Efficacy of FLUTIFORM ® vs Seretide® in Moderate to Severe Persistent Asthma in Subjects Aged ≥12 Years

NCT03387241 | Unknown Phase 3

• 1 other identifier: FLT13-CN-301
• Study Type: interventional
• Target: 330
• Locations: 1 country
• Sites: 1

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.

Conditions

Asthma

Keywords

moderate; severe; persistent; reversible; Seretide; Flutiform

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  12 weeks

Secondary Outcomes (16)

• The key secondary efficacy endpoint is the change in pre dose FEV1 from baseline to pre dose FEV1 at Week 12.

  12 weeks

• The change in pre dose FEV1 from baseline to 2-hours post dose FEV1 at Week 2 and Week 6

  2 weeks,6 weeks

• The change in pre dose FEV1 from baseline to pre dose FEV1 at Week 2 and Week 6

  2 weeks,6 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 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

Study Arms (2)

Fluticasone/ Formoterol (Flutiform)

EXPERIMENTAL

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

Drug: Fluticasone/ Formoterol

Fluticasone/ salmeterol (Seretide)

ACTIVE COMPARATOR

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

Drug: fluticasone/ salmeterol

Interventions

Fluticasone/ Formoterol DRUG

See above

Also known as: FLUTIFORM® pMDI (2 puffs bid)

Fluticasone/ Formoterol (Flutiform)

fluticasone/ salmeterol DRUG

See above

Also known as: Seretide® pMDI (2 puffs bid)

Fluticasone/ salmeterol (Seretide)

Eligibility Criteria

• Age: 12 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 2.
• Demonstrated satisfactory technique in the use of the study medication.
• Females of child bearing potential or less than one year post-menopausal must have a negative serum pregnancy test recorded at the screening visit and a negative urine pregnancy test result prior to the first dose of study medication, be non-lactating, and willing to use adequate and highly effective methods of contraception throughout the study. A highly effective method of birth control is defined as those which result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly such as sterilisation, implants, injectables, combined oral contraceptives, some IUDs (Intrauterine Device, hormonal), sexual abstinence or vasectomised partner.
• Willing and able to enter information in the diary and attend all study visits.
• Willing and able to substitute study medication for their pre-study prescribed asthma medication for the duration of the study.
• Written informed consent obtained, for \<18 years old subjects, both parental consent and subjects assent are needed.

You may not qualify if:

• Demonstrated a pre-dose FEV1 of ≥ 40% to ≤ 80% for predicted normal values at Randomisation Visit (Visit 3) following appropriate withholding of asthma medications (if applicable).
• ACQ score at Visit 3 ≥ 1.0.
• Subjects with a good compliance with treatment or patient dairy. The definition of good compliance is that the completeness of diary during the last 14 days of the run-in period is at least 80%. The compliance on diary completeness will be assessed from the aspects below and agreed by the investigator and study Medical Monitor:
• Diary info has been filled out on ≥80% of the days during the last 14 days before randomization (e.g., at least 11 days with diary filled completed out of the last 14 days prior to randomization).
• % main items including the study endpoints related ones have been filled out within the last 14 days prior to randomization.
• No other significant incompliance judged by the investigator that indicates the potential future incompliance for critical data collection during the study treatment period.
• 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).

Sponsors & Collaborators

• Mundipharma (China) Pharmaceutical Co. Ltd: lead

Study Sites (1)

China-Japanese Friendship Hospital

Beijing, Beijing Municipality, China

RECRUITING

Related Publications (1)

• Oba Y, Anwer S, Maduke T, Patel T, Dias S. Effectiveness and tolerability of dual and triple combination inhaler therapies compared with each other and varying doses of inhaled corticosteroids in adolescents and adults with asthma: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2022 Dec 6;12(12):CD013799. doi: 10.1002/14651858.CD013799.pub2.

  PMID: 36472162 DERIVED

MeSH Terms

Conditions

Asthma; Lymphoma, Follicular

Interventions

fluticasone-formoterol; Fluticasone-Salmeterol Drug Combination

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders

Intervention Hierarchy (Ancestors)

Salmeterol Xinafoate; Albuterol; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines; Fluticasone; Androstadienes; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Victoria Yu

  victoria.yu@mundipharma.com.cn

  STUDY DIRECTOR

Central Study Contacts

Ling Li

CONTACT

8610 65636891; ling.li@mundipharma.com.cn

Dan Zhu

CONTACT

dan.zhu@mundipharma.com.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: A double blind, double dummy, randomised, multicentre, two arm parallel design
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2017
• First Posted: January 2, 2018
• Study Start: June 2, 2017
• Primary Completion: December 30, 2019
• Study Completion: March 30, 2020
• Last Updated: April 29, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)