Single Blind Cross-over Dose Response Study in Subjects of Two Inhalers of Salmeterol and Fluticasone Propionate

Study Overview
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Brief Summary
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The purpose of this study is to test the body's response to several doses of two different inhalation products in healthy volunteers.

Detailed Description
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Healthy subjects will be enrolled and will receive 2, 6, and 12 inhalations from both the test and reference pMDI products according to a six-period cross-over design. Electrocardiograms (ECGs) and plasma potassium and glucose levels will be measured pre-dose and over 6 hours post-dose.

Official Title
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Phase I Single Blind, Randomised, Cross-over Pharmacodynamic Dose Response Study in Healthy Volunteers of Two Pressurized Metered Dose Inhalers (pMDIs) That Deliver Salmeterol and Fluticasone Propionate

Conditions
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Healthy

Intervention / Treatment
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* Drug: Salmeterol
* Drug: fluticasone propionate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Volunteer Willing and able to give informed consent Willing to withhold all alcoholic beverages for 48 hours and all xanthine- containing foods and beverages for 24 hours prior to reporting to clinic Male and female subjects aged 18 to 55 years (inclusive) Subjects must agree to use an adequate method of contraception from admission through 12 weeks after last administration Exclusion Criteria: Evidence or history of clinically significant abnormalities or disease or chronic respiratory disorders Any presence or history of a clinically significant allergy including any adverse reaction to study drug History of drug or alcohol abuse within the past 2 years Smoked tobacco within the past 6 months or have a history of more than 10- pack years (number of packs smoked per day x number of years smoked) Donation or loss of greater than 400 mL of blood within the previous 3 months Have received any prescription medication within 4 weeks or investigational medication within 12 weeks of study (exception: contraceptives are permitted) Have received any non-prescription medication within 14 days prior to dosing (exception: paracetamol use within 2 days) Upper respiratory tract infection (excluding otitis media) within 14 days of the first study day, or lower respiratory tract infection within the last 3 months If female, nursing, lactating or pregnant Regular alcohol consumption in males >21 units per week and females >14 units per week (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine) Surgery scheduled during the study or within 3 weeks after last dose History of familial long QT syndrome or history of sudden death in family members aged < 30 years

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: test product A<br>salmeterol and fluticasone propionate, 2 puffs | Drug: Salmeterol<br>* A, D 2 puffs; B, E 6 puffs; C, F 12 puffs<br>* Other names: Seretide Evohaler;Drug: fluticasone propionate<br>* A, D 2 puffs; B, E 6 puffs; C, F 12 puffs<br>* Other names: Seretide Evohaler;|
| Active Comparator: reference product D<br>salmeterol and fluticasone propionate, 2 puffs | Drug: Salmeterol<br>* A, D 2 puffs; B, E 6 puffs; C, F 12 puffs<br>* Other names: Seretide Evohaler;Drug: fluticasone propionate<br>* A, D 2 puffs; B, E 6 puffs; C, F 12 puffs<br>* Other names: Seretide Evohaler;|
| Experimental: test product B<br>salmeterol and fluticasone propionate, 6 puffs | Drug: Salmeterol<br>* A, D 2 puffs; B, E 6 puffs; C, F 12 puffs<br>* Other names: Seretide Evohaler;Drug: fluticasone propionate<br>* A, D 2 puffs; B, E 6 puffs; C, F 12 puffs<br>* Other names: Seretide Evohaler;|
| Active Comparator: reference product E<br>salmeterol and fluticasone propionate, 6 puffs | Drug: Salmeterol<br>* A, D 2 puffs; B, E 6 puffs; C, F 12 puffs<br>* Other names: Seretide Evohaler;Drug: fluticasone propionate<br>* A, D 2 puffs; B, E 6 puffs; C, F 12 puffs<br>* Other names: Seretide Evohaler;|
| Experimental: test product C<br>salmeterol and fluticasone propionate, 12 puffs | Drug: Salmeterol<br>* A, D 2 puffs; B, E 6 puffs; C, F 12 puffs<br>* Other names: Seretide Evohaler;Drug: fluticasone propionate<br>* A, D 2 puffs; B, E 6 puffs; C, F 12 puffs<br>* Other names: Seretide Evohaler;|
| Active Comparator: reference product F<br>salmeterol and fluticasone propionate, 12 puffs | Drug: Salmeterol<br>* A, D 2 puffs; B, E 6 puffs; C, F 12 puffs<br>* Other names: Seretide Evohaler;Drug: fluticasone propionate<br>* A, D 2 puffs; B, E 6 puffs; C, F 12 puffs<br>* Other names: Seretide Evohaler;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative Potency Max Heart Rate | Selection of steepest part of dose response curve for Relative Potency: 6 and 12 inhalation dose pairs. Slope of B and C line compared with slope of E and F to obtain relative potency value. Two inhalation dose not utilized as not on steepest part of curve. | Baseline, up to 6 hrs | 
| Relative Potency QTcB Interval | Selection of steepest part of dose response curve for Relative Potency: 2 and 6 inhalation dose pairs. Slope of A and B line compared with slope of D and E to obtain relative potency value. Twelve inhalation dose not utilized as not on steepest part of curve. | Baseline up to 6 hrs | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Max Heart Rate | max heart rate at the 2, 6, or 12 inhalations dose, assessed at multiple times over 6 hours | Baseline through 6 hours | 
| Plasma Potassium Level | maximum plasma levels of potassium at 2, 6 or 12 inhalations dose inhalations dose, assessed a multiple times over 6 hours. | baseline through 6 hours | 
| Max Plasma Glucose Level | maximum levels of glucose at the 2, 6 or 12 inhalations dose, assessed at multiple times over 6 hours. | baseline through 6 hours | 
| Max QTcB | For each dose, the 95% CIs for the mean difference for the test product versus the reference product were calculated. | Baseline through 6 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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long-acting beta agonist (LABA), corticosteroid, pMDI, inhaler