This phase 3, randomized, double-blind study in patients with moderate to severe COPD was conducted in 222 centers throughout North America, Australia, and New Zealand (NCT01437397) in accordance with the International Conference on Harmonization/Good Clinical Practice guidelines and the Declaration of Helsinki. The protocol was approved by the Institutional Review Board at each study center, and all patients gave written informed consent before participating in any study procedures. The study comprised a 2- to 3-week run-in period prior to a 24-week double-blind treatment period (Figure 1 ). Patients were equally randomized to twice-daily aclidinium/formoterol FDC 400/12 μg, aclidinium/formoterol FDC 400/6 μg, aclidinium 400 μg, formoterol 12 μg, or placebo, administered via a multidose, dry-powder inhaler (Genuair®/Pressair®)*. The first patient/first visit was October 4, 2011 and the last patient completed February 6, 2013.![]()
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Formoterol
Formoterol
Formoterol is a long-acting beta2-adrenergic receptor agonist used to treat bronchospasm associated with asthma and chronic obstructive pulmonary disease (COPD).
It works by relaxing and opening airways to improve breathing.
Formoterol has a rapid onset of action and a long duration of efect, making it an important therapeutic option for managing airway obstruction.
Researchers can use PubCompare.ai to easily locate protocols from the literature, preprints, and patents, while comparing them to identify the best protocols and products for their Formoterol studies.
This can enhance reproducibility and accuracy in Formoterol research.
It works by relaxing and opening airways to improve breathing.
Formoterol has a rapid onset of action and a long duration of efect, making it an important therapeutic option for managing airway obstruction.
Researchers can use PubCompare.ai to easily locate protocols from the literature, preprints, and patents, while comparing them to identify the best protocols and products for their Formoterol studies.
This can enhance reproducibility and accuracy in Formoterol research.
Most cited protocols related to «Formoterol»
Chronic Obstructive Airway Disease
Conferences
Dry Powder Inhaler
Ethics Committees, Research
Formoterol
Patients
Placebos
The efficacy analysis set (i.e. intent-to-treat population) included all randomized patients who received at least one dose of randomized study medication and contributed sufficient data for at least one co-primary or secondary efficacy endpoint to be calculated during the randomized treatment period. The safety analysis population included all randomized patients who received at least one dose of randomized study medication and from whom any post-randomization data were available. For the subsets of patients who underwent serial spirometry, 24-hour urinary cortisol, BMD, 24-hour Holter monitoring and ophthalmological analyses, analysis sets were defined as those patients who received at least one dose of randomized study medication and had baseline and on-treatment values for the variable being assessed. Patients who discontinued prematurely completed final visit (month 12) assessments at the time of discontinuation, followed by the 4-week follow-up. A sample size of approximately 400 patients per treatment group was calculated to allow 90% power to detect a reduction in the number of COPD exacerbations of approximately 30%, adjusting for overdispersion of 2.3. This sample size ensured >95% power to detect a difference of 0.10L in FEV1, given an estimated standard deviation of 0.3 L. All tests were two-sided, with p ≤ 0.05 considered significant.
The prespecified primary comparators were formoterol DPI for pre-dose FEV1 to demonstrate the contribution of budesonide and placebo for 1-hour post-dose FEV1. To address issues of multiplicity relating to multiple-dose comparisons and multiple variables of interest, a fixed-sequence testing procedure was adopted. The primary comparisons were prespecified as budesonide/formoterol pMDI 320/9 μg compared with (i) placebo for pre-dose FEV1 and 1-hour post-dose FEV1; and (ii) formoterol DPI 9 μg for pre-dose FEV1. If significant differences were obtained, comparisons continued with budesonide/formoterol pMDI 320/9 μg compared with placebo for (i) dyspnoea; (ii) SGRQ total score; and (iii) number of exacerbations. If significant differences were obtained for each of these key secondary variables, the lower dose of budesonide/formoterol pMDI was tested on the co-primary variables, as previously described, and, if significant differences were obtained, testing continued with number of exacerbations, dyspnoea and SGRQ total score compared with placebo. For all secondary efficacy variables, the primary comparison was budesonide/formoterol pMDI versus placebo.
Primary and secondary variables were assessed as the change from baseline to the average over the randomized treatment period except for average 12-hour FEV1, mean FEV1 at 12 hours and SGRQ at end of treatment. Changes from baseline in the co-primary efficacy variables were analysed via analysis of co-variance (ANCOVA), adjusting for treatment, country and baseline value. The following three key secondary efficacy variables were identified: (i) dyspnoea; (ii) SGRQ total score; and (iii) exacerbations. Secondary variables were analysed similar to the co-primary efficacy variables; however, exacerbation rate (number/patient-treatment year) was analysed using a Poisson regression model, adjusted for country and differential randomization time, and time to first COPD exacerbation was described via Kaplan-Meier plot and analysed using the log-rank test. The number and percentage of patients experiencing clinically meaningful changes (based on a prespecified minimal important difference) in dyspnoea were analysed using the Cochran-Mantel-Haenszel test, adjusting for country.
Geometric mean 24-hour urinary cortisol levels at end of treatment were compared between treatment groups using a multiplicative ANCOVA model. Mean changes from baseline to the average during the randomized treatment period in 12-lead ECG, and Holter variables and ophthalmology variables were analysed using a model similar to that used for the co-primary variables. BMD variables (natural logarithm of the analysis timepoint minus the natural logarithm of the respective baseline value for hip and spine) were analysed using an ANCOVA model adjusting for country, treatment and natural logarithm of the baseline value. Other safety data were summarized using descriptive statistics. No formal hypothesis testing of the safety data was performed.
The prespecified primary comparators were formoterol DPI for pre-dose FEV1 to demonstrate the contribution of budesonide and placebo for 1-hour post-dose FEV1. To address issues of multiplicity relating to multiple-dose comparisons and multiple variables of interest, a fixed-sequence testing procedure was adopted. The primary comparisons were prespecified as budesonide/formoterol pMDI 320/9 μg compared with (i) placebo for pre-dose FEV1 and 1-hour post-dose FEV1; and (ii) formoterol DPI 9 μg for pre-dose FEV1. If significant differences were obtained, comparisons continued with budesonide/formoterol pMDI 320/9 μg compared with placebo for (i) dyspnoea; (ii) SGRQ total score; and (iii) number of exacerbations. If significant differences were obtained for each of these key secondary variables, the lower dose of budesonide/formoterol pMDI was tested on the co-primary variables, as previously described, and, if significant differences were obtained, testing continued with number of exacerbations, dyspnoea and SGRQ total score compared with placebo. For all secondary efficacy variables, the primary comparison was budesonide/formoterol pMDI versus placebo.
Primary and secondary variables were assessed as the change from baseline to the average over the randomized treatment period except for average 12-hour FEV1, mean FEV1 at 12 hours and SGRQ at end of treatment. Changes from baseline in the co-primary efficacy variables were analysed via analysis of co-variance (ANCOVA), adjusting for treatment, country and baseline value. The following three key secondary efficacy variables were identified: (i) dyspnoea; (ii) SGRQ total score; and (iii) exacerbations. Secondary variables were analysed similar to the co-primary efficacy variables; however, exacerbation rate (number/patient-treatment year) was analysed using a Poisson regression model, adjusted for country and differential randomization time, and time to first COPD exacerbation was described via Kaplan-Meier plot and analysed using the log-rank test. The number and percentage of patients experiencing clinically meaningful changes (based on a prespecified minimal important difference) in dyspnoea were analysed using the Cochran-Mantel-Haenszel test, adjusting for country.
Geometric mean 24-hour urinary cortisol levels at end of treatment were compared between treatment groups using a multiplicative ANCOVA model. Mean changes from baseline to the average during the randomized treatment period in 12-lead ECG, and Holter variables and ophthalmology variables were analysed using a model similar to that used for the co-primary variables. BMD variables (natural logarithm of the analysis timepoint minus the natural logarithm of the respective baseline value for hip and spine) were analysed using an ANCOVA model adjusting for country, treatment and natural logarithm of the baseline value. Other safety data were summarized using descriptive statistics. No formal hypothesis testing of the safety data was performed.
Budesonide
Chronic Obstructive Airway Disease
Drug Combination, Budesonide-Formoterol
Dyspnea
Electrocardiography, 12-Lead
Formoterol
Hydrocortisone
Patients
Placebos
Safety
Spirometry
Urine
Vertebral Column
This 24-week, multicentre, randomised, double-blind, double-dummy, 3-arm, parallel-group trial (NCT03034915; GSK study: 201749) was conducted between June 2017 and June 2018 in 213 centres in Germany, USA, Argentina, Sweden, Canada, Italy, South Africa, Netherlands, Spain, Australia, France, and Mexico. Patients were randomised 1:1:1 to once-daily fixed-dose combination UMEC/VI (62.5/25 μg) via the ELLIPTA inhaler and twice-daily placebo via the DISKUS inhaler, once-daily UMEC (62.5 μg) via ELLIPTA inhaler and twice-daily placebo via DISKUS, or twice-daily salmeterol (50 μg) via DISKUS and once-daily placebo via ELLIPTA inhaler (Additional file 6 : Figure S1). Salmeterol was selected as a comparator as no once-daily LABAs were approved at standard doses in all countries participating in the study; its use also allowed the LABA treatment to be easily blinded compared with the alternative twice-daily LABA, formoterol. UMEC was selected as it is a component of the dual bronchodilator and it has also demonstrated superior lung function benefits compared with tiotropium [17 (link)].
This study was performed according to the Declaration of Helsinki and received appropriate ethical approval. All patients provided written informed consent via a form signed at either the Pre-screening or Screening visit.
This study was performed according to the Declaration of Helsinki and received appropriate ethical approval. All patients provided written informed consent via a form signed at either the Pre-screening or Screening visit.
Bronchodilator Agents
Formoterol
Inhaler
Patients
Placebos
Respiratory Physiology
Salmeterol
Tiotropium
Snapwell filters containing fully differentiated NHBE cells were rinsed with Krebs-Henseleit solution (KH), and then mounted in Ussing chambers (EasyMount Chambers; Physiologic Instruments, San Diego, CA, USA) containing KH in apical and basolateral chambers. Solutions were maintained at 37 °C by heated water jackets, and were continuously bubbled with a 95 % room air / 5 % CO2 mixture to maintain the pH at 7.4. To monitor short-circuit current (ISC), the transepithelial membrane potential was clamped at 0 mV with a six-channel voltage clamp (model VCC MC6; Physiologic Instruments) using Ag/AgCl electrodes in agar bridges. Signals were digitized and recorded with DAQplot software (VVI Software, College Station, PA, USA) via a LabJack A/D converter (LabJack Corp., Lakewood, CO, USA). The input resistance of each filter was measured by the application of 1 mV bipolar pulses of 2-s duration. To eliminate any contribution to the Isc by epithelial sodium channels, 10 μM amiloride was added to the apical chamber. Once the Isc stabilized, roflumilast (100 nM) was included in the apical and basolateral perfusate. After a 20 min pre-treatment with roflumilast, 10 μM albuterol or 10 μM forskolin was added to the apical perfusate, and the resulting increase in chloride conductance was measured as Isc. To assure that conductance changes were related to CFTR, Isc decreases upon apical addition of 10 μM CFTRinh 172 were measured as well. To study the combination effect of long acting ß-mimetics and roflumilast, cultures were incubated with 100 nM roflumilast, 100 nM formoterol, both or none for 2 h before exposures to smoke or air. In the Ussing chamber, an additional 10 μM of albuterol was added but to assess the overall influence on CFTR conductance; then Isc decreases upon addition of the CFTR inhibitor CFTRinh17 were assessed.
Agar
Albuterol
Amiloride
Cells
CFTR protein, human
Chlorides
Colforsin
Formoterol
Krebs-Henseleit solution
Membrane Potentials
physiology
Pulses
Roflumilast
Smoke
Sodium Channel, Epithelial
The ACLIFORM-COPD study (ClinicalTrials.gov NCT01462942) was a double-blind, randomised, parallel-group, active- and placebo-controlled, multicentre study conducted at 193 centres in 22 countries (see Additional file 1 ). The first patient enrolled on 26 October 2011; the last patient completed 4 January 2013.
Following screening and a 2–3-week run-in period, patients with stable, moderate-to-severe COPD were randomised 2:2:2:2:1 to 24 weeks of double-blind treatment with twice-daily aclidinium/formoterol FDC 400/12 μg or 400/6 μg, aclidinium 400 μg, formoterol 12 μg or placebo, all via a breath-actuated, multiple-dose dry powder inhaler (Genuair®/Pressair®a; Almirall S.A., Barcelona, Spain).
This study was conducted in accordance with the Declaration of Helsinki, International Conference on Harmonisation/Good Clinical Practice Guidelines, and local regulations. The protocol was approved by the regulatory authority for each country and an independent ethics committee at each centre (Additional file1 : Table S1). Patients gave written informed consent.
Following screening and a 2–3-week run-in period, patients with stable, moderate-to-severe COPD were randomised 2:2:2:2:1 to 24 weeks of double-blind treatment with twice-daily aclidinium/formoterol FDC 400/12 μg or 400/6 μg, aclidinium 400 μg, formoterol 12 μg or placebo, all via a breath-actuated, multiple-dose dry powder inhaler (Genuair®/Pressair®a; Almirall S.A., Barcelona, Spain).
This study was conducted in accordance with the Declaration of Helsinki, International Conference on Harmonisation/Good Clinical Practice Guidelines, and local regulations. The protocol was approved by the regulatory authority for each country and an independent ethics committee at each centre (Additional file
Chronic Obstructive Airway Disease
Conferences
Dry Powder Inhaler
Ethics Committees
Formoterol
Patients
Placebos
Most recents protocols related to «Formoterol»
Budesonide and formoterol fumarate powder for inhalation (AstraZeneca AB: 160 ug budesonide and 4.5 μg of formoterol per inhaler, one inhaler every 12 h) plus montelukast (Merck Sharp & Dohme Ltd.: 10 mg per night) for 8 weeks.
Budesonide
Formoterol
Formoterol Fumarate
Inhalation
Inhaler
montelukast
Powder
A total of 198 patients with asthma and 453 non-asthmatic healthy controls were recruited from China Medical University Hospital (CMUH) as previously described (Hsia et al., 2015 (link); Li et al., 2021 (link)). The diagnosis of asthma was based on the following inclusion criteria: (1) more than two or three episodes of wheezing and shortness of breath during the past year; (2) diagnosis of asthma by pulmonologists together with the demonstration of reversible and variable airflow obstruction by spirometry; (3) symptoms; and (4) prescription of medications for asthma. No children were recruited (the youngest being 25 years old) and there was no sex restriction. The controls were selected by frequency-matching to cases by age and sex after initial random sampling from the Health Examination Cohort of CMUH. The inclusion criteria for controls were: (1) no past or present physician’s diagnosis of asthma and other pulmonary diseases; (2) no history of wheezing, shortness of breath, or other symptoms of allergic diseases such as nasal and skin symptoms; (3) no use of medications for asthma; (4) absence of first-degree relatives with a history of asthma; and (5) older than 25 years. Those with chronic inflammatory responses, diabetes, stroke and cancer were also excluded for both cases and controls, the flow chart of participant recruitment scheme was shown in Fig. 1 . The symptom severity for each asthma case was verified by two experienced pulmonologists according to the Global Initiative for Asthma (GINA) guidelines (for Asthma, 2022 ). Specifically, symptom severities were classified into four groups based on the treatment to control the symptoms and exacerbations. Group 1 (mildest): treated with as-needed inhaled corticosteroid (ICS)-formoterol alone; Group 2, treated with low-intensity maintenance controller treatment of ICS-formoterol, leukotriene receptor antagonists or chromones; Group 3, treated with low dose ICS-long acting β2 agonist (LABA); and Group 4, treated (severest) with high dose ICS-LABA. Peripheral blood was collected from all subjects and genomic DNA was extracted and stored until genotyping (Yang et al., 2017b (link)). This study was approved by the Research Ethics Committee of the China Medical University Hospital (CMUH106-REC1-004). All protocols were conducted in accordance with relevant guidelines. All patients provided written informed consent at the time of recruitment.
Adrenal Cortex Hormones
Asthma
BLOOD
Cerebrovascular Accident
Child
Chromones
Diabetes Mellitus
Diagnosis
Dyspnea
Ethics Committees, Research
Formoterol
Genome
Hypersensitivity
Inflammation
Inhalation Therapy
Leukotriene Antagonists
Lung Diseases
Malignant Neoplasms
Nose
Patients
Pharmaceutical Preparations
Physicians
Prescription Drugs
Pulmonologists
Skin
Spirometry
For fluorescent CREB reporter experiments, cells were seeded on 6-well plates and transduced with lentiviral supernatant containing the fluorescent CREB reporter.8 (link) Cells were maintained for 5-7 days before experiments. On the experiment day, cells were treated for 4 hours with 1 μM Shield-1 ligand alone (basal) or with 1 μM Shield-1 ligand and one of the following: 1 μM isoproterenol, 10 μM epinephrine, 10μM norepinephrine, 50 nM salbuterol, 10 μM terbutaline, 10 μM formoterol prior to fluorescence reading using the BD FACS Canto2 flow cytometry instrument. For pCRE-DD-tdTomato experiments, cells were treated with 1 μM Shield-1 ligand alone (basal) or with 1 μM Shield-1 ligand and 1 μM isoproterenol for 6h. We used a BD LSRFortessa flow cytometry instrument and gated for gRNA-expressing (BFP+) and RBM12 construct-expressing (GFP+) singlets. From these measurements, the fold change (induced / basal) mean of the NTC gRNA + empty vector cells was averaged and set to 1, and the PE (tdTomato) mean for all other samples was normalized to this value (expressed as fold of mean NTC value).
Cells
Cloning Vectors
Epinephrine
Flow Cytometry
Fluorescence
Formoterol
Isoproterenol
Ligands
Norepinephrine
tdTomato
Terbutaline
The CPP test was used to determine the ability of Formoterol in exerting pain relief from ongoing pain, as described previously [35 (link)]. Test mice were conditioned to associate one of the two compartments with pain relief. Behavioral testing was performed between 9:00 a.m. and 4:00 p.m. in the 9-week-old mice and every session lasted 30 min. Baseline preferences were detected before the conditioning by placing the mice on the setup and letting them freely move between the chambers. Conditioning started one day after the baseline detection. Each day for three days, the mice were injected first with saline and after 10 min they were inserted in the assigned chamber. After at least 4 h from the saline injection, the mice were injected with Formoterol and 50 min later they were placed in the other chamber. The day after conditioning, the mice were placed on the setup and let to move freely across the chambers. The CPP sessions were video-recorded and scored using ANY-maze (Stoelting Europe, Churchtown, Dublin, Ireland, ANY-maze 7.1) for the time spent in the two compartments. The change in time spent in the Formoterol chamber, referred to as score, is calculated as the difference in time spent in the Formoterol-associated chamber on the baseline and test day.
Formoterol
MAZE protocol
Mice, House
Pain
Saline Solution
Mice were i.p. injected with 50 μg/kg of Formoterol (cat # 1448, Tocris, Wiesbaden-Nordenstadt, Germany) [32 (link)] or its solvent (0.9% NaCl) 1 h before behavioral analysis or perfusion for immunofluorescence experiments.
Formoterol
Immunofluorescence
Mice, House
Normal Saline
Perfusion
Solvents
Top products related to «Formoterol»
Sourced in Spain, Germany, United States, Canada
Formoterol is a selective long-acting beta2-adrenergic receptor agonist used in the management of asthma and chronic obstructive pulmonary disease (COPD).
Sourced in United Kingdom
Formoterol is a laboratory reagent used in cell culture and biochemical research applications. It functions as a beta-2 adrenergic receptor agonist, which can be utilized to study signaling pathways and cellular responses related to this receptor. The core function of Formoterol is to activate the beta-2 adrenergic receptor, enabling researchers to investigate its effects on cellular processes.
Sourced in United States, United Kingdom, Germany, France, Sao Tome and Principe
Isoprenaline is a laboratory reagent used as a research tool in various scientific applications. It functions as a synthetic catecholamine and is commonly utilized in experiments related to physiology, pharmacology, and biochemistry. The core function of Isoprenaline is to act as a non-selective beta-adrenergic agonist, which can be used to study the effects of beta-adrenergic receptor activation in various experimental models.
Sourced in United States, Germany, Sweden, United Kingdom
Budesonide is a synthetic corticosteroid used in the treatment of various respiratory conditions. It is a white or almost white, crystalline powder that is practically insoluble in water and slightly soluble in alcohol. Budesonide is commonly used in the development and manufacture of pharmaceutical products for respiratory diseases.
Sourced in United States, Germany, United Kingdom, France, Sao Tome and Principe, Canada, Italy, Japan, China, Switzerland, Macao, Australia
Forskolin is a lab equipment product manufactured by Merck Group. It is a compound derived from the roots of the Coleus forskohlii plant. Forskolin is used as a tool for research purposes in the laboratory setting.
Sourced in United States
Formoterol fumarate dehydrate is a chemical compound used in the production of pharmaceutical products. It is a beta-2 adrenergic agonist, which means it can stimulate the beta-2 receptors in the body. This compound is commonly used in the development of medications for respiratory conditions, such as asthma and chronic obstructive pulmonary disease (COPD).
Sourced in United Kingdom
Bevespi® is a combination inhalation device that contains two active ingredients: glycopyrrolate and formoterol fumarate. It is designed for the maintenance treatment of chronic obstructive pulmonary disease (COPD).
Sourced in United States, Germany, United Kingdom, Canada, Brazil, Australia, France
Bradykinin is a lab equipment product manufactured by Merck Group. It is a peptide that plays a role in the regulation of blood pressure and inflammation. Bradykinin functions by interacting with specific receptors on cell surfaces.
Sourced in United States, United Kingdom
Salmeterol is a lab equipment product manufactured by the Merck Group. It is a metered-dose inhaler used for the treatment of respiratory conditions.
Sourced in United Kingdom
SYBR green Precision MasterMix is a ready-to-use qPCR reagent. It contains SYBR Green I dye, optimized buffer, and enzymes necessary for real-time PCR amplification and detection.
More about "Formoterol"
Formoterol is a long-acting beta-2 adrenergic agonist (LABA) medication used to treat the symptoms of asthma and chronic obstructive pulmonary disease (COPD).
It works by relaxing and opening the airways, making it easier to breathe.
Formoterol has a rapid onset of action and a long duration of effect, making it an important therapeutic option for managing airway obstruction.
Researchers can utilize PubCompare.ai, an AI-driven platform, to easily locate and compare protocols from the literature, preprints, and patents related to Formoterol.
This can help identify the best protocols and products for their Formoterol studies, enhancing reproducibility and accuracy in their research.
Formoterol is often used in combination with other medications, such as the corticosteroid Budesonide, to provide more comprehensive treatment for respiratory conditions.
The bronchodilator Isoprenaline and the adenylyl cyclase activator Forskolin are also related compounds that may be of interest in Formoterol research.
When studying Formoterol, researchers may also encounter the Formoterol fumarate dehydrate salt form, which is used in some Formoterol-containing products like the Bevespi® inhaler.
Additionally, Salmeterol, another LABA, and SYBR green Precision MasterMix, a fluorescent dye used in qPCR experiments, may be relevant in the context of Formoterol research.
Bradykinin, a peptide that can cause bronchoconstriction, is another factor that may be considered when investigating the mechanisms of Formoterol and its effects on the respiratory system.
By understanding the broader context of Formoterol and related terms, researchers can optimize their studies and enhance the impact of their Formoterol research.
It works by relaxing and opening the airways, making it easier to breathe.
Formoterol has a rapid onset of action and a long duration of effect, making it an important therapeutic option for managing airway obstruction.
Researchers can utilize PubCompare.ai, an AI-driven platform, to easily locate and compare protocols from the literature, preprints, and patents related to Formoterol.
This can help identify the best protocols and products for their Formoterol studies, enhancing reproducibility and accuracy in their research.
Formoterol is often used in combination with other medications, such as the corticosteroid Budesonide, to provide more comprehensive treatment for respiratory conditions.
The bronchodilator Isoprenaline and the adenylyl cyclase activator Forskolin are also related compounds that may be of interest in Formoterol research.
When studying Formoterol, researchers may also encounter the Formoterol fumarate dehydrate salt form, which is used in some Formoterol-containing products like the Bevespi® inhaler.
Additionally, Salmeterol, another LABA, and SYBR green Precision MasterMix, a fluorescent dye used in qPCR experiments, may be relevant in the context of Formoterol research.
Bradykinin, a peptide that can cause bronchoconstriction, is another factor that may be considered when investigating the mechanisms of Formoterol and its effects on the respiratory system.
By understanding the broader context of Formoterol and related terms, researchers can optimize their studies and enhance the impact of their Formoterol research.