Clinical study design strategies to mitigate confounding effects of time-dependent clearance on dose optimization of therapeutic antibodies.

Time-dependent pharmacokinetics (TDPK) is a frequent confounding factor that misleads exposure-response (ER) analysis of therapeutic antibodies, where a decline in clearance results in increased drug exposure over time in patients who respond to therapy, causing a false-positive ER finding. The object of our simulation study was to explore the influence of clinical trial designs on the frequency of false-positive ER findings. Two previously published population PK models representative of slow- (pembrolizumab) and fast-onset (rituximab) TDPK were used to simulate virtual patient cohorts with time-dependent clearance and the frequency of false-positive ER findings.

Pentosan polysulfate and a pigmentary maculopathy: causation versus correlation?

Introduction: Interstitial cystitis (IC) is a chronic disease with urinary tract symptoms and pain. Pentosan polysulfate (PPS) is the only U.S.

Time-dependent clearance can confound exposure-response analysis of therapeutic antibodies: A comprehensive review of the current literature.

Exposure-response (ER) analysis is used to optimize dose and dose regimens during clinical development. Characterization of relationships between drug exposure and efficacy or safety outcomes can be utilized to make dose adjustments that improve patient response. Therapeutic antibodies typically show predictable pharmacokinetics (PK) but can exhibit clearance that decreases over time due to treatment.

Rationale and design of an implant procedure and pivotal study to evaluate safety and effectiveness of Medtronic's tibial neuromodulation device.

Percutaneous tibial neuromodulation is a medical guideline recommended therapy for treating symptoms of overactive bladder. Stimulation is delivered to the tibial nerve via a thin needle placed percutaneously for 30 min once a week for 12-weeks, and monthly thereafter. Studies have shown that this therapy can effectively relieve symptoms of overactive bladder; however, the frequent office visits present a barrier to patients and can impact therapy effectiveness.

Population pharmacokinetics of zanidatamab, an anti-HER2 biparatopic antibody, in patients with advanced or metastatic cancer.

Purpose: To characterize the pharmacokinetics (PK) of zanidatamab including evaluation of the impact of intrinsic and extrinsic patient factors. To investigate alternative dosing regimens to improve caregiver convenience and reduce zanidatamab wastage.

Methods: Serum zanidatamab concentrations were obtained from 305 patients with advanced or metastatic breast cancer, gastroesophageal adenocarcinoma (GEA), biliary tract cancer, and other HER2-expressing cancers from four ongoing phase I and II clinical trials.

Role of urinary cations in the etiology of interstitial cystitis: A multisite study.

Objective: To determine whether patients with interstitial cystitis have elevated levels of toxic urinary cations, to identify and quantify these cationic metabolites, and to assess their cytotoxicity.

Methods: Isolation of cationic fraction was achieved by solid phase extraction using an Oasis MCX cartridge on urine specimens from interstitial cystitis patients and controls. C reverse phase high-performance liquid chromatography was used to profile cationic metabolites, and they were quantified by the area under the peaks and normalized to creatinine.

Impact of drug and equipment preparation on pre-hospital emergency Anaesthesia (PHEA) procedural time, error rate and cognitive load.

Background: We examined the effect of advanced preparation and organisation of equipment and drugs for Pre-hospital Emergency Anaesthesia (PHEA) and tracheal intubation on procedural time, error rates, and cognitive load.

Methods: This study was a randomised, controlled experiment with a crossover design. Clinical teams (physician and paramedic) from the Emergency Medical Retrieval Service and the Scottish Air Ambulance Division were randomised to perform a standardised pre-hospital clinical simulation using either unprepared (standard practice) or pre-prepared (experimental method) PHEA equipment and drugs.

Heparin and alkalinized lidocaine versus alkalinized lidocaine for treatment of interstitial cystitis symptoms.

Introduction: Interstitial cystitis (IC), sometimes referred to as IC/bladder pain syndrome, is a substantial health care problem. Once considered a rare, orphan disease, it is now believed to be relatively common. This pilot study was undertaken to determine if the combination of heparin and alkalinized lidocaine (heparin-lidocaine) was more efficacious than alkalinized lidocaine at relieving pain and urgency symptoms associated with IC and also capable of yielding higher lidocaine absorption.

Alkalinized lidocaine and heparin provide immediate relief of pain and urgency in patients with interstitial cystitis.

Introduction: It has been reported in an open-label study that the combination of alkalinized lidocaine and heparin can immediately relieve the symptoms of urinary urgency, frequency, and pain associated with interstitial cystitis (IC). This combination has also been reported to relieve pain associated with sex in patients with IC.

Aim: The aim of this study was to corroborate these findings in a multicenter setting.

A multi-site study confirms abnormal glycosylation in the Tamm-Horsfall protein of patients with interstitial cystitis.

Purpose: We confirm the single site observation of decreased sialylation and abnormal glycosylation of Tamm-Horsfall protein in patients with interstitial cystitis compared to control subjects.

Materials And Methods: Urine samples from 41 controls and 48 patients with interstitial cystitis from a total of 5 North American sites were obtained in blinded fashion as to participant status. Tamm-Horsfall protein was isolated from urine samples by salt precipitation.

Defective Tamm-Horsfall protein in patients with interstitial cystitis.

Purpose: Normal urinary Tamm-Horsfall protein shows a urothelial cytoprotective effect against potentially toxic compounds in urine that may injure the urothelium and cause bladder disease. One such disease is interstitial cystitis. In patients with interstitial cystitis this protective effect is decreased.