A Pharmacokinetic/Pharmacodynamic Inhaler Comparison Study in Healthy Volunteers

Study Overview
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Brief Summary
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A 2-group healthy volunteer study to compare a breath actuated inhaler (BAI) and a pressurised metered dose inhaler (pMDI) with and without spacer.

Detailed Description
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Group 1 will assess pharmacokinetics, Group 2 will assess pharmacodynamics. PK interim analysis to determine requirement for PK extension. Group 1 (PK) blood sampling and safety assessments up to 36 hours post-dose for 3 study periods. Results from PK stage will determine if Group 2 (PD) is required. Group 2 (PD) will assess LABA only effects (as confirmed in interim analysis). Group 2 (PD) to include 2 overnight stays for 5 study periods. Volunteers will receive a single dose of study medication, with discharge on Day 2. Study treatments are fluticasone/formoterol BAI, fluticasone/formoterol pMDI with/without spacer, formoterol alone without spacer, and low dose fluticasone/formoterol without spacer. Volunteers will undergo blood sampling, and safety assessments up to the morning of discharge. An inspiratory flow recorder (IPR) will be used for training and to monitor inspiratory flow rate, inhaled volume and inhalation technique.

Official Title
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A Randomised, Open-label, 2-group PK (3-period) and PD (5-period) Crossover Study to Compare Systemic Exposure and Pharmacodynamic Effects of Fluticasone/Formoterol BAI and pMDI in Healthy Volunteers

Conditions
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Asthma

Intervention / Treatment
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* Drug: Fluticasone/formoterol BAI
* Drug: Formoterol
* Drug: Fluticasone/formoterol PMDI without spacer
* Drug: Fluticasone/formoterol PMDI with spacer
* Drug: Fluticasone/formoterol PMDI without spacer low dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects aged 18 years or over. Healthy and free of significant abnormal findings as determined by medical history, physical examination, vital signs, laboratory tests and ECG. Normal lung function (FEV1 >90% of predicted normal value). Demonstrate satisfactory technique in the use of the study drug devices. No use of steroid medication (systemic or topical) within 8 weeks prior to study screening. Exclusion Criteria: Subjects who use any asthma medication or are knowingly regularly exposed to asthma medication. Any history of drug or alcohol abuse. Any history of conditions that might interfere with drug absorption, distribution, metabolism or excretion. History of asthma, COPD, or other bronchial or lung diseases. User of steroid medication (systemic or topical) within 8 weeks prior to study screening.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test Treatment<br>Fluticasone/formoterol 125/5 µg BAI | Drug: Fluticasone/formoterol BAI<br>* Fluticasone/formoterol 125/5 µg breath actuated inhaler (BAI) (250/10 µg total dose)<br>|
| Active Comparator: Active Comparator 1<br>Fluticasone/formoterol 125/5 µg pMDI with spacer | Drug: Fluticasone/formoterol PMDI with spacer<br>* Fluticasone/Formoteral 125/5µg pMDI with spacer<br>|
| Active Comparator: Active Comparator 2<br>Fluticasone/formoterol 125/5 µg pMDI without spacer | Drug: Fluticasone/formoterol PMDI without spacer<br>* Fluticasone/Formoteral 125/5µg pMDI without spacer<br>|
| Active Comparator: Active Comparator 3<br>Fluticasone/formoterol pMDI (125/5 μg) without spacer, low dose | Drug: Fluticasone/formoterol PMDI without spacer low dose<br>* Fluticasone/Formoteral 125/5µg pMDI without spacer, low dose<br>|
| Active Comparator: Active Comparator 4<br>Formoterol (12 µg) without spacer | Drug: Formoterol<br>* Formoterol<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameters Composite measurement of Pharmacokinetic parameters (Cmax, AUCt, AUCINF). |  | Pre dose to 36 hours post dose | 
| Serum Potassium | Maximum reduction in serum potassium from pre-dose. | Pre Dose to 6 hours post first dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vital Signs | Composite measurement of vital signs (heart rate and blood pressure) | Pre Dose to 6 hours post dose | 
| Serum Glucose | Maximum increase in Serum Glucose | Pre Dose to 6 hours post dose |