A Pharmacokinetic/Pharmacodynamic Inhaler Comparison Study in Healthy Volunteers

Phase 1

Completed

• Conditions: Asthma
• Interventions: Drug: Fluticasone/formoterol BAI; Drug: Fluticasone/formoterol PMDI with spacer; Drug: Fluticasone/formoterol PMDI without spacer; Drug: Fluticasone/formoterol PMDI without spacer low dose; Drug: Formoterol

• Registration Number: NCT02403713
• Lead Sponsor: Mundipharma Research Limited

Brief Summary

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

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.

Study Timeline

• Study Start: 2014-08
• Primary Completion: 2014-10
• Study First Submitted: 2015-02-19
• Study First Submitted QC: 2015-03-30
• Study First Posted: 2015-03-31
• Status Verified: 2015-09
• Study Completion: 2015-09
• Last Update Submitted: 2015-09-25
• Last Update Posted: 2015-09-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 125

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Test Treatment	Fluticasone/formoterol BAI	Fluticasone/formoterol 125/5 µg BAI
Active Comparator 1	Fluticasone/formoterol PMDI with spacer	Fluticasone/formoterol 125/5 µg pMDI with spacer
Active Comparator 2	Fluticasone/formoterol PMDI without spacer	Fluticasone/formoterol 125/5 µg pMDI without spacer
Active Comparator 3	Fluticasone/formoterol PMDI without spacer low dose	Fluticasone/formoterol pMDI (125/5 μg) without spacer, low dose
Active Comparator 4	Formoterol	Formoterol (12 µg) without spacer

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Vital Signs	Pre Dose to 6 hours post dose	Composite measurement of vital signs (heart rate and blood pressure)
Serum Glucose	Pre Dose to 6 hours post dose	Maximum increase in Serum Glucose