Case Studies on the Use of Patient-centric Sampling for Clinical Studies in Pharmaceutical Drug Development.

The current gold standard of blood sample collection in clinical trials involves venous draws performed by trained phlebotomists in clinical settings. However, recent technological advancements have enabled the emergence of patient-centric sampling (PCS) methods, offering more flexible and accessible alternatives. This paper examines the motivation behind the pharmaceutical industry's growing interest in PCS devices and explores their application in drug development through seven case studies.

Quantitation of TAK-981 in human plasma via LC-MS/MS and its application in clinical trials.

Aim: TAK-981 is a highly effective and selective inhibitor of the small ubiquitin-like modifier (SUMO) activating enzyme, and it promotes the expression of type I interferons (IFN-Is). Developing a sensitive bioanalytical assay for quantitating TAK-981 is essential in the clinical investigations for oncology drug development.

Materials & Methods: TAK-981 and its stable isotope labeled compound (TAK-981C, N) as the internal standard were employed in this LC-MS/MS assay.

A simple surrogate approach for the quantitation of C4 (7α-hydroxy-4-cholesten-3-one) in human serum via LC-MS/MS and its application in a clinical study.

We present a validated LC-MS/MS assay for the quantitation of 7α-hydroxy-4-cholesten-3-one (C4), a key intermediate in the bile acid synthesis pathway from cholesterol, in human serum. A surrogate matrix approach was employed to overcome the challenges posed by the endogenous C4 levels in the biological matrix. Human serum samples were spiked with stable isotope labeled internal standard (SIL-IS), processed using supported liquid extraction (SLE), and analyzed by LC-MS/MS.

2024 White Paper on Recent Issues in Bioanalysis: Three Way-Cross Validation; Urine Clinical Analysis; Automated Methods; Regulatory Queries on Plasma Protein Binding; Automated Biospecimen Management; ELN Migration; Ultra-Sensitivity Mass Spectrometry ( - Recommendations on Advanced Strategies for Mass Spectrometry Assays, Chromatography, Sample Preparation and BMV/Regulated Bioanalysis - Regulatory Agencies' Inputs on Regulated Bioanalysis/BMV).

The 18 Workshop on Recent Issues in Bioanalysis (18 WRIB) took place in San Antonio, TX, USA on May 6-10, 2024. Over 1100 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 18 WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week to allow an exhaustive and thorough coverage of all major issues in bioanalysis of biomarkers, immunogenicity, gene therapy, cell therapy and vaccines.

Effect of Food on the Pharmacokinetics, Safety, and Tolerability of Budesonide Oral Suspension in Healthy Adult Participants: A Randomized Phase 1 Study.

Budesonide oral suspension (BOS) is a swallowed corticosteroid indicated for 12-week therapy in eosinophilic esophagitis with minimal systemic exposure following administration. We aimed to assess the relative bioavailability of a single dose of BOS administered under fasting and fed (high-fat/high-calorie meal) conditions. Healthy adult volunteers (N = 20) were enrolled in an open-label, single-center, crossover study and were randomized (1:1) to receive a single oral dose of BOS 2.

Phase 1 pharmacokinetic and safety study of soticlestat in participants with mild or moderate hepatic impairment or normal hepatic function.

This phase 1, open-label, three-arm study (NCT05098054) compared the pharmacokinetics and safety of soticlestat (TAK-935) in participants with hepatic impairment. Participants aged ≥18 to <75 years had moderate (Child-Pugh B) or mild (Child-Pugh A) hepatic impairment or normal hepatic function (matched to hepatic-impaired participants by sex, age, and body mass index). Soticlestat was administered as a single oral 300 mg dose.

Effects of Strong Inhibition of Cytochrome P450 3A and UDP glucuronosyltransferase 1A9 and Strong Induction of Cytochrome P450 3A on the Pharmacokinetics, Safety, and Tolerability of Soticlestat: Two Drug-Drug Interaction Studies in Healthy Volunteers.

Two open-label, phase 1 studies (NCT05064449, NCT05098041) investigated the effects of cytochrome P450 (CYP) 3A inhibition (via itraconazole), UDP glucuronosyltransferase (UGT) 1A9 inhibition (via mefenamic acid), and CYP3A induction (via rifampin) on the pharmacokinetics of soticlestat and its metabolites M-I and M3. In period 1 of both studies, participants received a single dose of soticlestat 300 mg. In period 2, participants received itraconazole on days 1-11 and soticlestat 300 mg on day 5 (itraconazole/mefenamic acid study; part 1); mefenamic acid on days 1-7 and soticlestat 300 mg on day 2 (itraconazole/mefenamic acid study; part 2); or rifampin on days 1-13 and soticlestat 300 mg on day 11 (rifampin study).

Comparative analytical performance of multiple plasma Aβ42 and Aβ40 assays and their ability to predict positron emission tomography amyloid positivity.

Introduction: This report details the approach taken to providing a dataset allowing for analyses on the performance of recently developed assays of amyloid beta (Aβ) peptides in plasma and the extent to which they improve the prediction of amyloid positivity.

Methods: Alzheimer's Disease Neuroimaging Initiative plasma samples with corresponding amyloid positron emission tomography (PET) data were run on six plasma Aβ assays. Statistical tests were performed to determine whether the plasma Aβ measures significantly improved the area under the receiver operating characteristic curve for predicting amyloid PET status compared to age and apolipoprotein E (APOE) genotype.

2021 White Paper on Recent Issues in Bioanalysis: Mass Spec of Proteins, Extracellular Vesicles, CRISPR, Chiral Assays, Oligos; Nanomedicines Bioanalysis; ICH M10 Section 7.1; Non-Liquid & Rare Matrices; Regulatory Inputs ( - Recommendations on Endogenous Compounds, Small Molecules, Complex Methods, Regulated Mass Spec of Large Molecules, Small Molecule, PoC & - Regulatory Agencies' Inputs on Bioanalysis, Biomarkers, Immunogenicity, Gene & Cell Therapy and Vaccine).

The 15th edition of the Workshop on Recent Issues in Bioanalysis (15th WRIB) was held on 27 September to 1 October 2021. Even with a last-minute move from in-person to virtual, an overwhelmingly high number of nearly 900 professionals representing pharma and biotech companies, contract research organizations (CROs), and multiple regulatory agencies still eagerly convened to actively discuss the most current topics of interest in bioanalysis. The 15th WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week in order to allow exhaustive and thorough coverage of all major issues in bioanalysis, biomarkers, immunogenicity, gene therapy, cell therapy and vaccines.

Evaluation of the Pharmacokinetics of Trazpiroben (TAK-906), a Peripherally Selective D/D Dopamine Receptor Antagonist, in the Presence and Absence of Itraconazole, a Potent CYP 3A4 Inhibitor.

Purpose: Treatment options for gastroparesis, such as metoclopramide and domperidone, are limited because of safety concerns, which may be exacerbated in the presence of inhibitors of drug metabolism. This study evaluated the effect of itraconazole on the pharmacokinetics, safety, and tolerability of trazpiroben (previously TAK-906), a novel, peripherally selective D/D dopamine receptor antagonist.

Methods: This was a phase 1, two-period, crossover trial in healthy participants (NCT03161405).

Single-Dose Pharmacokinetics and Tolerability of the Oral Epidermal Growth Factor Receptor Inhibitor Mobocertinib (TAK-788) in Healthy Volunteers: Low-Fat Meal Effect and Relative Bioavailability of 2 Capsule Products.

Mobocertinib (TAK-788) is a tyrosine kinase inhibitor under investigation for treatment of non-small cell lung cancer with activating EGFR exon 20 insertions. This study examined the safety; tolerability; pharmacokinetics (PK), including food effects; and bioavailability of mobocertinib in healthy volunteers. In part 1, fasted volunteers were randomized to placebo or mobocertinib in single-ascending-dose cohorts (20-160 mg).

Assessment of Vedolizumab Disease-Drug-Drug Interaction Potential in Patients With Inflammatory Bowel Diseases.

Disease-drug-drug interactions (DDDIs) have been identified in some inflammatory diseases in which elevated proinflammatory cytokines can downregulate the expression of cytochrome P450 (CYP) enzymes, potentially increasing systemic exposure to drugs metabolized by CYPs. Following anti-inflammatory treatments, CYP expression may return to normal, resulting in reduced drug exposure and diminished clinical efficacy. Vedolizumab has a well-established positive benefit-risk profile in patients with ulcerative colitis (UC) or Crohn's disease (CD) and has no known systemic immunosuppressive activity.

Identification of interspecies difference in efflux transporters of hepatocytes from dog, rat, monkey and human.

The large interspecies differences of hepatobiliary transport present a challenge for the allometric prediction of human biliary excretion for drug candidates primarily cleared via hepatobiliary secretion. In the present study, we determined the metabolic stabilities of common fluorescent substrates of hepatobiliary efflux transporters and developed a rapid efflux assay to determine the functional activities of MRP/Mrp, BCRP/Bcrp and P-gp in hepatocytes of four species. The specificities of transporter-mediated dye efflux were confirmed by selective transporter inhibitors.