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randomized, double-bind, phase iii

J Tabernero, R R Hozak, T Yoshino, A L Cohn, R Obermannova, G Bodoky, R Garcia-Carbonero, T-E Ciuleanu, D C Portnoy, J Prausová, K Muro, R W Siegel, R J Konrad, H Ouyang, S A Melemed, D Ferry, F Nasroulah, E Van Cutsem
Background: The phase III RAISE trial (NCT01183780) demonstrated that the vascular endothelial growth factor (VEGF) receptor (VEGFR)-2 binding monoclonal antibody ramucirumab plus 5-fluororuracil, leucovorin, and irinotecan (FOLFIRI) significantly improved overall survival (OS) and progression-free survival (PFS) compared with placebo+FOLFIRI as second-line metastatic colorectal cancer (mCRC) treatment. To identify patients who benefit the most from VEGFR-2 blockade, the RAISE trial design included a prospective and comprehensive biomarker program that assessed the association of biomarkers with ramucirumab efficacy outcomes...
December 7, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Susanne Ostrowitzki, Robert A Lasser, Ernest Dorflinger, Philip Scheltens, Frederik Barkhof, Tania Nikolcheva, Elizabeth Ashford, Sylvie Retout, Carsten Hofmann, Paul Delmar, Gregory Klein, Mirjana Andjelkovic, Bruno Dubois, Mercè Boada, Kaj Blennow, Luca Santarelli, Paulo Fontoura
BACKGROUND: Gantenerumab is a fully human monoclonal antibody that binds aggregated amyloid-β (Aβ) and removes Aβ plaques by Fc receptor-mediated phagocytosis. In the SCarlet RoAD trial, we assessed the efficacy and safety of gantenerumab in prodromal Alzheimer's disease (AD). METHODS: In this randomized, double-blind, placebo-controlled phase III study, we investigated gantenerumab over 2 years. Patients were randomized to gantenerumab 105 mg or 225 mg or placebo every 4 weeks by subcutaneous injection...
December 8, 2017: Alzheimer's Research & Therapy
Willie Earley, Suresh Durgam, Kaifeng Lu, István Laszlovszky, Marc Debelle, John M Kane
Cariprazine, a potent dopamine D3 and D2 receptor partial agonist antipsychotic with preferential binding to D3 receptors, is Food and Drug Administration approved for treating schizophrenia and manic or mixed episodes of bipolar I disorder. A post-hoc safety/tolerability analysis of data from the four acute trials in the cariprazine schizophrenia clinical development program (NCT00404573; NCT00694707; NCT01104766; NCT01104779) was carried out using the overall safety population (all patients who received ≥1 dose of study drug) and modal daily dose subgroups (1...
November 2017: International Clinical Psychopharmacology
Biswadeep Das, Chayna Sarkar, Debasmita Das, Amit Gupta, Arnav Kalra, Shubham Sahni
Telavancin (TD-6424), a semisynthetic lipoglycopeptide vancomycin-derivative, is a novel antimicrobial agent developed by Theravance for overcoming resistant Gram-positive bacterial infections, specifically methicillin-resistant Staphylococcus aureus (MRSA). The US Food and Drug Administration (USFDA) had approved telavancin in 2009 for the treatment of complicated skin and skin structure infections (cSSSIs) caused by Gram-positive bacteria, including MRSA (S. aureus, Streptococcus agalactiae, Streptococcus pyogenes, Streptococcus anginosus group, or Enterococcus faecalis)...
March 2017: Therapeutic Advances in Infectious Disease
Andrew J Cutler, Suresh Durgam, Yao Wang, Raffaele Migliore, Kaifeng Lu, István Laszlovszky, György Németh
OBJECTIVE: Cariprazine, a dopamine D3/D2 partial agonist atypical antipsychotic with preferential binding to D3 receptors, is approved for the treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder. The efficacy and safety of cariprazine was established in three randomized, double-blind, placebo-controlled, 6-week trials in patients with acute exacerbation of schizophrenia. This 53-week study evaluated the long-term safety and tolerability of cariprazine in patients with schizophrenia...
May 8, 2017: CNS Spectrums
Johanna C Bendell, Howard Hochster, Lowell L Hart, Irfan Firdaus, Joseph R Mace, Joshua J McFarlane, Mark Kozloff, Daniel Catenacci, Jessie J Hsu, Stephen P Hack, David S Shames, See-Chun Phan, Hartmut Koeppen, Allen L Cohn
BACKGROUND: Dysregulated hepatocyte growth factor/mesenchymal-epithelial transition (MET) signaling is associated with poor prognosis and resistance to vascular endothelial growth factor inhibition in metastatic colorectal cancer (mCRC). We report outcomes from a double-blind, multicenter phase II trial of the MET inhibitor onartuzumab in combination with mFOLFOX-6 and bevacizumab for mCRC (GO27827; NCT01418222). MATERIALS AND METHODS: Patients were randomized 1:1 to receive onartuzumab (10 mg/kg intravenously [IV]) or placebo plus mFOLFOX-6 and bevacizumab (5 mg/kg IV)...
March 2017: Oncologist
Tomasz M Beer, Eugene D Kwon, Charles G Drake, Karim Fizazi, Christopher Logothetis, Gwenaelle Gravis, Vinod Ganju, Jonathan Polikoff, Fred Saad, Piotr Humanski, Josep M Piulats, Pablo Gonzalez Mella, Siobhan S Ng, Dirk Jaeger, Francis X Parnis, Fabio A Franke, Javier Puente, Roman Carvajal, Lisa Sengeløv, M Brent McHenry, Arvind Varma, Alfonsus J van den Eertwegh, Winald Gerritsen
Purpose Ipilimumab increases antitumor T-cell responses by binding to cytotoxic T-lymphocyte antigen 4. We evaluated treatment with ipilimumab in asymptomatic or minimally symptomatic patients with chemotherapy-naive metastatic castration-resistant prostate cancer without visceral metastases. Patients and Methods In this multicenter, double-blind, phase III trial, patients were randomly assigned (2:1) to ipilimumab 10 mg/kg or placebo every 3 weeks for up to four doses. Ipilimumab 10 mg/kg or placebo maintenance therapy was administered to nonprogressing patients every 3 months...
January 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Nobuko Yamaguchi, Sonoko Misawa, Yasunori Sato, Kengo Nagashima, Kanako Katayama, Yukari Sekiguchi, Yuta Iwai, Hiroshi Amino, Tomoki Suichi, Takanori Yokota, Yoichiro Nishida, Nobuo Kohara, Koichi Hirata, Kazutoshi Nishiyama, Ichiro Yabe, Ken-Ichi Kaida, Norihiro Suzuki, Hiroyuki Nodera, Shoji Tsuji, Haruki Koike, Jun-Ichi Kira, Hideki Hanaoka, Susumu Kusunoki, Satoshi Kuwabara
BACKGROUND: Guillain-Barré syndrome (GBS) is an immune-mediated neuropathy that causes acute flaccid paralysis. Immunoglobulin and plasma exchange are established treatments for GBS; however, a substantial number of patients, particularly those with severe disease, have poor recovery and residual deficits. Recent studies suggest that complement activation plays a pivotal role in GBS-associated axonal degeneration, and eculizumab is a humanized monoclonal antibody that specifically binds to complement component 5 and potently inhibits complement activation...
November 7, 2016: JMIR Research Protocols
Antoinette de Waha, Sigrid Sandner, Moritz von Scheidt, Andreas Boening, Katharina Koch-Buettner, Dieter Hammel, Rainer Hambrecht, Bernhard C Danner, Friedrich A Schöndube, Gerold Goerlach, Theodor Fischlein, Michael Schmoeckel, Martin Oberhoffer, Rainer Schulz, Thomas Walther, Tibor Ziegelhöffer, Christoph Knosalla, Felix Schönrath, Friedhelm Beyersdorf, Matthias Siepe, Tim Attmann, Martin Misfeld, Friedrich-Wilhelm Mohr, Hans-Hinrich Sievers, Alexander Joost, Leon M Putman, Günther Laufer, Christian Hamm, Uwe Zeymer, Adnan Kastrati, Peter W Radke, Rüdiger Lange, Jochen Cremer, Heribert Schunkert
BACKGROUND: For patients with coronary artery disease undergoing coronary bypass surgery, acetylsalicylic acid (ASA) currently represents the gold standard of antiplatelet treatment. However, adverse cardiovascular event rates in the first year after coronary artery bypass grafting (CABG) still exceed 10%. Graft failure, which is predominantly mediated by platelet aggregation, has been identified as a major contributing factor in this context. Therefore, intensified platelet inhibition is likely to be beneficial...
September 2016: American Heart Journal
Kristin E Linder, Michelle A Krawczynski, Dayne Laskey
Hyperkalemia is a potentially life-threatening electrolyte abnormality that may be caused by select medications, underlying organ dysfunction, or alterations in potassium homeostasis. Treatment for this condition has remained largely unchanged since the release of sodium polystyrene sulfonate (SPS) in 1958. Despite its widespread use, the safety and efficacy of SPS remains controversial. Two novel potassium-binding resins have emerged in recent years. Patiromer was the first of these to receive U.S. Food and Drug Administration approval for the treatment of hyperkalemia in October 2015...
August 2016: Pharmacotherapy
Ignace Vergote, Deborah Armstrong, Giovanni Scambia, Michael Teneriello, Jalid Sehouli, Charles Schweizer, Susan C Weil, Aristotelis Bamias, Keiichi Fujiwara, Kazunori Ochiai, Christopher Poole, Vera Gorbunova, Wenquan Wang, Daniel O'Shannessy, Thomas J Herzog
PURPOSE: Farletuzumab is a humanized monoclonal antibody that binds to folate receptor-α, which is highly expressed in ovarian carcinoma and largely absent from normal tissue. Farletuzumab was investigated in a double-blind, randomized phase III study in platinum-sensitive ovarian cancer. PATIENTS AND METHODS: Eligible patients had first recurrent ovarian cancer 6-24 months following completion of platinum-taxane chemotherapy. All patients received carboplatin plus paclitaxel or docetaxel (for six cycles combined with randomly assigned test products in a 1:1:1 ratio: farletuzumab 1...
July 1, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Steven E Nissen, Ricardo E Dent-Acosta, Robert S Rosenson, Erik Stroes, Naveed Sattar, David Preiss, G B John Mancini, Christie M Ballantyne, Alberico Catapano, Ioanna Gouni-Berthold, Evan A Stein, Allen Xue, Scott M Wasserman, Rob Scott, Paul D Thompson
Statins are the accepted standard for lowering low-density lipoprotein cholesterol (LDL-C). However, 5% to 10% of statin-treated patients report intolerance, mostly due to muscle-related adverse effects. Challenges exist to objective identification of statin-intolerant patients. Evolocumab is a monoclonal antibody that binds proprotein convertase subtilisin/kexin type 9 (PCSK9), resulting in marked LDL-C reduction. We report the design of Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin-Intolerant Subjects 3 (GAUSS-3), a phase 3, multicenter, randomized, double-blind, ezetimibe-controlled study to compare effectiveness of 24 weeks of evolocumab 420 mg monthly vs ezetimibe 10 mg daily in hypercholesterolemic patients unable to tolerate an effective statin dose...
March 2016: Clinical Cardiology
Roger A Rodby, Kausik Umanath, Robert Niecestro, T Christopher Bond, Mohammed Sika, Julia Lewis, Jamie P Dwyer
BACKGROUND: Patients with end-stage renal disease (ESRD) require phosphate binders for hyperphosphatemia and erythropoiesis-stimulating agents (ESAs) and intravenous (i.v.) iron for anemia. Ferric citrate (FC) is a novel, iron-based phosphate binder that increases iron stores and decreases i.v. iron and ESA usage while maintaining hemoglobin levels, and may decrease the cost of ESRD care. The study objectives were to (1) quantify differences in ESA and i.v. iron usage among ESRD patients receiving FC compared with active control (AC) (sevelamer carbonate and/or calcium acetate) on the basis of data from a 52-week phase III clinical trial and (2) standardize trial data to the general United States (US) ESRD population and calculate the potential impact of FC on ESRD cost/patient/year in the USA...
September 2015: Drugs in R&D
Aurelija Jucaite, Per Svenningsson, Juha O Rinne, Zsolt Cselényi, Katarina Varnäs, Peter Johnström, Nahid Amini, Anna Kirjavainen, Semi Helin, Margaret Minkwitz, Alan R Kugler, Joel A Posener, Samantha Budd, Christer Halldin, Andrea Varrone, Lars Farde
Impaired mitochondrial function, oxidative stress and formation of excessive levels of reactive oxygen species play a key role in neurodegeneration in Parkinson's disease. Myeloperoxidase is a reactive oxygen generating enzyme and is expressed by microglia. The novel compound AZD3241 is a selective and irreversible inhibitor of myeloperoxidase. The hypothesized mechanism of action of AZD3241 involves reduction of oxidative stress leading to reduction of sustained neuroinflammation. The purpose of this phase 2a randomized placebo controlled multicentre positron emission tomography study was to examine the effect of 8 weeks treatment with AZD3241 on microglia in patients with Parkinson's disease...
September 2015: Brain: a Journal of Neurology
John M Kane, Stephen Zukin, Yao Wang, Kaifeng Lu, Adam Ruth, Krisztián Nagy, István Laszlovszky, Suresh Durgam
This phase III study evaluated the efficacy and safety of cariprazine, a dopamine D3 and D2 receptor partial agonist with preferential binding to D3 receptors, in patients with acute exacerbation of schizophrenia. Patients were randomized to 6-week double-blind treatment with placebo, cariprazine 3 to 6 mg/d, or cariprazine 6 to 9 mg/d. Primary and secondary efficacy: change from baseline to week 6 in Positive and Negative Syndrome Scale total and Clinical Global Impressions-Severity scores, respectively, analyzed using a mixed-effects model for repeated measures adjusting for multiple comparisons...
August 2015: Journal of Clinical Psychopharmacology
K Papp, D Thaçi, K Reich, E Riedl, R G Langley, J G Krueger, A B Gottlieb, H Nakagawa, E P Bowman, A Mehta, Q Li, Y Zhou, R Shames
BACKGROUND: Tildrakizumab is a high-affinity, humanized, IgG1/κ, anti-interleukin (IL)-23p19 monoclonal antibody that does not bind human IL-12 or p40 is being developed for the treatment of chronic plaque psoriasis. OBJECTIVES: To evaluate the safety and efficacy of subcutaneous tildrakizumab in patients with moderate-to-severe chronic plaque psoriasis. METHODS: A three-part, randomized, double-blind, phase IIb trial was conducted in 355 adults with chronic plaque psoriasis...
October 2015: British Journal of Dermatology
Antonio Laurenza, Haichen Yang, Betsy Williams, Sharon Zhou, Jim Ferry
OBJECTIVE: The liver plays a major role in the metabolism and elimination of many antiepileptic drugs (AEDs), including perampanel. Some of the metabolites identified for perampanel are likely formed via reactive intermediates, which have the potential to covalently bind to protein and cause idiosyncratic toxicities, including hepatotoxicity. The approved AED perampanel is a selective, noncompetitive AMPA receptor antagonist. The safety and tolerability of perampanel have been well documented in 3 double-blind, randomized, placebo-controlled, phase III studies...
July 2015: Epilepsy Research
Ana María Hernández, Ana María Vázquez
Racotumomab-alum vaccine is an anti-idiotypic vaccine able to mimic the tumor-associated antigen NeuGcGM3. Different Phase I clinical trials and compassionate use studies demonstrated its low toxicity and capacity to induce a strong anti-NeuGcGM3 response, able to bind and directly kill tumor cells expressing the antigen. A Phase II/III randomized double-blind clinical trial in advanced non-small cell lung cancer patients showed a significant improvement in overall survival and progression-free survival for racotumomab-alum versus placebo...
January 2015: Expert Review of Vaccines
Hidetomo Nakamoto, Toshiro Fujita, Hideki Origasa, Masanao Isono, Hajimu Kurumatani, Kiyonobu Okada, Hiroyuki Kanoh, Takashi Kiriyama, Shunsuke Yamada
BACKGROUND: Chronic kidney disease (CKD) is public health concern even in Asian countries. TRK-100STP, a sustained release tablet of an orally-active prostacyclin analogue, beraprost sodium, is suggested to suppress worsening of some parameters of renal filtration function, containing in slope of 1/serum creatinine (1/SCr) vs. time in a phase II clinical trial. METHODS/DESIGN: We describe the design of the phase IIb/III trial of TRK-100STP, CASSIOPEIR (CRF Asian Study with Oral PGI2 derivative for Evaluating Improvement of Renal function) conducted in approximately 160 centers in China, Hong Kong, Japan, Malaysia, Republic of Korea, Taiwan, and Thailand...
September 19, 2014: BMC Nephrology
John R Mackey, Manuel Ramos-Vazquez, Oleg Lipatov, Nicole McCarthy, Dmitriy Krasnozhon, Vladimir Semiglazov, Alexey Manikhas, Karen A Gelmon, Gottfried E Konecny, Marc Webster, Roberto Hegg, Sunil Verma, Vera Gorbunova, Dany Abi Gerges, Francois Thireau, Helena Fung, Lorinda Simms, Marc Buyse, Ayman Ibrahim, Miguel Martin
PURPOSE: Currently, antiangiogenic strategies in metastatic breast cancer have demonstrated modest improvements in progression-free survival (PFS) but not improved quality or duration of survival, warranting evaluation of new agents in a placebo-controlled setting. Ramucirumab is a human immunoglobulin G1 antibody that binds vascular endothelial growth factor receptor-2 and blocks ligand-stimulated activation. The ROSE/TRIO-012 trial evaluated ramucirumab with docetaxel in unresectable, locally recurrent, or metastatic breast cancer...
January 10, 2015: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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