IN-VIVO DEPOSITION MEASUREMENT OF BECLOMETASONE AND FORMOTEROL AFTER INHALATION OF A SINGLE DOSE OF THE COMBINATION BDP PLUS FORMOTEROL NEXT (TM) DPI IN HEALTHY VOLUNTEERS, ASTHMATIC AND COPD PATIENTS

• Register: EUCTR
• Last refreshed on: 4 February 2013
• Main ID: EUCTR2009-010267-17-DE
• Date of registration: 21/10/2009
• Prospective Registration: Yes
• Primary sponsor: Chiesi Farmaceutici S.p.A.
• Public title: IN-VIVO DEPOSITION MEASUREMENT OF BECLOMETASONE AND FORMOTEROL AFTER INHALATION OF A SINGLE DOSE OF THE COMBINATION BDP PLUS FORMOTEROL NEXT (TM) DPI IN HEALTHY VOLUNTEERS, ASTHMATIC AND COPD PATIENTS
• Scientific title: IN-VIVO DEPOSITION MEASUREMENT OF BECLOMETASONE AND FORMOTEROL AFTER INHALATION OF A SINGLE DOSE OF THE COMBINATION BDP PLUS FORMOTEROL NEXT (TM) DPI IN HEALTHY VOLUNTEERS, ASTHMATIC AND COPD PATIENTS
• Date of first enrolment: 03/03/2010
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-010267-17
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other:

Countries of recruitment

Germany

Key inclusion & exclusion criteria

Inclusion criteria:
Inclusion criteria
Healthy volunteers:
1.Males and females without childbearing potential aged 21-65 years;
2.Ability to use the NEXT(TM)DPI;
3.Body Mass Index (BMI) between 18.0 and 28.0 kg/m2;
4.Non- or ex-smokers who smoked < 5 pack years (pack-years = the number of cigarette packs per day times the number of years e.g. < 20 cigarettes per day for 5 years and 40 cigarettes per day for 2.5 years) and stopped smoking > 1 year;
5.Good physical and mental status, determined on the basis of the medical history and a general clinical examination;
6.Normal blood pressure and heart rate (100 = SBP = 150; 45 = DBP =90; 40 = HR = 100);
7.Electrocardiogram (ECG) (12 lead) with computerized protocol interpretation considered as normal (120 ms = PR = 220 ms, QRS = 120 ms, QTc = 450 ms). Minor deviations are acceptable provided the at they are not judged clinically significant by the investigator.
8.Results of laboratory tests within the normal ranges. Minor deviations are acceptable provided that they are not judged clinically significant by the investigator.
9.Understanding of the study and agreement to give written informed consent before the first selection procedure

Patients with Asthma:
1.Males and females (without childbearing potential) asthma patients aged 21-65 years;
2.Ability to use the NEXT(TM)DPI;
3.Body Mass Index (BMI) between 18.0 and 28.0 kg/m2;
4.Non- or ex-smokers who smoked < 5 pack years (e.g. < 20 cigarettes per day for 5 years and 40 cigarettes per day for 2.5 years) and stopped smoking > 1 year;
5.Normal blood pressure and heart rate (100 = SBP = 150; 45 = DBP =90; 40 = HR = 100);
6.ECG (12 lead) with computerized protocol interpretation considered as normal (120 ms = PR = 220 ms, QRS = 120 ms, QTc = 450 ms). Minor deviations are acceptable provided that they are not judged clinically significant by the investigator.
7.FEV1 = 30% and < 80% of predicted for the patient’s normal value (according to the predicted value for spirometric function, European Coal and Steel Community values [2]) measured at least 8 hours after the last use of short-acting ß2-agonist bronchodilators or short-acting anticholinergics, 72 hours after the last use of long-acting ß2-agonist bronchodilators and 72 hours after the last use of long-acting anticholinergics;
8.Reversibility of FEV1 = 12% and at least 200 ml of the initial value 15 minutes after inhalation of 200 µg Salbutamol within the screening period;
9.In good health on the basis of a medical history, physical examination, clinical laboratory studies and ECG with the exception of asthma;
10.Understanding of the study and agreement to give written informed consent before the first selection procedure.


Patients with COPD:
1.Males and females without childbearing potential aged 40 – 70 years
2.Ability to use the NEXT(TM)DPI;
3.Body Mass Index (BMI) between 18.0 and 30.0 kg/m2;
4.Normal blood pressure and heart rate (100 = SBP = 150; 45 = DBP =90; 40 = HR = 100);
5.ECG (12 lead) with computerized protocol interpretation considered as normal (120 ms = PR = 220 ms, QRS= 120 ms, QTc= 450 ms). Minor deviations are acceptable provided that they are not judged clinically significant by the investigator;
6.Stable COPD within the past 4 weeks;
7.Post bronchodilator FEV1 between 30% and 50% predicted values (30% = FEV1 < 50%) documented at screening visit ;
8.Post bronchodilator FEV1/Forced Vital Capacity (FEV1/FVC) ? 0.70 (absolute value) documented at screening visit;
9.Minimum
Exclusion criteria:
Exclusion criteria
All subjects:
1.Blood donation (equal or more than 450 ml) or blood loss less than 8 weeks before inhalation of the study medication;
2.Positive HIV1 or HIV2 serology;
3.Positive results from the Hepatitis serology which indicates acute or chronic Hepatitis B or Hepatitis C;
4.Unsuitable veins for repeated venipuncture;
5.Female patients: pregnant, positive pregnancy test, lactating mother or lack of efficient contraception (according to CPMP/ICH 286/95 note 3 1). Postmenopausal women < 1 year must have efficient contraception;
6.History of substance abuse or drug abuse within 12 months or with a positive urine drug screen;
7.Clinically relevant abnormal laboratory values suggesting an unknown disease and requiring further clinical investigation;
8.Clinically significant and uncontrolled cardiac, hepatic, renal, gastrointestinal, endocrine, metabolic, neurologic, or psychiatric disorder that may interfere with successful completion of this protocol;
9.Participation in another clinical trial less than 8 weeks prior to inhalation of the study medication; participation in study using radioactive material within 1 calendar year;
10.Known sensitivity to Formoterol or Beclometasone or any of the excipients contained in any of the formulations used in the trial;
11.Enzyme-inducing or inhibiting drugs taken within 2 months before the inhalation of the study medication.
12.Concomitant severe diseases or diseases which are contra indications for the use of inhaled ß2-agonist or steroids;
13.Use of any prescription drug for which concomitant beta-agonist or steroid administration are contraindicated;
14.History of significant sensitivity, allergy or intolerance to study drug formulation ingredients;
15.Recent relevant infectious disease (less than two months);
16.Flu vaccination within 4 weeks prior to the screening visit;
17.Other vaccination within 4 weeks prior to the screening visit;
18.Subjects unlikely to comply with the study protocol or unable to understand the nature and scope of the study but also the possible benefits or unwanted effects of the study treatments;


Additional exclusion criteria for healthy volunteers
1.Lung function measurements outside normal limits (Normal values: FEV1/FVC > 0.70 (absolute value) and FEV1 and FVC > 80% for the European Community for Coal and Steel 1993 predicted values) or other standard values for healthy volunteers;

Additional exclusion criteria for patients with Asthma:
1.Use of systemic steroids 4 weeks prior to inclusion (injectable depot steroids 6 weeks) or more than 3 periods during the last 6 months;
2.Life-threatening/unstable respiratory status including upper or lower respiratory tract infection, within the previous 30 days;
3.Requirement of continuous supplemental oxygen therapy; the use of supplemental oxygen not exceeding 2 l/min, at night time only and/or only during exercise is allowed;
4.Change in dose or type of any medications for asthma within 4 weeks prior to the screening visit;
5.Asthma exacerbation within the 4 weeks prior to inclusion.

Additional exclusion criteria for patients with COPD:
1.Use of systemic steroids 4 weeks prior to inclusion (injectable depot steroids 6 weeks) or more than 3 periods during the last 6 months;
2.Life-threatening/unstable respiratory status including upper or lower respiratory tract infection, within the previous 30 days;
3.Requirement of continuous supplemental oxygen therapy; the use of supplemental oxygen not exceedi

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

Health Condition(s) or Problem(s) studied

This study is focused on asthma bronchiale and chronic obstructive pulmonary disease COPD).
MedDRA version: 9.1 Level: PT Classification code 10003553 Term: Asthma
MedDRA version: 9.1 Level: LLT Classification code 10010952 Term: COPD

Intervention(s)

Product Name: CHF 1535 NEXT DPI
Product Code: CHF 1535 NEXT DPI
Pharmaceutical Form: Inhalation powder
INN or Proposed INN: Beclometasone Dipropionate
CAS Number: 5534098
Other descriptive name: BDP
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 100-
INN or Proposed INN: Formoterol Fumarate
CAS Number: 43229807
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)

Secondary Objective: Secondary:
•To evaluate the intrapulmonary distribution and the extrathoracic deposition
•To evaluate Formoterol, BDP and B17MP pharmacokinetics.
•To evaluate the efficacy by lung function assessment

Primary end point(s): Intrapulmonary lung deposition (DL, N) expressed as % of nominal dose

Main Objective: Primary:
To evaluate the amount of drug deposited within the lungs (intrapulmonary drug deposition relative to the nominal dose, DL, N) in healthy volunteers, asthmatic and COPD patients.

Secondary ID(s)

CCD-0815-PR-0011