Explorative Clinical Investigation to Investigate the Ability of PreciseInhale to Direct Regional Lung Targeting and Reduce the Degree of Throat Deposition and Subsequent Gastrointestinal Absorption in Healthy Volunteers After Inhalation of Test Drug Substances Via the PreciseInhale System

NCT04946630 | Completed

• 1 other identifier: CLIN01-PI
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single site, open label, 4-inhalation sessions, explorative clinical investigation to investigate the ability of PreciseInhale to direct regional lung targeting and reduce the degree of throat deposition and subsequent gastrointestinal absorption of test drug substances in healthy volunteers after inhalation of test drug substances via the PreciseInhale system. The study will include a screening visit, 8 consecutive treatment visits and a follow-up telephone call 3-5 days after the last inhalation session. There will be a screening period of up to 35 days and an at least 1-week washout between treatments.

Conditions

Nebulizers and Vaporizers

Outcome Measures

Primary Outcomes (11)

• Cmax

  Maximum plasma concentration. Venous blood samples (approximately 4 mL) for the determination of plasma concentrations of salmeterol and fluticasone propionate after administration of the test drug substances via the Evohaler or the PreciseInhale-device will be collected. Cmax (in plasma) will be compared for PreciseInhale versus inhalation directly from pMDI (Evohaler). Outcome measured in session 1-4.

  From pre-dose to up to 24 hours post-dose.

• AUC0-t

  Area under the curve from time 0 to time t. Venous blood samples (approximately 4 mL) for the determination of plasma concentrations of salmeterol and fluticasone propionate after administration of the test drug substances via the Evohaler or the PreciseInhale-device will be collected. AUC0-t (in plasma) will be compared for PreciseInhale versus inhalation directly from pMDI (Evohaler). AUC0-t (in plasma) will be compared for PreciseInhale versus inhalation directly from pMDI (Evohaler). Outcome measured in session 1-4.

  From pre-dose to up to 24 hours post-dose

• Tmax

  Time to Cmax. Venous blood samples (approximately 4 mL) for the determination of plasma concentrations of salmeterol and fluticasone propionate after administration of the test drug substances via the Evohaler or the PreciseInhale-device will be collected.Tmax (in plasma) will be compared for PreciseInhale versus inhalation directly from pMDI (Evohaler). Outcome measured in session 1-4.

  From pre-dose to up to 24 hours post-dose

• Inhaled and exhaled dose, fraction inhaled/exhaled dose

  Calculated inhaled dose (µg), dose in exhaled air (µg) and fraction inhaled/exhaled dose (analysed from PARI filter, data collected from inhalation sessions No. 2, 3 and 4). Outcome measured in session 2-4.

  Collected post-dose at one occasion, approx. for 2 min

• Inhaled and exhaled dose, fraction inhaled/exhaled dose

  Demonstrate that one inhaler aerosol dose from the pMDI can be subdivided into several smaller dose increments using the PreciseInhale (data collected from inhalation sessions No. 3 and 4). Outcome measured in session 3-4

  Collected post-dose at one occasion, approx. for 2 min

• Air flow rate

  Measure air flow rates and aerosol concentration- and timing in the ventilation manoeuvre to demonstrate that regional targeting can be achieved with PreciseInhale bolus-breath hold method (data collected from inhalation sessions No 3 and 4). Outcome measured in session 3-4

  Collected during inhalation session, approx. for 5 min

• Aerosol concentration

  Measure air flow rates and aerosol concentration- and timing in the ventilation manoeuvre to demonstrate that regional targeting can be achieved with PreciseInhale bolus-breath hold method (data collected from inhalation sessions No 3 and 4). Outcome measured in session 3-4.

  Collected during inhalation session, approx. for 5 min

• Acutal bolus volume

  Measure air flow rates and aerosol concentration- and timing in the ventilation manoeuvre to demonstrate that regional targeting can be achieved with PreciseInhale bolus-breath hold method (data collected from inhalation sessions No 3 and 4). Outcome measured in session 3-4.

  Collected during inhalation session, approx. for 5 min

• Chase air volume

  Measure air flow rates and aerosol concentration- and timing in the ventilation manoeuvre to demonstrate that regional targeting can be achieved with PreciseInhale bolus-breath hold method (data collected from inhalation sessions No 3 and 4). Outcome measured in session 3-4.

  Collected during inhalation session, approx. for 5 min

• Actual number of inhalations

  Measure air flow rates and aerosol concentration- and timing in the ventilation manoeuvre to demonstrate that regional targeting can be achieved with PreciseInhale bolus-breath hold method (data collected from inhalation sessions No 3 and 4). Outcome measured in session 3-4.

  Collected during inhalation session, approx. for 5 min

• Correlation between two outcomes: AUC (weight-adjusted) -inhaled/exhaled dose

  Area under the curve from time 0 to time t adjusted for weight and correlated to inhaled/exhaled dose. Outcome measured in session 2-4.

  AUC from pre-dose to up to 24 hours post-dose. Inhaled/exhaled dose collected post-dose at one occasion.

Secondary Outcomes (8)

• Adverse events (AEs)

  From start of first inhalation training until the end-of- study visit, an average of 5 weeks.

• Device deficiencies (DD)

  From start of first inhalation training until the end-of- study visit, an average of 5 weeks

• Number of changes in vital signs judged as clinically significant by Principal Investigator

  Vital signs will be checked at pre-defined timepoints from the screening visit until the end-of-study visit, an average of 6 weeks

• Number of changes in electrocardiogram (ECG) judged as clinically significant by Principal Investigator

  ECG will be checked at pre-defined timepoints from the screening visit until the end-of-study visit, an average of 6 weeks

• Number of changes in safety laboratory parameters judged as clinically significant by Principal Investigator

  Blood samples will be collected at pre-defined timepoints from the screening visit until the end-of-study visit, an average of 6 weeks

Study Arms (4)

Seretide Evohaler forte according to SmPc

EXPERIMENTAL

Single dose inhalation of fluticasone propionate/salmeterol 250 µg/25 µg administered via the Evohaler in accordance with instruction in the SmPC for Seretide Evohaler forte.

Other: Seretide Evohaler forte

Whole lung exposure

EXPERIMENTAL

Single dose of fluticasone propionate/salmeterol 250 µg/25 µg administered via the PreciseInhale system set up for whole lung exposure. The entire 300 mL aerosol volume produced by the single dose from the inhaler will be inhaled at a flow rate in accordance with instructions for the Evohaler.

Device: PreciseInhale; Other: Seretide Evohaler forte

Alveolar bolus/ Breath hold exposures

EXPERIMENTAL

A subdivided dose of fluticasone propionate/salmeterol 250 µg/25 µg administered via the PreciseInhale system set up for six repetitive 70 mL Alveolar bolus/ Breath hold exposures. Each 70 mL bolus will be extracted from a freshly generated volume of 300 mL aerosol produced by actuation of a single dose from the inhaler.

Device: PreciseInhale; Other: Seretide Evohaler forte

Bronchial bolus/ Breath hold exposures

EXPERIMENTAL

A subdivided dose of fluticasone propionate/salmeterol 250 µg/25 µg administered via the PreciseInhale system set up for six repetitive 70 mL Bronchial bolus/ Breath hold exposures. Each 70 mL bolus will be extracted from a freshly generated volume of 300 mL aerosol produced by actuation of a single dose from the inhaler.

Device: PreciseInhale; Other: Seretide Evohaler forte

Interventions

PreciseInhale DEVICE

Three different settings of the medical device PreciseInhale will be used in the study; PreciseInhale Whole Lung Exposure, PreciseInhale Bronchial Bolus/Breath hold Exposure and PreciseInhale Alveolar Bolus/Breath hold Exposure.

Alveolar bolus/ Breath hold exposures; Bronchial bolus/ Breath hold exposures; Whole lung exposure

Seretide Evohaler forte OTHER

Single dose of Seretide Evohaler forte (fluticasone propionate/salmeterol 250 µg/25 µg) administered according to SmPc or via the PreciseInhale system.

Alveolar bolus/ Breath hold exposures; Bronchial bolus/ Breath hold exposures; Seretide Evohaler forte according to SmPc; Whole lung exposure

Eligibility Criteria

• Age: 18 Years - 30 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Willing and able to give written informed consent for participation in the study.
• Healthy male or female subject aged ≥18 and ≤30 years inclusive.
• Body Mass Index (BMI) ≥18 and ≤30 kg/m2 and weight ≥50 kg to ≤100 kg at screening.
• Clinically normal medical history, physical findings, vital signs and laboratory values at the time of screening, as judged by the Investigator.

You may not qualify if:

• History of any clinically significant disease or disorder (including clinically significant disease affecting the respiratory tract, thoracic deformities affecting lung function and/or lung volumes, muscle diseases affecting lung function and/or lung volumes and any known mouth or nasal passage deformities) which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.
• Any clinically significant illness, medical/surgical procedure or trauma within two weeks prior to the first inhalation with the investigational device, which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.
• Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody and Human Immunodeficiency Virus (HIV).
• After 10 minutes supine rest at the time of screening, any vital signs values outside the following ranges:
• Systolic blood pressure \> 140 mm Hg
• Diastolic blood pressure \> 90 mm Hg
• Pulse \< 40 or \> 85 beats per minute
• Former regular daily smoker.
• Current smokers or users of nicotine products (including vaping/e-cigarettes). Irregular use of nicotine (e.g. smoking, snuffing, chewing tobacco, vaping) less than three times per week is allowed before the screening visit.
• FVC or FEV1 outside of normal ranges (depending on subject's gender, height and age) at screening.
• Female subjects who are pregnant or who are currently breast feeding.
• Administration of a new chemical entity (defined as a compound which has not been approved for marketing) or has participated in any other clinical study that included drug treatment with less than one month before the first inhalation session.
• History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity (including pollen allergy), as judged by the Investigator.
• History of hypersensitivity to drugs with a similar chemical structure or class to fluticasone or salmeterol, as judged by the Investigator.
• Positive screen for drugs of abuse or alcohol at screening or on admission to the research unit prior to any of the inhalation sessions.

Sponsors & Collaborators

• Inhalation Sciences Sweden AB: lead
• CTC Clinical Trial Consultants AB: collaborator
• PlantVision AB: collaborator
• Pharm-Analyt Labor GmbH: collaborator

Study Sites (1)

Clinical Trial Consultants AB

Uppsala, 75756, Sweden

Location

Study Officials

• Manoush Masarrat

  Inhalation Sciences AB

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DEVICE FEASIBILITY
• Intervention Model: FACTORIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The 4 treatment periods will include 4 inhalation sessions. The 12 included subjects will participate in all 4 treatment periods and the same order of treatment periods will be followed for all included subjects. There will be a wash-out period of at least 1 week between treatments.

Study Record Dates

• First Submitted: June 4, 2021
• First Posted: July 1, 2021
• Study Start: June 7, 2021
• Primary Completion: July 22, 2021
• Study Completion: July 26, 2021
• Last Updated: April 11, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)