Cabozantinib is a small molecule tyrosine kinase inhibitor that has been approved for the treatment of patients with progressive, metastatic medullary thyroid cancer. exhibits pH-dependent solubility profile in vitro. Two phase 1 clinical pharmacology studies were conducted healthy subjects to evaluate whether factors may affect cabozantinib and gastric pH could alter bioavailability: food effect study (study 1) drug-drug interaction (DDI) proton pump (PPI) esomeprazole 2). Following...

Animal studies suggest that kappa opioid receptor antagonists (KORAn) potentially could treat a wide variety of addictive and depressive disorders. We assessed the KORAn JDTic for safety, tolerability, pharmacokinetics in double-blind, placebo-controlled, randomized trial evaluating single oral doses healthy adult males. Predose postdose safety assessments included orthostatic vital signs; 6-lead continuous telemetry monitoring (approximately 16 h predose to 24 postdose); 12-lead...

To evaluate the effect of lansoprazole, a proton-pump inhibitor, on absorption, pharmacokinetics, and safety neratinib, pan-HER tyrosine kinase in healthy subjects.This was an open-label, two-period, fixed-sequence study. Fifteen adult subjects received single oral dose neratinib 240 mg (Period 1), followed by washout period, then lansoprazole 30 once daily for 7 days Day 5 2). Pharmacokinetic sampling performed 72 h following each dose. Plasma concentration-time data were analysed using...

Cardiogenic shock (CS) is a severe condition with in-hospital mortality of up to 50%. Patients who develop CS may have previous cardiac history, but that not always be the case, adding challenges in optimally identifying and managing these patients. present medical facility or while emergency department (ED), general inpatient ward (WARD) critical care unit (CC). While different clinical pathways for management exist once recognized, there are patients timely manner, all settings, timeframe...

To investigate the safety, tolerability, and pharmacokinetics (PKs) of topical SAR 1118 Ophthalmic Solution in healthy adults. is an investigational small molecule lymphocyte function-associated antigen-1 (LFA-1; CD11a/CD18; αLβ2) antagonist that inhibits LFA-1 binding to intercellular adhesion molecule-1 (ICAM-1; CD54) targeting T-cell-mediated inflammation.A randomized, double-masked, placebo-controlled, dose-escalation study was performed 4 cohorts with 7 randomized subjects per cohort (2...

This study assessed the effect of mirabegron on ocular safety in healthy volunteers.This was an 8-week, randomized, double-masked, placebo-controlled study.Consenting adults aged ≥18 years with a normal intraocular pressure (IOP, ≥10 to ≤21 mmHg) were eligible enter study. Of 321 randomized subjects, 305 completed Subjects 1:1 supratherapeutic dose oral 100 mg or placebo once daily for 56 days. The IOP measured at screening, baseline, day 10, and 56/end treatment using Goldmann applanation...

<i>PURPOSE:</i> The purpose of this study was to estimate the diagnostic accuracy relative cerebral blood volume (rCBV) measurement in preoperative grading and differentiation solitary intra-axial malignant brain tumors. <i>METHODS:</i> Thirty-six low-grade glial tumors (LGGTs), 22 high-grade (HGGTs), 17 metastases (METs) were prospectively evaluated by MR imaging standard dynamic susceptibility contrast-enhanced gradient echo, echoplanar during first pass a bolus injection contrast...

The coadministration of prescription omega‐3‐acid ethyl esters (P‐OM3) with a statin may present treatment option for patients mixed hyperlipidemia. This open‐label, randomized, 2‐way crossover, drug‐drug interaction study evaluated the impact P‐OM3 capsules on plasma simvastatin pharmacokinetics in 24 healthy volunteers. Under fasted conditions, 80 mg was administered or without 4 g two 14‐day periods. After 14 days dosing to achieve steady state, no significant differences were found...

A Phase I, double-blind, randomized, crossover study in healthy males (N=106) was conducted between March 21, 2004, and May 17, to determine the magnitude duration of hemodynamic interaction avanafil (a phosphodiesterase type-5 inhibitor for treating with erectile dysfunction) when coadministered glyceryl trinitrate (NTG) compared sildenafil placebo. Subjects received (200 mg), (100 placebo (on separate days) via oral route followed by NTG (0.4 mg) 12, 8, 4, 1, or 0.5 hours post-dose...

The purpose of this study was to assess effects colesevelam on the pharmacokinetics glyburide, levothyroxine, estrogen estradiol (EE), norethindrone (NET), pioglitazone, and repaglinide in healthy volunteers. Six drugs with a potential interact were studied open‐label, randomized clinical studies. presence drug interaction concluded if 90% confidence intervals for geometric least squares mean ratios AUC 0‐t (AUC 0–48 levothyroxine) C max fell outside no‐effect limits (80.0%, 125.0%)....

β‐site amyloid precursor protein‐cleaving enzyme 1 ( BACE 1) is required for the production of β‐amyloid peptides, which are implicated in etiology Alzheimer's disease. The safety and pharmacokinetics inhibitor verubecestat have previously been studied young adults aged 19–45 years. In this randomized, placebo‐controlled, phase I study (protocol MK ‐8931‐006), we investigated safety, tolerability, a single dose (100 mg) or multiple doses (30, 80, 120 once daily 28 days healthy elderly...

Healthcare-associated infection (HAI) remains a significant risk for hospitalized patients and challenging burden the healthcare system. This study presents clinical decision support tool that can be used in workflows to proactively engage secondary assessments of pre-symptomatic at-risk patients, thereby enabling earlier diagnosis treatment.

Objective: Gabapentin immediate release (GBP-IR), gabapentin gastric retentive (GBP-GR), and the prodrug enacarbil extended formulation (GEn) have been approved for management of postherpetic neuralgia (PHN) in adults.This is first pharmacokinetic (PK) comparison all three formulations using FDA-recommended doses PHN.Materials: This study compared steady-state PK GBP-IR 600 mg t.i.d., GBP-GR 1,800 q.d., GEn b.i.d. healthy adults.Methods: The open-label consisted a 3-day lead-in escalating...

Abstract Omarigliptin is a dipeptidyl peptidase‐4 inhibitor being developed as once‐weekly treatment for type 2 diabetes. This double‐blind, double‐dummy, randomized, 3‐period balanced crossover study definitively evaluated the effects of supratherapeutic omarigliptin dose on QTc interval. Population‐specific correction QT interval (QTcP) was used primary analysis. Healthy subjects (n = 60) were enrolled and received treatments separated by ≥4‐week washout: (1) single‐dose 25 mg (day 1), 175...

Objectives This study aimed to investigate COVID-19-related disparities in clinical presentation and patient outcomes hospitalized Native American individuals. Methods The was performed within 30 hospitals of the Banner Health system Southwest United States included 8,083 adult patients who tested positive for SARS-CoV-2 infection were between 1 March 2020 4 September 2020. Bivariate multivariate analyses used assess racial ethnic differences outcomes. Results hospitalizations individuals...

ABSTRACT Background Healthcare-associated infection (HAI) remains a significant risk for hospitalized patients and challenging burden the healthcare system. This study presents clinical decision support tool that can be used in workflows to proactively engage secondary assessments of pre-symptomatic at-risk patients, thereby enabling earlier diagnosis treatment. Methods applies machine learning, specifically ensemble-based boosted trees, on large retrospective hospital datasets develop an...

Objective: To assess the effect of a novel oral tranexamic acid treatment on cardiac repolarization in randomized, double-blind, positive- and placebo-controlled, four-treatment single-dose cross-over inpatient study.Methods: QTc interval drug exposure relationship analyses were performed using triplicate digital electrocardiographs (ECGs) collected from 12-lead Holter monitors healthy females (n = 48) with plasma concentrations pharmacokinetics simultaneously evaluated over 24 h post-dose....

Abstract Solriamfetol, a dopamine and norepinephrine reuptake inhibitor, is approved (United States European Union; Sunosi) to treat excessive daytime sleepiness associated with narcolepsy (75‐150 mg/day) or obstructive sleep apnea (37.5‐150 mg/day). A thorough QT/QTc study assessed solriamfetol effects on QT interval (Fridericia correction for heart rate; QTcF). This randomized, double‐blind, placebo‐ positive‐controlled, 4‐period crossover compared single doses of 300 900 mg solriamfetol,...