scholarly journals Genetic epidemiology of dengue viruses in phase III trials of the CYD tetravalent dengue vaccine and implications for efficacy

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Maia A Rabaa ◽  
Yves Girerd-Chambaz ◽  
Kien Duong Thi Hue ◽  
Trung Vu Tuan ◽  
Bridget Wills ◽  
...  
Keyword(s):  
Genetic Epidemiology ◽  
Phase Iii ◽  
Envelope Gene ◽  
Dengue Vaccine ◽  
Virus Genotype ◽  
Pivotal Phase ◽  
Dengue Viruses ◽  
High Amino Acid ◽  
Phase Iii Trials ◽  
Trial Participants

This study defined the genetic epidemiology of dengue viruses (DENV) in two pivotal phase III trials of the tetravalent dengue vaccine, CYD-TDV, and thereby enabled virus genotype-specific estimates of vaccine efficacy (VE). Envelope gene sequences (n = 661) from 11 DENV genotypes in 10 endemic countries provided a contemporaneous global snapshot of DENV population genetics and revealed high amino acid identity between the E genes of vaccine strains and wild-type viruses from trial participants, including at epitope sites targeted by virus neutralising human monoclonal antibodies. Post-hoc analysis of all CYD14/15 trial participants revealed a statistically significant genotype-level VE association within DENV-4, where efficacy was lowest against genotype I. In subgroup analysis of trial participants age 9–16 years, VE estimates appeared more balanced within each serotype, suggesting that genotype-level heterogeneity may be limited in older children. Post-licensure surveillance is needed to monitor vaccine performance against the backdrop of DENV sequence diversity and evolution.

scholarly journals Author response: Genetic epidemiology of dengue viruses in phase III trials of the CYD tetravalent dengue vaccine and implications for efficacy

2017 ◽  
Author(s):  
Maia A Rabaa ◽  
Yves Girerd-Chambaz ◽  
Kien Duong Thi Hue ◽  
Trung Vu Tuan ◽  
Bridget Wills ◽  
...  
Keyword(s):  
Genetic Epidemiology ◽  
Phase Iii ◽  
Author Response ◽  
Dengue Vaccine ◽  
Dengue Viruses ◽  
Phase Iii Trials

scholarly journals Population pharmacokinetics of paritaprevir, ombitasvir, dasabuvir, ritonavir and ribavirin in hepatitis C virus genotype 1 infection: analysis of six phase III trials

2016 ◽  
Vol 83 (3) ◽  
pp. 527-539 ◽  
Author(s):  
Sven Mensing ◽  
Doerthe Eckert ◽  
Shringi Sharma ◽  
Akshanth R. Polepally ◽  
Amit Khatri ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Population Pharmacokinetics ◽  
Phase Iii ◽  
Genotype 1 ◽  
Virus Genotype ◽  
Phase Iii Trials

Pimavanserin: A Novel Antipsychotic for Parkinson’s Disease Psychosis

2017 ◽  
Vol 51 (6) ◽  
pp. 479-487 ◽  
Author(s):  
Kevin M. Bozymski ◽  
Denise K. Lowe ◽  
Kiersten M. Pasternak ◽  
Travis L. Gatesman ◽  
Ericka L. Crouse
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Practice ◽  
Phase Ii ◽  
English Language ◽  
Phase Iii ◽  
Pivotal Phase ◽  
Phase Iii Trials ◽  
Tract Infections ◽  
Motor Effects

Objective: To review the pharmacology, pharmacokinetics, efficacy, safety, and place in therapy of pimavanserin for the treatment of hallucinations and delusions of Parkinson’s disease psychosis (PDP). Data Sources: A comprehensive PubMed search (1966 to January 2017) was conducted using the search terms Parkinson’s disease psychosis, hallucinations, delusions, pimavanserin, and ACP-103. Additional data were obtained from references of identified articles, governmental sources, manufacturer product labeling and website, and Clinicaltrials.gov. Study Selection and Data Extraction: All English-language trials evaluating pimavanserin in PDP were included. Data from review articles were included if relevant to clinical practice. One phase II and 3 phase III trials are discussed. Data Synthesis: Pimavanserin was approved in April 2016 for the treatment of delusions and hallucinations of PDP. One phase II and 2 phase III trials reported no difference for primary outcomes when pimavanserin was compared with placebo. The pivotal phase III ACP-103-020 trial adapted a scale to target more specific symptoms prevalent in PDP and showed that least-squares mean differences of the total PD-adapted Scale for the Assessment of Positive Symptoms score were significantly improved for pimavanserin-treated patients as compared with placebo-treated patients (difference = −3.06; 95% CI [−4.91 to −1.20]; P = 0.0014]). Pimavanserin’s adverse effect profile includes urinary tract infections, falls, peripheral edema, hallucinations, confusion, nausea, and headaches. Conclusion: Pimavanserin is a novel 5-HT2A inverse agonist that has shown promising results for managing hallucinations and delusions in patients with PDP without worsening motor effects or orthostasis. Yet its high cost and specialty pharmacy access may limit use in clinical practice.

scholarly journals Direct Oral Anticoagulants in Patients with Obesity and Atrial Fibrillation: Position Paper of Italian National Association of Hospital Cardiologists (ANMCO)

2021 ◽  
Vol 10 (18) ◽  
pp. 4185
Author(s):  
David Mocini ◽  
Stefania Angela Di Fusco ◽  
Edoardo Mocini ◽  
Lorenzo Maria Donini ◽  
Carlo Lavalle ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
High Body Mass Index ◽  
Normal Weight ◽  
Phase Iii ◽  
Fixed Dose ◽  
Pivotal Phase ◽  
Phase Iii Trials

The use of the direct oral anticoagulants dabigatran, rivaroxaban, apixaban and edoxaban (DOACs) offers some major advantages over warfarin and other vitamin K antagonists (VKAs). One advantage is the possibility to use a fixed dose in normal-weight patients, overweight patients and patients with obesity. However, the “one size fits all” strategy raised a concern regarding the possibility to undertreat patients with a high body mass index. No randomized controlled trials (RCTs) have ever compared VKAs and DOACs in this population. We analyzed data from the literature on DOAC pharmacokinetics and pharmacodynamics, results from the four pivotal phase III trials on non-valvular atrial fibrillation, retrospective observational studies and metanalyses. While we are aware of the limitation imposed by the absence of specific RCTs, we propose the position of the Italian Association of Hospital Cardiologists (ANMCO) on the use of DOACs in patients with obesity based on the existing evidence.

scholarly journals Time to abandon placebo control in pivotal phase III trials?

2015 ◽  
Vol 14 (3) ◽  
pp. 306-307 ◽  
Author(s):  
John R. Geddes ◽  
Andrea Cipriani
Keyword(s):  
Phase Iii ◽  
Placebo Control ◽  
Pivotal Phase ◽  
Phase Iii Trials

scholarly journals The role of golimumab in inflammatory arthritis. A review of the evidence

2018 ◽  
Vol 10 (9) ◽  
pp. 181-194
Author(s):  
Zunera Tahir ◽  
Arthur Kavanaugh
Keyword(s):  
Inflammatory Arthritis ◽  
Tumor Necrosis Factor Inhibitor ◽  
Phase Iii ◽  
Pivotal Phase ◽  
Double Blind ◽  
Pubmed Central ◽  
Factor Inhibitor ◽  
Phase Iii Trials ◽  
Necrosis Factor

Background: Golimumab (GOL) is a tumor necrosis factor inhibitor that is used for various types of inflammatory arthritis such as rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). This article is a systematic review of the evidence for the efficacy and safety of golimumab in inflammatory arthritides, specifically RA, PsA and AS. Methods: We conducted a search of randomized controlled trails in MEDLINE [PubMed], CENTRAL, Embase, and Current Controlled Trials databases (ClinicalTrials.gov) through 2017 for studies that evaluated golimumab in inflammatory arthritides. We focused on pivotal, phase III trials for this review of the safety and efficacy of the drug. However, as some important information is not available in detail in publications from the phase III studies, additional individual studies pertaining to antidrug antibodies were also included. Results: A total of 12, randomized, double-blind, placebo-controlled studies were included in this review of literature. Two trials focused on the GOL response in the PsA population, four trials focused on the GOL response in the AS population, and five trials focused on the GOL response in the RA population. Additional studies that evaluated autodrug antibodies produced in patients using GOL were also included. Conclusion: Golimumab was found to be clinically effective and also have a good safety profile in the treatment of RA, PsA, and AS based on data available from large studies.

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