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https://www.readbyqxmd.com/read/29775810/a-validated-uplc-ms-ms-method-for-the-quantitation-of-an-unstable-peptide-monocyte-locomotion-inhibitory-factor-mlif-in-human-plasma-and-its-application-to-a-pharmacokinetic-study
#1
Xuemei Liu, Pei Hu, Yongsheng Wang, Xizhu Wang, Jinghua Huang, Jin Li, Cheng Li, Hongyun Wang, Ji Jiang
Monocyte locomotion inhibitory factor (MLIF, Met-Gln-Cys-Asn-Ser), a pentapeptide with anti-inflammatory activity, was developed for neural protection in acute ischemic stroke. Determination of MLIF in human plasma samples is of great importance for pharmacokinetic evaluation in clinical studies. A reliable and sensitive method based on ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) was established for the measurement of MLIF in human plasma. Instability of peptide in matrix was the primary challenge in method development, which was properly resolved by addition of acidification reagents like sulfuric acid...
April 10, 2018: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29752796/transdermal-optical-renal-function-monitoring-in-humans-development-verification-and-validation-of-a-prototype-device
#2
Martin P Debreczeny, Richard B Dorshow
A prototype medical device for monitoring kidney function by transdermal measurement of the clearance rate of the exogenous fluorescent tracer agent MB-102 (administered intravenously) was developed. Verification of the device with an in vitro protocol is described. The expected renal clearance of the agent was mimicked by preparing a dilution series of MB-102 in the presence of a scattering agent. The slope of a linear fit to the logarithm of fluorescence intensity as a function of dilution step agreed with predictions within 5%, a level of accuracy that would be adequate in assessment of GFR to prevent misdiagnosis of kidney disease...
May 2018: Journal of Biomedical Optics
https://www.readbyqxmd.com/read/29750201/3d-printing-of-a-wearable-personalized-oral-delivery-device-a-first-in-human-study
#3
Kun Liang, Simone Carmone, Davide Brambilla, Jean-Christophe Leroux
Despite the burgeoning interest in three-dimensional (3D) printing for the manufacture of customizable oral dosage formulations, a U.S. Food and Drug Administration-approved tablet notwithstanding, the full potential of 3D printing in pharmaceutical sciences has not been realized. In particular, 3D-printed drug-eluting devices offer the possibility for personalization in terms of shape, size, and architecture, but their clinical applications have remained relatively unexplored. We used 3D printing to manufacture a tailored oral drug delivery device with customizable design and tunable release rates in the form of a mouthguard and, subsequently, evaluated the performance of this system in the native setting in a first-in-human study...
May 2018: Science Advances
https://www.readbyqxmd.com/read/29749253/lc-ms-ms-assay-for-n-1-methylnicotinamide-in-humans-an-endogenous-probe-for-renal-transporters
#4
Lina Luo, Jared Kay, Jenny Zhang, Christopher L Holliman, A D Rodrigues, Martin Dowty, Christopher Banfield, Ragu Ramanathan
AIM: N1 -methylnicotinamide (1-NMN) has been proposed as a potential clinical biomarker to assess drug-drug interactions involving organic cation transporters (OCT2) and multidrug and toxin extrusion protein transporters. RESULTS: A hydrophilic interaction liquid chromatography-MS/MS assay, to quantify 1-NMN, in human plasma and urine is reported. MATERIALS & METHODS: A hydrophilic interaction chromatography (HILIC)-tandem mass spectrometry (MS/MS) assay to quantify 1-NMN in human plasma and urine is reported...
May 11, 2018: Bioanalysis
https://www.readbyqxmd.com/read/29742388/the-challenges-of-first-in-human-stem-cell-clinical-trials-what-does-this-mean-for-ethics-and-institutional-review-boards
#5
REVIEW
Roger A Barker, Melissa K Carpenter, Stuart Forbes, Steven A Goldman, Catriona Jamieson, Charles E Murry, Jun Takahashi, Gordon Weir
Stem cell-based clinical interventions are increasingly advancing through preclinical testing and approaching clinical trials. The complexity and diversity of these approaches, and the confusion created by unproven and untested stem cell-based "therapies," create a growing need for a more comprehensive review of these early-stage human trials to ensure they place the patients at minimal risk of adverse events but are also based on solid evidence of preclinical efficacy with a clear scientific rationale for that effect...
May 8, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29737533/a-randomized-first-in-human-healthy-volunteer-trial-of-bivv009-a-humanized-antibody-for-the-specific-inhibition-of-the-classical-complement-pathway
#6
Johann Bartko, Christian Schoergenhofer, Michael Schwameis, Christa Firbas, Martin Beliveau, Colin Chang, Jean-Francois Marier, Darrell Nix, James C Gilbert, Sandip Panicker, Bernd Jilma
Aberrant activation of the classical complement pathway is the common underlying pathophysiology of orphan diseases such as bullous pemphigoid, antibody-mediated rejection of organ transplants, cold agglutinin disease and warm autoimmune haemolytic anaemia. Therapeutic options for these complement-mediated disorders are limited and BIVV009, a humanized monoclonal antibody directed against complement factor C1s, may be potentially useful for inhibition of the classical complement pathway. A phase-1, first-in-human, double-blind, randomized, placebo-controlled, dose-escalation trial of single and multiple doses of BIVV009 or placebo was conducted in 64 volunteers to evaluate safety, tolerability, pharmacokinetic, and pharmacodynamic profiles...
May 8, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29731779/early-changes-in-tumor-perfusion-from-t1-weighted-dynamic-contrast-enhanced-mri-following-neural-stem-cell-mediated-therapy-of-recurrent-high-grade-glioma-correlate-with-overall-survival
#7
Prativa Sahoo, Paul Frankel, Julie Ressler, Margarita Gutova, Alexander J Annala, Behnam Badie, Jana Portnow, Karen S Aboody, Massimo D'Apuzzo, Russell C Rockne
Background: The aim of this study was to correlate T1-weighted dynamic contrast-enhanced MRI- (DCE-MRI-) derived perfusion parameters with overall survival of recurrent high-grade glioma patients who received neural stem cell- (NSC-) mediated enzyme/prodrug gene therapy. Methods: A total of 12 patients were included in this retrospective study. All patients were enrolled in a first-in-human study (NCT01172964) of NSC-mediated therapy for recurrent high-grade glioma...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29730375/twelve-month-results-from-the-first-in-human-randomized-study-of-the-ranger-paclitaxel-coated-balloon-for-femoropopliteal-treatment
#8
Sabine Steiner, Andrea Willfort-Ehringer, Horst Sievert, Volker Geist, Michael Lichtenberg, Costantino Del Giudice, Antoine Sauguet, Juan Diaz-Cartelle, Claudia Marx, Armin Ströbel, Ingolf Schult, Dierk Scheinert
OBJECTIVES: The authors sought to evaluate the performance of the Ranger paclitaxel-coated balloon versus uncoated balloon angioplasty for femoropopliteal lesions at 12 months. BACKGROUND: Drug-coated balloons (DCBs) are a promising endovascular treatment option for peripheral artery disease of the femoropopliteal segment, and each unique device requires dedicated clinical study. METHODS: The prospective, randomized RANGER SFA (Comparison of the Ranger™ Paclitaxel-Coated PTA Balloon Catheter and Uncoated PTA Balloons in Femoropopliteal Arteries) study (NCT02013193) enrolled 105 patients with symptomatic lower limb ischemia (Rutherford category 2 to 4) and stenotic lesions in the nonstented femoropopliteal segment at 10 European centers...
April 27, 2018: JACC. Cardiovascular Interventions
https://www.readbyqxmd.com/read/29728897/translational-pk-pd-modeling-analysis-of-mcla-128-a-her2-her3-bispecific-monoclonal-antibody-to-predict-clinical-efficacious-exposure-and-dose
#9
Aurelia H M de Vries Schultink, Robert P Doornbos, Alexander B H Bakker, Kees Bol, Mark Throsby, Cecile Geuijen, David Maussang, Jan H M Schellens, Jos H Beijnen, Alwin D R Huitema
Introduction MCLA-128 is a bispecific monoclonal antibody targeting the HER2 and HER3 receptors. Pharmacokinetics (PK) and pharmacodynamics (PD) of MCLA-128 have been evaluated in preclinical studies in cynomolgus monkeys and mice. The aim of this study was to characterize the PK and PD of MCLA-128 and to predict a safe starting dose and efficacious clinical dose for the First-In-Human study. Methods A PK-PD model was developed based on PK data from cynomolgus monkeys and tumor growth data from a mouse JIMT-1 xenograft model...
May 5, 2018: Investigational New Drugs
https://www.readbyqxmd.com/read/29728519/first-in-human-pet-study-of-3-novel-tau-radiopharmaceuticals-11-c-ro6924963-11-c-ro6931643-and-18-f-ro6958948
#10
Dean F Wong, Robert Comley, Hiroto Kuwabara, Paul B Rosenberg, Susan M Resnick, Susanne Ostrowitzki, Cristina Vozzi, Frank Boess, Esther Oh, Constantine G Lyketsos, Michael Honer, Luca Gobbi, Gregory Klein, Noble George, Lorena Gapasin, Kelly Kitzmiller, Joshua Roberts, Jeff Sevigny, Ayon Nandi, James R Brasic, Chakradhar Mishra, Madhav Thambisetty, Abhay Moghekar, Anil Mathur, Marilyn Albert, Robert F Dannals, Edilio Borroni
Background: [11 C]RO-963, [11 C]RO-643 and [18 F]RO-948 (previously referred as [11 C]RO6924963, [11 C]RO6931643, and [18 F]RO6958948, respectively) have been reported as promising PET tracers for tau imaging based on in vitro and preclinical PET data (1,2). Here we describe the first human evaluation of these novel radiotracers. Methods: Amyloid PET positive Alzheimer's disease (AD) patients and young healthy subjects (YC) each received two different tau tracers. Dynamic 90 min scans were obtained after bolus injection of [11 C]RO-963, [11 C]RO-643 or [18 F]RO-948...
May 4, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29726923/a-phase-1-dose-escalation-and-dose-expansion-study-of-brontictuzumab-in-subjects-with-selected-solid-tumors
#11
R Ferrarotto, G Eckhardt, A Patnaik, P LoRusso, L Faoro, J V Heymach, A M Kapoun, L Xu, P Munster
Background: Brontictuzumab is a monoclonal antibody that targets Notch1 and inhibits pathway activation. The purpose of this first-in-human study was to determine the maximum tolerated dose (MTD), safety, pharmacokinetics, immunogenicity and preliminary efficacy of brontictuzumab in patients with solid tumors. Patients ans Methods: Subjects with selected refractory solid tumors were elegible. Brontictuzumab was administered intravenously at various dose levels and schedule during dose escalation, and at 1...
May 3, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29721096/first-in-human-study-of-pet-and-optical-dual-modality-image-guided-surgery-in-glioblastoma-using-68-ga-irdye800cw-bbn
#12
Deling Li, Jingjing Zhang, Chongwei Chi, Xiong Xiao, Junmei Wang, Lixin Lang, Iqbal Ali, Gang Niu, Liwei Zhang, Jie Tian, Nan Ji, Zhaohui Zhu, Xiaoyuan Chen
Purpose : Despite the use of fluorescence-guided surgery (FGS), maximum safe resection of glioblastoma multiforme (GBM) remains a major challenge. It has restricted surgeons between preoperative diagnosis and intraoperative treatment. Currently, an integrated approach combining preoperative assessment with intraoperative guidance would be a significant step in this direction. Experimental design : We developed a novel 68 Ga-IRDye800CW-BBN PET/near-infrared fluorescence (NIRF) dual-modality imaging probe targeting gastrin-releasing peptide receptor (GRPR) in GBM...
2018: Theranostics
https://www.readbyqxmd.com/read/29720571/first-in-human-topical-microbiome-transplantation-with-roseomonas-mucosa-for-atopic-dermatitis
#13
Ian A Myles, Noah J Earland, Erik D Anderson, Ian N Moore, Mark D Kieh, Kelli W Williams, Arhum Saleem, Natalia M Fontecilla, Pamela A Welch, Dirk A Darnell, Lisa A Barnhart, Ashleigh A Sun, Gulbu Uzel, Sandip K Datta
The underlying pathology of atopic dermatitis (AD) includes impaired skin barrier function, susceptibility to Staphylococcus aureus skin infection, immune dysregulation, and cutaneous dysbiosis. Our recent investigation into the potential role of Gram-negative skin bacteria in AD revealed that isolates of one particular commensal, Roseomonas mucosa, collected from healthy volunteers (HVs) improved outcomes in mouse and cell culture models of AD. In contrast, isolates of R. mucosa from patients with AD worsened outcomes in these models...
May 3, 2018: JCI Insight
https://www.readbyqxmd.com/read/29708281/pharmacokinetics-safety-and-tolerability-of-obe022-a-selective-prostaglandin-f2%C3%AE-receptor-antagonist-tocolytic-a-first-in-human-trial-in-healthy-post-menopausal-women
#14
Oliver Pohl, Line Marchand, Jean-Pierre Gotteland, Simon Coates, Jörg Täubel, Ulrike Lorch
AIMS: Preterm birth remains a significant risk for later disability. The selective inhibition of the prostaglandin F2α receptor (FP) has significant advantages for a tocolytic. The pro-drug OBE022 and its metabolite OBE002 are novel FP antagonists under development for treating preterm labour. METHODS: We performed a prospective, first in human, Phase I, dose escalation, placebo-controlled, randomised trial at a clinical trial site in the UK. Placebo, single ascending doses (SAD) of 10, 30, 100, 300, 1000 or 1300 mg, and multiple ascending doses (MAD) over seven days of 100, 300 or 1000 mg per day; were administered to post-menopausal female volunteers...
April 30, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29706900/short-term-dosage-regimen-for-stimulation-induced-long-lasting-desynchronization
#15
Thanos Manos, Magteld Zeitler, Peter A Tass
In this paper, we computationally generate hypotheses for dose-finding studies in the context of desynchronizing neuromodulation techniques. Abnormally strong neuronal synchronization is a hallmark of several brain disorders. Coordinated Reset (CR) stimulation is a spatio-temporally patterned stimulation technique that specifically aims at disrupting abnormal neuronal synchrony. In networks with spike-timing-dependent plasticity CR stimulation may ultimately cause an anti-kindling, i.e., an unlearning of abnormal synaptic connectivity and neuronal synchrony...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29702733/how-often-do-safety-signals-occur-by-chance-in-first-in-human-trials
#16
Gemma L Clayton, Asher D Schachter, Baldur Magnusson, Yue Li, Laurence Colin
Clinicians working on first-in-human clinical studies need to be able to judge whether safety signals observed on an investigational drug were more likely to have occurred by chance or to have been caused by the drug. We retrospectively reviewed 84 Novartis studies including 1,234 healthy volunteers receiving placebo to determine the expected incidence of changes in commonly measured laboratory parameters and vital signs, in the absence of any active agent. We calculated the frequency of random incidence of safety signals, focusing on the liver, cardiovascular system, kidney, and pancreas...
April 27, 2018: Clinical and Translational Science
https://www.readbyqxmd.com/read/29681239/inhaled-formulation-and-device-selection-bridging-the-gap-between-preclinical-species-and-first-in-human-studies
#17
Jennifer L Wylie, Aileen House, Peter J Mauser, Shari Sellers, Jenna Terebetski, Zhenyu Wang, Jason D Ehrick
The factors that influence inhaled first-in-human (FIH) device and formulation selection often differ significantly from the factors that have influenced the preceding preclinical experiments and inhalation toxicology work. In order to minimize the risk of delivery issues negatively impacting a respiratory pipeline program, the preclinical and FIH delivery systems must be considered holistically. This topic will be covered in more detail in this paper. Several examples will be presented that highlight how appropriate scientific strategy can help bridge the gap between delivering to preclinical species and human...
May 2018: Therapeutic Delivery
https://www.readbyqxmd.com/read/29674421/anti-misrii-radiolabeled-antibodies-new-tools-for-a-theranostic-approach-in-ovarian-cancer
#18
Emmanuel Deshayes, Riad Ladjohounlou, Pierre Le Fur, Alexandre Pichard, Catherine Lozza, Vincent Boudousq, Samuel Sevestre, Marta Jarlier, Roxana Kashani, Joanna Koch, Jane Sosabowski, Julie Foster, Nicolas Chouin, Frank Bruchertseifer, Alfred Morgenstern, Pierre-Olivier Kotzki, Isabelle Navarro-Teulon, Jean-Pierre Pouget
We have developed the 16F12 mouse monoclonal antibody (mAb) that targets the MISRII receptor expressed by ovarian tumors. Here, we assessed in preclinical models the possibility to use radiolabeled 16F12 in a theranostic approach for small-volume ovarian peritoneal carcinomatosis, for instance after cytoreductive surgery. Methods: DOTA-, DTPA- or DFO-conjugated 16F12 mAb was radiolabeled with beta (177 Lu) or alpha (213 Bi) particle emitters for therapeutic use, and with 89 Zr for positron emission tomography (PET) imaging...
April 19, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29672897/evaluation-of-a-janus-kinase-1-inhibitor-pf-04965842-in-healthy-subjects-a-phase-1-randomized-placebo-controlled-dose-escalation-study
#19
Elena Peeva, Martin R Hodge, Elizabeth Kieras, Michael L Vazquez, Kosalaram Goteti, Sanela G Tarabar, Christine W Alvey, Christopher Banfield
AIMS: To determine the safety, tolerability, pharmacokinetics and pharmacodynamics of the Janus Kinase (JAK) 1-selective inhibitor, PF-04965842. METHODS: This was a phase 1, first-in-human, randomized, double-blind, placebo-controlled, combination single- and multiple-dose escalation, parallel design study in healthy subjects (ClinicalTrials.gov, NCT01835197). Subjects received a single dose of placebo or 3, 10, 30, 100, 200, 400 or 800 mg PF-04965842 (single ascending dose phase) and placebo or 30 mg once daily (QD), 100 mg QD, 200 mg QD, 400 mg QD, 100 mg twice daily (BID) or 200 mg BID PF-04965842 for 10 consecutive days (multiple ascending dose phase)...
April 19, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29669780/microinterventional-endocapsular-nucleus-disassembly-novel-technique-and-results-of-first-in-human-randomised-controlled-study
#20
Tsontcho Ianchulev, David F Chang, Edward Koo, Susan MacDonald, Ernesto Calvo, Farrell Toby Tyson, Andrea Vasquez, Iqbal Ike K Ahmed
AIM: To assess the safety and efficacy of microinterventional endocapsular nuclear fragmentation in moderate to severe cataracts. METHODS: This was a prospective single-masked multisurgeon interventional randomised controlled trial (ClinicalTrials.gov NCT02843594) where 101 eyes of 101 subjects with grade 3-4+ nuclear cataracts were randomised to torsional phacoemulsification alone (controls) or torsional phacoemulsification with adjunctive endocapsular nuclear fragmentation using a manual microinterventional nitinol filament loop device (miLOOP group)...
April 18, 2018: British Journal of Ophthalmology
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