Association of immune response with efficacy and safety outcomes in adults with phenylketonuria administered pegvaliase in phase 3 clinical trials

Abstract Background The objective of this analysis was to evaluate the efficacy and safety of oritavancin compared with vancomycin for patients with acute bacterial skin and skin structure infections (ABSSSIs) who received treatment in the outpatient setting in the Phase 3 SOLO clinical trials. Methods SOLO I and SOLO II were 2 identically designed comparative, multicenter, double-blind, randomized studies to evaluate the efficacy and safety of a single 1200-mg dose of intravenous (IV) oritavancin versus 7–10 days of twice-daily IV vancomycin for the treatment of ABSSSI. Protocols were amended to allow enrolled patients to complete their entire course of antimicrobial therapy in an outpatient setting. The primary efficacy outcome was a composite endpoint (cessation of spread or reduction in size of the baseline lesion, absence of fever, and no rescue antibiotic at early clinical evaluation [ECE]) (48 to 72 hours). Key secondary endpoints included investigator-assessed clinical cure 7 to 14 days after end of treatment (posttherapy evaluation [PTE]) and 20% or greater reduction in lesion area at ECE. Safety was assessed until day 60. Results Seven hundred ninety-two patients (oritavancin, 392; vancomycin, 400) received entire course of treatment in the outpatient setting. Efficacy response rates at ECE and PTE were similar (primary composite endpoint at ECE: 80.4% vs 77.5% for oritavancin and vancomycin, respectively) as was incidence of adverse events. Five patients (1.3%) who received oritavancin and 9 (2.3%) vancomycin patients were subsequently admitted to a hospital. Conclusions Oritavancin provides a single-dose alternative to multidose vancomycin for treatment of ABSSSI in the outpatient setting.

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The impact of inclusion, dose and duration of pyrazinamide (PZA) on efficacy and safety outcomes in tuberculosis: systematic review and meta-analysis protocol

Systematic Reviews ◽

10.1186/s13643-019-1231-1 ◽

2019 ◽

Vol 8 (1) ◽

Cited By ~ 1

Author(s):

James D. Millard ◽

Elizabeth A. Mackay ◽

Laura J. Bonnett ◽

Geraint R. Davies

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Meta Analysis ◽

World Health ◽

Controlled Trials ◽

Cochrane Central Register ◽

Efficacy And Safety ◽

Safety Outcomes ◽

Meta Regression ◽

Indirect Comparisons

Abstract Background Pyrazinamide (PZA) is a key component of current and future regimens for tuberculosis (TB). Inclusion of PZA at higher doses and for longer durations may improve efficacy outcomes but must be balanced against the potential for worse safety outcomes. Methods We will search for randomised and quasi-randomised clinical trials in adult participants with and without the inclusion of PZA in TB treatment regimens in the Cochrane infectious diseases group’s trials register, Cochrane central register of controlled trials (CENTRAL), MEDLINE, EMBASE, LILACS, the metaRegister of Controlled Trials (mRCT) and the World Health Organization (WHO) international clinical trials registry platform. One author will screen abstracts and remove ineligible studies (10% of which will be double-screened by a second author). Two authors will review full texts for inclusion. Safety and efficacy data will be extracted to pre-piloted forms by one author (10% of which will be double-extracted by a second author). The Cochrane risk of bias tool will be used to assess study quality. The study has three objectives: the association of (1) inclusion, (2) dose and (3) duration of PZA with efficacy and safety outcomes. Risk ratios as relative measures of effect for direct comparisons within trials (all objectives) and proportions as absolute measures of effect for indirect comparisons across trials (for objectives 2 and 3) will be calculated. If there is insufficient data for direct comparisons within trials for objective 1, indirect comparisons between trials will be performed. Measures of effect will be pooled, with corresponding 95% confidence intervals and p values. Meta-analysis will be performed using the generalised inverse variance method for fixed effects models (FEM) or the DerSimonian-Laird method for random effects models (REM). For indirect comparisons, meta-regression for absolute measures against dose and duration data will be performed. Heterogeneity will be quantified through the I2-statistic for direct comparisons and the τ2 statistic for indirect comparisons using meta-regression. Discussion The current use of PZA for TB is based on over 60 years of clinical trial data, but this has never been synthesised to guide rationale use in future regimens and clinical trials. Systematic review registration: International Prospective Register of Systematic Reviews (PROSPERO) CRD42019138735

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Efficacy and safety of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide in Asian participants with human immunodeficiency virus 1 infection: A sub-analysis of phase 3 clinical trials

HIV Research & Clinical Practice ◽

10.1080/15284336.2019.1589232 ◽

2019 ◽

Vol 20 (3) ◽

pp. 73-81 ◽

Cited By ~ 2

Author(s):

Yeon-Sook Kim ◽

Shinichi Oka ◽

Ploenchan Chetchotisakd ◽

Amanda Clarke ◽

Khuanchai Supparatpinyo ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Clinical Trials ◽

Efficacy And Safety ◽

Phase 3 ◽

Immunodeficiency Virus ◽

Tenofovir Alafenamide ◽

Human Immunodeficiency Virus 1

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Effect on efficacy and safety trial outcomes of also enrolling patients on ongoing glucocorticoid therapy in rheumatoid arthritis clinical trials of tocilizumab or adalimumab or methotrexate monotherapy

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2019-216537 ◽

2020 ◽

Vol 79 (4) ◽

pp. 460-463 ◽

Cited By ~ 3

Author(s):

Mary Safy-Khan ◽

Johannes W G Jacobs ◽

Maria J H de Hair ◽

Paco M J Welsing ◽

Michael D Edwardes ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Clinical Trials ◽

Radiographic Progression ◽

Joint Damage ◽

Incidence Rates ◽

Efficacy And Safety ◽

Serious Adverse Events ◽

Double Blind ◽

Safety Outcomes ◽

Trial Outcomes

BackgroundIn rheumatoid arthritis (RA) trials, inclusion of patients on background treatment with glucocorticoids (GCs) might impact efficacy and safety outcomes.ObjectivesTo determine if inclusion of patients on background GC use influenced efficacy and safety outcomes of RA randomised clinical trials on initiation of tocilizumab (TCZ) or adalimumab (ADA) or methotrexate (MTX) monotherapy.MethodsData of four double-blind RA randomised controlled trials (AMBITION, ACT-RAY, ADACTA and FUNCTION) with in total four TCZ, one ADA and two MTX monotherapy arms were analysed. Analyses of covariance of changes from baseline to week 24 in efficacy endpoints and radiographic progression up to week 104 were performed, correcting for relevant covariates. Incidence rates of serious adverse events (SAEs) were assessed.ResultsNo statistically significant differences were found in efficacy parameters between background GC users and non-GC users, except for less radiographic progression associated with GC usage in one MTX arm. SAE rates were not statistically significantly different between GC users and non-GC users in the treatment arms.ConclusionNo effect of including patients on background GC treatment on efficacy and safety trial outcomes was found, with the exception of reduced radiological joint damage in one MTX arm.

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