Evaluation of Pharmacokinetic and Pharmacodynamic Drug-Drug Interaction of Sacubitril/Valsartan (LCZ696) and Sildenafil in Patients With Mild-to-Moderate Hypertension.

Sacubitril/valsartan (LCZ696) is indicated for the treatment of patients with heart failure and reduced ejection fraction (HFrEF). Since patients with HFrEF may receive sacubitril/valsartan and sildenafil, both increasing cyclic guanosine monophosphate, the present study evaluated the pharmacokinetic and pharmacodynamic drug interaction potential between sacubitril/valsartan and sildenafil. In this open-label, three-period, single sequence study, patients with mild-to-moderate hypertension (153.

Phase 1/2 multiple ascending dose trial of the prostate-specific membrane antigen-targeted antibody drug conjugate MLN2704 in metastatic castration-resistant prostate cancer.

Background: This phase 1/2 study evaluated the dose-limiting toxicity and maximum tolerated dose of MLN2704, a humanized monoclonal antibody MLN591 targeting prostate-specific membrane antigen, linked to the maytansinoid DM1 in patients with progressive metastatic castration-resistant prostate cancer.

Patients And Methods: A total of 62 patients received MLN2704 at ascending doses on 4 schedules: weekly (60, 84, 118, and 165mg/m; 12 patients); every 2 weeks (120, 168, 236, and 330mg/m; 15 patients); every 3 weeks (330 and 426mg/m; 18 patients); and on days 1 and 15 of a 6-week schedule (6-week cycle, 330mg/m; 17 patients). The primary efficacy endpoint was a sustained ≥50% decline from baseline prostate-specific antigen (PSA) without evidence of disease progression.

Single therapeutic and supratherapeutic doses of sacubitril/valsartan (LCZ696) do not affect cardiac repolarization.

Purpose: Sacubitril/valsartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor (ARNI) indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA class II-IV) and reduced ejection fraction. This study was aimed to evaluate the effect of single oral therapeutic (400 mg) and supratherapeutic (1200 mg) doses of LCZ696 on cardiac repolarization.

Method: This randomized double-blind crossover study in healthy male subjects compared the effect of therapeutic and supratherapeutic doses of LCZ696 with placebo and moxifloxacin 400 mg (open-label treatment) as positive control.

Effects of age and sex on the pharmacokinetics of LCZ696, an angiotensin receptor neprilysin inhibitor.

LCZ696, a novel angiotensin receptor neprilysin inhibitor, is in development for the treatment of heart failure. Administration of LCZ696 results in systemic exposure to sacubitril (inactive prodrug of LBQ657), LBQ657 (neprilysin inhibitor), and valsartan (angiotensin II receptor blocker). We investigated the potential effects of age and sex on the pharmacokinetics of LCZ696 analytes (LBQ657 and valsartan) in an open-label, single oral dose (400 mg), parallel-group study in healthy subjects.