keyword
MENU ▼
Read by QxMD icon Read
search

First-in-human phase 1 study

keyword
https://www.readbyqxmd.com/read/29674030/molecularly-imprinted-polymer-for-determination-of-lumefantrine-in-human-plasma-through-chemometric-assisted-solid-phase-extraction-and-liquid-chromatography
#1
Pedro Henrique Reis da Silva, Melina Luiza Vieira Diniz, Gerson Antônio Pianetti, Isabela da Costa César, Maria Elisa Scarpelli Ribeiro E Silva, Roberto Fernando de Souza Freitas, Ricardo Geraldo de Sousa, Christian Fernandes
Lumefantrine is the first-choice treatment of Falciparum uncomplicated malaria. Recent findings of resistance to lumefantrine has brought attention for the importance of therapeutic monitoring, since exposure to subtherapeutic doses of antimalarials after administration is a major cause of selection of resistant parasites. Therefore, this study focused on the development of innovative, selective, less expensive and stable molecularly imprinted polymers (MIPs) for solid-phase extraction (SPE) of lumefantrine from human plasma to be used in drug monitoring...
July 1, 2018: Talanta
https://www.readbyqxmd.com/read/29673765/three-dimensional-ionic-liquid-ferrite-functionalized-graphene-oxide-nanocomposite-for-pipette-tip-solid-phase-extraction-of-16-polycyclic-aromatic-hydrocarbons-in-human-blood-sample
#2
Yun Zhang, Yong-Gang Zhao, Wei-Sheng Chen, He-Li Cheng, Xiu-Qiong Zeng, Yan Zhu
Polycyclic aromatic hydrocarbons (PAHs) are ubiquitously found in the environment and have been proved to be prospectively associated with the risk of cancer. In this study, a simple method based on pipette-tip solid phase extraction (PT-SPE) and gas chromatography-mass spectrometry (GC-MS) has been firstly developed for the determination of 16 PAHs in human whole blood. Three-dimensional ionic liquid-ferrite functionalized graphene oxide nanocomposite (3D-IL-Fe3 O4 -GO) was used as sorbent in PT-SPE. Compared with conventional SPE method, the PT-SPE method was solvent-saving (1...
March 21, 2018: Journal of Chromatography. A
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
#3
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/29669026/first-in-human-randomized-controlled-trial-of-mosaic-hiv-1-immunogens-delivered-via-a-modified-vaccinia-ankara-vector
#4
Lindsey R Baden, Stephen R Walsh, Michael S Seaman, Yehuda Z Cohen, Jennifer A Johnson, J Humberto Licona, Rachel D Filter, Jane A Kleinjan, Jon A Gothing, Julia Jennings, Lauren Peter, Joseph Nkolola, Peter Abbink, Erica N Borducchi, Marinela Kirilova, Kathryn E Stephenson, Poonam Pegu, Michael A Eller, Hung V Trinh, Mangala Rao, Julie A Ake, Michal Sarnecki, Steven Nijs, Katleen Callewaert, Hanneke Schuitemaker, Jenny Hendriks, Maria G Pau, Frank Tomaka, Bette T Korber, Galit Alter, Raphael Dolin, Patricia L Earl, Bernard Moss, Nelson L Michael, Merlin L Robb, Dan H Barouch
Background: Mosaic immunogens are bioinformatically engineered HIV-1 sequences designed to elicit clade independent coverage against globally circulating HIV-1 strains. Methods: This Phase 1 double-blind, randomized, placebo-controlled trial enrolled healthy HIV uninfected adults who received two doses of a modified vaccinia Ankara (MVA) vectored HIV-1 bivalent mosaic immunogen vaccine or placebo on days 0 and 84. Two groups were enrolled: those who were HIV-1 vaccine naïve (N=15) and those who had received an HIV-1 vaccine four to six years earlier (Ad26...
April 13, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29666122/iontophoretic-delivery-of-dexamethasone-phosphate-for-non-infectious-non-necrotising-anterior-scleritis-dose-finding-clinical-trial
#5
Erin C O'Neil, Jiayan Huang, Eric B Suhler, James P Dunn, Victor L Perez, David C Gritz, Kathy McWilliams, Ellen Peskin, Gui-Shuang Ying, Vatinee Y Bunya, Maureen G Maguire, John H Kempen
Currently available treatment options for non-infectious scleritis, including non-steroidal anti-inflammatory drugs, systemic corticosteroids and immunosuppressive therapies, have both efficacy and side effect limitations. Iontophoretic delivery of corticosteroids has been demonstrated to be effective for anterior uveitis and represents a potential new approach to scleritis therapy. We hypothesised that iontophoretic delivery would provide effective and precise medication delivery to the sclera, while limiting systemic exposure and side effects...
April 17, 2018: British Journal of Ophthalmology
https://www.readbyqxmd.com/read/29666026/cervical-cancer-state-of-the-science-from-angiogenesis-blockade-to-checkpoint-inhibition
#6
REVIEW
Lindsey E Minion, Krishnansu S Tewari
Vascular endothelial growth factor (VEGF) has emerged as a therapeutic target in several malignancies, including cervical cancer. Chemotherapy doublets combined with the fully humanized monoclonal antibody, bevacizumab, now constitute first-line therapy for women struggling with recurrent/metastatic cervical carcinoma. Regulatory approval for this indication was based on the phase III randomized trial, GOG 240, which demonstrated a statistically significant and clinically meaningful improvement in overall survival when bevacizumab was added to chemotherapy: 17...
March 2018: Gynecologic Oncology
https://www.readbyqxmd.com/read/29665030/dermatologic-toxicity-from-novel-therapy-using-antimicrobial-peptide-ll-37-in-melanoma-a-detailed-examination-of-the-clinicopathologic-features
#7
Tsetan Dolkar, Celestine M Trinidad, Kelly C Nelson, Rodabe N Amaria, Priyadharsini Nagarajan, Carlos A Torres-Cabala, Doina Ivan, Victor G Prieto, Michael T Tetzlaff, Jonathan L Curry, Phyu P Aung
LL-37 is a naturally occurring 37-amino acid that is part of innate immunity in human skin. Preclinical studies have demonstrated that intra-tumoral injections of LL-37 stimulate the innate immune system by activation of plasmacytoid dendritic cells, which mediate tumor destruction. LL-37 intra-tumoral injections have been utilized in a Phase 1 clinical trial for melanoma patients with cutaneous metastases. We report dermatologic toxicity in a 63-year-old woman with stage IIIC melanoma of the right calf and inguinal lymph nodes...
April 17, 2018: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/29664215/the-plasma-bile-acid-alterations-of-type-2-diabetes-correlated-with-insulin-secretion-in-two-step-hyperglycemic-clamp
#8
Shujie Wang, Yuying Deng, Xiaoyan Xie, Jing Ma, Min Xu, Xinjie Zhao, Weiqiong Gu, Jie Hong, Weiqing Wang, Guowang Xu, Guang Ning, Yanyun Gu, Yifei Zhang
BACKGROUND: Bile acids (BAs) conduct crucial signals in human metabolism. Correlations between human plasma BA alterations and insulin secretion defects and type 2 diabetes (T2D) progression have been insufficiently studied. This study was performed to explore the trajectories of human plasma BA alterations and their association with the insulin secretion dynamics during a two-step hyperglycemic clamp. METHODS: Eleven healthy (NGT) and 33 drug-naïve T2D subjects (T2Ds) were enrolled to undertake a two-step hyperglycemic clamp...
April 17, 2018: Journal of Diabetes
https://www.readbyqxmd.com/read/29663420/phase-1-first-in-human-single-and-multiple-ascending-dose-and-food-effect-studies-to-assess-the-safety-tolerability-and-pharmacokinetics-of-presatovir-for-the-treatment-of-respiratory-syncytial-virus-infection
#9
Polina German, Yan Xin, Jason W Chien, Winnie Weng, Richard Mackman, Sandra A Lewis, Amy Meng, John Ling, Anita Mathias
Respiratory syncytial virus (RSV)-associated respiratory tract infection is a leading cause of hospitalizations in infants for which no effective treatment exists. RSV infection is also an important cause of respiratory disease in adults and immunocompromised patients. Presatovir (GS-5806) is an orally bioavailable antiviral agent that inhibits fusion of RSV with host cell membranes. Here, results from 2 phase 1 studies that evaluated safety, tolerability, and pharmacokinetics of presatovir in healthy adults following administration of single and multiple (7 days) once- or twice-daily ascending doses (first-in-human study) and in the presence or absence of food (food effect study) are described...
April 17, 2018: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29661232/cmpd1-inhibited-human-gastric-cancer-cell-proliferation-by-inducing-apoptosis-and-g2-m-cell-cycle-arrest
#10
Yu Li, Depeng Zhang, Kaikai Yu, Yudong Hu, Qiong Wu, Feng Qian, Zishu Wang
BACKGROUND: Gastric cancer occupies the fourth highest morbidity rate of cancers worldwide. Clinical therapies of gastric cancer remain limited because of uncertainty of mechanisms and shortness of effective medicine. Thus, new drug candidates for gastric cancer treatment is urgently needed. RESULTS: In this study, CMPD1 as a wildly used MK2 phosphorylation inhibitor was employed to find its impact on gastric cancer cell proliferation, apoptosis and cell cycle using colony formation assay and flow cytometry analysis...
April 16, 2018: Biological Research
https://www.readbyqxmd.com/read/29660667/high-performance-thin-layer-chromatographic-methods-for-the-determination-of-febuxostat-and-febuxostat-diclofenac-combination-in-human-plasma
#11
Fawzi A El-Yazbi, Omayma A Amin, Eman I El-Kimary, Essam F Khamis, Sameh E Younis
Two simple, sensitive and specific high-performance thin-layer chromatographic (HPTLC) methods were developed for the determination of febuxostat (FEB) individually, and simultaneously with diclofenac (DIC) in human plasma. Method A presents the first HPTLC-ultraviolet attempt for FEB determination in human plasma. FEB was separated from endogenous plasma components (at hRF  = 70) with ethyl acetate-methanol-water (9:2:1, v/v) mixture as mobile phase and quantified by densitometry at its λmax (315 nm)...
April 10, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29660598/first-in-human-phase-1-dose-escalation-pharmacokinetic-and-pharmacodynamic-study-of-the-oral-dual-pi3k-and-mtorc1-2-inhibitor-pqr309-in-patients-with-advanced-solid-tumors-sakk-67-13
#12
Andreas Wicki, Nicholas Brown, Alexandros Xyrafas, Vincent Bize, Hanne Hawle, Simona Berardi, Nataša Cmiljanović, Vladimir Cmiljanović, Michael Stumm, Saša Dimitrijević, Richard Herrmann, Vincent Prêtre, Reto Ritschard, Alexandar Tzankov, Viviane Hess, Alexa Childs, Cinta Hierro, Jordi Rodon, Dagmar Hess, Markus Joerger, Roger von Moos, Cristiana Sessa, Rebecca Kristeleit
BACKGROUND: PQR309 is an orally bioavailable, balanced pan-phosphatidylinositol-3-kinase (PI3K), mammalian target of rapamycin (mTOR) C1 and mTORC2 inhibitor. PATIENTS AND METHODS: This is an accelerated titration, 3 + 3 dose-escalation, open-label phase I trial of continuous once-daily (OD) PQR309 administration to evaluate the safety, pharmacokinetics (PK) and pharmacodynamics in patients with advanced solid tumours. Primary objectives were to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D)...
April 13, 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/29652520/hemolysis-induced-lung-vascular-leakage-contributes-to-the-development-of-pulmonary-hypertension
#13
Olga Rafikova, Elissa R Williams, Matthew L McBride, Marina Zemskova, Anup Srivastava, Vineet Nair, Ankit A Desai, Paul R Langlais, Evgeny Zemskov, Marc Simon, Lawrence J Mandarino, Ruslan Rafikov
RATIONALE: While hemolytic anemia-associated pulmonary hypertension (PH) and pulmonary arterial hypertension (PAH) are more common than the prevalence of idiopathic PAH alone, the role of hemolysis in the development of PAH is poorly characterized. OBJECTIVES: We hypothesized that hemolysis independently contributes to PAH pathogenesis via endothelial barrier dysfunction with resulting perivascular edema and inflammation. METHODS: Plasma samples from patients with and without PAH (both confirmed by right heart catheterization) were used to measure free hemoglobin (Hb) and its correlation with PAH severity...
April 13, 2018: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29650362/tazemetostat-an-ezh2-inhibitor-in-relapsed-or-refractory-b-cell-non-hodgkin-lymphoma-and-advanced-solid-tumours-a-first-in-human-open-label-phase-1-study
#14
Antoine Italiano, Jean-Charles Soria, Maud Toulmonde, Jean-Marie Michot, Carlo Lucchesi, Andrea Varga, Jean-Michel Coindre, Stephen J Blakemore, Alicia Clawson, Benjamin Suttle, Alice A McDonald, Mark Woodruff, Scott Ribich, Eric Hedrick, Heike Keilhack, Blythe Thomson, Takashi Owa, Robert A Copeland, Peter T C Ho, Vincent Ribrag
BACKGROUND: Activating enhancer of zeste homolog 2 (EZH2) mutations or aberrations of the switch/sucrose non-fermentable (SWI/SNF) complex (eg, mutations or deletions of the subunits INI1 or SMARCA4) can lead to aberrant histone methylation, oncogenic transformation, and a proliferative dependency on EZH2 activity. In this first-in-human study, we aimed to investigate the safety, clinical activity, pharmacokinetics, and pharmacodynamics of tazemetostat, a first-in-class selective inhibitor of EZH2...
April 9, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29629373/assessment-of-a-nutritional-rehabilitation-model-in-two-modern-broilers-and-their-jungle-fowl-ancestor-a-model-for-better-understanding-childhood-undernutrition
#15
Mikayla F A Baxter, Juan D Latorre, Dawn A Koltes, Sami Dridi, Elizabeth S Greene, Stephen W Bickler, Jae H Kim, Ruben Merino-Guzman, Xochitl Hernandez-Velasco, Nicholas B Anthony, Walter G Bottje, Billy M Hargis, Guillermo Tellez
This article is the first in a series of manuscripts to evaluate nutritional rehabilitation in chickens as a model to study interventions in children malnutrition (Part 1: Performance, Bone Mineralization, and Intestinal Morphometric Analysis). Inclusion of rye in poultry diets induces a nutritional deficit that leads to increased bacterial translocation, intestinal viscosity, and decreased bone mineralization. However, it is unclear the effect of diet on developmental stage or genetic strain. Therefore, the objective was to determine the effects of a rye diet during either the early or late phase of development on performance, bone mineralization, and intestinal morphology across three diverse genetic backgrounds...
2018: Frontiers in Nutrition
https://www.readbyqxmd.com/read/29617817/decreased-pecam1-mediated-tgf-%C3%AE-1-expression-in-the-mid-secretory-endometrium-in-women-with-recurrent-implantation-failure
#16
Feng Guo, Chenchen Si, Mingjuan Zhou, Jingwen Wang, Dan Zhang, Peter C K Leung, Bufang Xu, Aijun Zhang
STUDY QUESTION: Is recurrent implantation failure (RIF) associated with decreased expression of platelet and endothelial cell adhesion molecule 1 (PECAM1) and transforming growth factor β1 (TGF-β1) in the endometrium during the implantation window? SUMMARY ANSWER: The present study demonstrates that the expression of PECAM1 and TGF-β1 is significantly decreased in the mid-secretory endometrium in women with RIF, which may account for embryo implantation failure...
March 30, 2018: Human Reproduction
https://www.readbyqxmd.com/read/29616034/specific-inhibition-of-complement-activation-significantly-ameliorates-autoimmune-blistering-disease-in-mice
#17
Sidonia Mihai, Misa Hirose, Yi Wang, Joshua M Thurman, V Michael Holers, B Paul Morgan, Jörg Köhl, Detlef Zillikens, Ralf J Ludwig, Falk Nimmerjahn
Epidermolysis bullosa acquisita (EBA) is an antibody-mediated blistering skin disease associated with tissue-bound and circulating autoantibodies to type VII collagen (COL7). Transfer of antibodies against COL7 into mice results in a subepidermal blistering phenotype, strictly depending on the complement component C5. Further, activation predominantly by the alternative pathway is required to induce experimental EBA, as blistering was delayed and significantly ameliorated only in factor B-/- mice. However, C5 deficiency not only blocked the activation of terminal complement components and assembly of the membrane attack complex (MAC) but also eliminated the formation of C5a...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29616019/the-syk-coupled-c-type-lectin-receptors-dectin-2-and-dectin-3-are-involved-in-paracoccidioides-brasiliensis-recognition-by-human-plasmacytoid-dendritic-cells
#18
Nycolas Willian Preite, Claudia Feriotti, Dhêmerson Souza de Lima, Bruno Borges da Silva, Antônio Condino-Neto, Alessandra Pontillo, Vera Lúcia Garcia Calich, Flávio Vieira Loures
Plasmacytoid dendritic cells (pDCs), which have been extensively studied in the context of the immune response to viruses, have recently been implicated in host defense mechanisms against fungal infections. Nevertheless, the involvement of human pDCs during paracoccidioidomycosis (PCM), a fungal infection endemic to Latin America, has been scarcely studied. However, pDCs were found in the cutaneous lesions of PCM patients, and in pulmonary model of murine PCM these cells were shown to control disease severity...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29610030/clinical-implications-of-targeting-xpo1-mediated-nuclear-export-in-multiple-myeloma
#19
REVIEW
Ujjawal H Gandhi, William Senapedis, Erkan Baloglu, Thaddeus J Unger, Ajai Chari, Dan Vogl, Robert F Cornell
Multiple myeloma (MM) is a malignancy of plasma cells that is typically chronic, and relapse is common. Current therapeutic strategies include combination and sequential treatments with corticosteroids, alkylating agents, proteasomal inhibitors, immunomodulators, and monoclonal antibodies. These drugs prolong survival but ultimately become ineffective. Exportin 1 (XPO1), a nuclear export protein, is overexpressed in MM cells, and knockdown studies have suggested that XPO1 is essential for MM cell survival. Selective inhibitor of nuclear export (SINE) compounds are novel, orally bioavailable class of agents that specifically inhibit XPO1...
March 14, 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29606543/a-phase-i-open-label-single-dose-micro-tracer-mass-balance-study-of-14-c-labeled-asp7991-in-healthy-japanese-male-subjects-using-accelerator-mass-spectrometry
#20
Daisuke Miyatake, Naoyuki Nakada, Akitsugu Takada, Kota Kato, Yuta Taniuchi, Masataka Katashima, Taiji Sawamoto
ASP7991 is a calcimimetic that acts on the calcium-sensing receptor on parathyroid cell membranes and suppresses parathyroid hormone (PTH) secretion in the treatment of secondary hyperparathyroidism. The mass balance and metabolite profile of [14 C]ASP7991 were investigated in six healthy male subjects after a single oral dose of [14 C]ASP7991 [1 mg, 18.5 kBq (500 nCi)] in solution. [14 C] radioactivity in plasma, urine and feces was analyzed using Accelerator mass spectrometry. ASP7991 was rapidly absorbed, metabolized and excreted...
March 7, 2018: Drug Metabolism and Pharmacokinetics
keyword
keyword
28751
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"