A study to evaluate the effects of two different doses given once of the combination of two components (beclomethasone plus formoterol) given in two different inhalation formulations to patients with chronic obstructive pulmonary disease.

• Register: EUCTR
• Last refreshed on: 3 April 2017
• Main ID: EUCTR2013-002966-38-GB
• Date of registration: 20/09/2013
• Prospective Registration: Yes
• Primary sponsor: Chiesi Farmaceutici S.p.A.
• Public title: A study to evaluate the effects of two different doses given once of the combination of two components (beclomethasone plus formoterol) given in two different inhalation formulations to patients with chronic obstructive pulmonary disease.
• Scientific title: A PHASE II, PARTIAL-BLIND, RANDOMIZED, PLACEBO-CONTROLLED, 5-WAY CROSS-OVER CLINICAL PHARMACOLOGY STUDY TO EVALUATE THE PHARMACODYNAMICS OF BDP/B17MP AND FORMOTEROL ACROSS TWO DIFFERENT DOSE LEVELS OF CHF 1535 NEXThaler® DPI AND CHF 1535 pMDI (BOTH FIXED COMBINATION OF BECLOMETHASONE DIPROPIONATE PLUS FORMOTEROL FUMARATE) IN ADULT COPD PATIENTS.
• Date of first enrolment: 20/11/2013
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-002966-38
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: no Parallel group: no Cross over: yes Other: yes Other trial design description: partial blind If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no Number of treatment arms in the trial: 5
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

United Kingdom

Contacts

• Name: Giorgia Ciurlia
• Affiliation: Chiesi Farmaceutici S.p.A.

• Name: Giorgia Ciurlia
• Affiliation: Chiesi Farmaceutici S.p.A.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male and female adults (= 40 and = 75 years old).
2. Female subjects must either be of non-childbearing potential, using at least one acceptable method of contraception or sexually abstinent, from screening until the end of the study.
3. Written informed consent obtained by the patient prior to any study-related procedures.
4. Outpatients with diagnosis of moderate/severe stable COPD, according to GOLD guidelines update 2013 at least in the 6 months before the screening visit.
5. A post-bronchodilator FEV1 = 40 and < 80% of the predicted normal value and FEV1/FVC < 0.7, within 30 min after 4 puffs (4 x 100 µg) of salbutamol pMDI. If this criterion is not met at screening, the test can be repeated once before commencing of the run-in period.
6. Current or past smoker of at least 10 pack/years where one pack-year is equivalent to 20 cigarettes per day for 1 year. (If the subjects underwent smoking cessation therapy, it must be completed 3 months prior to the screening visit and smoking status should not change between the subjects screening visit and subjects last study visit).

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 34
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 16

Exclusion criteria:
1. Pregnant or lactating female subjects.
2. Current diagnosis of Asthma.
3. Hospitalization for COPD or pneumonia within 3 months prior to screening and until randomization.
4. COPD exacerbations requiring systemic steroids and /or antibiotics and/or oral or nebulized ß2-agonists in the 4 weeks prior to screening and until randomization.
5. LRTI in the 4 weeks prior to screening and until randomization.
6. Patients with serum potassium levels < 3.5 mEq/L.
7. Known respiratory disorders other than COPD including but not limited to a1 antitrypsine deficiency, active tuberculosis, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, restrictive lung disease and interstitial lung disease.
8. Intolerance or contra-indication to treatment with ß2-agonists and/or inhaled corticosteroids or allergy to any component of the study treatments.
9. Having received an investigational drug within 2 months before the screening visit.
10. Patients treated with non-cardioselective ß-blockers in the month preceding the screening visit or during the study period.
11. Patients who have clinically significant cardiovascular disease according to investigator’s judgement. Thus includes but is not limited to congestive heart failure (NYHA class > 3); acute ischemic heart disease within the past 12 months of screening; Sustained cardiac arrhythmias (supraventricular or ventricular, >30 seconds duration) at or within 6 months of screening; Non sustained cardiac arrhythmias (supraventricular or ventricular, > 3 beats < 30 seconds and or ending spontaneously and or asymptomatic); History of sustained and non-sustained cardiac arrhythmias (supraventricular or ventricular); 2nd or 3rd degree AV conduction block; Left Bundle Branch Block.
12. Known respiratory disorders other than COPD
13. Patients whose DBP/SBP is higher than: DBP 90 mmHg or SBP 160 mmHg at screening or at randomization.
14. Patients taking Cardiac Anti-Arrythmics drugs, chronically or in the 4 weeks preceding the Screening Visit, patients taking oral/IV/IM corticosteroids, oral or nebulized ß2-agonists and/or antibiotics for LRTI and xanthine derivative (e.g. theophylline) formulations in the 4 weeks preceding the screening visit.
15. Unstable concurrent disease
16. Any patient with active cancer or a history of cancer with less than 5 years disease free survival time (whether or not there is evidence of local recurrence or metastases). Localized basal cell carcinoma
(without metastases) of the skin is acceptable



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

Health Condition(s) or Problem(s) studied

COPD patients
MedDRA version: 16.0 Level: LLT Classification code 10010952 Term: COPD System Organ Class: 100000004855

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

Intervention(s)

Trade Name: Foster®
Pharmaceutical Form: Pressurised inhalation, solution
INN or Proposed INN: BECLOMETASONE DIPROPIONATE
CAS Number: 5534-09-8
Other descriptive name: BDP
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 100-
INN or Proposed INN: FORMOTEROL FUMARATE DIHYDRATE
CAS Number: 43229-80-7
Other descriptive name: FF
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 6-
Pharmaceutical form of the placebo: Pressurised inhalation, solution
Route of administration of the placebo: Inhalation use

Trade Name: Foster® NEXThaler®
Pharmaceutical Form: Inhalation powder
INN or Proposed INN: beclometasone dipropionate
CAS Number: 5534-09-8
Other descriptive name: BDP
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 100-
INN or Proposed INN: formoterol fumarate
CAS Number: 43229-80-7
Other descriptive name: FF
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 6-
Pharmaceutical form of the placebo: Inhalation powder
Route of administration of the placebo: Inhalation use

Primary Outcome(s)

Main Objective: To compare the average heart rate over 4 hours after administration of BDP and Formoterol using CHF 1535 100/6 NEXThaler® DPI and CHF 1535 100/6 pMDI at two different dose levels

Primary end point(s): Average 4-hour Heart Rate

Timepoint(s) of evaluation of this end point: 4-hour rate

Secondary Objective: • To evaluate the effects of both formulations on serum potassium and serum glucose and cardiovascular parameters
• To assess the safety and the tolerability of the study treatments

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: See section E.5.2

Secondary end point(s): Cardiovascular:
• Average Hourly HR 0-1hr, 1-2hr, 2-3hr, 3-4hr
• Maximum 4-hour Heart Rate
• Average 0-12 hour Heart Rate
• Heart Rate at 5 minutes post-dose (expected time of Formoterol Cmax)
• QTcF, PR, QRS
• PAC burden
• PVC burden
• Blood Pressure: SBP AUC0-12h/12h, DBP AUC0-12h/12h

Metabolic response:
• Serum Potassium (AUC0-4h, Cmin, tmin)
• Serum Glucose (AUC0-4h, Cmax, tmax)

Secondary ID(s)

CCD-01535BC1-02

Source(s) of Monetary Support

Chiesi Farmaceutici S.p.A.