A Randomized Placebo-Controlled Efficacy and Safety Study of 1-Year Duration with High and Medium Dose Inhaled Mometasone Furoate/Formoterol Combination Formulation Compared With Formoterol and High Dose Inhaled Mometasone Furoate Monotherapy in Subjects with Moderate to Severe COPD.

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2006-002308-32-DK
• Date of registration: 06/12/2006
• Prospective Registration: Yes
• Primary sponsor: Schering-Plough Research Institute, a division of Schering Corporation
• Public title: A Randomized Placebo-Controlled Efficacy and Safety Study of 1-Year Duration with High and Medium Dose Inhaled Mometasone Furoate/Formoterol Combination Formulation Compared With Formoterol and High Dose Inhaled Mometasone Furoate Monotherapy in Subjects with Moderate to Severe COPD.
• Scientific title: A Randomized Placebo-Controlled Efficacy and Safety Study of 1-Year Duration with High and Medium Dose Inhaled Mometasone Furoate/Formoterol Combination Formulation Compared With Formoterol and High Dose Inhaled Mometasone Furoate Monotherapy in Subjects with Moderate to Severe COPD.
• Date of first enrolment: 06/02/2007
• Target sample size: 1000
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-002308-32
• 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: yes Other: no

Countries of recruitment

Denmark, Hungary, Netherlands

Key inclusion & exclusion criteria

Inclusion criteria:
- A diagnosis of moderate to severe COPD based on a pre-bronchodilator FEV1/FVC ratio of <=70%.
- At Screening, the subject’s post-bronchodilator FEV1 must be <=60% predicted normal and >=25% predicted normal.
- A subject must have symptoms of COPD (chronic cough and sputum production that are not attributable to another disease process) for at least 24 months.
- A subject must be an ex-smoker or current smoker with a smoking history of >=10 pack years. NOTE: Current smokers must provide verbal notification or written documentation that attests to their inability to stop smoking after participation (or declining to participate) in a smoking cessation program. Ex-smokers are defined as those who have stopped smoking at least 12 months prior to Visit 1.
- A subject must have been on only SABA/short-acting anticholinergics for relief, for at least 2 weeks prior to randomization (Visit 2).
- A subject must have a documented history of one or more COPD exacerbations requiring a course of oral corticosteroid and/or antibiotics within 2 to 14 months before screening.
- A subject must withdraw from parenteral steroids, oral steroids and antibiotics at least 4 weeks prior to Screening (Visit 1).
- If, based on the medical judgment of the investigator, there is no inherent harm in changing the subject’s current COPD therapy, the subject must be willing to discontinue his/her prescribed short-acting anticholinergics, ICS or ICS/LABA combination at the Screening Visit, and be transferred to treatment with SABA/short-acting anticholinergics for relief for 2 weeks prior to the Baseline/Randomization Visit.
- The subject must have two valid scans, as confirmed by the local dual energy X-ray absorptiometry (DXA) centre for
lumbar spine, left total femur (right femur will not be an acceptable substitute), and femoral neck prior to randomization. ’Valid scans’ are defined in the protocol.
- Clinical laboratory tests (complete differential blood counts [CBC], blood chemistries, C-reactive protein, and urinalysis) conducted at the Screening Visit must be clinically acceptable to the investigator/sponsor. An electrocardiogram (ECG)
performed at the Screening Visit must be clinically acceptable to the investigator. A chest X-ray performed at the Screening Visit or within 12 months prior to the Screening Visit must be clinically acceptable to the investigator.
- A female subject of childbearing potential must be using a medically acceptable, adequate form of birth control, as defined in the protocol, and must have a negative serum pregnancy test at Screening in order to be considered eligible for enrollment.

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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. A subject who demonstrates an increase in absolute volume of =400 mL at the Screening Visit or prior to the Baseline Visit within 30 minutes after administration of four inhalations of albuterol/salbutamol (total dose of 360 to 400 mcg), or nebulized 2.5 mg albuterol/salbutamol.
2. A current diagnosis of asthma.
3. Blood eosinophil count greater than 0.57 x 103/µL.
4. A subject who has undergone lobectomy, pneumonectomy or lung volume reduction surgery.
5. A diagnosis of lung cancer.
6. A subject who requires long-term administration of oxygen (>15 hours per day).
7. A subject who experiences an exacerbation of COPD requiring medical intervention within 4 weeks prior to randomization or treatment with 3 additional excluded medication (other than SABA/short acting anticholintergic to be used as rescue medication.)
8. Alpha-1-antitrypsin deficiency
9. A subject with cataract extractions on both eyes.
10. A subject with a history and/or presence of intraocular pressure in either eye ³22 mm Hg, glaucoma, and/or posterior subcapsular cataracts. A subject who has undergone incisional or intraocular surgery in which the natural lens is still present in the eye. A subject with a history of penetrating trauma to both eyes. A subject with one or more of the following LOCS III grades at screening:
• NO: ³3.0
• NC: ³3.0
• C: ³2.0
• P: ³0.5



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

Health Condition(s) or Problem(s) studied

Chronic Obstructive Pulmonary Disease (COPD)
MedDRA version: 8.1 Level: LLT Classification code 10009033 Term: Chronic obstructive pulmonary disease

Intervention(s)

Product Name: Mometasone Furoate/Formoterol (MF/F) Metered Dose Inhaler
Product Code: SCH 418131
Pharmaceutical Form: Pressurised inhalation, suspension
INN or Proposed INN: MOMETASONE FUROATE
Other descriptive name: MF
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 200-
INN or Proposed INN: FORMOTEROL
CAS Number: 73573872
Other descriptive name: F
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Pressurised inhalation*
Route of administration of the placebo: Inhalation use

Product Name: Mometasone furoate metered dose inhaler
Product Code: SCH 032088
Pharmaceutical Form: Pressurised inhalation, suspension
INN or Proposed INN: MOMETASONE FUROATE
Other descriptive name: MF
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Pressurised inhalation*
Route of administration of the placebo: Inhalation use

Product Name: Formoterol
Product Code: F
Pharmaceutical Form: Pressurised inhalation, suspension
INN or Proposed INN: FORMOTEROL
CAS Number: 73573872
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

Product Name: Mometasone Furoate/Formoterol (MF/F) Metered Dose Inhaler
Product Code: SCH 418131
Pharmaceutical Form: Pressurised inhalation, suspension
INN or Proposed INN: MOMETASONE FUROATE
Other descriptive name: MF
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 100-
INN or Proposed INN: FORMOTEROL
CAS Number: 73573872
Other descriptive name: F
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Pressurised inhalation*
Route of administration of the placebo: Inhalation use

Primary Outcome(s)

Secondary Objective: To evaluate safety and to assess the efficacy of MF/F MDI 400/10 mcg BID and MF/F MDI 200/10 mcg BID compared with placebo by evaluating the change from baseline to Endpoint in quality-of-life assessments using the St George’s Respiratory Questionnaire (SGRQ), nocturnal COPD symptoms, a composite score reflecting partly stable COPD control, and the time-to-first COPD exacerbation.

Main Objective: 1. To determine the efficacy (as defined by FEV1 (AUC0-12 hr)) of MF/F MDI 400/10 mcg BID compared with MF 400 mcg BID, in order to assess the added benefit of F to the combination
2. To determine the efficacy (as defined by pre-dose FEV1 in the morning) of MF/F 400/10 mcg BID and MF/F 200/10 mcg BID compared with F 10 mcg BID, in order to assess the benefit of the steroid component to the combination.

Primary end point(s): 1. To assess the contribution of F 10 mcg BID to the combination: The mean AUC (0-12 hr) of the change from Baseline to Week 13 Endpoint. The baseline FEV1 will be the average of the two predose FEV1 measurements (30 minutes prior to dosing and 0 hour, immediately prior to dosing) at the baseline Visit.
2. To assess the contribution of MF to the combination: The mean change from Baseline to the Week 13 Endpoint in AM predose FEV1.

Secondary ID(s)

P04229

2006-002308-32-NL