Lung Deposition of the BDP/Formoterol Combination Administered Via the NEXT DPI in Healthy, Asthmatic and COPD Patients

Study Overview
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Brief Summary
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The purpose of this study is to investigate the lung deposition and distribution pattern of Beclometasone and Formoterol using a gamma-scintigraphic technique after inhalation of a single dose of 99mTc-radiolabelled BDP/formoterol fixed combination administered Via the NEXT DPI in healthy volunteers, asthmatic and COPD patients. Additionally, the systemic exposures to formoterol, BDP and its monopropionate metabolite (B17MP) will be investigated.

Official Title
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In-vivo Deposition Measurement of Beclometasone and Formoterol After Inhalation of a Single Dose of the Combination BDP Plus Formoterol NEXT DPI in Healthy Volunteers, Asthmatic and COPD Patients.

Conditions
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Pulmonary Disease, Chronic Obstructive, Asthma

Intervention / Treatment
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* Drug: BDP/formoterol NEXT DPI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy volunteers: Males and females aged 18-65 years; Body Mass Index (BMI) between 18.0 and 28.0 kg/m2; Non- or ex-smokers who smoked < 5 pack years and stopped smoking > 1 year; Normal blood pressure and heart rate; Normal electrocardiogram (ECG,12 lead); Normal laboratory tests; Patients with Asthma: Males and females aged 21-65 years; BMI between 18.0 and 28.0 kg/m2; Non- or ex-smokers who smoked < 5 pack years and stopped smoking > 1 year; Normal blood pressure and heart rate; Normal ECG (12 lead); FEV1 ≥ 30% and < 80% of predicted according to European Coal and Steel Community values (ECSC) Reversibility of FEV1 ≥ 12% and at least 200 ml of the initial value 15 minutes after inhalation of 200 µg Salbutamol; Patients with COPD: Males and females aged 40 - 70 years BMI between 18.0 and 30.0 kg/m2; Normal blood pressure and heart rate; Normal ECG (12 lead); Stable COPD within the past 4 weeks; Post bronchodilator FEV1 between 30% and 50% predicted values (ECSC); Post bronchodilator FEV1/FVC < 0.70 (absolute value); Minimum smoking history of 10 pack-years; Exclusion Criteria: All subjects: Blood donation or blood loss in the previous 8 weeks; Positive HIV1 or HIV2 serology; Positive acute or chronic Hepatitis B or Hepatitis C; Unsuitable veins for repeated venipuncture; Female patients: pregnant, positive pregnancy test, lactating mother or lack of efficient contraception. History of substance abuse or positive urine drug screen; Abnormal laboratory values suggesting an unknown disease and requiring further clinical investigation; Uncontrolled cardiac, hepatic, renal, gastrointestinal, endocrine, metabolic, neurologic, or psychiatric clinically significant disorder; Participation in another clinical trial in the previous 8 weeks; participation in study using radioactive material within 1 calendar year; Known sensitivity to Formoterol or Beclometasone or any of the excipients; Concomitant severe diseases or diseases which are contra indications for the use of inhaled Beta-2-agonist or steroids; Use of any prescription drug for which concomitant beta-agonist or steroid administration are contraindicated; Recent relevant infectious disease (less than two months); Flu vaccination or other vaccination within 4 weeks prior to the screening visit; Additional exclusion criteria for healthy volunteers: Lung function measurements outside normal limits (normal values: FEV1/FVC > 0.70 and FEV1 and FVC > 80% for the ECSC predicted values); Additional exclusion criteria for patients with Asthma: Use of systemic steroids 4 weeks prior to inclusion (injectable depot steroids 6 weeks) or more than 3 periods during the last 6 months; Life-threatening/unstable respiratory status within the previous 30 days; Requirement of supplemental oxygen therapy; Change in dose or type of any medications for asthma within 4 weeks prior to the screening visit; Asthma exacerbation within the 4 weeks prior to inclusion. Additional exclusion criteria for patients with COPD: Use of systemic steroids 4 weeks prior to inclusion (injectable depot steroids 6 weeks) or more than 3 periods during the last 6 months; Life-threatening/unstable respiratory status within the previous 30 days; Requirement of supplemental oxygen therapy; Change in dose or type of any medications for COPD within 4 weeks prior to the screening visit; COPD exacerbation within the 4 weeks prior to inclusion; History of asthma or any chronic respiratory diseases other than COPD.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BDP/formoterol NEXT DPI<br>Radiolabelled BDP/formoterol 100/6 µg dry powder administered via the NEXT inhaler | Drug: BDP/formoterol NEXT DPI<br>* Single inhalation of radiolabelled BDP/formoterol 100/6 µg NEXT DPI (4 puffs giving a total dose of 400 µg BDP + 24 µg formoterol)<br>* Other names: CHF 1535 NEXT DPI;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lung deposition of BDP and Formoterol (expressed as % of emitted dose) when inhaled using the NEXT dry powder inhaler | Calculated using the individual Gamma camera images and the regions of interest defined from the 81mKrypton-ventilation scan. | Immediately after dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Distribution of lung deposition |  | Immediately after dosing | 
| Extrathoracic deposition |  | Immediately after dosing | 
| Exhaled activity |  | Immediately after dosing | 
| Plasma pharmacokinetics of formoterol, BDP and its monopropionate metabolite (B17MP) |  | over 24 h post dose | 
| Lung function parameters |  | over 24 h post dose |