Comparative Study of Lung Bioavailability of HFA-Seretide Via Current Spacer Devices in Healthy Volunteers

The purpose of this study is to determine the effect of plastic spacers and breath actuated spacers on respirable drug delivery of combination steroid inhaler (Seretide/Advair) and whether electrostatic charge within plastic spacers has a clinically relevant impact on the inhaled steroid delivery.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Seretide 250(8puffs) via Evohaler actuator; Drug: Seretide 250 (8 puffs)/placebo via Volumatic spacer; Drug: Seretide 250/placebo 8 puffs via Aerochamber Plus spacer; Drug: Seretide 250/placebo via Synchro-Breathe

Detailed Description

Conventional plastic spacers are bulky and can be influenced by electrostatic charge, which can reduce respirable dose delivery especially when used brand new "out of the box". Breath actuated integrated vortex spacer (Synchro-Breathe) is a compact palm sized antistatic device with a vortex chamber which is designed to be more patient friendly and free from the effects of electrostatic charge. The systemic bioavailability from the lung of inhaled fluticasone and salmeterol is dependent on respirable dose delivery, and hence the performance of inhaler devices can be quantified by measuring the degree of adrenal suppression and fall in serum potassium(K) as surrogates for delivered lung dose. This study attempts to compares the systemic bioavailability from the lung in real life conditions for Fluticasone/Salmeterol combination (measured in terms of relative adrenal suppression and fall in serum K) via the breath actuated Synchro-Breathe device, pMDI( Seretide Evohaler), and Aerochamber Plus & Volumatic spacer used brand new "out of the box" in healthy volunteers.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 4

Contacts and Locations

Study Locations

• United Kingdom
  • Tayside
    • Dundee, Tayside, United Kingdom, DD1 9SY
      • Asthma & Allergy Research Group, Department of cardiovascular & lung biology, Division of medicine, Ninewells Hospital & Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy Volunteers
2. Male or female 18-65
3. Informed Consent
4. Ability to comply with the requirements of the protocol

Exclusion Criteria:

1. No respiratory disease
2. Smokers
3. Recent respiratory tract infection (2 months).
4. Any other clinically significant medical condition such as unstable angina, acute myocardial infarction in the preceding 3 months, recent TIA/ CVA,that may endanger the health or safety of the participant, or jeopardise the protocol.
5. Any significant abnormal laboratory result as deemed by the investigators
6. Pregnancy, planned pregnancy or lactation
7. Known or suspected contra-indication to any of the IMP's
8. Concomitant use of medicines (prescribed, over the counter or herbal) that may interfere with the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Evohaler	Drug: Seretide 250(8puffs) via Evohaler actuator; 8 puffs of Seretide250/Placebo via Evohaler actuator; Other Names: Advair; Drug: Seretide 250 (8 puffs)/placebo via Volumatic spacer; 8 puffs of Seretide 250/placebo via volumatic spacer; Other Names: Advair; Drug: Seretide 250/placebo 8 puffs via Aerochamber Plus spacer; Seretide 250/placebo 8 puffs via Aerochamber Plus; Other Names: Advair; Drug: Seretide 250/placebo via Synchro-Breathe; Seretide 250/placebo 8puffs via breath actuated Synchro-Breathe device; Other Names: Advair
Experimental: Volumatic spacer	Drug: Seretide 250(8puffs) via Evohaler actuator; 8 puffs of Seretide250/Placebo via Evohaler actuator; Other Names: Advair; Drug: Seretide 250 (8 puffs)/placebo via Volumatic spacer; 8 puffs of Seretide 250/placebo via volumatic spacer; Other Names: Advair; Drug: Seretide 250/placebo 8 puffs via Aerochamber Plus spacer; Seretide 250/placebo 8 puffs via Aerochamber Plus; Other Names: Advair; Drug: Seretide 250/placebo via Synchro-Breathe; Seretide 250/placebo 8puffs via breath actuated Synchro-Breathe device; Other Names: Advair
Experimental: Aerochamber Plus	Drug: Seretide 250(8puffs) via Evohaler actuator; 8 puffs of Seretide250/Placebo via Evohaler actuator; Other Names: Advair; Drug: Seretide 250 (8 puffs)/placebo via Volumatic spacer; 8 puffs of Seretide 250/placebo via volumatic spacer; Other Names: Advair; Drug: Seretide 250/placebo 8 puffs via Aerochamber Plus spacer; Seretide 250/placebo 8 puffs via Aerochamber Plus; Other Names: Advair; Drug: Seretide 250/placebo via Synchro-Breathe; Seretide 250/placebo 8puffs via breath actuated Synchro-Breathe device; Other Names: Advair
Experimental: Synchro-Breathe	Drug: Seretide 250(8puffs) via Evohaler actuator; 8 puffs of Seretide250/Placebo via Evohaler actuator; Other Names: Advair; Drug: Seretide 250 (8 puffs)/placebo via Volumatic spacer; 8 puffs of Seretide 250/placebo via volumatic spacer; Other Names: Advair; Drug: Seretide 250/placebo 8 puffs via Aerochamber Plus spacer; Seretide 250/placebo 8 puffs via Aerochamber Plus; Other Names: Advair; Drug: Seretide 250/placebo via Synchro-Breathe; Seretide 250/placebo 8puffs via breath actuated Synchro-Breathe device; Other Names: Advair

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overnight Urinary Cortisol creatinine ratio	This outcome measure evaluates the amount of cortisol being suppressed after inhaled steroid administration. This helps to assess the systemic effect of steroid inhalation and therefore the propensity for adrenal suppression which is a noted adverse effect with high dose inhaled steroids	within 24 hours after study drug inhalation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Potassium	The serum potassium is monitored 60 minutes post study drug inhalation to assess the systemic beta-2-adrenoreceptor metabolic response. Long acting beta agonists like Salmeterol exhibit dose related reduction in serum potassium.	60 minutes post treatment

Collaborators and Investigators

• Sponsor: Brian J Lipworth
• Investigators: Principal Investigator: Arun Nair, University of Dundee; Study Director: Brian J Lipworth, University of Dundee

Publications and helpful links

General Publications

• Nair A, McKinlay L, Williamson P, Short P, Burns P, Lipworth BJ. Comparative lung bioavailability of fluticasone/salmeterol via a breath-actuated spacer and conventional plastic spacers. Eur J Clin Pharmacol. 2011 Apr;67(4):355-363. doi: 10.1007/s00228-010-0989-9. Epub 2011 Jan 15. Erratum In: Eur J Clin Pharmacol. 2017 Jun;73(6):793.

Study record dates

Study Major Dates

• Study Start: November 1, 2009
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: September 2, 2010
• First Submitted That Met QC Criteria: September 2, 2010
• First Posted (Estimate): September 3, 2010

Study Record Updates

• Last Update Posted (Actual): April 12, 2019
• Last Update Submitted That Met QC Criteria: April 10, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: asthma; Spacer; lung bioavailability; seretide
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Sympathomimetics; Fluticasone-Salmeterol Drug Combination
• Other Study ID Numbers: NAI008; 2007-003627-20 (EudraCT Number)