Use of Exhaled Particles to Assess Lung Pharmacokinetics

NCT04914273 | Completed

• 1 other identifier: 21-15 EXPLORE
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy; Lung Pharmacokinetic

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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

Study Arms (2)

Sequence A: 1. Ingestion 2. Inhalation

EXPERIMENTAL

Group A is treated in the following sequence: 1. oral drug 2. inhalative drug

Drug: Inhalation Spray; Drug: Tablet

Sequence B: 1. Inhalation 2. Ingestion

EXPERIMENTAL

Group B is treated in the following sequence: 1. inhalative drug 2. oral drug

Drug: Inhalation Spray; Drug: Tablet

Interventions

Inhalation Spray DRUG

400 mcg salbutamol administered per metered dose inhaler

Sequence A: 1. Ingestion 2. Inhalation; Sequence B: 1. Inhalation 2. Ingestion

Tablet DRUG

8 mg salbutamol administered per tablet for ingestion

Sequence A: 1. Ingestion 2. Inhalation; Sequence B: 1. Inhalation 2. Ingestion

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able and willing to give written informed consent.
• 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).
• Body mass index between 18 and 32 kg/m2
• 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).
• Nonsmokers with a history of less than 1 pack year having been nonsmokers for at least the last 12 months
• Emission of acceptable quantities of exhaled particles at screening (\>200ng particle mass within 15 min)

You may not qualify if:

• 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
• 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).
• 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 salbutamol
• 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.
• Participation in another clinical trial with an IMP 30 days or five half-lives, whichever is longer, prior to enrollment
• 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
• Significant nasal deformity, recent nasal surgery or obstructing nasal polyps

Sponsors & Collaborators

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

Study Sites (1)

Fraunhofer Institute for Toxicology and Experimental Medicine

Hanover, Lower Saxony, 30625, Germany

Location

Related Publications (2)

• 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.

  PMID: 20500095 BACKGROUND

• 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.

  PMID: 24914577 BACKGROUND

MeSH Terms

Interventions

Tablets

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. Jens M Hohlfeld

Study Record Dates

• First Submitted: May 31, 2021
• First Posted: June 4, 2021
• Study Start: June 14, 2021
• Primary Completion: August 3, 2021
• Study Completion: August 3, 2021
• Last Updated: October 15, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)