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

Phase 1

Completed

Brief Summary: 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: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
test product A	Salmeterol	salmeterol and fluticasone propionate, 2 puffs
test product A	fluticasone propionate	salmeterol and fluticasone propionate, 2 puffs
reference product D	Salmeterol	salmeterol and fluticasone propionate, 2 puffs
reference product D	fluticasone propionate	salmeterol and fluticasone propionate, 2 puffs
reference product E	fluticasone propionate	salmeterol and fluticasone propionate, 6 puffs
test product B	Salmeterol	salmeterol and fluticasone propionate, 6 puffs
test product B	fluticasone propionate	salmeterol and fluticasone propionate, 6 puffs
reference product E	Salmeterol	salmeterol and fluticasone propionate, 6 puffs
test product C	Salmeterol	salmeterol and fluticasone propionate, 12 puffs
reference product F	Salmeterol	salmeterol and fluticasone propionate, 12 puffs
reference product F	fluticasone propionate	salmeterol and fluticasone propionate, 12 puffs
test product C	fluticasone propionate	salmeterol and fluticasone propionate, 12 puffs

Primary Outcome Measures

Name	Time	Method
Relative Potency QTcB Interval	Baseline up to 6 hrs	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.
Relative Potency Max Heart Rate	Baseline, up to 6 hrs	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.

Secondary Outcome Measures

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