A5034116722- Computational Drug Discovery Methods
- Statistical Methods in Clinical Trials
- Cholinesterase and Neurodegenerative Diseases
- Alzheimer's disease research and treatments
- Biosimilars and Bioanalytical Methods
- Digital Mental Health Interventions
- Pharmaceutical studies and practices
- Pharmacological Effects and Toxicity Studies
- Mobile Health and mHealth Applications
- Migraine and Headache Studies
- Medication Adherence and Compliance
- Telemedicine and Telehealth Implementation
- HIV/AIDS Research and Interventions
- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- Drug Transport and Resistance Mechanisms
- Schizophrenia research and treatment
- Mental Health Research Topics
- Trigeminal Neuralgia and Treatments
- Neuroscience and Music Perception
- Obsessive-Compulsive Spectrum Disorders
- Biomedical Ethics and Regulation
- Antifungal resistance and susceptibility
- Sympathectomy and Hyperhidrosis Treatments
- Antiplatelet Therapy and Cardiovascular Diseases
Merck & Co., Inc., Rahway, NJ, USA (United States)
2016-2025
United States Military Academy
2008-2011
β-Amyloid (Aβ) peptides are thought to be critically involved in the etiology of Alzheimer's disease (AD). The aspartyl protease β-site amyloid precursor protein cleaving enzyme 1 (BACE1) is required for production Aβ, and BACE1 inhibition thus an attractive target treatment AD. We show that verubecestat (MK-8931) a potent, selective, structurally unique inhibitor reduced plasma, cerebrospinal fluid (CSF), brain concentrations Aβ40, Aβ42, sAPPβ (a direct product enzymatic activity) after...
Doravirine is a novel non-nucleoside inhibitor of HIV-1 reverse transcriptase with potent activity against wild-type virus (95% inhibitory concentration 19 nM, 50% human serum). has low potential to cause drug-drug interactions since it primarily eliminated by oxidative metabolism and does not inhibit or significantly induce drug-metabolizing enzymes.The pharmacokinetics safety doravirine were investigated in two double-blind, dose-escalation studies healthy males. Thirty-two subjects...
Although information about the efficacy and safety experience with caspofungin at 50 mg/m(2) daily is available for children adolescents, dosing regimen in infants toddlers 3 to 24 months of age has yet be established. We studied pharmacokinetics once nine patients 10 22 (median, 13 months) fever neutropenia who received 2 21 (mean, 9.3) days. Plasma concentrations were measured by high-performance liquid chromatography assay on days 1 4. On day 4, area under curve from 0 h (AUC(0-24)) was...
Despite the increasing use of remote measurement technologies (RMT) such as wearables or biosensors in health care programs, challenges associated with selecting and implementing these persist. Many programs that RMT rely on commercially available, "off-the-shelf" devices to collect patient data. However, validation is sparse, technology landscape constantly changing, relative benefits between device options are often unclear, research provider preferences lacking.
Current methods of measuring disease progression neurodegenerative disorders, including Parkinson's (PD), largely rely on composite clinical rating scales, which are prone to subjective biases and lack the sensitivity detect signals in a timely manner. Digital health technology (DHT)-derived measures offer potential solutions provide objective, precise, sensitive that address these limitations. However, complexity DHT datasets derive numerous digital features were not previously possible...
Dried blood spot (DBS) sample collection has gained increased interest across the pharmaceutical industry as a potential alternative to plasma for pharmacokinetic (PK) evaluations. However, regulatory guidelines and examples of late-stage clinical trial applications in literature are lacking. This paper communicates Merck's strategy implementation DBS exemplified by experience on program (MK-8931). In this program, was proposed sole matrix phase 3 studies decrease logistical burden an aging...
Abstract The incidence of migraine is higher among women than men and peaks during the reproductive years, when contraceptive medication use common. Atogepant, a potent, selective antagonist calcitonin gene‒related peptide receptor—in development for prevention—is thus likely to be used by taking oral contraceptives. This phase 1, open‐label, single‐center, 2‐period, fixed‐sequence study examined effect multiple‐dose atogepant 60 mg once daily on single‐dose pharmacokinetics combination...
Atogepant is a potent, selective, oral calcitonin gene-related peptide (CGRP) receptor antagonist in development for migraine prevention. The chemical structure of atogepant distinct from previous CGRP antagonists, which were associated with elevated serum alanine aminotransferase (ALT) clinical trials. Here, we report the safety, tolerability, and pharmacokinetics (PKs) once-daily supratherapeutic dose (170 mg) 28 days randomized, double-blind, placebo-controlled phase I trial healthy...
Machine learning-based facial and vocal measurements have demonstrated relationships with schizophrenia diagnosis severity. Demonstrating utility validity of remote automated assessments conducted outside controlled experimental or clinical settings can facilitate scaling such measurement tools to aid in risk assessment tracking treatment response populations that are difficult engage.This study aimed determine the accuracy machine acquired through remotely smartphones.Measurements...
Compelling evidence implicates abnormal accumulation of Aβ peptides in the pathogenesis Alzheimer's disease (AD). Inhibition BACE to reduce production is a promising approach test amyloid hypothesis. Here we report pharmacodynamic effects novel inhibitor MK-8931, as reflected by reduction CSF first studies human. Randomized, double-blind, placebo-controlled rising single dose (RSD) and multiple (RMD) were conducted healthy adults, 18-45 years age. In RSD, MK-8931 (20, 100, 550-mg) assessed 3...
Compelling evidence implicates the abnormal accumulation of Aβ in pathogenesis Alzheimer's disease (AD). Inhibition BACE1 to reduce production is a promising approach test amyloid hypothesis. In prior studies healthy volunteers, inhibitor MK-8931 was generally well-tolerated and resulted dose-dependent reduction CSF Ab. Here we report initial characterization pharmacodynamics AD patients. Randomized, double-blind, placebo-controlled, multiple-dose study mild-to-moderate Subjects were...
Abstract Merck & Co., Inc. (Kenilworth, New Jersey) has recently published an integrated strategy for implementation of dried blood spots (DBS) in late‐stage trials population pharmacokinetic (PK) modeling. We applied this another clinical program: ubrogepant (MK‐1602), a novel oral calcitonin gene‐related peptide receptor antagonist acute treatment migraine. At the time implementation, was entering phase 2 development. DBS implemented to acquire PK information proximal migraine event...
We describe the pharmacokinetics (PKs) of caspofungin, an echinocandin antifungal, administered once daily as a 1-hour intravenous infusion in children and adolescents (ages, 3 months to 17 years), based on pooled data from four prospective pediatric studies. Caspofungin dosing was body-surface-area (BSA) (50 mg/m2 after 70 day 1). The area under concentration-time curve time zero 24 h (AUC0-24), concentration at end (1 start infusion; C1), trough (24 C24) were obtained for 32 patients with...
Ubrogepant is a novel, oral calcitonin gene‐related peptide (CGRP) receptor antagonist intended for the acute treatment of migraine attacks. has chemical structure distinct from previous small‐molecule CGRP antagonists that were associated with elevated serum alanine aminotransferase (ALT) in clinical trials. Here, we report overall and hepatic safety data two placebo‐controlled phase I trials ubrogepant, spray‐dried compressed tablet (SD‐OCT) healthy male volunteers. Trial A was...
β‐site amyloid precursor protein cleaving enzyme 1 (BACE 1) is required for the production of β‐amyloid (Aβ) peptides and considered a potential treatment target Alzheimer's disease ( AD ). To support Japan's participation in global clinical development program, we characterized safety, pharmacokinetics (PKs), pharmacodynamics BACE inhibitor verubecestat MK ‐8931) 24 healthy Japanese adults two‐part, single‐center, randomized, placebo‐controlled phase I trial (protocol MK‐8931‐007) compared...
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...
Merck & Co, Inc (Kenilworth, NJ) is investing in approaches to enrich clinical trial data and augment decision making through use of digital health technologies, outpatient sampling, real‐time access. As part this strategy, a phase I study was conducted explore few technologies interest. In fixed‐sequence two‐period trial, 16 healthy subjects were administered 50‐mg once‐daily sitagliptin packaged bottle that electronically captured the date time medication dispensed (period 1)...
Vorapaxar is a proteaseactivated receptor (PAR)-1 antagonist being developed for the prevention and treatment of thrombotic vascular events. To evaluate race/ethnic differences between Caucasians Chinese in pharmacokinetics vorapaxar its active metabolite SCH 2046273 (M20) or metabolite/parent ratio, we conducted cross-study comparison on pharmacokinetic data M20 obtained from two similarly designed studies: one healthy subjects other Western (United States, [U.S.]) population.The profiles...
Background/Hypothesis: Atogepant, an oral calcitonin gene-related peptide receptor antagonist, is approved for the preventive treatment of migraine in adults. This manuscript characterizes safety, tolerability, pharmacokinetics and pharmacokinetic/pharmacodynamic relationship atogepant healthy males. Methods: Data from two single-ascending dose phase 1 studies were utilized to characterize demonstrate proof activity a capsaicin-induced dermal vasodilatation model determine dosage(s) that...