Absorption of Indacaterol and Glycopyrronium From Ultibro Breezhaler

Study Overview
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Brief Summary
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The objective of this study is to assess pharmacokinetics (PK) of indacaterol and glycopyrronium, and methodology and practical arrangements for future studies.

Official Title
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A Pharmacokinetic Feasibility Study on Ultibro Breezhaler, an Indacaterol-glycopyrronium Inhalation Powder Capsule, in Healthy Subjects

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Indacaterol maleate and glycopyrronium bromide
* Drug: Indacaterol maleate and glycopyrronium bromide
* Drug: Indacaterol maleate and glycopyrronium bromide
* Drug: Ultibro Breezhaler with oral charcoal


Participation Criteria
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Eligibility Criteria
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Main inclusion criteria: Healthy males and females 18-60 years of age Body mass index 19-30 kg/m2 Weight at least 50 kg Written informed consent obtained Main exclusion criteria: Evidence of a clinically significant cardiovascular, renal, hepatic, haematological, GI, pulmonary, metabolic, endocrine, neurological or psychiatric disease Any condition requiring regular concomitant treatment Any clinically significant abnormal laboratory value, vital sign or physical finding that in the opinion of the investigator could interfere with the interpretation of study results or cause a health risk for the subject Known hypersensitivity to indacaterol or glycopyrronium Pregnant or lactating females and females of childbearing potential not using contraception of acceptable effectiveness Blood donation or loss of significant amount of blood within 90 days prior to the first study treatment administration

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: The study is a 2-part crossover study where the study subjects participate either in part 1 (18 subjects) or in part 2 (16 subjects). The parts can run in sequence or in parallel. The study subjects in part 1 receive single doses of Ultibro Breezhaler on 3 periods and the study subjects in part 2 receive single doses of Ultibro Breezhaler on 2 periods.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1 Ultibro Breezhaler 2 capsules, Batch A<br> | Drug: Indacaterol maleate and glycopyrronium bromide<br>* Batch A Ultibro Breezhaler 85/43 μg 2 capsules<br>|
| Experimental: Part 1 Ultibro Breezhaler 2 capsules with charcoal, Batch A<br> | Drug: Indacaterol maleate and glycopyrronium bromide<br>* Batch A Ultibro Breezhaler 85/43 μg 2 capsules<br>Drug: Ultibro Breezhaler with oral charcoal<br>* Activated charcoal suspension, granules 50 g / bottle<br>|
| Experimental: Part 1 Ultibro Breezhaler 1 capsule, Batch A<br> | Drug: Indacaterol maleate and glycopyrronium bromide<br>* Batch A Ultibro Breezhaler 85/43 μg 1 capsule<br>|
| Experimental: Part 2 Ultibro Breezhaler 2 capsules, Batch A<br> | Drug: Indacaterol maleate and glycopyrronium bromide<br>* Batch A Ultibro Breezhaler 85/43 μg 2 capsules<br>|
| Experimental: Part 2 Ultibro Breezhaler 2 capsules, Batch B<br> | Drug: Indacaterol maleate and glycopyrronium bromide<br>* Batch B Ultibro Breezhaler 85/43 μg 2 capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak indacaterol concentration in plasma (Cmax) |  | between 0-72 hours after dosing | 
| Peak glycopyrronium concentration in plasma (Cmax) |  | between 0-72 hours after dosing | 
| Indacaterol area under the concentration-time curve from time zero to 30 minutes (AUC30min) |  | 0-30 minutes after dosing | 
| Glycopyrronium area under the concentration-time curve from time zero to 30 minutes (AUC30min) |  | 0-30 minutes after dosing | 
| Indacaterol area under the concentration-time curve from time zero to 72 hours (AUC72h) |  | 0-72 hours after dosing | 
| Glycopyrronium area under the concentration-time curve from time zero to 72 hours (AUC72h) |  | 0-72 hours after dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Indacaterol area under the concentration-time curve from time zero to the last sample with a quantifiable concentration (AUCt) |  | 0-18 days after dosing | 
| Glycopyrronium area under the concentration-time curve from time zero to the last sample with a quantifiable concentration (AUCt) |  | 0-18 days after dosing | 
| Indacaterol area under the concentration-time curve from time zero to infinity (AUCinf) |  | 0-18 days after dosing | 
| Glycopyrronium area under the concentration-time curve from time zero to infinity (AUCinf) |  | 0-18 days after dosing | 
| Time to reach peak indacaterol concentration in plasma |  | between 0-72 hours after dosing | 
| Time to reach peak glycopyrronium concentration in plasma |  | between 0-72 hours after dosing | 
| Indacaterol terminal elimination half-life (t1/2) |  | 0-18 days after dosing | 
| Glycopyrronium terminal elimination half-life (t1/2) |  | 0-18 days after dosing | 
| Number of adverse events as event counts and subjects counts |  | throughout the study, average 9-12 weeks |