Use of Exhaled Particles to Assess Lung Pharmacokinetics (EXPLORE)

Exhaled Particles in Lung Pharmacokinetics

This research project in humans aims at increasing the general understanding of lung pharmakokinetic by sampling exhaled particles. The central hypothesis of this study is that pharmacokinetics of Salbutamol (model drug) can be monitored in exhaled particles.

Study Overview

• Status: Completed
• Conditions: Healthy; Lung Pharmacokinetic
• Intervention / Treatment: Drug: Inhalation Spray; Drug: Tablet

Detailed Description

The aim of the present study is to increase the general understanding of lung pharmakokinetic by systematically sampling exhaled particles at pre-specified quantities to reproduce and extent existing pilot data. For comparison, samples of blood plasma and nasal filter samples (nasosorption) will be collected for pharmakokinetic analyzes. Nasosorption will be performed to explore the possibility of detecting drug concentrations in nasal filter paper samples.

Salbutamol will be administered by inhalation and orally in a cross-over study design and both application routes shall be comparised regarding the detection of pharmakokinetic data. 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.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Lower Saxony
    • Hannover, Lower Saxony, Germany, 30625
      • Fraunhofer Institute for Toxicology and Experimental Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Able and willing to give written informed consent.

2. Healthy male and female subjects, aged 18-65 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 or double-barrier methods, i.e. any double combination of IUD, condom with spermicidal gel, diaphragm, sponge, and cervical cap).

3. Body mass index between 18 and 32 kg/m2
4. Normal lung function with FEV1 predicted ≥ 80% and FEV1/FVC ≥ 70% at screening V1 ( or performed within 12 months prior to the screening visit at Fraunhofer ITEM and no evidence of clinical relevant abnormal findings in the lung function in the previous year before screening in the anamnesis).
5. Nonsmokers with a history of less than 1 pack year having been nonsmokers for at least the last 12 months
6. Emission of acceptable quantities of exhaled particles at screening (>200ng particle mass within 15 min)

Exclusion Criteria:

1. Any clinically relevant abnormal findings, 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
2. Past or present disease, which as judged by the investigator, may affect the outcome of this study. These diseases include, but are not limited to, cardiovascular disease, malignancy, hepatic disease, renal disease, hematological disease, neurological disease, endocrine disease or pulmonary disease (including but not confined to asthma, chronic bronchitis, emphysema, tuberculosis, bronchiectasis or cystic fibrosis).
3. 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
4. Clinically relevant history of allergy as judged by the investigator
5. Intolerance or contraindications to salbutamol
6. 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.
7. Participation in another clinical trial with an IMP 30 days or five half-lives, whichever is longer, prior to enrollment
8. History of drug or alcohol abuse
9. Risk of non-compliance with study procedures
10. Suspected inability to understand the protocol requirements, instructions and study-related restrictions, the nature, scope, and possible consequences of the study
11. Significant nasal deformity, recent nasal surgery or obstructing nasal polyps

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Sequence A: 1. Ingestion 2. Inhalation; Group A is treated in the following sequence: 1. oral drug 2. inhalative drug	Drug: Inhalation Spray; 400 mcg salbutamol administered per metered dose inhaler; Drug: Tablet; 8 mg salbutamol administered per tablet for ingestion
EXPERIMENTAL: Sequence B: 1. Inhalation 2. Ingestion; Group B is treated in the following sequence: 1. inhalative drug 2. oral drug	Drug: Inhalation Spray; 400 mcg salbutamol administered per metered dose inhaler; Drug: Tablet; 8 mg salbutamol administered per tablet for ingestion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Salbutamol concentration assessed in exhaled particles over 5 hours after inhaled versus oral administration	Before, 0 min, 20 min, 40 min, 60 min, 120 min, 180 min, 240 min, 270 min, 300 min after drug administration

Secondary Outcome Measures

Outcome Measure	Time Frame
Salbutamol concentration assessed in blood plasma over 5 hours after inhaled versus oral administration	Before, 0 min, 15 min, 35 min, 55 min, 75 min, 135 min, 195 min, 255 min, 285 min, 315 min after drug administration
Salbutamol concentration assessed in nasal filter samples (nasosorption) over 5 hours after inhaled versus oral administration	Before, 0 min, 15 min, 35 min, 55 min, 75 min, 135 min, 195 min, 255 min, 285 min, 315 min after drug administration
Safety and tolerability of the sampling method by assessing adverse events	Day 1 to Day 18

Collaborators and Investigators

• Sponsor: Fraunhofer-Institute of Toxicology and Experimental Medicine
• Collaborators: AstraZeneca

Publications and helpful links

General Publications

• Schwarz K, Biller H, Windt H, Koch W, Hohlfeld JM. Characterization of exhaled particles from the healthy human lung--a systematic analysis in relation to pulmonary function variables. J Aerosol Med Pulm Drug Deliv. 2010 Dec;23(6):371-9. doi: 10.1089/jamp.2009.0809. Epub 2010 May 25.
• Schwarz K, Biller H, Windt H, Koch W, Hohlfeld JM. Characterization of exhaled particles from the human lungs in airway obstruction. J Aerosol Med Pulm Drug Deliv. 2015 Feb;28(1):52-8. doi: 10.1089/jamp.2013.1104. Epub 2014 Jun 10.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 14, 2021
• Primary Completion (ACTUAL): August 3, 2021
• Study Completion (ACTUAL): August 3, 2021

Study Registration Dates

• First Submitted: May 31, 2021
• First Submitted That Met QC Criteria: May 31, 2021
• First Posted (ACTUAL): June 4, 2021

Study Record Updates

• Last Update Posted (ACTUAL): August 19, 2021
• Last Update Submitted That Met QC Criteria: August 18, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: 21-15 EXPLORE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No