an inhibitor of the sodium/hydrogen exchanger isoform 3. Tenapanor acts locally in the gut, where it reduces absorption of sodium and phosphate. It is being studied in patients with chronic kidney disease requiring dialysis, who are often administered phosphate binders such as sevelamer to help control hyperphosphatemia.

A phase 1 study of the safety, tolerability, pharmacodynamics, and pharmacokinetics of tenapanor in healthy Japanese volunteers.

Background: Tenapanor (RDX5791, AZD1722), a small molecule with minimal systemic availability, is an inhibitor of the sodium/hydrogen exchanger isoform 3 (NHE3). Tenapanor acts locally in the gut to reduce absorption of sodium and phosphate. It is being developed for the treatment of patients with hyperphosphatemia in CKD requiring dialysis and patients with constipation-predominant irritable bowel syndrome.

Effect of Tenapanor on Interdialytic Weight Gain in Patients on Hemodialysis.

Background And Objectives: Interdialytic weight gain in patients on hemodialysis is associated with adverse cardiovascular outcomes and increased mortality. The degree of interdialytic weight gain is influenced by sodium intake. We evaluated the effects of tenapanor (AZD1722 and RDX5791), a minimally systemically available inhibitor of the sodium/hydrogen exchanger isoform 3, on interdialytic weight gain in patients with CKD stage 5D treated with hemodialysis.

Dose-ranging study with the glucokinase activator AZD1656 as monotherapy in Japanese patients with type 2 diabetes mellitus.

Aim: To assess the glucose-lowering effects of monotherapy with the glucokinase activator AZD1656 in Japanese patients with type 2 diabetes mellitus.

Methods: This was a randomized, double-blind, placebo-controlled study performed in Japan (NCT01152385). Patients (n = 224) were randomized to AZD1656 (40-200, 20-140 or 10-80 mg titrated doses) or placebo.

Dose-ranging study with the glucokinase activator AZD1656 in patients with type 2 diabetes mellitus on metformin.

Aim: To investigate the effect of glucokinase activator AZD1656 on glycated haemoglobin (HbA1c) as an add-on to metformin in patients with type 2 diabetes.

Methods: This randomized, double-blind, placebo-controlled study (NCT01020123) was conducted over 4 months with an optional 2-month extension. Patients (n = 458) with HbA1c 7.

Tolerability, pharmacokinetics, and pharmacodynamics of the glucokinase activator AZD1656, after single ascending doses in healthy subjects during euglycemic clamp.

Objectives: AZD1656 is a novel glucokinase activator with a postulated dual mechanism of action by activating glucokinase in both the pancreas and the liver, and with the potential to deliver effective glucose-lowering in Type 2 diabetes mellitus. Here, we present the tolerability, pharmacokinetics and pharmacodynamics of AZD1656 in two single-blind, randomized, placebo-controlled studies, one with Western and the other with Japanese healthy adult male subjects.

Methods: Both studies evaluated oral single ascending doses of AZD1656 of up to 180 mg, administered during euglycemic clamp conditions to explore a wide dose range without risking hypoglycemia.

Safety, pharmacokinetics and pharmacodynamics of multiple-ascending doses of the novel glucokinase activator AZD1656 in patients with type 2 diabetes mellitus.

Aims: To assess the safety, pharmacokinetics and pharmacodynamics of multiple-ascending doses of the novel glucokinase activator AZD1656 in patients with type 2 diabetes mellitus (T2DM).

Methods: This randomized, single-blind, placebo-controlled, monotherapy study was carried out in two parts. In part A, 32 patients received AZD1656 (7, 20, 40 or 80 mg) twice daily or placebo for 8 days in hospital.

Glucokinase activators AZD6370 and AZD1656 do not affect the central counterregulatory response to hypoglycemia in healthy males.

Context: Glucokinase is expressed in the hypothalamus, but effects of glucokinase activators (GKAs) on counterregulatory responses to hypoglycemia are unknown.

Objective: Two separate studies assessed the counterregulatory hormone responses to hypoglycemia induced by the GKAs, AZD6370 and AZD1656, compared with insulin infusion.

Design And Setting: Both studies were randomized, open, two-way crossover studies, conducted in separate clinical research centers.

Premature mortality in patients with Addison's disease: a population-based study.

Background: The survival rate of patients with primary adrenal insufficiency (Addison's disease) undergoing currently accepted replacement therapy is not known, although well-informed patients are considered to have a normal survival rate. In this study, we evaluated the mortality of patients with Addison's disease in Sweden.

Methods: A population-based, retrospective, observational study was performed, using the National Swedish Hospital and Cause of Death Registers, covering the period from 1987-2001.