Efficacy of a Cell-Culture-Derived Quadrivalent Influenza Vaccine in Children.

Background: Cell-culture-derived influenza vaccines may enable a closer antigenic match to circulating strains of influenza virus by avoiding egg-adapted mutations.

Methods: We evaluated the efficacy of a cell-culture-derived quadrivalent inactivated influenza vaccine (IIV4c) using a Madin-Darby canine kidney cell line in children and adolescents 2 to less than 18 years of age. During three influenza seasons, participants from eight countries were enrolled in an observer-blinded, randomized clinical trial comparing IIV4c with a noninfluenza vaccine (meningococcal ACWY).

Comparability of Titers of Antibodies against Seasonal Influenza Virus Strains as Determined by Hemagglutination Inhibition and Microneutralization Assays.

We compared titers of antibodies against A/H1N1, A/H3N2, and B influenza virus strains collected pre- and postvaccination using hemagglutination inhibition (HI) and microneutralization (MN) assays and data from two vaccine trials: study 1, performed with a cell-grown trivalent influenza vaccine (TIVc) using cell-grown target virus in both assays, and study 2, performed with an egg-grown adjuvanted quadrivalent influenza vaccine (aQIVe) using egg-grown target virus. The relationships between HI- and MN-derived log-transformed titers were examined using different statistical techniques. Deming regression analyses showed point estimates for slopes generally close to 1 across studies and strains.

In vitro and in vivo characterisation of ASP9521: a novel, selective, orally bioavailable inhibitor of 17β-hydroxysteroid dehydrogenase type 5 (17βHSD5; AKR1C3).

Background: Aldo-keto reductase 1C3 [AKR1C3;17β-hydroxysteroid dehydrogenase type 5 (17βHSD5)], plays a crucial role in persistent production of androgens despite castration, by catalysing conversion of the adrenal androgens dehydroepiandrosterone and androstenedione (AD) into androstenediol and testosterone (T). Hence, AKR1C3 is a promising therapeutic target in castration-resistant prostate cancer, as combination of an AKR1C3 inhibitor and a gonadotropin-releasing hormone analogue may lead to complete androgen blockade. This study describes the preclinical characterisation of the novel AKR1C3 inhibitor ASP9521.

The pharmacokinetics of darexaban (YM150), an oral direct factor Xa inhibitor, are not affected by ketoconazole, a strong inhibitor of CYP3A and P-glycoprotein.

We investigated the effects of ketoconazole on the pharmacokinetics (PK) of the direct clotting factor Xa inhibitor darexaban (YM150) and its main active metabolite darexaban glucuronide (YM-222714) which almost entirely determines the antithrombotic effect. In this open-label, randomized, two-period crossover study, 26 healthy male volunteers received in one treatment period a single dose of darexaban 60 mg, and in the other treatment period, ketoconazole 400 mg once daily on Days 1-9 with a single dose of darexaban 60 mg on Day 4. Washout between periods was at least 1 week.

Safety, tolerability and anti-tumour activity of the androgen biosynthesis inhibitor ASP9521 in patients with metastatic castration-resistant prostate cancer: multi-centre phase I/II study.

Background: ASP9521 is a first-in-class orally available inhibitor of the enzyme 17 β-hydroxysteroid dehydrogenase type 5 (17 βHSD5; AKR1C3), catalysing the conversion of dehydroepiandrosterone and androstenedione into 5-androstenediol and testosterone. It has demonstrated anti-tumour activity in in vitro and in vivo preclinical models.

Material And Methods: This first-in-man phase I/II study utilised a 3 + 3 dose escalation design starting at 30 mg ASP9521/day, with the aim of defining a maximum tolerated dose, as defined by the incidence of dose-limiting toxicities.

Clinical pharmacokinetics, pharmacodynamics, safety and tolerability of darexaban, an oral direct factor Xa inhibitor, in healthy Caucasian and Japanese subjects.

Background: Darexaban (YM150) is a potent direct factor Xa (FXa) inhibitor developed for the prophylaxis of venous and arterial thromboembolic disease. This drug is rapidly and extensively metabolized to darexaban glucuronide (YM-222714), which is a pharmacologically active metabolite. The objective of the present study was to evaluate the clinical pharmacokinetics (PK), pharmacodynamics (PD), safety and tolerability of ascending multiple oral doses of darexaban in healthy non-elderly Caucasian and Japanese subjects.

Darexaban (YM150), an oral direct factor Xa inhibitor, has no effect on the pharmacokinetics of digoxin.

To investigate the impact of the direct Factor Xa inhibitor darexaban administered in a modified-release formulation (darexaban-MR) on the pharmacokinetic (PK) profile of digoxin. In this Phase I, randomized, double-blind, two-period crossover study (8 days for each treatment, 10 days washout), 24 healthy subjects received darexaban-MR 120 mg once/day (qd) + digoxin 0.25 mg qd in one treatment period, and placebo + digoxin 0.

Serum biomarkers in nonalcoholic steatohepatitis: value for assessing drug effects?

Nonalcoholic steatohepatitis (NASH) is a common chronic liver disease throughout the world. In the USA, approximately 3-5% of the population are affected, and the prevalence of this condition is increasing. NASH is associated with an increased risk of liver-related morbidity, such as cirrhosis and fibrosis, as well as cardiovascular disease, and in spite of several clinical studies investigating putative new drugs, no approved treatment is currently available.

Absorption, metabolism and excretion of darexaban (YM150), a new direct factor Xa inhibitor in humans.

1. The absorption, metabolism and excretion of darexaban (YM150), a novel oral direct factor Xa inhibitor, were investigated after a single oral administration of [(14)C]darexaban maleate at a dose of 60 mg in healthy male human subjects. 2.

The pharmacokinetics of darexaban are not affected to a clinically relevant degree by rifampicin, a strong inducer of P-glycoprotein and CYP3A4.

Aims: We investigated the effects of rifampicin on the pharmacokinetics (PK) of the direct clotting factor Xa inhibitor darexaban (YM150) and its main active metabolite, darexaban glucuronide (YM-222714), which almost entirely determines the antithrombotic effect.

Methods: In this open-label, single-sequence study, 26 healthy men received one dose of darexaban 60 mg on day 1 and oral rifampicin 600 mg once daily on days 4-14. On day 11, a second dose of darexaban 60 mg was given with rifampicin.

A randomized, dose-response study of sugammadex given for the reversal of deep rocuronium- or vecuronium-induced neuromuscular blockade under sevoflurane anesthesia.

Background: Sugammadex is the first of a new class of selective muscle relaxant binding drugs developed for the rapid and complete reversal of neuromuscular blockade induced by rocuronium and vecuronium. Many studies have demonstrated a dose-response relationship with sugammadex for reversal of neuromuscular blockade in patients induced and maintained under propofol anesthesia. However, sevoflurane anesthesia, unlike propofol, can prolong the effect of neuromuscular blocking drugs (NMBDs) such as rocuronium and vecuronium.

Reversal of neuromuscular blockade by sugammadex after continuous infusion of rocuronium in patients randomized to sevoflurane or propofol maintenance anesthesia.

Background: Sugammadex rapidly reverses neuromuscular blockade induced by bolus rocuronium doses, but it has not been investigated after continuous rocuronium infusion in surgical patients. We therefore examined the clinical effect of sugammadex for neuromuscular blockade induced by continuous rocuronium infusion in adults undergoing surgery under maintenance anesthesia with sevoflurane or propofol.

Methods: This four-center, comparative, parallel-group study, randomly assigned 52 adult patients (American Society of Anesthesiologists Class I-III) to maintenance anesthesia with sevoflurane or propofol.

Reversal of rocuronium-induced (1.2 mg/kg) profound neuromuscular block by sugammadex: a multicenter, dose-finding and safety study.

Background: Reversal of rocuronium-induced neuromuscular blockade can be accomplished by chemical encapsulation of rocuronium by sugammadex, a modified gamma-cyclodextrin derivative. This study investigated the efficacy and safety of sugammadex in reversing rocuronium-induced profound neuromuscular blockade at 5 min in American Society of Anesthesiologists physical status I and II patients.

Methods: Forty-five American Society of Anesthesiologists physical status I and II patients (aged 18-64 yr) scheduled to undergo surgical procedures (anticipated anesthesia duration >/= 90 min) were randomly assigned to a phase II, multicenter, assessor-blinded, placebo-controlled, parallel, dose-finding study.

Effective reversal of moderate rocuronium- or vecuronium-induced neuromuscular block with sugammadex, a selective relaxant binding agent.

Background: Sugammadex rapidly reverses rocuronium-induced neuromuscular block. This study explored the dose-response relation of sugammadex given as a reversal agent at reappearance of the second muscle twitch after rocuronium- and vecuronium-induced block. A secondary objective was to investigate the safety of single doses of sugammadex.