Efficacy and Safety of Flutiform K-haler in Patients With Uncontrolled Asthma Following Mid-dose ICS/LABA DPI Therapy
Efficacy and Safety of Flutiform K-haler in Patients With Uncontrolled Asthma Following Mid-dose ICS/LABA DPI Therapy
The purpose of this study is to evaluate the efficacy of the Asthma improvement of Flutiform
 K-haler after 12 weeks of treatment in patients with moderate to severe uncontrolled* asthma
 following mid-dose ICS/LABA DPI therapy.
Asthma is a chronic inflammatory allergic disease of airway involving many cells and various
 media. Airway inflammation causes various symptoms of airway hypersensitivity, including
 repeated wheezing, dyspnea, and tightness in the chest. An estimated 300 million people
 worldwide suffer from asthma, and in South Korea, an estimated asthma prevalence rate for
 adults is approximately 5% [1]. For more effective management of asthma, Global Initiative
 for Asthma (GINA) guideline[2] and Korean Asthma Management Guideline for Adults [1] suggests
 that for patients who cannot have asthma symptoms under control with ICS (Inhaled
 Corticosteroid) alone, concomitant treatment of ICS/LABA is more effective than dose increase
 of ICS, and therefore recommends ICS combined with Long-acting β2-agonist (LABA) products.
 Common ICS/LABA products that are available in the Korea market including dry power inhaler
 (DPI) and pressured metered dose inhaler (pMDI).

 It is known that small airway significantly contributes to total airway resistance, so the
 inflammation of the small airways could lead to the poor asthma control observed since small
 airways are not directly reached by inhaler's particles [3,4]. Fluticasone/formoterol
 (Flutiform®) shows a high fine particle fraction (FPF) of about 40% for both the ICS and the
 LABA components regardless the inhalation flow rate[5]. FPF of Fluticasone/formoterol is
 significantly higher than other ICS/LABA combinations. It is expected that small particles of
 fluticason/formoterol could reach to the large/small airways easier than other ICS/LABA
 combinations even if these ICS/LABAs shows a similar efficacy for asthma treatment. However
 Asthma patients can struggle to use their pMDI inhalers correctly due to the need to properly
 co-ordinate the press and inhale, which can worsen their asthma and lead to exacerbations.

 Flutiform K-haler is the first breath-actuated inhaled corticosteroid (ICS) long-acting
 β2-agonist (LABA) combination aerosol inhaler for adults and adolescents. The flutiform
 k-haler has been designed with patients in mind, requiring only a gentle inhalation to
 trigger the dose release, with the aim to help patients reduce critical errors and improve
 long-term outcomes.

 Therefore, It is expected that Flutiform K-haler prevents exacerbation and improves symptom
 of Asthma. Especially it will be beneficial to patients who did not response to existing
 ICS/LABA DPI in Korea. This study is planned to examine the efficacy and safety of Flutiform
 K-haler in patients who are not adequately controlled by previous mid-dose ICS/LABA DPI
 treatment.
Inclusion Criteria:

 1. Korean asthma patients age ≥ 19 years old

 2. Patients who have moderate to severe persistent asthma, as defined by GINA 2018
 guideline, with ICS/LABA DPI use history

 3. Patients who have uncontrolled asthma in FEV1 up to 60% and Asthma control test score
 < 20

 4. Female subjects of child bearing potential must have a negative urine pregnancy test
 prior to first dose of study medication and that they must be agree to use adequate
 contraception during the study period

 5. Patients who are able to use the inhaler

 6. Patients who is willing to voluntarily sign the study consent form

 Exclusion Criteria:

 1. Patients who have diagnosed as clinically significant pulmonary diseases

 2. Patients who have experienced life-threatening asthma within 12 months prior to
 screening or respiratory infection within 4 weeks prior to screening, or patients who
 have experienced any emergency visit or hospitalization due to acute asthma symptoms
 within 4 weeks prior to screening

 3. Current and past smoker: Smoker defined as below

 -  Current smoker: smoking history within 90 days prior to screening

 -  Past smoker: smoking amount >10 pack year

 4. Patients who currently are pregnant or lactating

 5. Patients who are participating or going to participate in any interventional clinical
 trials

 6. QT interval prolongation in ECG result at screening (420msec > male, 440msec > female)

 7. Patients with hypersensitive to investigational products or to any component of the
 drug

 8. Patients requiring treatment with any of the prohibited concomitant medications Use of
 the following medications is prohibited during the study due to drug-to-drug
 interaction with the study drug

 9. Patients who took SPIRIVA within 3 month prior to enrollment

 10. Patients who did not show previous DPI drug compliance between 70% ~130%