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https://www.readbyqxmd.com/read/28818217/thirty-sixth-month-follow-up-of-first-in-human-use-of-cyanoacrylate-adhesive-for-treatment-of-saphenous-vein-incompetence
#1
Jose I Almeida, Julian J Javier, Edward G Mackay, Claudia Bautista, Daniel J Cher, Thomas M Proebstle
OBJECTIVE: The objective of this study was to evaluate the long-term safety and effectiveness of endovenous cyanoacrylate (CA)-based closure of incompetent great saphenous veins. METHODS: This was a prospective, single-arm, single-center feasibility study conducted at the Canela Clinic (La Romana, Dominican Republic) to assess the effectiveness and safety of a CA-based adhesive for great saphenous vein closure at 36 months after treatment. Thirty-eight subjects were treated by injection of small boluses of CA under ultrasound guidance and without the use of perivenous tumescent anesthesia or postprocedure graduated compression stockings...
September 2017: Journal of Vascular Surgery. Venous and Lymphatic Disorders
https://www.readbyqxmd.com/read/28815639/safety-tolerability-and-pharmacokinetic-characteristics-of%C3%A2-a-novel-nonopioid-analgesic-vvz-149-injections-in-healthy-volunteers-a-first-in-class-first-in-human-study
#2
Jaeseong Oh, SeungHwan Lee, Anhye Kim, Jangsoo Yoon, Kyungho Jang, Doo H Lee, Sunyoung Cho, Sang Rim Lee, Kyung-Sang Yu, Jae-Yong Chung
VVZ-149, a dual antagonist of GlyT2 and 5HT2 A receptors, is an investigational analgesic with a novel mechanism of action that is currently under early-stage clinical development as an injectable agent for the treatment of postoperative pain. Here, the safety, tolerability, and pharmacokinetics of VVZ-149 injections in healthy male volunteers were explored in a randomized, double-blind, single- and multiple-ascending-dose (SAD and MAD, respectively), placebo-controlled clinical study. Subjects randomly received a 4-hour intravenous infusion of 0...
August 16, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28808818/first-in-human-study-of-the-epichaperome-inhibitor-pu-h71-clinical-results-and-metabolic-profile
#3
Giovanna Speranza, Larry Anderson, Alice P Chen, Khanh Do, Michelle Eugeni, Marcie Weil, Larry Rubinstein, Eva Majerova, Jerry Collins, Yvonne Horneffer, Lamin Juwara, Jennifer Zlott, Rachel Bishop, Barbara A Conley, Howard Streicher, Joseph Tomaszewski, James H Doroshow, Shivaani Kummar
Background Molecular chaperone targeting has shown promise as a therapeutic approach in human cancers of various histologies and genetic backgrounds. The purine-scaffold inhibitor PU-H71 (NSC 750424), selective for Hsp90 in epichaperome networks, has demonstrated antitumor activity in multiple preclinical cancer models. The present study was a first in-human trial of PU-H71 aimed at establishing its safety and tolerability and characterizing its pharmacokinetic (PK) profile on a weekly administration schedule in human subjects with solid tumors refractory to standard treatments...
August 12, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28800169/global-multi-electrode-contact-mapping-plus-ablation-with-a-single-catheter-preclinical-and-preliminary-experience-in-humans-with-atrial-fibrillation
#4
Hans Kottkamp, Fabian Moser, Andreas Rieger, Doreen Schreiber, Christian Pönisch, Monica Trofin
INTRODUCTION: One question for the technological advancement of catheter ablation of atrial fibrillation (AF) is whether a creative new concept can combine and even improve the diagnostic mapping options of single-tip and basket catheters with the simplicity of the use of balloon catheters for ablation. Herein, we describe the first in-human experience with a single catheter offering such a complete solution. METHODS AND RESULTS: A new catheter (Globe®) with a distal multi-electrode array consisting of 16 ribs with 122 gold-plated electrodes was used...
August 11, 2017: Journal of Cardiovascular Electrophysiology
https://www.readbyqxmd.com/read/28799641/new-requirements-for-phase-i-trials-a-challenge-for-italian-clinical-research
#5
Emanuela Marchesi, Manuela Monti, Oriana Nanni, Lisette Bassi, Martina Piccinni-Leopardi, Celeste Cagnazzo
BACKGROUND: In 2015, the Italian Medicines Agency (Agenzia Italiana del Farmaco; AIFA) issued the Determination 809/2015 with new requirements for phase I clinical trials. Before it came into force, we explored the extent to which several Italian oncology centers were working to implement it. METHODS: A survey was conducted among 80 Italian centers involved in clinical trials. Investigators and research coordinators were surveyed. RESULTS: Answers from 42 institutions were collected: among them 88...
August 7, 2017: Tumori
https://www.readbyqxmd.com/read/28799285/a-first-in-human-study-of-ds-1040-an-inhibitor-of-the-activated-form-of-thrombin-activatable-fibrinolysis-inhibitor-in-healthy-subjects-response
#6
J Zhou, N Miyoshi
We appreciate the thoughtful comments from Gurewich et al. on our recent article [1]. The results of the first-in-human study of DS-1040 demonstrated substantial fibrinolysis-related pharmacological effects, without any impact on bleeding time in healthy subjects. Currently, clinical trials are underway to investigate this first-in-class inhibitor that targets the active form of thrombin-activatable fibrinolysis inhibitor (TAFIa) in thromboembolic diseases (ClinicalTrials. gov: NCT02586233, NCT02923115, NCT03198715)...
August 11, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28799246/a-first-in-human-study-of-ds-1040-an-inhibitor-of-the-activated-form-of-thrombin-activatable-fibrinolysis-inhibitor-in-healthy-subjects-comment
#7
V Gurewich, R Pannell
In the interesting study by Zhou et al [1] of a TAFI inhibitor, DS1040, the authors state (p 962, col 1, para 3) that "When plasmin cleaves fibrin … [it] exposes C-terminal lysine residues [that] can bind both plasminogen and tPA." While this is technically correct, it is functionally misleading, as is also Figure 1 showing tPA binding to lysines. The reason is that the lysine affinity of tPA is the same as that of plasminogen [2]. This article is protected by copyright. All rights reserved.
August 11, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28798270/a-phase-i-dose-escalation-study-of-the-safety-and-pharmacokinetics-of-pictilisib-in-combination-with-erlotinib-in-patients-with-advanced-solid-tumors
#8
Stephen Leong, Rebecca A Moss, Daniel W Bowles, Joseph A Ware, Jing Zhou, Jill M Spoerke, Mark R Lackner, Geetha Shankar, Jennifer L Schutzman, Ruud van der Noll, Emile E Voest, Jan H M Schellens
BACKGROUND: Epidermal growth factor receptor (EGFR) and phosphatidylinositol 3-kinase (PI3K) are involved in the proliferation and survival of many cancer types. Enhanced antitumor activity may be achieved through combined inhibition of these pathways. We report results for pictilisib (GDC-0941, a class I pan-PI3K inhibitor) plus erlotinib (an EGFR tyrosine kinase inhibitor) in patients with advanced solid tumors. MATERIALS AND METHODS: A 3 + 3 dose-escalation study was carried out at a starting daily dose of 60 mg pictilisib on days 1-21 of a 28-day cycle and 150 mg erlotinib from day 2 of cycle 1...
August 10, 2017: Oncologist
https://www.readbyqxmd.com/read/28795506/oral-apolipoprotein-a-i-mimetic-d-4f-lowers-hdl-inflammatory-index-in-high-risk-patients-a-first-in-human-multiple-dose-randomized-controlled-trial
#9
Richard L Dunbar, Rajesh Movva, LeAnne T Bloedon, Danielle Duffy, Robert B Norris, Mohamad Navab, Alan M Fogelman, Daniel J Rader
A single dose of the apolipoprotein (apo)A-I mimetic peptide D-4F rendered high-density lipoprotein (HDL) less inflammatory, motivating the first multiple-dose study. We aimed to assess safety/tolerability, pharmacokinetics, and pharmacodynamics of daily, orally administered D-4F. High-risk coronary heart disease (CHD) subjects added double-blinded placebo or D-4F to statin for 13 days, randomly assigned 1:3 to ascending cohorts of 100, 300, then 500 mg (n = 62; 46 men/16 women). D-4F was safe and well-tolerated...
August 9, 2017: Clinical and Translational Science
https://www.readbyqxmd.com/read/28795416/the-acute-effect-of-beta-guanidinopropionic-acid-versus-creatine-or-placebo-in-healthy-men-abc-trial-a-randomized-controlled-first-in-human-trial
#10
F A Karamat, D L Horjus, Y C Haan, L van der Woude, M C Schaap, I Oudman, G A van Montfrans, R Nieuwland, G S Salomons, J F Clark, L M Brewster
AIM: Increasing evidence indicates that the ATP-generating enzyme creatine kinase (CK) is involved in hypertension. CK rapidly regenerates ATP from creatine phosphate and ADP. Recently, we showed that beta-guanidinopropionic acid (GPA), a kidney-synthesized creatine analogue and competitive CK inhibitor, reduced blood pressure in spontaneously hypertensive rats. To further develop the substance as a potential blood pressure-lowering agent, we assessed the tolerability of a sub-therapeutic GPA dose in healthy men...
August 10, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28790501/conquering-the-challenges-of-genotypic-and-phenotypic-tumor-heterogeneity-to-realize-the-promise-of-personalized-cancer-therapy-the-role-of-academia
#11
Sofia Merajver, Sameer Phadke, Matthew Soellner
The advent of rapid and progressively more affordable sequencing and gene expression studies have spurred research on therapies for cancer targeted to specific gene alterations. With few exceptions, such as those cancers with either a paucity of mutations or major chromosomal rearrangements driving the neoplastic transformation, the approaches based on one mutational target-one drug have achieved only modest outcomes in cancer. Using the paradigm of aggressive breast cancers, we will show the mathematical explanation that predicts our failures and indicates a plausible way forward...
2017: Transactions of the American Clinical and Climatological Association
https://www.readbyqxmd.com/read/28777101/new-graft-insertion-device-for-descemet-stripping-automated-endothelial-keratoplasty
#12
Takeshi Soma, Shizuka Koh, Naoyuki Maeda, Kikuo Mitomo, Andrew J Quantock, Kohji Nishida
PURPOSE: Corneal endothelial dysfunction is a major indication for corneal graft surgery worldwide, and although surgical intervention through a range of posterior lamellar surgeries has proven to be hugely beneficial, challenges remain. This is especially so where the anterior chamber is relatively shallow, as is often the case in the Asian population, though not exclusively so. In this study, we introduce a new insertion device to deliver endothelial graft tissue for Descemet stripping automated endothelial keratoplasty (DSAEK)...
August 2, 2017: Cornea
https://www.readbyqxmd.com/read/28776922/efficacy-and-pharmacokinetics-of-subcutaneous-exendin-9-39-in-patients-with-post-bariatric-hypoglycemia
#13
Colleen M Craig, Li-Fen Liu, Thi Nguyen, Candice Price, Justus Bingham, Tracey L McLaughlin
AIM: Post-bariatric hypoglycemia (PBH) is a rare but growing complication of bariatric surgery with severe, debilitating, potentially life-threatening consequences and no safe and effective treatment. Previous studies involving continuous intravenous (IV) infusion of the glucagon-like peptide-1 (GLP-1) receptor antagonist, exendin (9-39) (Ex-9) in patients with PBH have demonstrated efficacy in preventing symptomatic postprandial hypoglycemia. Subcutaneous (SC) injection of Ex-9 would represent a more practical therapeutic approach...
August 4, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28774381/first-in-human-closed-chest-transcatheter-superior-cavopulmonary-anastomosis
#14
Kanishka Ratnayaka, John W Moore, Rodrigo Rios, Robert J Lederman, Sanjeet R Hegde, Howaida G El-Said
BACKGROUND: In the care of patients with congenital heart disease, percutaneous interventional treatments have supplanted many surgical approaches for simple lesions, such as atrial septal defect. By contrast, complex congenital heart defects continue to require open-heart surgery. In single-ventricle patients, a staged approach is employed, which requires multiple open-heart surgeries and significant attendant morbidity and mortality. A nonsurgical transcatheter alternative would be attractive...
August 8, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28769925/pharmacodynamic-monitoring-of-ro5459072-a-small-molecule-inhibitor-of-cathepsin-s
#15
Michel Theron, Darren Bentley, Sandra Nagel, Marianne Manchester, Michael Gerg, Thomas Schindler, Ana Silva, Barbara Ecabert, Priscila Teixeira, Camille Perret, Bernhard Reis
Major histocompatibility complex class II (MHCII)-restricted antigen priming of CD4(+) T cells is both involved in adaptive immune responses and the pathogenesis of autoimmune diseases. Degradation of invariant chain Ii, a protein that prevents premature peptide loading, is a prerequisite for nascent MHCII-peptide complex formation. A key proteolytic step in this process is mediated by cathepsin S. Inhibition of this cysteine protease is known to result in the intracellular accumulation of Lip10 in B cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28766409/phase-1-healthy-volunteer-willingness-to-participate-and-enrollment-preferences
#16
Stephanie C Chen, Ninet Sinaii, Gabriella Bedarida, Mark A Gregorio, Ezekiel Emanuel, Christine Grady
BACKGROUND/AIMS: Healthy volunteers in phase 1 clinical trials contribute to the development of safe drugs and other biologics and accept risks and burdens without anticipated health benefits from participation. Although emerging data have shown that healthy volunteers are influenced by risk, some still worry that financial incentives lead them to take on unreasonable risk. Yet little is known about healthy volunteers' preferences and how they make choices about enrolling in research studies...
August 1, 2017: Clinical Trials: Journal of the Society for Clinical Trials
https://www.readbyqxmd.com/read/28764807/akt1-low-quiescent-cancer-cells-persist-after-neoadjuvant-chemotherapy-in-triple-negative-breast-cancer
#17
Sheheryar Kabraji, Xavier Solé, Ying Huang, Clyde Bango, Michaela Bowden, Aditya Bardia, Dennis Sgroi, Massimo Loda, Sridhar Ramaswamy
BACKGROUND: Absence of pathologic complete response (pCR) to neoadjuvant chemotherapy (NACT) correlates with poor long-term survival in patients with triple negative breast cancer (TNBC). These incomplete treatment responses are likely determined by mechanisms that enable cancer cells to resist being killed. However, the detailed characterization of a drug-resistant cancer cell state in residual TNBC tissue after NACT has remained elusive. AKT1(low) quiescent cancer cells (QCCs) are a quiescent, epigenetically plastic, and chemotherapy-resistant subpopulation initially identified in experimental cancer models...
August 1, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28762115/erratum-to-intraoperative-tumor-detection-using-a-ratiometric-activatable-fluorescent-peptide-a-first-in-human-phase-1-study
#18
Jonathan T Unkart, Steven L Chen, Irene L Wapnir, Jesús E González, Alec Harootunian, Anne M Wallace
No abstract text is available yet for this article.
July 31, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28755409/a-first-in-human-pharmacodynamic-and-pharmacokinetic-study-of-a-fully-human-anti-glucagon-receptor-monoclonal-antibody-in-normal-healthy-volunteers
#19
Ana Kostic, Alexander T King, Feng Yang, Kuo-Chen Chan, George D Yancopoulos, Jesper Gromada, Joyce B Harp
AIMS: Glucagon receptor (GCGR) blockers are being investigated as potential therapeutics for type 1 and 2 diabetes. Here we report the safety, tolerability, pharmacokinetics [PK], and pharmacodynamics [PD] of REGN1193, a fully human glucagon receptor blocking monoclonal antibody from a first-in-human healthy volunteer randomized double blind trial. MATERIALS AND METHODS: Healthy men and women received single ascending doses of REGN1193 ranging from 0.05 mg/kg to 0...
July 28, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28754494/safety-and-immunogenicity-of-a-mrna-rabies-vaccine-in-healthy-adults-an-open-label-non-randomised-prospective-first-in-human-phase-1-clinical-trial
#20
Martin Alberer, Ulrike Gnad-Vogt, Henoch Sangjoon Hong, Keyvan Tadjalli Mehr, Linus Backert, Greg Finak, Raphael Gottardo, Mihai Alexandru Bica, Aurelio Garofano, Sven Dominik Koch, Mariola Fotin-Mleczek, Ingmar Hoerr, Ralf Clemens, Frank von Sonnenburg
BACKGROUND: Vaccines based on mRNA coding for antigens have been shown to be safe and immunogenic in preclinical models. We aimed to report results of the first-in-human proof-of-concept clinical trial in healthy adults of a prophylactic mRNA-based vaccine encoding rabies virus glycoprotein (CV7201). METHODS: We did an open-label, uncontrolled, prospective, phase 1 clinical trial at one centre in Munich, Germany. Healthy male and female volunteers (aged 18-40 years) with no history of rabies vaccination were sequentially enrolled...
July 25, 2017: Lancet
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