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

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.

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.

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive; Asthma
• Intervention / Treatment: Drug: BDP/formoterol NEXT DPI

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Germany
  • Gauting, Germany, 82131
    • Inamed Research GmbH & Co. KG

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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	Time Frame
Lung function parameters	over 24 h post dose
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

Collaborators and Investigators

• Sponsor: Chiesi Farmaceutici S.p.A.
• Investigators: Principal Investigator: Thomas Meyer, MD, Inamed Research GmbH & Co. KG

Publications and helpful links

General Publications

• 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.

Helpful Links

• Study Record on EU Clinical Trials Register including results
• CSR Synopsis available in the CHIESI Clinical Study Register

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (ACTUAL): September 1, 2010
• Study Completion (ACTUAL): October 1, 2010

Study Registration Dates

• First Submitted: August 5, 2010
• First Submitted That Met QC Criteria: August 5, 2010
• First Posted (ESTIMATE): August 6, 2010

Study Record Updates

• Last Update Posted (ACTUAL): October 29, 2021
• Last Update Submitted That Met QC Criteria: October 28, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Formoterol Fumarate
• Other Study ID Numbers: CCD-0815-PR-0011; 2009-010267-17 (EUDRACT_NUMBER)