A Double Blind, Double Dummy, Randomised, Multicentre, Two Arm Parallel Group Study to Assess the Efficacy and Safety of FLUTIFORM® pMDI (2 Puffs Bid) vs Seretide® pMDI (2 Puffs Bid) in Subjects Aged ≥12 Years With Moderate to Severe Persistent, Reversible Asthma

Mundipharma (China) Pharmaceutical Co. Ltd1 site in 1 country330 target enrollmentJune 2, 2017

ConditionsAsthma

InterventionsFluticasone/ Formoterol fluticasone/ salmeterol

DrugsFluticasone/ Formoterol fluticasone/ salmeterol

Overview

Phase: Phase 3
Intervention: Fluticasone/ Formoterol
Conditions: Asthma
Sponsor: Mundipharma (China) Pharmaceutical Co. Ltd
Enrollment: 330
Locations: 1
Primary Endpoint: The primary efficacy endpoint is the change in pre dose Forced Expiratory Volume in one second (FEV1) from baseline to 2-hours post dose FEV1 at Week 12.
Last Updated: 7 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

A double blind, double dummy, randomised, multicentre, two arm parallel group study to assess the efficacy and safety of FLUTIFORM® pMDI (2 puffs bid) vs Seretide® pMDI (2 puffs bid) in subjects aged ≥12 years with moderate to severe persistent, reversible asthma.

Detailed Description

The primary objective is to show non-inferiority in the efficacy of FLUTIFORM ® pMDI (2 puffs bid) versus Seretide® pMDI (2 puffs bid) based on the change from the pre-dose forced expiratory volume in the first second (FEV1) at baseline to 2 hours post-dose FEV1 at Week 12.

Registry

clinicaltrials.gov

Start Date

June 2, 2017

End Date

March 30, 2020

Last Updated

7 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Mundipharma (China) Pharmaceutical Co. Ltd

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Male or female subjects at least aged ≥12 years old.
•Known history of moderate to severe persistent, reversible asthma for ≥ 6 months prior to the Screening Visit characterized by inadequate asthma control on treatment with an ICS alone OR controlled asthma on treatment with an ICS-LABA combination.
•Demonstrated a pre-dose FEV1 of ≥ 40% to ≤ 80% for predicted normal values during the Screening Visit (Visit 1) following appropriate withholding of asthma medications (if applicable).
•No LABA use within 12 hours and/or no SABA use within 6 hours of the PFT.
•No SAMA (e.g., ipratropium) use within 8 hours and/or no LAMA (e.g., tiotropium) use within 72 hours of the PFT.
•No use of inhaled ICS-LABA combination asthma therapy within 12 hours of the PFT.
•Inhaled corticosteroids are allowed on the day of screening.
•Oral Aminophylline should be withheld for at least 24 hours prior to the PFT.
•Documented FEV1 reversibility of ≥ 12% (plus ≥ 200ml if the subject is older than 18 years old) within last 12 months which could be accepted by the investigator, or during the screening phase or at Visit
•Demonstrated satisfactory technique in the use of the study medication.

Exclusion Criteria

•The adolescent subjects (age ≥ 12 years to \<18 years) who are on ICS alone at a dose \>250μg bid fluticasone or equivalent OR ICS-LABA combination at a dose of Seretide \> 250/50 μg bid or equivalent.
•Near fatal or life-threatening (including intubation) asthma within the past year.
•Chest X-ray at the Investigator's discretion from clinical perspective that reveals evidence of clinically significant abnormalities not believed to be due to asthma.
•Hospitalization or an emergency visit for asthma within the 4 weeks before the screening visit or during the screening visit.
•Use of systemic (injectable or oral) corticosteroid medication within 1 month of the Screening Visit.
•Omalizumab use within the past 6 months prior to the Screening Visit.
•Current evidence or known history of any clinically significant disease or abnormality including uncontrolled coronary artery disease, congestive heart failure, myocardial infarction, or cardiac dysrhythmia. 'Clinically significant' is defined as any disease that, in the opinion of the Investigator, would put the subject at risk through study participation, or which would affect the outcome of the study.
•In the investigator's opinion a clinically significant upper or lower respiratory infection within 4 weeks prior to the Screening Visit.
•Significant, non-reversible, active pulmonary disease (e.g., chronic obstructive pulmonary disease (COPD), cystic fibrosis, bronchiectasis, tuberculosis).
•Subject has a smoking history equivalent to ≥ 10 pack years (i.e., at least 1 pack of 20 cigarettes /day for 10 years or 10 packs/day for 1 year, etc.) or significant history of exposure to biomass fuel combustion which may be considered a plausible contributory cause to the subject's obstructive lung disease.

Arms & Interventions

Fluticasone/ Formoterol (Flutiform)

Dosage Form:2 puffs Unit Strength: Low dose: 50/5 µg Mid dose: 125/5 µg High dose 250/10 µg Dosing Frequency:BID Mode of Administration:Inhaled

Intervention: Fluticasone/ Formoterol

Fluticasone/ salmeterol (Seretide)

Dosage Form:2 puffs Unit Strength: Low dose: 50/25 µg Mid dose: 125/25 µg High dose 250/25 µg Dosing Frequency:BID Mode of Administration:Inhaled

Intervention: fluticasone/ salmeterol

Outcomes

Primary Outcomes

The primary efficacy endpoint is the change in pre dose Forced Expiratory Volume in one second (FEV1) from baseline to 2-hours post dose FEV1 at Week 12.

Time Frame: 12 weeks

The change in pre-dose FEV1 from baseline to the 2-hours post dose FEV1 values at Week 12 will be analysed using a repeated measures ANCOVA model with fixed terms for treatment, baseline pre-dose FEV1, asthma severity, dose group, week and treatment by week interaction, and centre as a random effect. The statistical model will be used to calculate the treatment difference for the change in pre-dose FEV1 to 2 hours post-dose FEV1 at Week 12 (FLUTIFORM® - Seretide), corresponding 95% CI and p-value from the one-sided test for non-inferiority.

Secondary Outcomes

The change in pre dose FEV1 from baseline to 2-hours post dose FEV1 at Week 2 and Week 6(2 weeks,6 weeks)
Change in asthma symptom scores from baseline at Week 2, 6, and 12 and on average during the 12 week treatment period.(2 weeks, 6 weeks, 12 weeks)
The key secondary efficacy endpoint is the change in pre dose FEV1 from baseline to pre dose FEV1 at Week 12.(12 weeks)
The number and percentage of subjects who discontinue due to lack of efficacy will be summarised for each treatment group(up to 12 weeks)
Change from baseline in other lung function parameters (FEF25-75) at Week 2, Week 6 and Week 12.(2 weeks, 6 weeks, 12 weeks)
Asthma exacerbations (incidence of subjects with at least one treatment emergent asthma exacerbation and time to first treatment emergent asthma exacerbation).(12 weeks)
The change in pre dose FEV1 from baseline to pre dose FEV1 at Week 2 and Week 6(2 weeks,6 weeks)
Change from baseline in daily morning and evening peak expiratory flow rate (PEFR) at Week 2, 6 and 12 and on average during the 12 week treatment period.(2 weeks, 6 weeks, 12 weeks)
Change from baseline in other lung function parameters (PEFR) at Week 2, Week 6 and Week 12.(2 weeks, 6 weeks, 12 weeks)
Change in sleep disturbance scores from baseline at Week 2, 6, and 12 and on average during the 12 week treatment period(2 weeks, 6 weeks, 12 weeks)
Change in average number of occasions of daily rescue medication (salbutamol) use from baseline during the 12 week treatment period.(salbutamol) will as assessed based on subject diaries records(12 weeks)
Change from baseline in other lung function parameters (FVC) at Week 2, Week 6 and Week 12.(2 weeks, 6 weeks, 12 weeks)
Change in percentage of asthma control days from baseline at Week 2, 6, and 12 and on average during the 12 week treatment period.(2 weeks, 6 weeks, 12 weeks)
Proportion of patients achieving well controlled asthma [ ACQ(Asthma Control Questionnaire) score ≤ 0.75 units] at Week 12.(12 weeks)
Change in asthma control questionnaire (ACQ) score from baseline to Week 2 and Week 12.(2 weeks,12 weeks)
Proportion of subjects achieving a decrease from baseline to Week 12 in ACQ(Asthma Control Questionnaire) score ≥ 0.5 units.(12 weeks)