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

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ClinicalTrials.gov Identifier: NCT03524066
Recruitment Status : Completed
First Posted : May 14, 2018
Last Update Posted : February 15, 2019
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Fraunhofer-Institute of Toxicology and Experimental Medicine

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.

Condition or disease Intervention/treatment Phase
Healthy Drug: Inhalation Drug: Systemic Other: Bronchoscopy Not Applicable

Detailed Description:
This study will investigate drug levels of selected compounds at multiple sites in the lung and explore different innovative sampling methods to obtain information on lung PK. The aim of the study is not to generate safety or efficacy data of the selected licensed drugs. The choice of drugs is based on general considerations regarding therapy of airway diseases and the physical-chemical properties of the compounds. It is not driven by the compounds per se.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 21 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Understanding the Lung Pharmacokinetics (PK) in Humans by Direct Sampling of Epithelial Lining Fluid (ELF) After Inhalation and Oral Administration of Model Drugs
Actual Study Start Date : April 10, 2018
Actual Primary Completion Date : December 31, 2018
Actual Study Completion Date : December 31, 2018

Arm Intervention/treatment
Experimental: Inhaled + Bronchoscopy
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
Salbutamol(200µg), Salmeterol (50µg) and Fluticasone propionate (500µg) by inhalation

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

Experimental: Systemic + Bronchoscopy
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
Salbutamol 8mg M/R Tablet, Propranolol 40 mg administered orally

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




Primary Outcome Measures :
  1. Maximum concentration of Salbutamol in the lung [ Time Frame: change from baseline to 1 hour and 24,5 hours post dose ]
    Maximum concentration of Salbutamol in samples from bronchoscopy (bronchoadsorption, bronchial brushing, mucosal biopsy, Bronchoalveolar lavage (BAL))

  2. Maximum concentration of Salmeterol in the lung [ Time Frame: change from baseline to 1 hour and 24,5 hours post dose ]
    Maximum concentration of Salmeterol in samples from bronchoscopy (bronchoadsorption, bronchial brushing, mucosal biopsy, Bronchoalveolar lavage (BAL))

  3. Maximum concentration of Fluticasone in the lung [ Time Frame: change from baseline to 1 hour and 24,5 hours post dose ]
    Maximum concentration of Fluticasone in samples from bronchoscopy (bronchoadsorption, bronchial brushing, mucosal biopsy, Bronchoalveolar lavage (BAL))

  4. Maximum concentration of Propranolol in the lung [ Time Frame: change from baseline to 1 hour and 24,5 hours post dose ]
    Maximum concentration of Propranolol in samples from bronchoscopy (bronchoadsorption, bronchial brushing, mucosal biopsy, Bronchoalveolar lavage (BAL))


Secondary Outcome Measures :
  1. Maximum concentration of Salbutamol in plasma [ Time Frame: 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 Salbutamol in plasma samples

  2. Maximum concentration of Salmeterol in plasma [ Time Frame: 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 samples

  3. Maximum concentration of Fluticasone in plasma [ Time Frame: 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 samples

  4. Maximum concentration of Propranolol in plasma [ Time Frame: 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 samples



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Male and female subjects, aged 18-50 years. Women will be considered for inclusion if they are: Not pregnant, as confirmed by pregnancy test (see flow chart), and not nursing. Of non-child bearing potential (i.e. physiologically incapable of becoming pregnant, including any female who is pre-menarchial or post-menopausal, with documented proof of hysterectomy or tubal ligation, or meets clinical criteria for menopause and has been amenorrhoeic for more than 1 year prior to the screening visit). Of childbearing potential and using a highly effective method of contraception during the entire study (vasectomised partner, sexual abstinence - the lifestyle of the female should be such that there is complete abstinence from intercourse from two weeks prior to the first dose of study medication until at least 72 hours after treatment -, implants, injectables, combined oral contraceptives, hormonal IUDs (Intrauterine devices) or double-barrier methods, i.e. any double combination of IUD, condom with spermicidal gel, diaphragm, sponge, and cervical cap).
  • 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.

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03524066


Locations
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Germany
Fraunhofer Institute for Toxicology and Experimental Medicine
Hannover, Germany, 30625
Sponsors and Collaborators
Fraunhofer-Institute of Toxicology and Experimental Medicine
AstraZeneca
Investigators
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Principal Investigator: Jens Hohlfeld, MD Fraunhofer ITEM

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Responsible Party: Fraunhofer-Institute of Toxicology and Experimental Medicine
ClinicalTrials.gov Identifier: NCT03524066    
Other Study ID Numbers: 17-15 BROSO
First Posted: May 14, 2018    Key Record Dates
Last Update Posted: February 15, 2019
Last Verified: February 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Albuterol
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents
Tocolytic Agents
Reproductive Control Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists