This video introduces the active ingredient of Arnuity Ellipta, i.e., fluticasone furoate (FF) for the once-daily treatment of asthma. FF is a dry inhalation powder which has recently been introduced to the market at 2014. It had underwent different phases of clinical trial, with each having a specific purpose in order to test the safety, dosage and efficacy of the drug. The video includes introduction of asthma, pharmacology of drug, clinical trial, adverse effect and current status of FF. This video was made students from University of Malaya, undertaking an elective course of MIX3003 Drugs: From Target to Market
Asthma is a chronic disease of the airways that makes breathing difficult with asthma there is inflammation of the air passages that results in a temporary narrowing of the airways that carry oxygen to the lungs in an inflamed airway of an asthma patient the airway experienced reduced lumen diameter blood vessels filled with immune cell infiltration excess mucus
Was produced and contracted smooth muscle with inflammation and swelling from dk zone if you’re out ff it is a synthetic dry fluorinated corticosteroid and this is the chemical structure of ff fonti tessoni feraud is modified from fluticasone e propionate it has higher affinity longer half-life and suitable for one’s daily administration the precise mechanism of
Ff is not known corticosteroids reduce our waste sensitivity and inflammation they are also crucial in preventing long-term damage from chronic inflammation which can cause scarring of the airways the pharmacodynamic of drug was shown by hypothalamic-pituitary-adrenal axis effect in both althea invation group none of them have significant decrease in serum or
Urinary cortisone level after absorption of the drug it would be delivered into the lung the mean volume of distribution of drug is 661 liter ff will be metabolized and cleared form the body by the liver finally ff will pass out from body by feces before introducing into human clinical trials the candidate drug is to go through a series of preclinical studies
Preclinical studies were conducted on cell lines and animal models in vitro studies were conducted on human lung epithelial cell lines to study the anti-inflammatory activity protective effects selectivity and retention activity of fluty casoni feraud ffs with other glucocorticoids gc available in the market the study concludes that ff shows the highest potency
Greatest protective potency highly selected and bind in to a greater degree and as compared with other gc in vivo study was conducted on oval human induced as in the res model to study the anti-inflammatory effect of ffs when ff was given and fortran chile and a dose of just 30 microgram it was essentially completely inhibited the longo scene ophelia in the brown
Norway rat after that ffs and her clinical trial fees one trial was conducted to investigate safety tolerability safe dosage range and potential side effects of ffs it involved twenty participants those with clinically stable persistent asthma screening pre bronchodilator fev1 greater or equal to sixty percent and nonsmoker were involved on the other hand pregnant
Or nursing females and those with history of life-threatening asthma are excluded the trial participants were randomly assigned to experimental or control groups from the findings ff was well tolerated by trial subjects so ff is safe to proceed to phase two phase two trial investigate effectiveness optimal dose required and short-term safety of ff the trials were
Double blinded randomized studies to evaluate morning versus evening dosing the timing and frequency of dosing and the frequency of dosing with one’s daily doses or twice daily doses the results suggested that either morning or evening dosing was reasonable and once daily dosing frequency was appropriate then eight doses of ff ranging from 25 to 800 micrograms
Once daily were evaluated to compare one’s daily dose of ff subjects were uncontrolled at baseline on treatments of medium doses low doses or none inhaled corticosteroid therapy the primary endpoint was the mean change from baseline and trough fev1 as a result a dose related increase in trough fev1 at week eight was seen four doses from 25 to 200 micrograms with
No consistent additional benefit produces above 200 micrograms to evaluate dosing frequency ff 200 micrograms once daily and 100 micrograms twice daily was compared the results supported the selection of the once daily dosing frequency the most frequently reported adverse effect for phase 2 is upper respiratory tract infection sinusitis today can cough ff proceed
To phase 3 trial in order to generate statically significant evidence and confirmed the safety and effectiveness the trials were multicenter double blinded randomized and placebo controlled clinical trials conducted for 24 weeks in subjects aged above 12 years old with persistent asthma the trials were designed to evaluate the efficacy of ff given once daily in
The dose of 100 and 200 micrograms on lung function in subjects who were not controlled on their current treatments of inhaled corticosteroids her combination therapy the study showed the improvement from baseline and trough fev1 with difference of 77 ml for ff with 200 micrograms another trial evaluated the efficacy of ff 200 micrograms with a standard treatment
Fluticasone e propionate f pe 500 micrograms twice daily the study showed the improvement from baseline and weighted mean fev1 with difference of 70 ml 4 ff subjects receiving ff 200 micrograms once daily head of statistically significantly greater improvement in 2 days without the need of emergency medication besides lung function improvements were sustained 1.5
Days from the baseline ff 200 micrograms also show 64.8% reduction in rate of exacerbations per patient per year adverse reactions of ff include nasopharyngitis headache oral candidiasis sinusitis bronchitis and coughing based on findings of the three dose ranging trials and four confirmatory trials and finally get approval from fda in august 2014 this drug is
Patented by gsk pharmaceutical company ff is still under prescription as it legally requires a medical prescription to be dispensed currently phase four trial is still ongoing to evaluate the benefits potential risk optimal use and studies in specific populations which involve a larger population
Transcribed from video
Once-daily Fluticasone furoate: the saviour for asthma By Kar Cheng Wong
