keyword
MENU ▼
Read by QxMD icon Read
search

First-in-human phase 1 study

keyword
https://www.readbyqxmd.com/read/29226626/randomized-clinical-study-of-safety-pharmacokinetics-and-pharmacodynamics-of-ripk1-inhibitor-gsk2982772-in-healthy-volunteers
#1
Kathleen Weisel, Nicola E Scott, Debra J Tompson, Bartholomew J Votta, Sujith Madhavan, Kat Povey, Allen Wolstenholme, Monica Simeoni, Todd Rudo, Lauren Richards-Peterson, Tarjinder Sahota, J Gene Wang, John Lich, Joshua Finger, Adeline Verticelli, Michael Reilly, Peter J Gough, Philip A Harris, John Bertin, Mei-Lun Wang
GSK2982772 is a highly selective inhibitor of receptor-interacting protein kinase 1 (RIPK1) being developed to treat chronic inflammatory diseases. This first-in-human study evaluated safety, tolerability, pharmacokinetics (PK), and exploratory pharmacodynamics (PD) of GSK2982772 administered orally to healthy male volunteers. This was a Phase I, randomized, placebo-controlled, double-blind study. In Part A, subjects received single ascending doses of GSK2982772 (0.1-120 mg) or placebo in a crossover design during each of 4 treatment periods...
December 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/29221182/differential-modulation-of-bax-bcl-2-ratio-and-onset-of-caspase-3-7-activation-induced-by-derivatives-of-justicidin-b-in-human-melanoma-cells-a375
#2
Aljawharah Al-Qathama, Simon Gibbons, Jose M Prieto
Diphyllin and its derivatives are well known cytotoxic natural products structurally related to the anti-cancer drug podophyllotoxin. We here study their structure-activity relationship upon human melanoma cells for first time. To this end, human melanoma A375 cells were incubated with Justicidin B and its 4-methoxylated or 4-glycosylated derivatives to evaluate their selective cytotoxicity and study their effects on cell cycle distribution, caspase activation, apoptosis induction using Annexin V-FITC/PI staining, cell morphology and western blot analysis...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29219016/pembrolizumab-in-the-treatment-of-advanced-urothelial-cancer
#3
Kevin T Lundgren, Matthew S Farina, Joaquim Bellmunt
Pembrolizumab is a humanized monoclonal antibody that targets PD-1. In the Phase III trial KEYNOTE-045, pembrolizumab was associated with a significant overall survival benefit when compared with docetaxel, paclitaxel and vinflunine in second line metastatic urothelial carcinoma (UC). Additionally, in the first line, early results from an interim analysis of the Phase II trial Keynote-052 study indicated that pembrolizumab is efficacious for cisplatin-ineligible patients. Based on data from these trials, pembrolizumab was the most recent among the five checkpoint inhibitors tested in UC to be approved by the US FDA in May 2017...
December 2017: Future Oncology
https://www.readbyqxmd.com/read/29218326/study-protocol-a-multi-centre-double-blind-randomised-placebo-controlled-parallel-group-phase-ii-trial-ridd-to-determine-the-efficacy-of-intra-nodular-injection-of-anti-tnf-to-control-disease-progression-in-early-dupuytren-s-disease-with-an-embedded-dose-response
#4
Jagdeep Nanchahal, Catherine Ball, Jennifer Swettenham, Susan Dutton, Vicki Barber, Joanna Black, Bethan Copsey, Melina Dritsaki, Peter Taylor, Alastair Gray, Marc Feldmann, Sarah Lamb
Dupuytren's disease is a common fibrotic condition of the hand affecting 4% of the population and causes the fingers to curl irreversibly into the palm. It has a strong familial tendency, there is no approved treatment for early stage disease, and patients with established digital contractures are most commonly treated by surgery. This is associated with prolonged recovery, and less invasive techniques have high recurrence rates.The myofibroblasts, the cells responsible for the excessive matrix deposition and contraction, are aggregated in nodules...
2017: Wellcome Open Research
https://www.readbyqxmd.com/read/29218117/basis-and-statistical-design-of-the-passive-hiv-1-antibody-mediated-prevention-amp-test-of-concept-efficacy-trials
#5
Peter B Gilbert, Michal Juraska, Allan C deCamp, Shelly Karuna, Srilatha Edupuganti, Nyaradzo Mgodi, Deborah J Donnell, Carter Bentley, Nirupama Sista, Philip Andrew, Abby Isaacs, Yunda Huang, Lily Zhang, Edmund Capparelli, Nidhi Kochar, Jing Wang, Susan H Eshleman, Kenneth H Mayer, Craig A Magaret, John Hural, James G Kublin, Glenda Gray, David C Montefiori, Margarita M Gomez, David N Burns, Julie McElrath, Julie Ledgerwood, Barney S Graham, John R Mascola, Myron Cohen, Lawrence Corey
Background: Anti-HIV-1 broadly neutralizing antibodies (bnAbs) have been developed as potential agents for prevention of HIV-1 infection. The HIV Vaccine Trials Network and the HIV Prevention Trials Network are conducting the Antibody Mediated Prevention (AMP) trials to assess whether, and how, intravenous infusion of the anti-CD4 binding site bnAb, VRC01, prevents HIV-1 infection. These are the first test-of-concept studies to assess HIV-1 bnAb prevention efficacy in humans. Methods: The AMP trials are two parallel phase 2b HIV-1 prevention efficacy trials conducted in two cohorts: 2700 HIV-uninfected men and transgender persons who have sex with men in the United States, Peru, Brazil, and Switzerland; and 1500 HIV-uninfected sexually active women in seven countries in sub-Saharan Africa...
January 2017: Statistical Communications in Infectious Diseases
https://www.readbyqxmd.com/read/29212801/roles-of-high-mobility-group-box-1-and-thrombin-in-murine-pulmonary-fibrosis-and-the-therapeutic-potential-of-thrombomodulin
#6
Takashi Kida, Takahiro Seno, Hidetake Nagahara, Takuya Inoue, Amane Nakabayashi, Yuji Kukida, Kazuki Fujioka, Wataru Fujii, Makoto Wada, Masataka Kohno, Yutaka Kawahito
Cross-talk between inflammation and coagulation plays important roles in acute or subacute progressive pulmonary fibrosis characterized by diffuse alveolar damage. Thrombomodulin is a physiological inhibitor of high-mobility group box 1 (HMGB1) and thrombin, and may be effective for this condition. This study investigated the roles of HMGB1 and thrombin in the pathophysiology of bleomycin-induced pulmonary fibrosis and the efficacy of recombinant human soluble thrombomodulin (rhTM). Pulmonary fibrosis was induced in wild-type C57BL/6 mice by intratracheal instillation of bleomycin...
December 6, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29211690/assessment-of-a-combined-gas-chromatography-mass-spectrometer-sensor-system-for-detecting-biologically-relevant-volatile-compounds
#7
Oliver Gould, Tom Wieczorek, Ben de Lacy Costello, Raj Persad, Norman Ratcliffe
There have been a number of studies in which metal oxide sensors (MOS) have replaced conventional analytical detectors in gas chromatography systems. However, despite the use of these instruments in a range of applications including breath research the sensor responses (i.e. resistance changes w.r.t. concentration of VCs) remain largely unreported. This paper addresses that issue by comparing the response of a metal oxide sensor directly with a mass spectrometer (MS), whereby both detectors are interfaced to the same GC column using an s-swafer...
December 6, 2017: Journal of Breath Research
https://www.readbyqxmd.com/read/29208017/a-multisession-evaluation-of-an-adaptive-competitive-arm-rehabilitation-game
#8
Maja Goršič, Imre Cikajlo, Nika Goljar, Domen Novak
BACKGROUND: People with neurological injuries such as stroke should exercise frequently and intensely to regain their motor abilities, but are generally hindered by lack of motivation. One way to increase motivation in rehabilitation is through competitive exercises, but such exercises have only been tested in single brief sessions and usually did not adapt difficulty to the patient's abilities. METHODS: We designed a competitive arm rehabilitation game for two players that dynamically adapts its difficulty to both players' abilities...
December 6, 2017: Journal of Neuroengineering and Rehabilitation
https://www.readbyqxmd.com/read/29204990/apoptosis-induction-of-colorectal-cancer-cells-htl-9-in-vitro-by-the-transformed-products-of-soybean-isoflavones-by-ganoderma-lucidum
#9
Mei-Lin Cui, Huan-Yi Yang, Guo-Qing He
Soybean isoflavones have been one of the potential preventive candidates for antitumor research in recent years. In this paper, we first studied the transformation of soybean isoflavones with the homogenized slurry of Ganoderma lucidum. The resultant transformed products (TSI) contained (703.21±4.35) mg/g of genistein, with transformed rates of 96.63% and 87.82% of daidzein and genistein, respectively, and TSI also could enrich the bioactive metabolites of G. lucidum. The antitumor effects of TSI on human colorectal cancer cell line HTL-9, human breast cancer cell line MCF-7, and human immortalized gastric epithelial cell line GES-1 were also studied...
2017: Journal of Zhejiang University. Science. B
https://www.readbyqxmd.com/read/29203590/a-first-in-human-phase-1-study-of-subcutaneous-outpatient-recombinant-human-il-15-rhil-15-in-adults-with-advanced-solid-tumors
#10
Jeffrey S Miller, Chihiro Morishima, Douglas G McNeel, Manish R Patel, Holbrook E Kohrt, John A Thompson, Paul M Sondel, Heather A Wakelee, Mary L Disis, Judith C Kaiser, Martin A Cheever, Howard Streicher, Stephen P Creekmore, Thomas A Waldmann, Kevin C Conlon
PURPOSE: Preclinical data established Interleukin-15 as a homeostatic factor and powerful stimulator of NK and CD8+ T cell function, the basis for clinical testing. EXPERIMENTAL DESIGN: A first-in-human outpatient phase I dose escalation trial of subcutaneous (SC) rhIL-15 was conducted in refractory solid tumor cancer patients. Therapy consisted of daily (Monday - Friday) SC injections of rhIL-15 for two consecutive weeks (10 total doses/cycle). Clinical response was assessed by RECIST...
December 4, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29202623/nonclinical-development-of-anx005-a-humanized-anti-c1q-antibody-for-treatment-of-autoimmune-and-neurodegenerative-diseases
#11
Janice A Lansita, Kirsten M Mease, Haiyan Qiu, Ted Yednock, Sethu Sankaranarayanan, Susan Kramer
ANX005 is a humanized immunoglobulin G4 recombinant antibody against C1q that inhibits its function as the initiating molecule of the classical complement cascade. The safety and tolerability of ANX005 are currently being evaluated in a phase I trial in healthy volunteers ( www.clinicaltrials.gov Identifier: NCT03010046). Inhibition of C1q can be applied therapeutically in a broad spectrum of diseases, including acute antibody-mediated autoimmune disease, such as Guillain-Barré syndrome (GBS), and in chronic diseases of the central nervous system involving complement-mediated neurodegeneration, such as Alzheimer's disease (AD)...
January 1, 2017: International Journal of Toxicology
https://www.readbyqxmd.com/read/29190672/first-in-human-phase-i-study-of-isth0036-an-antisense-oligonucleotide-selectively-targeting-transforming-growth-factor-beta-2-tgf-%C3%AE-2-in-subjects-with-open-angle-glaucoma-undergoing-glaucoma-filtration-surgery
#12
Norbert Pfeiffer, Bogomil Voykov, Giulia Renieri, Katharina Bell, Paul Richter, Melanie Weigel, Hagen Thieme, Barbara Wilhelm, Katrin Lorenz, Martin Feindor, Katja Wosikowski, Michel Janicot, Daniela Päckert, Regina Römmich, Carola Mala, Petra Fettes, Eugen Leo
PURPOSE: To evaluate the safety and tolerability of intravitreal ISTH0036, an antisense oligonucleotide selectively targeting transforming growth factor beta 2 (TGF-β2), in patients with primary open angle glaucoma (POAG) undergoing trabeculectomy (TE; glaucoma filtration surgery). METHODS: In this prospective phase I trial glaucoma patients scheduled for TE with mitomycin C (MMC) received a single intravitreal injection of ISTH0036 at the end of surgery in escalating total doses of 6...
2017: PloS One
https://www.readbyqxmd.com/read/29187868/cisplatin-nephrotoxicity-might-have-a-sex-difference-an-analysis-based-on-women-s-sex-hormone-changes
#13
Wei-Yu Chen, Ching-Hsing Hsiao, Yi-Chen Chen, Chung-Han Ho, Jhi-Joung Wang, Chung-Hsi Hsing, Hsien-Yi Wang, Wei-Chih Kan, Chia-Chun Wu
Background: A sex difference in cisplatin-induced nephrotoxicity (CIN) has been reported in human and animal studies. We examined in humans whether it is associated with sex-hormone changes. Methods: In this retrospective nationwide cohort study, we used Taiwan's National Health Insurance Research Database (NHIRD) to identify patients with a history of malignancy and cisplatin treatment. Patients diagnosed with kidney disease before cisplatin treatment and those with sex-organ malignancies were excluded. A diagnosis of kidney disease within 90 days after the first administration of cisplatin was the study outcome...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29178577/dispersive-magnetic-solid-phase-extraction-of-phthalate-esters-from-water-samples-and-human-plasma-based-on-a-nanosorbent-composed-of-mil-101-cr-metal-organic-framework-and-magnetite-nanoparticles-before-their-determination-by-gc-ms
#14
Rosa Dargahi, Homeira Ebrahimzadeh, Ali Akbar Asgharinezhad, Alireza Hashemzadeh, Mostafa M Amini
In this study, a magnetic metal-organic framework was synthesized simply and utilized in the dispersive magnetic solid-phase extraction of five phthalate esters followed by their determination by gas chromatography with mass spectrometry. First, MIL-101(Cr) was prepared hydrothermally in water medium without using highly corrosive hydrofluoric acid, utilizing an autoclave oven heat supply. Afterward, Fe3 O4 nanoparticles were decorated into the matrix of MIL-101(Cr) to fabricate magnetic MIL-101 nanocomposite...
November 26, 2017: Journal of Separation Science
https://www.readbyqxmd.com/read/29173170/first-in-human-phase-1-crispr-gene-editing-cancer-trials-are-we-ready
#15
Francoise Baylis, Marcus McLeod
A prospective first-in-human Phase 1 CRISPR gene editing trial in the United States for patients with melanoma, synovial sarcoma, and multiple myeloma offers hope that gene editing tools may usefully treat human disease. An overarching ethical challenge with first-in-human Phase 1 clinical trials, however, is knowing when it is ethically acceptable to initiate such trials on the basis of safety and efficacy data obtained from pre-clinical studies. If the pre-clinical studies that inform trial design are themselves poorly designed - as a result of which the quality of pre-clinical evidence is deficient - then the ethical requirement of scientific validity for clinical research may not be satisfied...
November 21, 2017: Current Gene Therapy
https://www.readbyqxmd.com/read/29171818/fremanezumab-for-the-preventive-treatment-of-chronic-migraine
#16
Stephen D Silberstein, David W Dodick, Marcelo E Bigal, Paul P Yeung, Peter J Goadsby, Tricia Blankenbiller, Melissa Grozinski-Wolff, Ronghua Yang, Yuju Ma, Ernesto Aycardi
BACKGROUND: Fremanezumab, a humanized monoclonal antibody targeting calcitonin gene-related peptide (CGRP), is being investigated as a preventive treatment for migraine. We compared two fremanezumab dose regimens with placebo for the prevention of chronic migraine. METHODS: In this phase 3 trial, we randomly assigned patients with chronic migraine (defined as headache of any duration or severity on ≥15 days per month and migraine on ≥8 days per month) in a 1:1:1 ratio to receive fremanezumab quarterly (a single dose of 675 mg at baseline and placebo at weeks 4 and 8), fremanezumab monthly (675 mg at baseline and 225 mg at weeks 4 and 8), or matching placebo...
November 30, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/29164599/neurocognition-and-subjective-experience-following-acute-doses-of-the-synthetic-cannabinoid-jwh-018-a-phase-1-placebo-controlled-pilot-study
#17
Eef L Theunissen, Nadia R P W Hutten, Natasha L Mason, Stefan W Toennes, Kim P C Kuypers, Eliza B de Sousa Fernandes Perna, Johannes G Ramaekers
BACKGROUND AND PURPOSE: Synthetic cannabinoids (often sold as Spice or K2) have become a very popular alternative to cannabis due to the easy access and portrayed safety. Controlled studies on the behavioral effects of synthetic cannabinoids are currently lacking, which hampers risk assessments of these compounds. EXPERIMENTAL APPROACH: This is a first attempt to assess the influence of a synthetic cannabinoid, JWH-018, on neurocognition and subjective experience in humans after controlled administration...
November 22, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29163168/atheroregressive-potential-of-the-treatment-with-a-chimeric-monoclonal-antibody-against-sulfated-glycosaminoglycans-on-pre-existing-lesions-in-apolipoprotein-e-deficient-mice
#18
Victor Brito, Katia Mellal, Karina F Zoccal, Yosdel Soto, Liliane Ménard, Roger Sarduy, Lucia H Faccioli, Huy Ong, Ana M Vázquez, Sylvie Marleau
The retention of lipoprotein particles in the intima, in particular to glycosaminoglycan side chains of proteoglycans, is a critical step in atherosclerosis initiation. Administration of chP3R99, a chimeric mouse/human monoclonal antibody inducing an anti-idiotypic network response against glycosaminoglycans was previously shown to prevent atherosclerotic lesion progression, yet its effect in the late-stage progression of lesions remains unknown. This study investigated the effect of chP3R99 at a late stage of disease development in apolipoprotein E-deficient mice and the vascular mechanisms involved...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29163061/cyclodextrins-and-iatrogenic-hearing-loss-new-drugs-with-significant-risk
#19
REVIEW
Mark A Crumling, Kelly A King, R Keith Duncan
Cyclodextrins are a family of cyclic oligosaccharides with widespread usage in medicine, industry and basic sciences owing to their ability to solubilize and stabilize guest compounds. In medicine, cyclodextrins primarily act as a complexing vehicle and consequently serve as powerful drug delivery agents. Recently, uncomplexed cyclodextrins have emerged as potent therapeutic compounds in their own right, based on their ability to sequester and mobilize cellular lipids. In particular, 2-hydroxypropyl-β-cyclodextrin (HPβCD) has garnered attention because of its cholesterol chelating properties, which appear to treat a rare neurodegenerative disorder and to promote atherosclerosis regression related to stroke and heart disease...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29162103/phenolic-compounds-apigenin-hesperidin-and-kaempferol-reduce-in-vitro-lipid-accumulation-in-human-adipocytes
#20
Saioa Gómez-Zorita, Arrate Lasa, Naiara Abendaño, Alfredo Fernández-Quintela, Andrea Mosqueda-Solís, Maria Pilar Garcia-Sobreviela, Jose M Arbonés-Mainar, Maria P Portillo
BACKGROUND: Adipocytes derived from human mesenchymal stem cells (MSCs) are widely used to investigate adipogenesis. Taking into account both the novelty of these MSCs and the scarcity of studies focused on the effects of phenolic compounds, the aim of the present study was to analyze the effect of apigenin, hesperidin and kaempferol on pre-adipocyte and mature adipocytes derived from this type of cells. In addition, the expression of genes involved in TG accumulation was also measured...
November 21, 2017: Journal of Translational Medicine
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"