Comparison of Flutiform, Fluticasone and Seretide in Treatment of Moderate to Severe Asthma in Paediatric Patients

A Double-blind, Double Dummy, Randomised, Parallel Group, Multicentre Study to Compare the Efficacy and Safety of Flutiform pMDI With Fluticasone pMDI and With Seretide pMDI in Paediatric Subjects Aged 5 to Less Than 12 Years With Moderate to Severe Persistent Reversible Asthma

This is a comparator study to assess safety and efficacy of Flutiform compared with Fluticasone pMDI and Seretide pMDI in paediatric asthma patients with moderate to severe persistent, reversible asthma.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Flutiform; Drug: Seretide; Drug: Flixotide

Detailed Description

This is a study involving a 2-4 week run-in phase followed by a 12 week double blind treatment phase. During the run-in phase, all subjects receive Flixotide. In the treatment phase subjects will be randomised to one of the 3 treatment groups and will receive active Flutiform and placebo Flixotide or Active Seretide and placebo Flixotide or active Flixotide and either placebo seretide or placebo Flutiform. Efficacy will be assessed by lung function tests, asthma symptoms, sleep disturbance due to asthma and rescue medication use. Safety will be assessed by adverse events, lab tests, urinary cortisol and vital signs.

• Study Type: Interventional
• Enrollment (Anticipated): 498
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Plovdiv, Bulgaria
• Czechia
  • Ostrava-Marianske Hory, Czechia
    • Alergologie Skopkova s.r.o
• Hungary
  • Kiskunhalas, Hungary
    • Illés és Ádám Egészségügyi Szolgáltató Bt.
• India
  • New Dehli, India
• Poland
  • Tarnow, Poland
    • Alergo-Med Specjalistyczna Przychodnia Lekarska Sp.z.o.o.
• Romania
  • Deva, Hunedoara, Romania
    • Spitalul Judetean de Urgenta Deva
• Russian Federation
  • Moscow, Russian Federation
• Ukraine
  • Odessa, Ukraine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 10 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

1. Male and Female subjects 5 to <12 years old.
2. Known history of moderate to severe persistent reversible asthma1 for ≥ 6 months prior to the screening visit.

3. Demonstrated FEV1 of ≥ 60% to ≤ 90% for predicted normal values (Polgar 1971) during the screening period 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 use of inhaled ICS-LABA asthma therapy within 12 hours of the PFT
   • Inhaled corticosteroids are allowed on the day of screening
4. Documented reversibility of ≥ 15% in FEV1 in the screening period
5. Current use of an inhaled corticosteroid for asthma at a stable dose for at least 4 weeks prior to the screening visit
6. Inadequate asthma control on an ICS alone at a dose of ≤ 500 µg fluticasone equivalents/day, OR controlled asthma on an ICS-LABA combination at a ICS dose of ≤ 200 µg fluticasone equivalents/day
7. Demonstrated satisfactory technique in the use of the pMDI and spacer device
8. Can perform spirometry adequately
9. Willing and able to enter information in the electronic diary with the help of a parent or guardian, if necessary and attend all study visits
10. Willing and able to substitute pre-study prescribed inhaled asthma medication for the entire duration of the study
11. If a female subject is post menarche a urine pregnancy test may be undertaken at the discretion of the investigator and the subjects' parent(s) /legal representative. This test must be negative.
12. Written informed consent and assent obtained as per national law

Exclusion Criteria

1. Near fatal or life-threatening (including intubation) asthma within the past year
2. Hospitalisation or an emergency visit for asthma within the past 6 months
3. History of systemic (injectable or oral) corticosteroid medication within 1 month of the screening visit
4. Current or prior non-response or partial response only to an ICS-LABA combination1
5. Evidence of a clinically unstable disease, as determined by medical history, clinical laboratory tests, and physical examination that, in the Investigator's opinion, preclude entry into the study. "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
6. In the Investigator's opinion a clinically significant upper or lower respiratory infection within 4 weeks prior to the screening visit
7. Significant, non-reversible active pulmonary disease (e.g. cystic fibrosis, bronchiecstasis, tuberculosis)
8. Known Human Immunodeficiency Virus (HIV)-positive status
9. Current smoking history within 12 months prior to the screening visit
10. Current evidence of alcohol or substance abuse within 12 months prior to the screening visit
11. Subjects who have taken β- blocking agents, tricyclic antidepressants, monoamine oxidase inhibitors, astemizole (Hismanal), quinidine type antiarrythmics, or potent CYP 3A4 inhibitors such as ketoconazole within 1 week prior to the screening visit
12. Current use of medications, other than those allowed in the protocol, that in the investigator's opinion will have an effect on bronchospasm and/or pulmonary function
13. Current evidence of hypersensitivity or idiosyncratic reaction to test medications or components
14. Receipt of an Investigational medicinal product within 30 days of the screening visit
15. Current participation in a clinical study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Flutiform	Drug: Flutiform; 50/5ug (fluticasone/formoterol) 2 puffs twice daily
Active Comparator: Seretide	Drug: Seretide; 50/25 ug (fluticasone/salmeterol) 2 puffs twice daily
Active Comparator: Flixotide	Drug: Flixotide; 50ug 2 puffs twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To show superiority in the efficacy of Flutiform pMDI 50/5μg (2 puffs bid) versus fluticasone pMDI 50 μg (2 puffs bid).	Change from pre-dose Forced Expiratory Volume in one second (FEV1) in litres at baseline to 2 hours post-dose FEV1 at the end of the 12 week treatment period.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Show non-inferiority in the efficacy of Flutiform to Seretide	Change from pre-dose FEV1 at baseline to 2 hours post-dose FEV1 at Day 1 and FEV1 AUC0-4 at Day 1 and Week 12 (Flutiform vs Seretide)	12 weeks

Collaborators and Investigators

• Sponsor: Mundipharma Research Limited

Publications and helpful links

Helpful Links

• Link to Results

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): September 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: December 7, 2011
• First Submitted That Met QC Criteria: January 12, 2012
• First Posted (Estimate): January 18, 2012

Study Record Updates

• Last Update Posted (Actual): October 24, 2018
• Last Update Submitted That Met QC Criteria: October 22, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: moderate to severe persistent reversible asthma
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Dermatologic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Sympathomimetics; Fluticasone; Fluticasone-Salmeterol Drug Combination
• Other Study ID Numbers: FLT3506; 2010-024635-16 (EudraCT Number)