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

Healthy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02232087
• Other study ID #: DDSD-1030-SAFL
• Status: Completed
• Phase: Phase 1
• Start date: July 2014
• Est. completion date: December 2014

Study information

• Verified date: October 2020
• Source: Kindeva Drug Delivery
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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 information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: December 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

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

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Salmeterol
A, D 2 puffs; B, E 6 puffs; C, F 12 puffs
• fluticasone propionate
A, D 2 puffs; B, E 6 puffs; C, F 12 puffs

Locations

Country	Name	City	State
United Kingdom	Quotient Clinical Ltd	Ruddington	Nottingham

Sponsors (1)

Lead Sponsor	Collaborator
Kindeva Drug Delivery

Country where clinical trial is conducted

United Kingdom, 

References & Publications (1)

Harrison LI, Sessions V, Wiggenhorn CJ, Chalmers D, Leung P, Efthimiou J. Comparison of systemic pharmacodynamic effects of two combination pressurized metered dose inhalers that deliver salmeterol and fluticasone propionate. Br J Clin Pharmacol. 2017 Nov — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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