Lung Pharmacokinetics (PK) in Epithelial Lining Fluid (ELF)

NCT03524066 | Completed

• 1 other identifier: 17-15 BROSO
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of the present study is to increase the general understanding of lung PK of selected compounds by sampling epithelial lining fluid ELF and lung tissue.

Conditions

Healthy

Outcome Measures

Primary Outcomes (4)

• Maximum concentration of Salbutamol in the lung

  Maximum concentration of Salbutamol in samples from bronchoscopy (bronchoadsorption, bronchial brushing, mucosal biopsy, Bronchoalveolar lavage (BAL))

  change from baseline to 1 hour and 24,5 hours post dose

• Maximum concentration of Salmeterol in the lung

  Maximum concentration of Salmeterol in samples from bronchoscopy (bronchoadsorption, bronchial brushing, mucosal biopsy, Bronchoalveolar lavage (BAL))

  change from baseline to 1 hour and 24,5 hours post dose

• Maximum concentration of Fluticasone in the lung

  Maximum concentration of Fluticasone in samples from bronchoscopy (bronchoadsorption, bronchial brushing, mucosal biopsy, Bronchoalveolar lavage (BAL))

  change from baseline to 1 hour and 24,5 hours post dose

• Maximum concentration of Propranolol in the lung

  Maximum concentration of Propranolol in samples from bronchoscopy (bronchoadsorption, bronchial brushing, mucosal biopsy, Bronchoalveolar lavage (BAL))

  change from baseline to 1 hour and 24,5 hours post dose

Secondary Outcomes (4)

• Maximum concentration of Salbutamol in plasma

  change from baseline to 0,25 hour (h) 0,5 h, 1 h, 2 h, 4h, 8 h, 12 h, 24 h, 36 h, 48 h post dose

• Maximum concentration of Salmeterol in plasma

  change from baseline to 0,25 hour (h) 0,5 h, 1 h, 2 h, 4h, 8 h, 12 h, 24 h, 36 h, 48 h post dose

• Maximum concentration of Fluticasone in plasma

  change from baseline to 0,25 hour (h) 0,5 h, 1 h, 2 h, 4h, 8 h, 12 h, 24 h, 36 h, 48 h post dose

• Maximum concentration of Propranolol in plasma

  change from baseline to 0,25 hour (h) 0,5 h, 1 h, 2 h, 4h, 8 h, 12 h, 24 h, 36 h, 48 h post dose

Study Arms (2)

Inhaled + Bronchoscopy

EXPERIMENTAL

One-time Inhalation of Salbutamol 200 µg, Salmeterol 50µg and Fluticasone 500µg. During two bronchoscopic procedures two pre-specified lung tissue sites (middle lobe and lingula) will be sampled. Bronchoadsorption sample, bronchial brushing, mucosal biopsy, and bronchoalveolar lavage (BAL) samples will be taken from each site.

Drug: Inhalation; Other: Bronchoscopy

Systemic + Bronchoscopy

EXPERIMENTAL

One-time Salbutamol (8 mg) and Propranolol (40mg) administered orally. During two bronchoscopic procedures two pre-specified lung tissue sites (middle lobe and lingula) will be sampled. Bronchoadsorption sample, bronchial brushing, mucosal biopsy, and BAL samples will be taken from each site.

Drug: Systemic; Other: Bronchoscopy

Interventions

Inhalation DRUG

Salbutamol(200µg), Salmeterol (50µg) and Fluticasone propionate (500µg) by inhalation

Inhaled + Bronchoscopy

Systemic DRUG

Salbutamol 8mg M/R Tablet, Propranolol 40 mg administered orally

Systemic + Bronchoscopy

Bronchoscopy OTHER

Bronchoadsorption sample, bronchial brushing, mucosal biopsy, and BAL samples during bronchoscopy

Inhaled + Bronchoscopy; Systemic + Bronchoscopy

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Normal lung function with Forced Expiratory Volume in the first second (FEV1) predicted ≥ 80% and FEV1/Forced Vital Capacity (FVC) \> 70%.
• Nonsmokers with a history of less than 1 pack year having been nonsmokers for at least the last five years
• Body mass index between 18 and 32 kg/m²
• Able and willing to give written informed consent.

You may not qualify if:

• Past or present disease, which as judged by the investigator, may affect the outcome of the study. These diseases include, but are not limited to, cardiovascular disease, malignancy, hepatic disease, renal disease, hematological disease, neurological disease, psychiatric disease, endocrine disease, infectious disease, inflammatory disease or pulmonary disease (including but not confined to asthma, tuberculosis, bronchiectasis or cystic fibrosis)
• Regular intake of any prescribed or over the counter medication. Exceptions include paracetamol for pain relief, oral contraceptive medication, hormonal replacement therapy, dietary and vitamin supplements
• Clinically relevant history of allergy as judged by the investigator
• Intolerance or contraindications to medications applied as model drugs (e.g. hyperthyreosis) or for sedation during bronchoscopy
• Infections of the lower respiratory tract within 4 weeks before visit 1, visit 2, or visit 3. These patients can be rescreened starting from visit 1.
• Any clinically relevant abnormal findings in physical examination, clinical chemistry, hematology, urinalysis, vital signs, lung function, or ECG at Visit 1, which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, or may influence the results of the study, or the subject's ability to participate in the study
• History of drug or alcohol abuse
• Risk of non-compliance with study procedures
• Suspected inability to understand the protocol requirements, instructions and study-related restrictions, the nature, scope, and possible consequences of the study

Sponsors & Collaborators

• Fraunhofer-Institute of Toxicology and Experimental Medicine: lead
• AstraZeneca: collaborator

Study Sites (1)

Fraunhofer Institute for Toxicology and Experimental Medicine

Hanover, 30625, Germany

Location

MeSH Terms

Interventions

Inhalation; Bronchoscopy

Intervention Hierarchy (Ancestors)

Respiratory Mechanics; Respiration; Respiratory Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena; Diagnostic Techniques, Respiratory System; Diagnostic Techniques and Procedures; Diagnosis; Endoscopy; Diagnostic Techniques, Surgical; Minimally Invasive Surgical Procedures; Surgical Procedures, Operative; Pulmonary Surgical Procedures; Thoracic Surgical Procedures

Study Officials

• Jens Hohlfeld, MD

  Fraunhofer ITEM

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 25, 2018
• First Posted: May 14, 2018
• Study Start: April 10, 2018
• Primary Completion: December 31, 2018
• Study Completion: December 31, 2018
• Last Updated: February 15, 2019

Record last verified: 2019-02

Locations

DE (1)