Clinical trial NCT02113436: Efficacy and Safety of Fluticasone Propionate(FP)/ Salmeterol Xinafoate (SLM) Hydro Fluoro Alkane (HFA) Metered Dose Inhaler (MDI) in Pediatric Patients With Bronchial Asthma
Official title: Clinical Assessment of Fluticasone Propionate/ Salmeterol Xinafoate HFA MDI in 6-month to 4-year-old Japanese Patients With Bronchial Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Asthma
Keywords: FP/SLM
Asthma
Infant
Efficacy
Safety
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2014-04-14
Enrollment: 300
Sex: ALL
Minimum age (years): 6
Maximum age (years): 4
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is a multicenter, stratified, randomized, active control, double-blinded, parallel-group comparative study with an open-label extension period. The study is designed to evaluate the efficacy and safety of FP/ SLM HFA MDI 50/25 microgram (mcg) one or two inhalation twice daily (BID) for 8 weeks in comparison with FP HFA MDI 50 mcg one or two inhalation BID, in 6-month to 4-year-old Japanese patients with bronchial asthma. The study is also designed to evaluate the safety of long-term treatment of FP/ SLM HFA MDI 50/25 mcg one or two BID for 16 weeks.

The subjects meeting the eligibility criteria will enter the run-in period of 2 weeks and receive FP 50 mcg 1 or 2 inhalation bid (FP 100 or 200 mcg/day), before randomization. The subjects under 2 years of age at Visit 1 will receive only 1 inhalation bid during the run-in period. The subjects who meet the eligibility criteria for randomization will be stratified according to their age (\<2 or \>=2 year-old) at Visit 1 and randomized to one of the two treatment groups.

The total duration of participation in the study will be 10 weeks for a comparison period completion and 27 weeks for a completion.


Eligibility criteria: Inclusion Criteria:

* The written informed consent must be obtained from his/her parent or legally acceptable representative. If the investigator can get the oral consent from the patient, the investigator should record so in the informed consent which is signed by his/her parent or legally acceptable representative.
* Ethnic origin is Japanese
* Aged \>=6 months and \<=4 years at Visit 1.
* Male and pre-menarchial female. Pre-menarchial females are defined as any female who has yet to begin menses.
* Patient: outpatient
* Diagnosis as a pediatric asthma has been made by reference to JPGL 2012 and the document which is of help as evidence should be kept as source document. As for \<2 years old, children are going to be diagnosed according to an instruction as follows in JPGL2012 as a reference. There are 3 or more episodes of marked expiratory wheezing, regardless of the presence of respiratory tract infection. It is also needed to confirm that there is asymptomatic period for about a week between each episode. In addition to this finding, if there is at least one of following findings, it is more helpful to diagnose infantile asthma: At least one of parents is diagnosed with bronchial asthma by a physician (including past history); Specific immunoglobulin E (IgE) antibody for inhalation antigen is detected in at least one of parents; Diseased child is diagnosed with atopic dermatitis by a physician (including past history); Specific IgE antibody for inhalation antigen is detected in diseased child; High serum IgE level in diseased child or his/her family (serum IgE level should be determined by considering age); Eosinophils and creola bodies found in sputum (examine nasal discharge eosinophilia and peripheral blood eosinophilia); Expiratory wheezing occurs when there is no airway infection; Expiratory wheezing and labored respiration or oxygen saturation are improved after beta-2 stimulant inhalation.
* A patient who needs to be treated with Inhaled corticosteroid (ICS)/ Long-acting beta 2 agonist (LABA) and fulfill following all conditions: At least one documented exacerbation in that the patient treated with systemic glucocorticosteroids, aminophylline dose intravenous(d.i.v) or continuous isoproterenol inhalation in the 12 months prior to Visit 1. Or a well-documented regular treatment with ICS (FP 200-400 mcg daily or equivalent) continuous use in the 12 months prior to Visit 1; The patient has not received systemic glucocorticosteroids, aminophylline d.i.v., ICS (FP\>200 mcg daily or equivalent) or continuous isoproterenol inhalation within 4 weeks prior to Visit 1.

Exclusion Criteria:

* A patient who has suffered from upper and lower respiratory tract infection and then received medication within 2 weeks prior to Visit 1.
* A patient who is diagnosed upper and lower respiratory tract infection at Visit 1. Or a patient who has or is suspected to have deep-seated mycosis or infection to which no effective antibacterial agent is available. Or a patient who is suspected to have respiratory syncytial (RS) virus infection and cannot be identified to be negative for RS virus antigen.
* A patient who has respiratory disorder other than bronchial asthma, and the investigator judges the respiratory disorder affect the assessment of efficacy in this study.
* A patient who has unstable liver disease or chronic stable hepatitis B receiving significant immunosuppressive agents due to risk of hepatitis B reactivation.
* A patient who has malformation/foreign particle lodged in an airway. Or subjects who have known, pre-existing, clinically significant gastroesophageal reflux disease , endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic, haematological or any other system abnormalities that are uncontrolled with standard treatment.
* A patient who has or is suspected to have hypersensitivity to study medications, the rescue medication or any ingredients of them.
* A patient who has been treated with another investigational product within 1 months prior to Visit 1 or within five half-lives (t-half) of the prior investigational study (whichever is the longer of the two).
* As for the patients who has evaluable ECG data at Visit 1, QT interval corrected (Fridericia) for heart rate (QTc\[F\])\>=450 milliseconds (msec). The QT interval corrected for heart rate (QTc) should be based on averaged QTc values of triplicate electrocardiograms (ECGs) obtained over a brief recording period. As for the patients who don't has evaluable ECG data at Visit 1, if the patient has known prolonged QTc\>=450 msec (any correction is valid), the patient will be excluded.
* A patient who is child in care (including foster parent system), or whom the investigator judges inappropriate for the study.

Randomization Inclusion Criterion :

* A patient who has asthma symptoms scores (total of daytime and night-time) both over \>=6 in total and \>=1 per day for \>=3 days at the last 7 consecutive days of the run-in period (excluding the day of Visit 2). Completion of symptom scores (daytime and night-time) on 5 or more days out of the last 7 consecutive days during the run-in period is required.

Randomization Exclusion Criteria :

* A patient who has received systemic steroids during run-in period.
* A patient who has suffered from or is suspected to have upper and lower respiratory tract infection that may affect the assessment of the efficacy during the run-in period. Or a patient who has or is suspected to have deep-seated mycosis or infection to which no effective antibacterial agent is available during the run-in period. Or a patient who is suspected to have RS virus infection and cannot be identified to be negative for RS virus antigen during run-in period.
* A patient who has no evaluable ECG data during the run-in period. As for the patients who has evaluable ECG data during the run-in period, QTc(F) \>=450 msec. The QTc should be based on averaged QTc values of triplicate electrocardiograms (ECGs) obtained over a brief recording period.
* A patient who has not been able to appropriately record patient diary or inhale FP appropriately during the run-in period, in the opinion of the investigator.

Primary outcomes:
measure: Mean Change From Baseline in Total Asthma Symptom Score (Daytime Plus Night Time) at the End of the Treatment Period 1 (TP1)
timeFrame: Baseline and Week 8
Secondary outcomes:
measure: Mean Change From Baseline in Night-time Asthma Symptoms Score at the End of Treatment Period 1 (TP1)
timeFrame: Baseline and Week 8
measure: Mean Change From Baseline in Daytime Asthma Symptoms Score at the End of Treatment Period 1 (TP1)
timeFrame: Baseline and Week 8
measure: Number of Participants With at Least One Asthma Exacerbation in Treatment Period 1 (TP1)
timeFrame: Up to 8 weeks
measure: Mean Change From Baseline in Japanese Pediatric Asthma Control Program (JPAC) Score at the End of Treatment Period 1 (TP1)
timeFrame: Baseline and Week 8
measure: Mean Change From Baseline in Use of Rescue Medication (Number of Occasions Used During a 24-hour Period) in Treatment Period 1 (TP1)
timeFrame: Baseline and Week 8
measure: Mean Change From Baseline in Use of Rescue Medication (Percentage of Days With Rescue-free 24-hour Period) at the End of Treatment Period 1 (TP1)
timeFrame: Baseline and Week 8
measure: Mean Change From Baseline in Total Asthma Symptom Score (Daytime Plus Night Time) at the End of the Treatment Period 2 (TP2)
timeFrame: Baseline and Week 24
Other outcomes:
Locations:
city: Aichi
country: Japan
facility: GSK Investigational Site
city: Aichi
country: Japan
facility: GSK Investigational Site
city: Chiba
country: Japan
facility: GSK Investigational Site
city: Chiba
country: Japan
facility: GSK Investigational Site
city: Chiba
country: Japan
facility: GSK Investigational Site
city: Ehime
country: Japan
facility: GSK Investigational Site
city: Fukui
country: Japan
facility: GSK Investigational Site
city: Fukui
country: Japan
facility: GSK Investigational Site
city: Fukui
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Gifu
country: Japan
facility: GSK Investigational Site
city: Gunma
country: Japan
facility: GSK Investigational Site
city: Gunma
country: Japan
facility: GSK Investigational Site
city: Hiroshima
country: Japan
facility: GSK Investigational Site
city: Hiroshima
country: Japan
facility: GSK Investigational Site
city: Hiroshima
country: Japan
facility: GSK Investigational Site
city: Hiroshima
country: Japan
facility: GSK Investigational Site
city: Hiroshima
country: Japan
facility: GSK Investigational Site
city: Hiroshima
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Hyogo
country: Japan
facility: GSK Investigational Site
city: Hyogo
country: Japan
facility: GSK Investigational Site
city: Hyogo
country: Japan
facility: GSK Investigational Site
city: Ibaraki
country: Japan
facility: GSK Investigational Site
city: Ibaraki
country: Japan
facility: GSK Investigational Site
city: Ibaraki
country: Japan
facility: GSK Investigational Site
city: Ishikawa
country: Japan
facility: GSK Investigational Site
city: Kagawa
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Kumamoto
country: Japan
facility: GSK Investigational Site
city: Mie
country: Japan
facility: GSK Investigational Site
city: Miyagi
country: Japan
facility: GSK Investigational Site
city: Okayama
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Saga
country: Japan
facility: GSK Investigational Site
city: Saitama
country: Japan
facility: GSK Investigational Site
city: Saitama
country: Japan
facility: GSK Investigational Site
city: Saitama
country: Japan
facility: GSK Investigational Site
city: Saitama
country: Japan
facility: GSK Investigational Site
city: Tochigi
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Wakayama
country: Japan
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Yoshihara S, Tsubaki T, Ikeda M, Lenney W, Tomiak R, Hattori T, Hashimoto K, Soutome T, Kato S. The efficacy and safety of fluticasone/salmeterol compared to fluticasone in children younger than four years of age. Pediatr Allergy Immunol. 2019 Mar;30(2):195-203. doi: 10.1111/pai.13010. Epub 2019 Feb 6.