Clinical assessment of fluticasone propionate/ salmeterol xinafoate HFA MDI in 6-month to 4-year-old Japanese patients with bronchial asthma

• Register: EUCTR
• Last refreshed on: 14 November 2016
• Main ID: EUCTR2016-003479-22-Outside-EU/EEA
• Date of registration: 09/11/2016
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline Research and development Ltd
• Public title: Clinical assessment of fluticasone propionate/ salmeterol xinafoate HFA MDI in 6-month to 4-year-old Japanese patients with bronchial asthma
• Scientific title: Clinical assessment of fluticasone propionate/ salmeterol xinafoate HFA MDI in 6-month to 4-year-old Japanese patients with bronchial asthma
• Target sample size: 370
• Recruitment status: NA
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-003479-22
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Japan

Contacts

• Name: GSK Clinical Support Help Desk
• Affiliation: GlaxoSmithKline Research & Development Ltd

• Name: GSK Clinical Support Help Desk
• Affiliation: GlaxoSmithKline Research & Development Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
Inclusion Criteria
Specific information regarding warnings, precautions, contraindications, adverse events, and other pertinent information on the GSK investigational product or other study treatment that may impact subject eligibility is provided in the product label, add other pertinent documents.
Deviations from inclusion criteria are not allowed because they can potentially jeopardise the scientific integrity of the study, regulatory acceptability or subject safety. Therefore, adherence to the criteria as specified in the protocol is essential.
Subjects eligible for enrolment in the study must meet all of the following criteria:
1.Obtaining consent: The written informed consent must be obtained from his/her parent or legally acceptable representative. If the investigator (or subinvestigator) obtains the oral consent from the patient, the investigator (or subinvestigator) should record so in the informed consent form which is signed by his/her parent or legally acceptable representative.
2.Race: Japanese
3.Age: = 6 months and =4 years at Visit 1.
4.Sex: Male and premenarcheal female. Premenarcheal females are defined as any female who has yet to have menstruation.
5.Patients: Outpatient
6.Diagnosis of asthma: Diagnosis of infantile bronchial asthma is made by reference to JPGL2012 and the rationale is documented.
As for diagnosis of children of < 2 years old, the following description in JPGL2012 should be referenced [Japanese Society of Pediatric Allergy and Clinical Immunology, 2011].
- There are 3 or more episodes of obvious 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 episodes.
In addition to this finding, if there is at least one of the 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 IgE antibody for inhalation antigen is detected in at least one of parents.
- The diseased child is diagnosed with atopic dermatitis by a physician (including past history).
- Specific IgE antibody for inhalation antigen is detected in the diseased child.
- High serum IgE level in the diseased child or his/her family (serum IgE level should be determined in consideration of age).
- Eosinophils and creola bodies found in the sputum (increased eosinophils in nasal discharge and peripheral blood will be referenced).
- Expiratory wheezing occurs when seemingly there is no airway infection.
- Expiratory wheezing and labored respiration or oxygen saturation are improved after beta-2 stimulant inhalation.
7.Treatment of asthma: A patient who needs to be treated with ICS/LABA and fulfils all of the following conditions,
•At least one documented asthma exacerbation in that the patient treated with systemic glucocorticosteroids, aminophylline intravenous drip infusion (continuous drip infusion) or continuous isoproterenol inhalation within the 12 months prior to Visit 1. Or a well-documented continuous treatment with ICS (FP 200-400 micro g daily or equivalent) within 12 months prior to Visit 1.
•The patient has not received systemic glucocorticosteroids, aminophylline intravenous drip infusion (continuous drip infusion), ICS (FP > 200 micro g daily or equivalent) or continuous isoproterenol inhalation within 4 weeks prior to Visit 1.


Are the trial subjects under 18? yes
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Exclusion criteria:
Exclusion Criteria
Deviations from exclusion criteria are not allowed because they can potentially jeopardise the scientific integrity of the study, regulatory acceptability or subject safety. Therefore, adherence to the criteria as specified in the protocol is essential.
Subjects meeting any of the following criteria must not be enrolled in the study:
1.Concomitant medication (infectious diseases): A patient who had upper or lower respiratory tract infection and received concomitant medication within 2 weeks prior to Visit 1.
2.Infectious diseases: A patient who has confirmatory diagnosis of upper or lower respiratory tract infection at Visit 1; or a patient who has or is suspected to have deep mycosis or infection for which no effective antibacterial agent is available; or a patient who is suspected to have RS virus infection and cannot be identified to be negative for RS virus antigen.
3.Respiratory comorbidities: A patient who has respiratory disorder other than bronchial asthma, and the respiratory disorder is likely to have an impact on the assessment of efficacy in this study.
4.Liver disease: A patient who has unstable liver disease or chronic stable hepatitis B, receiving immunosuppressive agents due to risk of hepatitis B reactivation.
5.Other comorbidities: A patient who has malformation/foreign particle 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 abnormalities that are poorly controlled with standard treatment.
6.Drug allergy/ hypersensitivity: A patient who has or is suspected to have hypersensitivity to study medications, rescue medication or any ingredients of them.
7.Other studies/ study drug: A patient who participated in other studies/ trials and was treated with other investigational product(s) and 1 month has not elapsed at Visit 1 or the period of five-fold of the half-lives (t½) has not elapsed yet.
8.ECG: As for the patients who has evaluable ECG data at Visit 1, QTc(F) is =450 msec. If the first assessment meets this criterion, ECG should be measured two more times with interval after the first ECG, and the mean value of the three assessments will be used for judgement.

As for the patients who do not have evaluable ECG data at Visit 1, if the patient has known prolonged QTc (=450 msec, any correction is valid), the patient will be excluded.
9.Other: A patient who is child in care (including foster parent system), or whom the investigator (or subinvestigator) judges inappropriate for the study.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

bronchial asthma
MedDRA version: 19.0 Level: LLT Classification code 10003555 Term: Asthma bronchial System Organ Class: 100000004855

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Intervention(s)

Product Name: Fluticasone Propionate/salmeterol
Pharmaceutical Form: Inhalation powder, pre-dispensed
INN or Proposed INN: SALMETEROL XINAFOATE
CAS Number: 94749-08-3
Other descriptive name: SALMETEROL XINAFOATE
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 25-
INN or Proposed INN: FLUTICASONE PROPIONATE
CAS Number: 80474-14-2
Other descriptive name: FLUTICASONE PROPIONATE
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 50-

Trade Name: Flixotide®
Accuhaler®

Product Name: Flixotide® Accuhaler®
Pharmaceutical Form: Inhalation powder
INN or Proposed INN: FLUTICASONE PROPIONATE
CAS Number: 80474-14-2
Other descriptive name: FLUTICASONE PROPIONATE
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 50-

Primary Outcome(s)

Primary end point(s): •Mean change from baseline in asthma symptom score (total of daytime and night-time) in patient diary at the end of the treatment period 1 among the subjects who have completed 8 weeks of treatment.
The baseline value is the mean value of the last 7 consecutive days during the run-in period (excluding the day of Visit 2).
The value at the end of the treatment period 1 is the mean value of the last 7 consecutive days during the treatment period 1 (excluding the last day of the treatment period 1).
The mean value of asthma symptom score (total of daytime and night-time) for at least 5 days is acceptable if some data are missing.

Secondary Objective: Not applicable

Timepoint(s) of evaluation of this end point: At 8 weeks (visit 5/the end of period 1)

Main Objective: To evaluate the efficacy and safety of fluticasone propionate (FP)/ salmeterol xinafoate (SLM) HFA MDI 50/25 µg 1 or 2 inhalation twice daily for 8 weeks in comparison with FP HFA MDI 50 µg 1 or 2 inhalation twice daily in 6-month to 4-year-old Japanese patients with infantile bronchial asthma.

In addition, the safety of long-term treatment of FP/ SLM HFA MDI 50/25 µg 1 or 2 inhalation twice daily will be evaluated in the 16 weeks of extension period.

Secondary Outcome(s)

Secondary end point(s): •Mean change from baseline in night-time asthma symptom score
•Mean change from baseline in daytime asthma symptom score
•Frequency of asthma exacerbations
•Use of rescue medication (number of occasions used during a 24-hour period and percentage of days with rescue-free 24-hour period)
•QOL : Mean change from baseline in JPAC score

Timepoint(s) of evaluation of this end point: At 8 weeks (visit 5/the end of period 1)

Secondary ID(s)

200860

Source(s) of Monetary Support

GlaxoSmithKline Research and development Ltd