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https://www.readbyqxmd.com/read/28323965/long-acting-ctp-modified-hgh-mod-4023-results-of-a-safety-and-dose-finding-study-in-ghd-children
#1
Nataliya Zelinska, Violeta Iotova, Julia Skorodok, Oleg Malievsky, Valentina Peterkova, Lubov Samsonova, Ron G Rosenfeld, Zvi Zadik, Michal Jaron-Mendelson, Ronit Koren, Leanne Amitzi, Dmitri Raduk, Oren Hershkovitz, Gili Hart
Context: Daily injections are required for growth hormone replacement therapy, which may cause low compliance as a result of inconvenience and distress in patients. Objective: CTP-modified human growth hormone (MOD-4023) is developed for once-a-week dosing regimen in GH-deficient (GHD) adults and children. The present trial was a safety and dose-finding study for weekly MOD-4023 in GHD children. Design: a multi-center, open-label, randomized, controlled Phase 2 study in children with GHD, evaluating the safety, tolerability, PK/PD and efficacy of 3 different weekly MOD-4023 doses, compared to daily r-hGH...
January 31, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28323838/bupropion-for-the-treatment-of-apathy-in-huntington-s-disease-a-multicenter-randomised-double-blind-placebo-controlled-prospective-crossover-trial
#2
Harald Gelderblom, Torsten Wüstenberg, Tim McLean, Lisanne Mütze, Wilhelm Fischer, Carsten Saft, Rainer Hoffmann, Sigurd Süssmuth, Peter Schlattmann, Erik van Duijn, Bernhard Landwehrmeyer, Josef Priller
OBJECTIVE: To evaluate the efficacy and safety of bupropion in the treatment of apathy in Huntington's disease (HD). METHODS: In this phase 2b multicentre, double-blind, placebo-controlled crossover trial, individuals with HD and clinical signs of apathy according to the Structured Clinical Interview for Apathy-Dementia (SCIA-D), but not depression (n = 40) were randomized to receive either bupropion 150/300mg or placebo daily for 10 weeks. The primary outcome parameter was a significant change of the Apathy Evaluation Scale (AES) score after ten weeks of treatment as judged by an informant (AES-I) living in close proximity with the study participant...
2017: PloS One
https://www.readbyqxmd.com/read/28323515/a-nested-group-sequential-framework-for-regional-evaluation-in-global-drug-development-program
#3
William Wang, Zhiwei Jiang, Jingjun Qiu, Jielai Xia, Xiang Guo
The primary objective of a multiregional clinical trial (MRCT) is to assess the efficacy of all participating regions and evaluate the probability of applying the overall results to a specific region. The consistency assessment of the target region with the overall results is the most common way of evaluating the efficacy in a specific region. Recently, Huang et al. (2012) proposed an additional trial in the target region to an MRCT to evaluate the efficacy in the target ethnic (TE) population under the framework of simultaneous global drug development program (SGDDP)...
February 10, 2017: Journal of Biopharmaceutical Statistics
https://www.readbyqxmd.com/read/28319848/treatment-of-premenstrual-dysphoric-disorder-with-the-gabaa-receptor-modulating-steroid-antagonist-sepranolone-uc1010-a-randomized-controlled-trial
#4
Marie Bixo, Karin Ekberg, Inger Sundström Poromaa, Angelica Lindén Hirschberg, Aino Fianu Jonasson, Lotta Andréen, Erika Timby, Marianne Wulff, Agneta Ehrenborg, Torbjörn Bäckström
CONTEXT: Allopregnanolone is a metabolite from progesterone and a positive modulator of the GABAA receptor. This endogenous steroid may induce negative mood in sensitive women when present in serum levels comparable to the premenstrual phase. Its endogenous isomer, isoallopregnanolone, has been shown to antagonize allopregnanolone effects in experimental animal and human models. OBJECTIVE: The objective was to test whether inhibition of allopregnanolone by treatment with the GABAA modulating steroid antagonist (GAMSA) Sepranolone (UC1010) during the premenstrual phase could reduce symptoms of the premenstrual dysphoric disorder (PMDD)...
March 1, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28319789/group-schema-therapy-for-personality-disorders-a-pilot-study-for-implementation-in-acute-psychiatric-in-patient-settings
#5
Igor Nenadić, Sina Lamberth, Neele Reiss
Group schema therapy (GST) has been proposed as a novel long-term treatment programme for borderline and cluster C personality disorders. We implemented a short-term GST programme (12-15 sessions, based on the manual by Farrell and Shaw (2012), including both cognitive / behavioural and experiential interventions for in-patients (n=9) with either borderline or cluster C personality disorders (and axis I co-morbidities) treated in a (sub)acute psychiatric in-patient setting. We evaluated pre- and post-treatment self-report of maladaptive and adaptive schema modes (using the SMI) and early maladaptive schemas (YSQ-3), as well as overall symptom severity (brief symptom check list, BSCL-53-S), patient satisfaction (ZUF-8) and group climate and coherence (GCQ-S)...
February 3, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/28317328/evaluating-dosage-optimality-for-tofacitinib-an-oral-janus-kinase-inhibitor-in-plaque-psoriasis-and-the-influence-of-body-weight
#6
M M Hutmacher, K Papp, S Krishnaswami, K Ito, H Tan, R Wolk, H Valdez, C Mebus, S T Rottinghaus, P Gupta
Tofacitinib is an oral Janus kinase inhibitor. An integrated analysis was conducted to evaluate dosage optimality for tofacitinib in patients with moderate-to-severe plaque psoriasis and the impact of body weight on optimality in this patient population. Data were pooled from one phase IIb trial (2, 5, and 15 mg twice daily (b.i.d.)) and four phase III trials (5 and 10 mg b.i.d.). A longitudinal exposure-response model for Psoriasis Area and Severity Index (PASI) improvement (percent change from baseline) was established...
March 20, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28317088/phase-i-trial-of-the-oral-smoothened-inhibitor-sonidegib-in-combination-with-paclitaxel-in-patients-with-advanced-solid-tumors
#7
A Stathis, D Hess, R von Moos, K Homicsko, G Griguolo, M Joerger, M Mark, C J Ackermann, S Allegrini, C V Catapano, A Xyrafas, M Enoiu, S Berardi, P Gargiulo, C Sessa
Purpose To establish a recommended phase II dose (RP2D) for the oral smoothened inhibitor sonidegib in combination with paclitaxel; secondary objectives include evaluation of safety, tolerability, markers of Hedgehog (Hh) signaling and preliminary antitumor activity. Methods Patients with advanced solid tumors were enrolled in cohorts of escalating sonidegib dose levels (400mg, 600mg and 800mg orally, once daily on days 1-28) in combination with paclitaxel 80 mg/m(2) on days 1, 8 and 15 in 4-weekly cycles. Dose-limiting toxicities (DLTs) were assessed using CTCAE v4...
March 20, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28315722/risk-mitigation-for-children-exposed-to-drugs-during-gestation-a-critical-role-for-animal-preclinical-behavioral-testing
#8
REVIEW
Irving Zucker
Many drugs with unknown safety profiles are administered to pregnant women, placing their offspring at risk. I assessed whether behavioral outcomes for children exposed during gestation to antidepressants, anxiolytics, anti-seizure, anti-nausea and sedative medications can be predicted by more extensive animal studies than are part of the FDA approval process. Human plus rodent data were available for only 8 of 33 CNS-active drugs examined. Similar behavioral and cognitive deficits, including autism and ADHD emerged in human offspring and in animal models of these disorders after exposure to fluoxetine, valproic acid, carbamazepine, phenytoin, phenobarbital, acetaminophen and ibuprofen...
March 15, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28314841/academic-cancer-center-phase-i-program-development
#9
Arthur E Frankel, Keith T Flaherty, George J Weiner, Robert Chen, Nilofer S Azad, Michael J Pishvaian, John A Thompson, Matthew H Taylor, Daruka Mahadevan, A Craig Lockhart, Ulka N Vaishampayan, Jordan D Berlin, David C Smith, John Sarantopoulos, Matthew Riese, Mansoor N Saleh, Chul Ahn, Eugene P Frenkel
Multiple factors critical to the effectiveness of academic phase I cancer programs were assessed among 16 academic centers in the U.S. Successful cancer centers were defined as having broad phase I and I/II clinical trial portfolios, multiple investigator-initiated studies, and correlative science. The most significant elements were institutional philanthropic support, experienced clinical research managers, robust institutional basic research, institutional administrative efforts to reduce bureaucratic regulatory delays, phase I navigators to inform patients and physicians of new studies, and a large cancer center patient base...
March 17, 2017: Oncologist
https://www.readbyqxmd.com/read/28314699/safety-and-tolerability-of-idelalisib-lenalidomide-and-rituximab-in-relapsed-and-refractory-lymphoma-the-alliance-for-clinical-trials-in-oncology-a051201-and-a051202-phase-1-trials
#10
Sonali M Smith, Brandelyn N Pitcher, Sin-Ho Jung, Nancy L Bartlett, Nina Wagner-Johnston, Steven I Park, Kristy L Richards, Amanda F Cashen, Anthony Jaslowski, Scott E Smith, Bruce D Cheson, Eric Hsi, John P Leonard
BACKGROUND: A new generation of biological and targeted agents might potentially replace traditional cytotoxic agents in lymphoma. Lenalidomide plus rituximab was felt to be a safe and promising backbone based on available data. Idelalisib is an oral phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor that has promising activity as a monotherapy in refractory indolent lymphomas. The primary objective of these two trials was to determine the maximum tolerated dose of lenalidomide in combination with rituximab and idelalisib in relapsed follicular and mantle cell lymphoma...
March 14, 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28306727/biodistribution-and-pet-imaging-of-pharmacokinetics-of-manganese-in-mice-using-manganese-52
#11
A Lake Wooten, Tolulope A Aweda, Benjamin C Lewis, Rebecca B Gross, Suzanne E Lapi
Manganese is essential to life, and humans typically absorb sufficient quantities of this element from a normal healthy diet; however, chronic, elevated ingestion or inhalation of manganese can be neurotoxic, potentially leading to manganism. Although imaging of large amounts of accumulated Mn(II) is possible by MRI, quantitative measurement of the biodistribution of manganese, particularly at the trace level, can be challenging. In this study, we produced the positron-emitting radionuclide 52Mn (t1/2 = 5.6 d) by proton bombardment (Ep<15 MeV) of chromium metal, followed by solid-phase isolation by cation-exchange chromatography...
2017: PloS One
https://www.readbyqxmd.com/read/28303593/sb-9200-a-novel-agonist-of-innate-immunity-shows-potent-antiviral-activity-against-resistant-hcv-variants
#12
Meleri Jones, Morven E Cunningham, Peter Wing, Sampath DeSilva, Rupa Challa, Anjaneyulu Sheri, Seetharamaiyer Padmanabhan, Radhakrishnan P Iyer, Brent E Korba, Nezam Afdhal, Graham R Foster
SB 9200 is a novel, first-in-class oral modulator of innate immunity that is believed to act via the activation of the RIG-I and NOD2 pathways. SB 9200 has broad-spectrum antiviral activity against RNA viruses including hepatitis C virus (HCV), norovirus, respiratory syncytial virus and influenza and has demonstrated activity against hepatitis B virus (HBV) in vitro and in vivo. In phase I clinical trials in chronically infected HCV patients, SB 9200 has been shown to reduce HCV RNA by up to 1.9 log10 . Here, we demonstrate the antiviral activity of SB 9200 against a HCV replicon system and patient derived virus...
March 17, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28299955/niraparib-for-the-treatment-of-ovarian-cancer
#13
Yada Kanjanapan, Stephanie Lheureux, Amit M Oza
Introduction Poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors are being developed in maintenance and recurrence treatment settings in ovarian cancer. They inhibit single-stranded DNA repair, inducing synthetic lethality in cells with underlying homologous recombination deficiency (HRD). Marked responses are seen in ovarian cancers with breast cancer gene 1 (BRCA1) or 2 (BRCA2) mutation, although up to 50% of high-grade serous ovarian cancers (HGSOC) have HRD may also benefit. Areas covered This review focuses on niraparib (oral PARP I and II inhibitor), its clinical testing in ovarian cancer, including the Myriad MyChoice HRD test as a potential companion diagnostic...
March 16, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28299378/factors-associated-with-acute-phase-response-of-bisphosphonate-na%C3%A3-ve-or-pretreated-women-with-osteoporosis-receiving-an-intravenous-first-dose-of-zoledronate-or-ibandronate
#14
A W Popp, R Senn, I Curkovic, C Senn, H Buffat, P F Popp, K Lippuner
A first intravenous dose of bisphosphonates may be associated with an acute-phase response (APR). In bisphosphonate-naïve women with postmenopausal osteoporosis, the characteristics and frequency of APR may differ by compound. Prior bisphosphonate exposure was predictive of APR risk and severity. INTRODUCTION: Intravenous (IV) administration of bisphosphonates (BP), such as zoledronate (ZOL) and ibandronate (IBN), may be associated with an APR. The characteristics of APR may differ by compound...
March 15, 2017: Osteoporosis International
https://www.readbyqxmd.com/read/28297569/administration-of-adult-human-bone-marrow-derived-cultured-pooled-allogeneic-mesenchymal-stromal-cells-in-critical-limb-ischemia-due-to-buerger-s-disease-phase-ii-study-report-suggests-clinical-efficacy
#15
Pawan K Gupta, Murali Krishna, Anoop Chullikana, Sanjay Desai, Rajkumar Murugesan, Santanu Dutta, Uday Sarkar, Radhakrishnan Raju, Anita Dhar, Rajiv Parakh, Lakshmanan Jeyaseelan, Pachaiyappan Viswanathan, Prasanth Kulapurathu Vellotare, Raviraja N Seetharam, Charan Thej, Mathiyazhagan Rengasamy, Sudha Balasubramanian, Anish S Majumdar
Critical limb ischemia (CLI) due to Buerger's disease is a major unmet medical need with a high incidence of morbidity. This phase II, prospective, nonrandomized, open-label, multicentric, dose-ranging study was conducted to assess the efficacy and safety of i.m. injection of adult human bone marrow-derived, cultured, pooled, allogeneic mesenchymal stromal cells (BMMSC) in CLI due to Buerger's disease. Patients were allocated to three groups: 1 and 2 million cells/kg body weight (36 patients each) and standard of care (SOC) (18 patients)...
March 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28297568/safety-studies-for-use-of-adipose-tissue-derived-mesenchymal-stromal-stem-cells-in-a-rabbit-model-for-osteoarthritis-to-support-a-phase-i-clinical-trial
#16
Scott M Riester, Janet M Denbeigh, Yang Lin, Dakota L Jones, Tristan de Mooij, Eric A Lewallen, Hai Nie, Christopher R Paradise, Darcie J Radel, Amel Dudakovic, Emily T Camilleri, Dirk R Larson, Wenchun Qu, Aaron J Krych, Matthew A Frick, Hee-Jeong Im, Allan B Dietz, Jay Smith, Andre J van Wijnen
Adipose-derived mesenchymal stem cells (AMSCs) offer potential as a therapeutic option for clinical applications in musculoskeletal regenerative medicine because of their immunomodulatory functions and capacity for trilineage differentiation. In preparation for a phase I clinical trial using AMSCs to treat patients with osteoarthritis, we carried out preclinical studies to assess the safety of human AMSCs within the intra-articular joint space. Culture-expanded human AMSCs grown in human platelet-lysate were delivered via intra-articular injections into normal healthy rabbit knees and knees at risk for the development of osteoarthritis after bilateral medial anterior hemimeniscectomy...
March 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28295903/feasibility-of-intraoperative-breast-mri-and-the-role-of-prone-versus-supine-positioning-in-surgical-planning-for-breast-conserving-surgery
#17
Melissa A Mallory, Yasuaki Sagara, Fatih Aydogan, Stephen DeSantis, Jagadeesan Jayender, Diana Caragacianu, Eva Gombos, Kirby G Vosburgh, Ferenc A Jolesz, Mehra Golshan
We assessed the feasibility of supine intraoperative MRI (iMRI) during breast-conserving surgery (BCS), enrolling 15 patients in our phase I trial between 2012 and 2014. Patients received diagnostic prone MRI, BCS, pre-excisional supine iMRI, and postexcisional supine iMRI. Feasibility was assessed based on safety, sterility, duration, and image-quality. Twelve patients completed the study; mean duration = 114 minutes; all images were adequate; no complications, safety, or sterility issues were encountered...
March 10, 2017: Breast Journal
https://www.readbyqxmd.com/read/28295513/toxicity-dependent-feasibility-bounds-for-the-escalation-with-overdose-control-approach-in-phase-i-cancer-trials
#18
Graham M Wheeler, Michael J Sweeting, Adrian P Mander
Phase I trials of anti-cancer therapies aim to identify a maximum tolerated dose (MTD), defined as the dose that causes unacceptable toxicity in a target proportion of patients. Both rule-based and model-based methods have been proposed for MTD recommendation. The escalation with overdose control (EWOC) approach is a model-based design where the dose assigned to the next patient is one that, given all available data, has a posterior probability of exceeding the MTD equal to a pre-specified value known as the feasibility bound...
March 15, 2017: Statistics in Medicine
https://www.readbyqxmd.com/read/28294526/phase-1-dose-escalating-study-of-the-safety-pharmacokinetics-and-pharmacodynamics-of-activated-factor-x-i-16l
#19
Dana Parsons-Rich, Fei Hua, Gang Li, Constantino Kantaridis, Debra D Pittman, Steven Arkin
BACKGROUND: FXa(I16L) (PF-05230907) is a zymogen-like variant of activated coagulation factor X (FXa). It exhibits enhanced resistance to inactivation by endogenous inhibitors compared with wild-type FXa and restores hemostatic activity in nonclinical models of various bleeding conditions. OBJECTIVES: To evaluate the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of FXa(I16L) , a phase 1, first-in-human, dose escalation clinical trial in healthy adult volunteers was conducted METHODS: Participants were assigned to 1 of 6 ascending single-dose cohorts (0...
March 14, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28293909/allergen-immunotherapy-clinical-trial-outcomes-and-design-working-toward-harmonization-of-methods-and-principles
#20
REVIEW
Harold S Nelson, Moises A Calderon, David I Bernstein, Thomas B Casale, Stephen R Durham, Jens S Andersen, Robert Esch, Linda S Cox, Hendrik Nolte
Progress has been made in the harmonization of efficacy and safety outcome measures for allergen immunotherapy (AIT) trials, but unresolved issues still remain. Furthermore, there are discrepancies in recommendations from professional medical societies and regulatory agencies regarding requirements for AIT trials. In this article, we reviewed published recommendations and current data from recent clinical trials, as well as the criteria applied by regulatory authorities for approval of AIT products, to provide updated considerations for conducting phase 3 AIT trials...
March 2017: Current Allergy and Asthma Reports
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