FACTO Study (Foster® As Complete Treatment Option) (FACTO)

A PHASE 4, MULTINATIONAL, MULTICENTRE, DOUBLE BLIND, DOUBLE DUMMY, RANDOMIZED, PARALLEL GROUP, CONTROLLED CLINICAL STUDY OF FIXED COMBINATION BECLOMETHASONE DIPROPIONATE 100 µg PLUS FORMOTEROL FUMARATE 6 µg pMDI WITH HFA-134A PROPELLANT (CHF1535, FOSTER®) VERSUS FLUTICASONE 250 µg PLUS SALMETEROL 50 µg DPI (SERETIDE® DISKUS®) AS MAINTENANCE TREATMENT IN CONTROLLED ASTHMATIC PATIENTS.

Double blind, multinational, multicentre, randomised, 2 arm parallel group study

Study Overview

• Status: Completed
• Conditions: Asthmatic Patients
• Intervention / Treatment: Drug: FOSTER; Drug: Seretide

Detailed Description

Aim of the present investigation is to demonstrate the clinical equivalence between fluticasone plus salmeterol 500/100 µg daily and an equipotent dose of CHF1535 in maintaining the same asthma control in patients adequately controlled with fluticasone plus salmeterol at the above mentioned daily dose.

• Study Type: Interventional
• Enrollment (Actual): 431
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Marseille, France, 13015
    • Hopital Nord
• Germany
  • Nordrhein-Westfalen
    • Gelsenkirchen, Nordrhein-Westfalen, Germany, 45879
      • Allergologie imUmkreis der Praxis Pneumologie
• Netherlands
  • Heerlen, Netherlands, 6419 PC
    • Atrium Medisch Centrum Heerlen,
• Spain
  • Valencia, Spain, 46009
    • Hospital Universitario La Fe

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Asthmatic patients will be enrolled at Visit 1 into the run-in period if they meet all of the following criteria:

1. Written informed consent obtained
2. Adult male and female (≥18 and ≤65 years)

3. Clinical diagnosis of controlled asthma according to Global Strategy for Asthma Management and Prevention (GINA) revised version 2007 in the previous week before study entry:

   • no daytime symptoms (twice or less/week)
   • no limitations of activities
   • no nocturnal symptoms/awakenings
   • no need for reliever/rescue medications (twice or less/week)
   • lung function (FEV1) > 80% predicted or personal best (if known)
4. Patients treated with fluticasone 500 µg + salmeterol 100 µg daily for ≥ 4 weeks
5. A co-operative attitude and ability to correctly use the device and to complete the diary cards.

Exclusion Criteria:

Patients will not be enrolled at visit 1 into the run-in period if they meet any of the following criteria:

1. Inability to carry out pulmonary function testing;
2. Diagnosis of Chronic Obstructive Pulmonary Disease (COPD) as defined by the National Heart Lung and Blood Institute/World Health Organisation (NHLBI/WHO) Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines;
3. History of near fatal asthma;
4. Evidence of severe asthma exacerbation or symptomatic infection of the lower airways in the previous six months;
5. Three or more courses of oral corticosteroids or hospitalisation due to asthma during the previous 6 months;
6. Patients treated with long-acting β2-agonists (LABAs) other than salmeterol, anticholinergics, and leukotriene antagonists during the previous 4 weeks;
7. Current smokers or recent (less than one year) ex-smokers defined as smoking at least 15 packs/year;
8. Clinically significant or unstable concurrent disease : e.g. uncontrolled hyperthyroidism, uncontrolled diabetes mellitus or other endocrine disease; significant hepatic impairment; significant renal impairment; significant other pulmonary disease; cardiovascular disease; gastrointestinal disease; neurological disease; haematological disease, autoimmune disorders, that may interfere with patient's safety, compliance, or study evaluations, according to the investigator's opinion;
9. Patients with a serum potassium value ≤ 3.5 mEq/L
10. Patients with QTc interval (Bazett's formula) higher than 450 msec at screening visit 1;
11. Cancer or any chronic diseases with prognosis < 2 years;
12. Female subjects: pregnant or with active desire to be pregnant, lactating mother or lack of efficient contraception in a subject with child-bearing potential (i.e. contraceptive methods other than oral contraceptives, IUD, tubal ligature). A pregnancy test in urine is to be carried out in women of a fertile age at screening
13. Significant alcohol consumption or drug abuse;
14. Patients treated with beta-blockers as regular use;
15. Patients treated with monoamine oxidase inhibitor, tricyclic antidepressants and Selective Serotonin Re-uptake Inhibitors (SSRIs), unless already taken at stable doses at the screening visit
16. Allergy, sensitivity or intolerance to study drugs and/or study drug formulation ingredients;
17. Patients unlikely to comply with the protocol or unable to understand the nature, scope and possible consequences of the study;
18. Patients who received any investigational new drug within the last 12 weeks;
19. Patients with asthma exacerbations during the run-in period will also be excluded from the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; CHF1535 (beclometasone dipropionate plus formoterol, 400/24 µg daily)	Drug: FOSTER; CHF1535 (beclometasone dipropionate 100 µg plus formoterol 6 µg) pMDI aerosol via HFA-134a propellant 2 inhalations b.i.d. (daily dose 400 µg + 24µg)
Active Comparator: 2; Seretide® Diskus® (fluticasone plus salmeterol, 500/100 µg /daily)	Drug: Seretide; Fluticasone 250 µg + salmeterol 50 µg DPI (Seretide® Diskus®) 1 inhalation b.i.d. (daily dose 500+100 µg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pre-dose morning FEV1 measured at clinic visit 5	12-week treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
FEV1 area under the curve (AUC) in the first hour post-dose measured at clinics at visit 2 and visit 5	12-week treatment
Pulmonary function tests measured at clinics (FEV1,PEF, FVC, FEF25-75%)	12-week treatment
ACQ score at baseline and at the end of treatment period	12-week treatment
Use of rescue medication	12-week treatment
Number of patients with controlled or partly controlled asthma at clinic visits according to GINA guidelines revised version 2007	12-week treatment
Days without asthma symptoms (%), days without use of rescue medication (%) and daily asthma symptoms' score from diary cards	12-week treatment
Pharmacoeconomic analyses assessing differences in direct medical costs (healthcare perspective) and in both direct healthcare and indirect costs (societal perspective).	12-week treatment
Adverse events and adverse drug reactions,ECG ,Vital signs, Haematology/blood chemistry tests, OUCC ratio in a in a subgroup of 15% of patients	12-week treatment

Collaborators and Investigators

• Sponsor: Chiesi Farmaceutici S.p.A.
• Investigators: Principal Investigator: Neil Barnes, MD, Department ofRespiratory Medicine, London Chest Hospital, Barts& The London NHS Trust,Bonner Road, E2 9JX, London (UK)

Publications and helpful links

General Publications

• Barnes N, van Noord JA, Brindicci C, Lindemann L, Varoli G, Perpina M, Guastalla D, Casula D, Patel S, Chanez P; FACTO (Foster(R) As Complete Treatment Option) Study Group. Stepping-across controlled asthmatic patients to extrafine beclometasone/formoterol combination. Pulm Pharmacol Ther. 2013 Oct;26(5):555-61. doi: 10.1016/j.pupt.2013.01.011. Epub 2013 Mar 22.

Helpful Links

• Study Record on EU Clinical Trials Register including results

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (Actual): September 1, 2010
• Study Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: May 12, 2009
• First Submitted That Met QC Criteria: May 12, 2009
• First Posted (Estimate): May 13, 2009

Study Record Updates

• Last Update Posted (Actual): March 30, 2017
• Last Update Submitted That Met QC Criteria: March 28, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• 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; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Sympathomimetics; Fluticasone-Salmeterol Drug Combination
• Other Study ID Numbers: CCD-0806-PR-0032; 2008-003740-11 (EudraCT Number)