Clinical trial NCT01176747: Lung Deposition of the BDP/Formoterol Combination Administered Via the NEXT DPI in Healthy, Asthmatic and COPD Patients
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Pulmonary Disease, Chronic Obstructive
Asthma
Lead sponsor: Chiesi Farmaceutici S.p.A.
Sponsor class: INDUSTRY
First posted: 2010-08-06
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Lung deposition of BDP and Formoterol (expressed as % of emitted dose) when inhaled using the NEXT dry powder inhaler
timeFrame: Immediately after dosing
Secondary outcomes:
measure: Distribution of lung deposition
timeFrame: Immediately after dosing
measure: Extrathoracic deposition
timeFrame: Immediately after dosing
measure: Exhaled activity
timeFrame: Immediately after dosing
measure: Plasma pharmacokinetics of formoterol, BDP and its monopropionate metabolite (B17MP)
timeFrame: over 24 h post dose
measure: Lung function parameters
timeFrame: over 24 h post dose
Other outcomes:
Locations:
city: Gauting
country: Germany
facility: Inamed Research GmbH & Co. KG
Study officials:
affiliation: Inamed Research GmbH & Co. KG
name: Thomas Meyer, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Virchow JC, Poli G, Herpich C, Kietzig C, Ehlich H, Braeutigam D, Sommerer K, Haussermann S, Mariotti F. Lung Deposition of the Dry Powder Fixed Combination Beclometasone Dipropionate Plus Formoterol Fumarate Using NEXThaler(R) Device in Healthy Subjects, Asthmatic Patients, and COPD Patients. J Aerosol Med Pulm Drug Deliv. 2018 Oct;31(5):269-280. doi: 10.1089/jamp.2016.1359. Epub 2018 Jul 10.