Randomized, Open-label, Parallel, Active-controlled, Multicenter Study of Efficacy and Safety of Fixed-dose Combination of Fluticasone /Formoterol /Glycopyrronium for the Treatment of Patients With Chronic Obstructive Pulmonary Disease

Several studies have demonstrated the benefits of the LAMA (Long-Acting Muscarinic Antagonists) + LABA (Long-Acting Beta-Agonists) + IC (inhaled corticosteroids) combination in the treatment of chronic obstructive pulmonary disease (COPD). The use of the triple combination in patients with severe airflow obstruction and a history of flares has been associated with improved lung function, improved patient-reported endpoints and prevention of flares, when compared to LABA, LABA + LAMA and LABA + IC. Furthermore, when compared to dual therapies LABA + IC and LABA + LAMA, triple therapy has been able to reduce all-cause deaths among chronic obstructive pulmonary disease (COPD) patients.
Previously published studies have demonstrated that the triple combination of Fluticasone 250 mcg/Formoterol 12 mcg/Glycopyrronium 12.5 mcg was able to improve lung function in chronic obstructive pulmonary disease (COPD) patients with a history of flares. There was also a significant improvement in the mMRC (modified-Medical Research Council) which began in the 2nd week of treatment and continued up to week 12. The association was considered safe and well tolerated, with only mild to moderate adverse events recorded in approximately 25% of the subjects treated in the study.
Furthermore, bioavailability studies performed with the components of the combination proposed as experimental drug - Fluticasone/Formoterol/Glycopyrronium - indicated that there is no pharmacokinetic interaction between the 3 active ingredients when they were administered concomitantly to healthy individuals under fasting conditions.

开始日期2026-02-28

申办/合作机构

Eurofarma Laboratórios SA

NCT06337552 / RecruitingN/AIIT

A Randomized High-Fermented Food Intervention Among Locally Advanced Rectal Cancer Patients (The FEED Trial)

The purpose of the study is to evaluate the feasibility and acceptability of a dietary intervention (FEED-FF) that includes fermented foods (FF), among locally advanced rectal cancer patients, and to explore whether this diet can improve outcomes in rectal cancer patients receiving chemoradiotherapy (CRT).

开始日期2024-02-19

申办/合作机构

H. Lee Moffitt Cancer Center & Research Institute, Inc.

NCT02666287 / Completed临床1期

An Open Label, Six-period Cross-over, Single and Repeat Dose Study to Determine the Pharmacokinetics of Fluticasone Furoate and GSK961081 When Administered Alone, in Combination, or Concurrently Via the ELLIPTA

Batefenterol (BAT) is a novel bifunctional molecule that combines muscarinic antagonism and beta2-agonism in a single molecule and is in development for the treatment of chronic obstructive pulmonary disease (COPD). FF is a corticosteroid approved as the inhaled corticosteroid (ICS) component of a combination product, with vilanterol (VI), a long-acting beta2-agonist for COPD. In the current study FF will be investigated as an inhaled product in combination with BAT, for treatment of COPD.
This study is an open-label, six-way crossover, single and repeat dose study to evaluate the systemic pharmacokinetics, safety and tolerability of FF and BAT when administered via the ELLIPTA™ alone, in combination, or concurrently at 3 times the clinical dose, following a single dose, and at the proposed clinical dose, following repeat doses.
This study will consist of screening period, 6 treatment periods, and a follow-up visit. Each subject will have 3 periods in which they receive a single dose treatment regimen (3 inhalations on Day 1 of each single dose study period) and 3 periods in which they receive a single dose treatment regimen followed by a 7-day, once-daily, repeated dose. On Day 1 of those periods, subjects will receive their single dose as 3 inhalations. On Days 2-8, subjects will receive 1 inhalation per day for the repeated dose regimen. There will be a minimum of 7-day washout between each treatment periods. All subjects will receive 9 treatments and follow-up procedures will be done 7 14 days after the last dose.
Forty eight healthy subjects will be enrolled into the study, such that approximately 40 subjects complete dosing and PK assessments. The total duration of participation for each subject in this study will be up to 15 weeks. ELLIPTA is a registered trademark of the GlaxoSmithKline [GSK] group of companies.

开始日期2016-01-27

申办/合作机构

GSK Plc

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100 项与丙酸氟替卡松/福莫特罗/格隆溴铵相关的临床结果

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100 项与丙酸氟替卡松/福莫特罗/格隆溴铵相关的转化医学

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100 项与丙酸氟替卡松/福莫特罗/格隆溴铵相关的专利（医药）

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160

项与丙酸氟替卡松/福莫特罗/格隆溴铵相关的文献（医药）

2023-08-03·Journal of animal science

Feeding dietary fermentable fiber improved fecal microbial composition and increased acetic acid production in a nursery pig model.

Article

作者: Gang Zhang ; Jinbiao Zhao ; Xiaoming Song ; Meiyu Yang ; Haotian Wang ; Yi Wu

The objective of this study was to determine the fermentable fiber (FF) content of several common fibrous ingredients fed to nursery pigs, and then evaluate the effect of dietary FF level on growth performance and fecal microbial composition. In Exp. 1, 54 nursery pigs were randomly allotted to be fed 9 diets with six replicate pigs per diet. Dietary treatments included a corn-soybean meal basal diet and 8 test diets based on a mixture of the corn-soybean meal diet and corn distillers dried grains with solubles, sunflower meal, oat bran, wheat bran, corn bran, sugar beet pulp (SBP), apple pomace (AP) or soybean hulls (SH). In Exp. 2, 180 nursery pigs were housed in 30 pens (6 pigs/pen) and randomly allotted to be fed 5 diets with different FF to TDF ratios, which were 0.52, 0.55, 0.58, 0.61 and 0.64, respectively. Results showed that the FF content in SBP, AP and SH was greater (P < 0.01) than that in other ingredients. Water binding capacity of fibrous ingredients was positively correlated (P < 0.05) to the digestibility of TDF, acid detergent fiber and non-starch polysaccharides in test ingredients. Pigs fed the00 SBP, AP and SH diets had greater (P < 0.05) fecal acetic acid and total short-chain fatty acids (SCFAs) concentrations compared with pigs fed other diets. Fecal acetic acid and total SCFAs concentrations were positively correlated (P < 0.05) with FF content in experimental diets. Average daily weight gain and average daily feed intake of pigs quadratically increased (P < 0.01) as the ratios of FF to TDF increased. Pigs in FF64% group showed higher (P < 0.05) ACE index and fecal acetic acid concentration compared with pigs fed the dietary FF/TDF ratio of 0.52 to 0.61. Compared with the classification system of soluble dietary fiber and insoluble dietary fiber, FF could better describe the mechanism by which dietary fiber has beneficial effects on pig gut health.

2023-06-27·Chest

Clinic versus home spirometry for monitoring lung function in patients with asthma.

Article

作者: John Oppenheimer ; Nicola A Hanania ; Rekha Chaudhuri ; Hironori Sagara ; Zelie Bailes ; Andrew Fowler ; Guy Peachey ; Emilio Pizzichini ; David Slade

BACKGROUND:

Studies examining agreement between home and clinic spirometry in patients with asthma are limited, with conflicting results. Understanding the strengths and limitations of telehealth and home spirometry is particularly important considering the SARS-CoV-2 pandemic.

RESEARCH QUESTION:

How well do home and clinic measurements of trough forced expiratory volume in 1 second (FEV₁) agree in patients with uncontrolled asthma?

STUDY DESIGN AND METHODS:

This post hoc analysis used trough FEV₁ data from the randomised, double-blind, parallel-group Phase IIIA CAPTAIN (205715; NCT02924688) and Phase IIB (205832; NCT03012061) trials in patients with uncontrolled asthma. CAPTAIN evaluated the impact of adding umeclidinium (UMEC) to fluticasone furoate/vilanterol (FF/VI) via a single inhaler; 205832 investigated adding UMEC to FF versus placebo. Trough FEV₁ measurements were collected via home spirometry and supervised in-person spirometry in the research clinic. To compare home and clinic spirometry, we examined the time-course analyses of home and clinic trough FEV₁, and generated post hoc Bland-Altman plots to assess agreement between home and clinic spirometry.

RESULTS:

Data from 2436 (CAPTAIN) and 421 (205832) patients were analysed. Treatment-related improvements in FEV₁ were observed in both trials using home and clinic spirometry. Improvements measured by home spirometry were of lower magnitude and less consistent than clinic measurements. Bland-Altman plots suggested poor agreement between home and clinic trough FEV₁ at baseline and Week 24.

INTERPRETATION:

This post hoc comparison of home and clinic spirometry is the largest conducted in asthma. Results showed that home spirometry was less consistent than and lacked agreement with clinic spirometry, suggesting that unsupervised home readings are not interchangeable with clinic measurements. However, these findings may only be applicable to home spirometry using the specific device and coaching methods employed in these studies. Post-pandemic, further research to optimise home spirometry use is needed.

CLINICAL TRIAL REGISTRATION:

Clinicaltrials.gov (NCT03012061; NCT02924688).

2023-04-03·Thorax

Estimating individual treatment effects on COPD exacerbations by causal machine learning on randomised controlled trials.

Article

作者: Kenneth Verstraete ; Iwein Gyselinck ; Helene Huts ; Nilakash Das ; Marko Topalovic ; Maarten De Vos ; Wim Janssens

RATIONALE:

Estimating the causal effect of an intervention at individual level, also called individual treatment effect (ITE), may help in identifying response prior to the intervention.

OBJECTIVES:

We aimed to develop machine learning (ML) models which estimate ITE of an intervention using data from randomised controlled trials and illustrate this approach with prediction of ITE on annual chronic obstructive pulmonary disease (COPD) exacerbation rates.

METHODS:

We used data from 8151 patients with COPD of the Study to Understand Mortality and MorbidITy in COPD (SUMMIT) trial (NCT01313676) to address the ITE of fluticasone furoate/vilanterol (FF/VI) versus control (placebo) on exacerbation rate and developed a novel metric, Q-score, for assessing the power of causal inference models. We then validated the methodology on 5990 subjects from the InforMing the PAthway of COPD Treatment (IMPACT) trial (NCT02164513) to estimate the ITE of FF/umeclidinium/VI (FF/UMEC/VI) versus UMEC/VI on exacerbation rate. We used Causal Forest as causal inference model.

RESULTS:

In SUMMIT, Causal Forest was optimised on the training set (n=5705) and tested on 2446 subjects (Q-score 0.61). In IMPACT, Causal Forest was optimised on 4193 subjects in the training set and tested on 1797 individuals (Q-score 0.21). In both trials, the quantiles of patients with the strongest ITE consistently demonstrated the largest reductions in observed exacerbations rates (0.54 and 0.53, p<0.001). Poor lung function and blood eosinophils, respectively, were the strongest predictors of ITE.

CONCLUSIONS:

This study shows that ML models for causal inference can be used to identify individual response to different COPD treatments and highlight treatment traits. Such models could become clinically useful tools for individual treatment decisions in COPD.

100 项与丙酸氟替卡松/福莫特罗/格隆溴铵相关的药物交易

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