Nebulizers and VaporizersNCT04946630
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
A study testing PreciseInhale and Seretide Evohaler forte in people with Nebulizers and Vaporizers, run by Inhalation Sciences Sweden AB at 1 site in Sweden.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 30 yearsHealthy volunteers can take part
- Conditions the study is for
- Nebulizers and Vaporizers
- What is being tested?
- PreciseInhale and Seretide Evohaler forte
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteSweden
- Study dates
- 7 Jun 2021to 26 Jul 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 30 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 18Show fewer
- 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.
- Current or history of alcohol abuse and/or use of anabolic steroids or drugs of abuse.
- Plasma donation within one month of screening or blood donation (or corresponding blood loss) during the three months prior to screening.
- Investigator considers the subject unlikely to comply with study procedures, restrictions and requirements.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Single Site, Open Label, 4-inhalation Session, 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
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.
Read the 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):
- 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.
- 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.
- 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.
- 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.
- Conditions
- Nebulizers and Vaporizers
- Being tested
- PreciseInhale, Seretide Evohaler forte
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PreciseInhaleDevice
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.
Seretide Evohaler forteOther
Single dose of Seretide Evohaler forte (fluticasone propionate/salmeterol 250 µg/25 µg) administered according to SmPc or via the PreciseInhale system.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Device: PreciseInhale; Other: Seretide Evohaler forte |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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)
Frequency, intensity and seriousness of adverse events (AEs). The intensity grades were defined as mild, moderate and severe. AEs were assessed as not related, possibly or probably related to the investigational device, the procedures or the test drug substances according to MDCG 2020-10/1. Outcome measured in session 1-4.
Measured: From start of first inhalation training until the end-of- study visit, an average of 5 weeks.
Device deficiencies (DD)
Frequency and nature of device deficiencies (DD). A device deficiency (DD) is defined as any inadequacy in the identity, quality, durability, reliability, safety or performance of an investigational device, including malfunction, use errors, or inadequacy in information supplied by the manufacturer. If a DD is assessed by the Investigator or the CTC's Pharmacovigilance department (CTC PV), as an event that could have led to an SAE if appropriate action not taken, intervention not made or circumstances less fortunate the event is to be reported as a reportable event. For registration of action taken with the device the following definitions will be used: removal, discarded, quarantined and treatment withdrawn. Outcome measured in session 1-4.
Measured: 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
Systolic and diastolic blood pressure and pulse will be measured in supine position after 10 minutes of rest. Outcome measured in session 1-4.
Measured: 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
Single 12-lead ECG will be recorded in supine position after 10 minutes of rest using an ECG machine. Heart rate and PQ/PR, QRS, QT and QTcF intervals will be recorded. Outcome measured in session 1-4.
Measured: 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 for analysis of clinical chemistry and haematology parameters will be collected and sent to the certified clinical chemistry laboratory at Uppsala University Hospital and analysed by routine analytical methods. Urinalysis will be performed at the research clinic using dip sticks. Outcome measured in session 1-4.
Measured: Blood samples will be collected at pre-defined timepoints from the screening visit until the end-of-study visit, an average of 6 weeks
Number of changes in physical examination judged as clinically significant by Principal Investigator
A complete physical examination included assessments of the head, eyes, ears, nose, throat, skin, thyroid, neurological, lungs, cardiovascular, abdomen (liver and spleen), lymph nodes and extremities. Outcome measured in session 1-4.
Measured: Physical examination will be performed at pre-defined timepoints from the screening visit until the end-of- study visit, an average of 6 weeks
Device user experience questionnaire completed by PreciseInhale operator
A device user experience questionnaire will be completed by the PreciseInhale operator after completion of last inhalation session with the PreciseInhale. Answers will be entered in the eCRF by the study personnel. Outcome measured after session 4 but operator experience from session 2-4 collected.
Measured: Completed once after treatment period 4 (visit 8), approximately 15 min
Device user experience questionnaire completed by study subject
A device user experience questionnaire will be completed by the study subject after completion of last inhalation session with the PreciseInhale. Answers will be entered in the electronic patient reported outcomes (ePRO) system ViedocMe by the study subjects. Outcome measured after session 4 but subject experience from session 2-4 collected.
Measured: Completed once after treatment period 4 (visit 8), approximately 15 min
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2021
- Study start7 Jun 2021
- Primary completion22 Jul 2021
- Study completion26 Jul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Nebulizers and VaporizersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Device feasibility
- Allocation
- Non-randomised
- Intervention model
- Factorial
- 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)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Inhalation Sciences Sweden AB
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- CTC Clinical Trial Consultants AB, PlantVision AB, Pharm-Analyt Labor GmbH
- Responsible party
- Sponsor
- Investigators
- Manoush Masarrat, Study chair, Inhalation Sciences AB
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04946630
- Sponsor's protocol ID
- CLIN01-PI
- Status last verified
- Apr 2022
- First submitted
- 4 Jun 2021
- Last updated
- 11 Apr 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Site, Open Label, 4-inhalation Session, 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
- ClinicalTrials.gov ID
- NCT04946630
- Acronym / sponsor ID
- CLIN01-PI
- Conditions
- Nebulizers and Vaporizers
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Inhalation Sciences Sweden ABIndustry (pharma, biotech, devices)
- Collaborators
- CTC Clinical Trial Consultants AB, PlantVision AB, Pharm-Analyt Labor GmbH
- Study start
- 7 Jun 2021 (actual)
- Primary completion
- 22 Jul 2021 (actual)
- Study completion
- 26 Jul 2021 (actual)
- First posted
- 1 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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):
- 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.
- 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.
- 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.
- 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.
Study design
- Primary purpose
- Device feasibility
- Allocation
- Non-randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 4
- 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.
| Arm | Type | Receives |
|---|---|---|
| Seretide Evohaler forte according to SmPc | Experimental | Other: Seretide Evohaler forteSingle 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. |
| Whole lung exposure | Experimental | Device: PreciseInhale, Other: Seretide Evohaler forteSingle 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. |
| Alveolar bolus/ Breath hold exposures | Experimental | Device: PreciseInhale, Other: Seretide Evohaler forteA 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. |
| Bronchial bolus/ Breath hold exposures | Experimental | Device: PreciseInhale, Other: Seretide Evohaler forteA 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. |
Who may qualify
- Ages
- 18 to 30 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (18 listed)
- 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:
- Former regular daily smoker.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PreciseInhaleThree 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. | Device | Alveolar bolus/ Breath hold exposures, Bronchial bolus/ Breath hold exposures, Whole lung exposure |
| Seretide Evohaler forteSingle dose of Seretide Evohaler forte (fluticasone propionate/salmeterol 250 µg/25 µg) administered according to SmPc or via the PreciseInhale system. | Other | Alveolar bolus/ Breath hold exposures, Bronchial bolus/ Breath hold exposures, Seretide Evohaler forte according to SmPc, Whole lung exposure |
Primary outcome
Cmax
Time frame: From pre-dose to up to 24 hours post-dose.
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.
AUC0-t
Time frame: From pre-dose to up to 24 hours post-dose
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.
Tmax
Time frame: From pre-dose to up to 24 hours post-dose
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.
Inhaled and exhaled dose, fraction inhaled/exhaled dose
Time frame: Collected post-dose at one occasion, approx. for 2 min
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.
Inhaled and exhaled dose, fraction inhaled/exhaled dose
Time frame: Collected post-dose at one occasion, approx. for 2 min
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
Air flow rate
Time frame: Collected during inhalation session, approx. for 5 min
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
Aerosol concentration
Time frame: Collected during inhalation session, approx. for 5 min
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.
Acutal bolus volume
Time frame: Collected during inhalation session, approx. for 5 min
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.
Chase air volume
Time frame: Collected during inhalation session, approx. for 5 min
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.
Actual number of inhalations
Time frame: Collected during inhalation session, approx. for 5 min
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.
Correlation between two outcomes: AUC (weight-adjusted) -inhaled/exhaled dose
Time frame: AUC from pre-dose to up to 24 hours post-dose. Inhaled/exhaled dose collected post-dose at one occasion.
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.
8 secondary outcomes
Adverse events (AEs)
Time frame: From start of first inhalation training until the end-of- study visit, an average of 5 weeks.
Device deficiencies (DD)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Blood samples will be collected at pre-defined timepoints from the screening visit until the end-of-study visit, an average of 6 weeks
Number of changes in physical examination judged as clinically significant by Principal Investigator
Time frame: Physical examination will be performed at pre-defined timepoints from the screening visit until the end-of- study visit, an average of 6 weeks
Device user experience questionnaire completed by PreciseInhale operator
Time frame: Completed once after treatment period 4 (visit 8), approximately 15 min
Device user experience questionnaire completed by study subject
Time frame: Completed once after treatment period 4 (visit 8), approximately 15 min
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Apr 2022.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Manoush Masarrat study chair
Inhalation Sciences AB
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing PreciseInhale and Seretide Evohaler forte in people with Nebulizers and Vaporizers, run by Inhalation Sciences Sweden AB at 1 site in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cmax (time frame: From pre-dose to up to 24 hours post-dose.). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Apr 2022.