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
Condition: Nebulizers and Vaporizers
MeSH terms: Respiratory Aspiration
Study type: Interventional

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.
    

Detailed description: 
      Intended use The PreciseInhale system is a benchtop aerosol generation and dispensation
      system set up for extracting aerosol from clinical inhalers. The PreciseInhale system is
      classified as a Class IIa device according to MDD Annex IX, Rule 11.

      PreciseInhale is intended to administer test drug substances in precise doses by producing
      exact amounts of inhalable aerosols from a clinical inhaler.

      Extraction of the aerosol and exposure to humans must comply with operator and test subject
      safety regulations and only conducted in accordance with permits from the Swedish Medical
      Products Agency (MPA) and Swedish Ethical Review Authority (SERA) if necessary.

      Indication PreciseInhale is not intended to treat any specific condition that requires
      medical attention. The purpose of the clinical investigation is to prove that the principle
      of operation of PreciseInhale is useful for administration of aerosols to humans.

      Methodology Screening (Visit 1) will take place from Day -35 to Day 1 and will include
      general health assessments and an eligibility check.

      At Visits 2 to 9, subjects will be admitted to the research clinic on Day -1 and will remain
      at the research clinic for PK and safety assessments until at least 12 hours after a single
      dose fluticasone propionate/salmeterol 250/25 µg is administered on the morning of Day 1
      (Visit 2, 4, 6 and 8). The subjects will be carefully monitored by clinical staff during and
      after dosing. Vital signs and ECG will be checked at pre-determined timepoints. There is
      immediate access to equipment and qualified staff in case of an emergency.

      Fluticasone propionate/salmeterol will be administered to each subject via the Evohaler or
      the PreciseInhale system, in the morning of Day 1 of each treatment period.

      The 4 treatment periods will include these 4 inhalation sessions (up to 5 minutes/per
      session):

        1. 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.

        2. 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.

        3. 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.

        4. 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.

      Inhalations will be administered by trained study personnel and the subjects will receive
      inhalation training before each inhalation session.

      Subjects will be served a light breakfast before each treatment administration. After 1 hour
      post dose, the meal intake is unrestricted within the meal selection available at the
      research clinic. Lunch, Snack, dinner and evening snack (optional) will be served
      approximately 4, 6, 9 and 12 hours post-dose, respectively. Fluids will be restricted 1 hour
      prior to dosing until 1 hour after dosing. An optional breakfast may be served in the morning
      of Day 2 before the subject leaves the clinic.

      PK samples will be collected at 17 time points in each treatment period: pre-dose, 2, 4, 6,
      15, 30, 45 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 24 hours after treatment.

      The subjects will be discharged from the research clinic in the evening of Day 1 (12 hours
      post treatment) and return to the research clinic in the morning (Visits 3, 5, 7 and 9; 24
      hours post treatment) of Day 2 for PK sampling (and follow up safety assessments on the last
      Day 2).

      There will be a wash-out period of at least 1 week between treatments. A follow-up telephone
      call (Visit 10, end-of-study) will be made 3-5 days after the last inhalation to follow-up on
      adverse events and device deficiencies.

      A device user experience questionnaire will be completed by the study subject and
      PreciseInhale operator after all inhalation sessions with the PreciseInhale have been
      completed, i.e after the fourth inhalation session.
    

Intervention name(s): PreciseInhale; Seretide Evohaler forte
Intervention type(s): Device; Other
Intervention description(s): 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.; Single dose of Seretide Evohaler forte (fluticasone propionate/salmeterol 250 µg/25 µg) administered according to SmPc or via the PreciseInhale system.
Intervention MeSH terms: Fluticasone-Salmeterol Drug Combination
Allocation: Non-Randomized
Intervention model: Factorial Assignment
Intervention model description: 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.
Masking: None (Open Label)
Primary purpose: Device Feasibility