scholarly journals Safety and tolerability of eptinezumab in patients with migraine: a pooled analysis of 5 clinical trials

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Timothy R. Smith ◽  
Egilius L. H. Spierings ◽  
Roger Cady ◽  
Joe Hirman ◽  
Barbara Schaeffler ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Placebo Group ◽  
Large Scale ◽  
Integrated Analysis ◽  
Tolerability Profile ◽  
Hypersensitivity Reactions ◽  
Infusion Site ◽  
Link Type ◽  
Percentage Points ◽  
Hot Flush

Abstract Background The humanized anti-CGRP monoclonal antibody eptinezumab has been evaluated in five large-scale clinical trials conducted in patients with migraine. This integrated analysis was conducted to evaluate the comprehensive safety and tolerability of eptinezumab in patients with migraine across these studies. Methods Data were pooled from four randomized, double-blind, placebo-controlled studies and the first year of one open-label study. Results The pooled population comprised 2867 adults with migraine: eptinezumab, n = 2076 (4797 infusions); placebo, n = 791 (1675 infusions). A total of 1137/2076 (54.8%) patients who received eptinezumab and 414/791 (52.3%) patients who received placebo experienced ≥1 treatment-emergent adverse event (TEAE); rates were similar across eptinezumab dose groups (10–1000 mg). For most patients with TEAEs, the events were mild or moderate in severity and considered unrelated to study drug by the investigators. Thirty infusion-site AEs occurred in 27/2076 (1.3%) patients who received eptinezumab and 7 in 7/791 (0.9%) patients who received placebo. Infusion-site AEs led to infusion interruption in 19/2076 (0.9%) and 5/791 (0.6%) patients in the eptinezumab and placebo groups, respectively. Nasopharyngitis occurred in ≥2% of patients in the eptinezumab 300-mg group and with an incidence of at least 2 percentage points greater than in the placebo group; however, in most patients (eptinezumab, 139/140; placebo 40/41), its occurrence was considered not related to study treatment. Adverse events coded to hypersensitivity occurred for 23/2076 (1.1%) patients treated with eptinezumab and no patients in the placebo group. If additional TEAE terms that could indicate hypersensitivity are considered (e.g., urticaria, flushing/hot flush, rash, and pruritus), hypersensitivity reactions in the two pivotal placebo-controlled phase 3 studies occurred in ≥2% of patients in the eptinezumab 100-mg and 300-mg groups, and the incidence was at least 2 percentage points greater in either of these groups than in the placebo group. Most hypersensitivity reactions were not serious and resolved with standard medical treatment or observation without treatment, usually within 1 day. Conclusions In adults with migraine, the intravenous administration of eptinezumab every 12 weeks demonstrated a favorable safety and tolerability profile. Trial registration ClinicalTrials.gov (Identifiers: NCT01772524, NCT02275117, NCT02559895, NCT02974153, NCT02985398).

Ongoing randomized clinical trials for the treatment of thrombosis in the antiphospholipid syndrome

2001 ◽  
Vol 21 (02) ◽  
pp. 77-81 ◽  
Author(s):  
G. Finazzi
Keyword(s):  
Clinical Trials ◽  
Large Scale ◽  
Low Dose ◽  
Randomized Clinical Trials ◽  
Oral Anticoagulants ◽  
Collaborative Study ◽  
Clinical Problem ◽  
Vascular Events ◽  
Dose Oral ◽  
Adverse Pregnancy

SummaryThrombotic events are a major clinical problem for patients with antiphospholipid antibodies (APA). However, current recommendations for their prevention and treatment are still based on retrospective studies. Data from large scale, prospective clinical trials are required to ultimately identify the optimal management of these patients. To date, at least four randomized studies are underway. The WAPS and PAPRE clinical trials are aimed to establish the correct duration and intensity of oral anticoagulation in APA patients with major arterial or venous thrombosis. The WARSS-APASS is a collaborative study to evaluate the efficacy and safety of aspirin or low-dose oral anticoagulants in preventing the recurrence of ischemic stroke. The recently announced UK Trial compares low-dose aspirin with or without low-intensity anticoagulation for the primary prevention of vascular events in APA-positive patients with SLE or adverse pregnancy history, but still thrombosis-free. It is hoped that the results of these trials will be available soon since clinicians urgently need more powerful data to treat their patients with the APA syndrome.

scholarly journals Effect of Tai Chi Training on Plantar Loads during Walking in Individuals with Knee Osteoarthritis

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Zhiwang Zhang ◽  
Lingyan Huang ◽  
Yu Liu ◽  
Lin Wang
Keyword(s):  
Clinical Trials ◽  
Knee Osteoarthritis ◽  
Education Program ◽  
Tai Chi ◽  
Peak Pressure ◽  
Maximum Force ◽  
Control Group ◽  
Link Type ◽  
Wellness Education ◽  
Metatarsophalangeal Joints

Tai Chi is an available method for the treatment of knee osteoarthritis (KOA). The impacts of Tai Chi on plantar loads of individuals with KOA are not fully understood. 46 participants with knee osteoarthritis were randomly assigned into the Tai Chi group (n=23) or the control group (n=23). The Tai Chi group attended a 6-month Tai Chi program, and the control group participated in a wellness education program. Novel Pedar-X system was used to collect the peak pressure (PP) and maximum force (MF) during walking before and 6 months after the intervention. Significant higher peak pressure and maximum force were observed in the 4th and 5th metatarsophalangeal joints in the Tai Chi group. However, there were significant declines in the peak pressure of the whole foot and the 2nd and 3rd metatarsophalangeal joints and maximum force of the heel in the control group. These results suggested that individuals with KOA might change the pattern of plantar loads during walking through Tai Chi, and plantar loads would be useful as a parameter to assess the effect of Tai Chi on knee osteoarthritis. This trial is registered with Clinical Trials: CHiCTR-TRC-13003264.

scholarly journals Proteomic profiling dataset of chemical perturbations in multiple biological backgrounds

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Deborah O. Dele-Oni ◽  
Karen E. Christianson ◽  
Shawn B. Egri ◽  
Alvaro Sebastian Vaca Jacome ◽  
Katherine C. DeRuff ◽  
...  
Keyword(s):  
Large Scale ◽  
Cell Model ◽  
Cellular Responses ◽  
Proteomic Profiling ◽  
Reduced Representation ◽  
Link Type ◽  
Original Dataset ◽  
Quality Control Metrics ◽  
Biological Insight ◽  
Chromatin Profiling

AbstractWhile gene expression profiling has traditionally been the method of choice for large-scale perturbational profiling studies, proteomics has emerged as an effective tool in this context for directly monitoring cellular responses to perturbations. We previously reported a pilot library containing 3400 profiles of multiple perturbations across diverse cellular backgrounds in the reduced-representation phosphoproteome (P100) and chromatin space (Global Chromatin Profiling, GCP). Here, we expand our original dataset to include profiles from a new set of cardiotoxic compounds and from astrocytes, an additional neural cell model, totaling 5300 proteomic signatures. We describe filtering criteria and quality control metrics used to assess and validate the technical quality and reproducibility of our data. To demonstrate the power of the library, we present two case studies where data is queried using the concept of “connectivity” to obtain biological insight. All data presented in this study have been deposited to the ProteomeXchange Consortium with identifiers PXD017458 (P100) and PXD017459 (GCP) and can be queried at https://clue.io/proteomics.

scholarly journals Randomised phase II trial of olaparib, chemotherapy or olaparib and cediranib in patients with platinum-resistant ovarian cancer (OCTOVA): a study protocol

BMJ Open ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. e041463
Author(s):  
Anita Mansouri ◽  
Naomi McGregor ◽  
Rachel Dunn ◽  
Sam Dobbie ◽  
Jane Holmes ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Trials ◽  
Antiangiogenic Therapy ◽  
Single Agent ◽  
Unmet Need ◽  
Dropout Rate ◽  
Weekly Paclitaxel ◽  
Type I ◽  
Link Type ◽  
Platinum Based Chemotherapy

IntroductionPatients relapsing within 12 months of platinum-based chemotherapy usually have a poorer response to subsequent treatments. To date, extensive research into the mechanism of resistance to platinum agents in the treatment of ovarian cancer has not resulted in improved responses or longer survival. Further experimental work and clinical trials with novel agents are therefore justified to address this unmet need.Patients with ovarian, fallopian tube or primary peritoneal cancer that has relapsed within 12 months of platinum-based chemotherapy will be randomised with stratification for BReast CAncer gene (BRCA) status, prior poly (ADP-ribose) polymerase (PARP) exposure and prior antiangiogenic therapy into weekly paclitaxel (chemotherapy), olaparib or the combination of cediranib and olaparib. They will be followed until disease progression or unacceptable toxicity develops. Our trial design permits two investigations. We will compare the efficacy and tolerability of single-agent olaparib with weekly paclitaxel. We will also compare the efficacy and tolerability of olaparib with the combination of olaparib and cediranib. The required sample size of 138 participants (46 per arm) was calculated using a 20% one-sided type I error, 80% power and 15% dropout rate. Recruitment will last 34 months with a follow-up of 18 months.Methods and analysisEthics and disseminationThis study will be conducted under a UK Medicines and Healthcare Products Regulatory Agency Clinical Trials Authorisation. Approval to conduct the study was obtained from the responsible authority before beginning the study. The sponsor will retain ownership of all data arising from the trial. We aim to publish this research in a specialist peer-reviewed scientific journal on study completion. EudraCT number: 2016-000559-28, ethics reference number: 16/LO/2150.Trial registration numberISRCTN: ISRCTN14784018, clinicaltrials.gov: NCT03117933; Pre-results.

scholarly journals SAT0121 PAIN AND OTHER PATIENT-REPORTED OUTCOMES IN PATIENTS WITH RHEUMATOID ARTHRITIS WHO DID OR DID NOT ACHIEVE TREATMENT RESPONSE BASED ON IMPROVEMENT IN SWOLLEN JOINTS IN TOCILIZUMAB CLINICAL TRIALS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 994.2-995
Author(s):  
A. Sebba ◽  
J. Han ◽  
S. Mohan
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Trials ◽  
Pain Score ◽  
Patient Reported Outcomes ◽  
Component Score ◽  
Link Type ◽  
Pain Scores ◽  
Sf 36 ◽  
Patient Reported ◽  
Nonresponder Group

Background:Significant improvements in pain and other patient-reported outcomes (PROs) have been shown in large clinical trials in patients with rheumatoid arthritis (RA) who receive tocilizumab (TCZ) compared with placebo (PBO). Recent data suggest that pain in RA may be noninflammatory as well as inflammatory, and improvement in pain scores and other PROs may be seen in patients who do not respond to treatment based on disease activity measures that evaluate inflammation.Objectives:To assess changes in pain scores and other PROs in patients with RA who did or did not achieve ≥ 20% improvement in SJC in TCZ clinical trials.Methods:Data from patients with active RA who received intravenous TCZ 8 mg/kg + MTX or PBO + MTX in 3 Phase III studies (OPTION [NCT00106548], TOWARD [NCT00106574] and LITHE [NCT00109408]) were included. All patients had moderate to severe RA with an inadequate response or intolerance of MTX (OPTION, LITHE) or conventional synthetic disease-modifying antirheumatic drugs (csDMARDs; TOWARD). Changes in pain (visual analog scale [VAS], 0-100 mm), Health Assessment Questionnaire Disability Index (HAQ-DI, 0-3), 36-Item Short Form Survey (SF-36) physical component score (PCS) and mental component score (MCS; 0-50) and Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score (0-52) from baseline to Week 24 were evaluated. Results were compared between patients receiving TCZ + MTX and those receiving PBO + MTX in both patients who achieved ≥ 20% improvement in SJC (responders) and those who did not (nonresponders). The changes from baseline were analyzed using a mixed model with repeated measures, including the following covariates and interactions: treatment, visit, baseline of endpoint, region, baseline DAS28 and interactions of visit with treatment and baseline of endpoint.Results:Data from 1254 responders (TCZ + MTX, n = 831; PBO + MTX, n = 423) and 620 nonresponders (TCZ + MTX, n = 225; PBO + MTX, n = 395) were included. Patients receiving TCZ + MTX had significantly greater improvement in pain scores and HAQ-DI compared with PBO + MTX in the responder group (–27.19 vs –16.77 and –0.55 vs –0.34, respectively;P< 0.0001 for both) and nonresponder group (–9.59 vs 2.53 and –0.20 vs 0.01;P< 0.0001 for both) at Week 24 (Figure 1). Similar results were seen at Week 16 in the nonresponder group (–11.06 vs –2.38 and –0.23 vs –0.04;P< 0.0001 for both) prior to initiation of rescue treatment. At Week 24 in the responder group, patients receiving TCZ + MTX had significantly greater improvements compared with PBO + MTX in SF-36 PCS and MCS (9.16 vs 5.71 and 6.55 vs 3.79, respectively;P< 0.0001 for both) (Figure 2) and FACIT-Fatigue (8.39 vs 5.11;P< 0.0001). In the nonresponder group, patients receiving TCZ + MTX had significantly greater improvements compared with PBO + MTX in SF-36 PCS at Week 16 (3.81 vs 1.65;P= 0.0006) and Week 24 (4.42 vs 1.01;P< 0.0001) (Figure 2) and FACIT-Fatigue at Week 16 (3.82 vs 1.32;P= 0.0039) and Week 24 (3.90 vs 1.40;P= 0.0111).Conclusion:Patients with RA who received TCZ + MTX had significantly greater improvements in pain score and other PROs than those who received PBO + MTX regardless of whether they achieved ≥ 20% improvement in SJC. Clinical outcome at Week 24 correlated well with PROs, with a relatively larger improvement in pain score and other PROs in the responder group than in the nonresponder group; relative to PBO + MTX, these improvements appear numerically similar in the responder and nonresponder groups with consistently smaller difference between the groups in TCZ-treated arms. The consistent effect of TCZ on PROs in both responder and nonresponder groups warrants further study on the impact of TCZ on sources of pain independent of that caused by joint inflammation.Figure:Acknowledgments:This study was sponsored by Genentech, Inc. Support for third-party writing assistance, furnished by Health Interactions, Inc, was provided by Genentech, Inc.Disclosure of Interests:Anthony Sebba Consultant of: Genentech, Gilead, Lilly, Regeneron Pharmaceuticals Inc., Sanofi, Speakers bureau: Lilly, Roche, Sanofi, Jian Han Shareholder of: Genentech, Inc., Employee of: Genentech, Inc., Shalini Mohan Shareholder of: Genentech, Inc., Employee of: Genentech, Inc.

scholarly journals An integrated life cycle and water footprint assessment of nonfood crops based bioenergy production

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jun Li ◽  
Fengyin Xiong ◽  
Zhuo Chen
Keyword(s):  
Life Cycle ◽  
Environmental Sustainability ◽  
Large Scale ◽  
Water Footprint ◽  
Arable Land ◽  
Integrated Analysis ◽  
Actual Performance ◽  
Bioenergy Production ◽  
Trade Offs ◽  
Hybrid Pennisetum

AbstractBiomass gasification, especially distribution to power generation, is considered as a promising way to tackle global energy and environmental challenges. However, previous researches on integrated analysis of the greenhouse gases (GHG) abatement potentials associated with biomass electrification are sparse and few have taken the freshwater utilization into account within a coherent framework, though both energy and water scarcity are lying in the central concerns in China’s environmental policy. This study employs a Life cycle assessment (LCA) model to analyse the actual performance combined with water footprint (WF) assessment methods. The inextricable trade-offs between three representative energy-producing technologies are explored based on three categories of non-food crops (maize, sorghum and hybrid pennisetum) cultivated in marginal arable land. WF results demonstrate that the Hybrid pennisetum system has the largest impact on the water resources whereas the other two technology options exhibit the characteristics of environmental sustainability. The large variances in contribution ratio between the four sub-processes in terms of total impacts are reflected by the LCA results. The Anaerobic Digestion process is found to be the main contributor whereas the Digestate management process is shown to be able to effectively mitigate the negative environmental impacts with an absolute share. Sensitivity analysis is implemented to detect the impacts of loss ratios variation, as silage mass and methane, on final results. The methane loss has the largest influence on the Hybrid pennisetum system, followed by the Maize system. Above all, the Sorghum system demonstrates the best performance amongst the considered assessment categories. Our study builds a pilot reference for further driving large-scale project of bioenergy production and conversion. The synergy of combined WF-LCA method allows us to conduct a comprehensive assessment and to provide insights into environmental and resource management.

scholarly journals How I treat pediatric venous thromboembolism

Blood ◽  
2017 ◽  
Vol 130 (12) ◽  
pp. 1402-1408 ◽  
Author(s):  
Guy Young
Keyword(s):  
Clinical Trials ◽  
Venous Thromboembolism ◽  
Large Scale ◽  
Central Venous Catheters ◽  
Rare Disorder ◽  
Central Venous ◽  
Management Decisions ◽  
Logical Approach ◽  
The Past ◽  
Medical Disorders

Abstract The incidence of pediatric venous thromboembolism (VTE) has been increasing significantly over the past decade in part as a result of increased recognition of this serious disorder but more so because of the increased use of central venous catheters and other technological advancements involved in the care of ill children. Management of pediatric VTE is a complex undertaking, considering that the vast majority of children who develop this complication have serious underlying medical disorders. Although the incidence is rising, in comparison with adults, this remains a relatively rare disorder, and as such, large-scale clinical trials have not been completed, rendering management decisions to be based on extrapolation from adult data and the experience of the treating physician. Clearly, both are fraught with problems. Thus, day-to-day management remains more art than science until such time that the results from clinical trials (many of which are under way) become available. This edition of “How I Treat” describes the author’s experience in managing 3 common scenarios that one may encounter in pediatric thrombosis and suggests a logical approach to such situations. Furthermore, the author provides 3 algorithms to help guide management decisions.

Large scale manufacturing strategy for production of umbilical cord-derived mesenchymal stem cells in support of clinical trials

Cytotherapy ◽  
2021 ◽  
Vol 23 (5) ◽  
pp. S166
Author(s):  
E. Linetsky ◽  
G. Lanzoni ◽  
X. Wang ◽  
C. Lenero ◽  
A. Patel ◽  
...  
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Large Scale ◽  
Manufacturing Strategy

scholarly journals Road Freight Transport Electrification Potential by Using Battery Electric Trucks in Finland and Switzerland

Energies ◽  
2021 ◽  
Vol 14 (4) ◽  
pp. 823
Author(s):  
Mehdi Jahangir Samet ◽  
Heikki Liimatainen ◽  
Oscar Patrick René van Vliet ◽  
Markus Pöllänen
Keyword(s):  
Large Scale ◽  
Ghg Emissions ◽  
Limited Range ◽  
Freight Transport ◽  
Heavy Duty ◽  
Range Extender ◽  
Percentage Points ◽  
Road Freight ◽  
Road Systems ◽  
Gross Vehicle Weight

Medium and heavy-duty battery electric trucks (BETs) may play a key role in mitigating greenhouse gas (GHG) emissions from road freight transport. However, technological challenges such as limited range and cargo carrying capacity as well as the required charging time need to be efficiently addressed before the large-scale adoption of BETs. In this study, we apply a geospatial data analysis approach by using a battery electric vehicle potential (BEVPO) model with the datasets of road freight transport surveys for analyzing the potential of large-scale BET adoption in Finland and Switzerland for trucks with gross vehicle weight (GVW) of over 3.5 t. Our results show that trucks with payload capacities up to 30 t have the most potential for electrification by relying on the currently available battery and plug-in charging technology, with 93% (55% tkm) and 89% (84% tkm) trip coverage in Finland and Switzerland, respectively. Electric road systems (ERSs) would be essential for covering 51% trips (41% tkm) of heavy-duty trucks heavier than 30 t in Finland. Furthermore, range-extender technology could improve the trip electrification potential by 3–10 percentage points (4–12 percentage points of tkm).

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