Study investigating a marketed medicine for asthma - flutiform® (branded name) in patients diagnosed with chronic obstructive pulmonary disease. Neither the doctor nor patient will know the treatment group, which will be established by chance (like flipping a coin). Some of the patients will be treated with flutiform®, while the others will be treated with Atimos®.

• Register: EUCTR
• Last refreshed on: 23 May 2016
• Main ID: EUCTR2012-004162-17-DE
• Date of registration: 15/04/2013
• Prospective Registration: Yes
• Primary sponsor: Mundipharma Research Limited
• Public title: Study investigating a marketed medicine for asthma - flutiform® (branded name) in patients diagnosed with chronic obstructive pulmonary disease. Neither the doctor nor patient will know the treatment group, which will be established by chance (like flipping a coin). Some of the patients will be treated with flutiform®, while the others will be treated with Atimos®.
• Scientific title: A randomised, double-blind, double dummy, parallel group study comparing Fluticasone propionate / formoterol fumarate (flutiform®) 250/10 µg (2 puffs BID) and flutiform® 125/5 µg (2 puffs BID) versus Formoterol fumarate dihydrate (Atimos®) 12 µg (1 puff BID) in subjects with chronic obstructive pulmonary disease (COPD).
• Date of first enrolment: 24/10/2013
• Target sample size: 1530
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-004162-17
• 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: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Bulgaria, Czech Republic, Germany, Hungary, Latvia, Lithuania, Macedonia, the former Yugoslav Republic of, Poland, Romania, Russian Federation, Slovakia, South Africa, Spain, Ukraine, United Kingdom

Contacts

• Name: European Medical Operations
• Affiliation: Mundipharma Research Limited

• Name: European Medical Operations
• Affiliation: Mundipharma Research Limited

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or Female subjects aged = 40 years at screening visit
a. Female subjects of child bearing potential (less than 1 year post-menopausal) must have a negative urine pregnancy test prior to first dose of study medication, be non-lactating, and willing to use adequate and highly effective methods of birth control throughout the study such as sterilisation, implants, injectables, combined oral contraceptives, some intra-uterine devices, sexual abstinence or vasectomised partner.
b. Male subjects with a partner of child bearing potential must be willing to use adequate and highly effective methods of birth control throughout the study.
2. Smoking history of = 10 pack years (equivalent to, for example, 20 cigarettes/day for 10 yrs or 10 cigarettes/day for 20 yrs ) (pack year = (number of cigarettes per day ÷ 20) x number of years of smoking)
3. Diagnosis of COPD as evidenced by:
a. Clinical symptoms of COPD (e.g. chronic cough, sputum production, dyspnoea) and
b. Post-bronchodilator FEV1 / FVC ratio < 0.7 measured at screening and
c. = 50 % FEV1 predicted normal measured at screening
4. Documented history of = 1 moderate or severe COPD exacerbation in previous year (requiring treatment with systemic corticosteroids and/or antibiotics and/or hospitalisation)
5. Willing and able to replace current COPD therapy with study medication
6. Able to demonstrate correct use of a pMDI without a spacer
7. Willing and able to attend all study visits and complete study assessments
8. Able to provide signed informed consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 765
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 765

Exclusion criteria:
1. Ongoing moderate or severe exacerbation of COPD (see section 10 of protocol)
2. Current diagnosis of asthma
3. Documented evidence of a1-antitrypsin deficiency as the underlying cause of COPD
4. Other active respiratory disease such as active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, interstitial lung disease, cystic fibrosis, bronchiolitis obliterans
5. Previous lung resection
6. Use of long-term oxygen therapy (LTOT) at least 12 hours daily or mechanical ventilation
7. Chest X-ray or CT scan that reveals evidence of clinically significant abnormalities reflective of active disease not believed to be due to COPD
8. Evidence of uncontrolled cardiovascular disease
9. Evidence of clinically significant renal, hepatic, gastrointestinal, or psychiatric disease
10. Current malignancy or a previous history of cancer which has been in remission for < 5 years (basal cell or squamous cell carcinoma of the skin which has been resected is not excluded)
11. Clinically significant sleep apnoea requiring use of continuous positive airway pressure (CPAP) device or non-invasive positive pressure ventilation (NIPPV) device
12. Participation in the acute phase of a pulmonary rehabilitation programme within 4 weeks prior to screening or during the study
13. Known or suspected history of drug or alcohol abuse in the last 2 years
14. Requiring treatment with any of the prohibited concomitant medications
15. Known or suspected hypersensitivity or contraindication to any of the study drugs or excipients
16. Received an investigational drug within 30 days of the screening visit (12 weeks if an oral or injectable steroid).


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

Health Condition(s) or Problem(s) studied

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

Chronic obstructive pulmonary disease (COPD)
MedDRA version: 18.1 Level: LLT Classification code 10010953 Term: COPD exacerbation System Organ Class: 100000004855

Intervention(s)

Trade Name: Flutiform® 125 microgram/5 microgram per actuation pressurised inhalation suspension.
Pharmaceutical Form: Pressurised inhalation, suspension
INN or Proposed INN: FLUTICASONE PROPIONATE
CAS Number: 80474-14-2
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 125-
INN or Proposed INN: FORMOTEROL FUMARATE DIHYDRATE
CAS Number: 183814-30-4
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Pressurised inhalation, suspension
Route of administration of the placebo: Inhalation use

Trade Name: Flutiform® 250 microgram/10 microgram per actuation pressurised inhalation suspension
Pharmaceutical Form: Pressurised inhalation, suspension
INN or Proposed INN: FLUTICASONE PROPIONATE
CAS Number: 80474-14-2
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 250-
INN or Proposed INN: FORMOTEROL FUMARATE DIHYDRATE
CAS Number: 183814-30-4
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Pressurised inhalation, suspension
Route of administration of the placebo: Inhalation use

Trade Name: Atimos
Pharmaceutical Form: Pressurised inhalation, solution
INN or Proposed INN: FORMOTEROL FUMARATE DIHYDRATE
CAS Number: 183814-30-4
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 12-
Pharmaceutical form of the placebo: Pressurised inhalation, solution
Route of administration of the placebo: Inhalation use

Primary Outcome(s)

Primary end point(s): Primary efficacy endpoint:
• Annualised rate of moderate and severe COPD exacerbations during the 52-week treatment period (based on medical intervention).

Main Objective: Show superiority in the efficacy of flutiform 250/10 µg (2 puffs bid) compared with formoterol 12 µg (1 puff bid) based on the annual rate of moderate and severe COPD exacerbations during the 52-week treatment period.

Secondary Objective: • Show superiority in the efficacy of flutiform 125/5 µg (2 puffs bid) compared with formoterol 12 µg (1 puff bid) based on the annual rate of moderate and severe COPD exacerbations during the 52-week treatment period
• Compare flutiform (at each dose) with formoterol 12 µg (1 puff bid) for the secondary efficacy and safety endpoints.

Timepoint(s) of evaluation of this end point: At the end of treatment.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: At the end of the treatment.

Secondary end point(s): Secondary Endpoints for high and medium dose of flutiform®
• The pre-morning dose FEV1 values at each post-baseline time-point
• Annualised Rate of COPD Exacerbations (EXACT)
• Time to First Moderate or Severe COPD Exacerbation (Medical Intervention)
• Saint George’s Respiratory Questionnaire for COPD
• COPD Assessment Test Score
• Study Rescue Medication Use
• Percentage Change in Awakening-free nights
• EXACT-RS dyspnoea score and EXACT-RS total score
• Other Pulmonary Function Parameters
• Time to Each COPD Exacerbation
• Other Annualised Rates of COPD Exacerbations
• Discontinuations Due to Lack of Efficacy
• Average Change in Sleep Disturbance Scores
• Days of Hospitalisaton
• Treatment Compliance Analyses

Secondary ID(s)

FLT3509

Source(s) of Monetary Support

Mundipharma Research Limited