Study to Compare Relative Bioavailability of 3 Indacaterol/Glycopyrronium Test Products and Reference Product

Study Overview
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Brief Summary
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This is a formulation feasibility study to to compare relative bioavailability of indacaterol and glycopyrronium after administration of single doses of 3 Easyhaler test products and Ultibro Breezhaler. The study treatments will be administered with concomitant oral charcoal to block absorption via gastrointestinal tract and to assess pulmonary absorption only.

Official Title
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Pharmacokinetic Formulation Feasibility Study to Compare Relative Bioavailability of 3 Indacaterol/Glycopyrronium Easyhaler Test Products and Reference Product Ultibro Breezhaler

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Indacaterol/glycopyrronium


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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Indacaterol/glycopyrronium Easyhaler® 85/43 µg/dose, inhalation powder, product variant A<br>Each subject will receive a single dose of 2 inhaled doses from Indacaterol/glycopyrronium Easyhaler product variant A in one of the four periods (cross-over) with concomitant charcoal administration (Carbomix granules). The total dose is 170 µg of indacaterol and 86 µg glycopyrronium (delivered doses). | Drug: Indacaterol/glycopyrronium<br>* In each period, subjects receive single dose of indacaterol/glycopyrronium consisting of 2 inhaled doses via Easyhaler or 2 capsules inhaled via Ultibro Breezhaler. In addition to study treatments, activated charcoal will be administered on each study period before and after study drug administration.<br>* Other names: Ultibro® Breezhaler® 85/43 µg inhalation powder, hard capsule with charcoal;|
| Experimental: Indacaterol/glycopyrronium Easyhaler® 85/43 µg/dose, inhalation powder, product variant B<br>Each subject will receive a single dose of 2 inhaled doses from Indacaterol/glycopyrronium Easyhaler product variant B in one of the four periods (cross-over) with concomitant charcoal administration (Carbomix granules). The total dose is 170 µg of indacaterol and 86 µg glycopyrronium (delivered doses). | Drug: Indacaterol/glycopyrronium<br>* In each period, subjects receive single dose of indacaterol/glycopyrronium consisting of 2 inhaled doses via Easyhaler or 2 capsules inhaled via Ultibro Breezhaler. In addition to study treatments, activated charcoal will be administered on each study period before and after study drug administration.<br>* Other names: Ultibro® Breezhaler® 85/43 µg inhalation powder, hard capsule with charcoal;|
| Experimental: Indacaterol/glycopyrronium Easyhaler® 85/43 µg/dose, inhalation powder, product variant C<br>Each subject will receive a single dose of 2 inhaled doses from Indacaterol/glycopyrronium Easyhaler product variant C in one of the four periods (cross-over) with concomitant charcoal administration (Carbomix granules). The total dose is 170 µg of indacaterol and 86 µg glycopyrronium (delivered doses). | Drug: Indacaterol/glycopyrronium<br>* In each period, subjects receive single dose of indacaterol/glycopyrronium consisting of 2 inhaled doses via Easyhaler or 2 capsules inhaled via Ultibro Breezhaler. In addition to study treatments, activated charcoal will be administered on each study period before and after study drug administration.<br>* Other names: Ultibro® Breezhaler® 85/43 µg inhalation powder, hard capsule with charcoal;|
| Active Comparator: Ultibro® Breezhaler® 85/43 µg inhalation powder, hard capsule<br>Each subject will receive 2 capsules of Ultibro® Breezhaler® (=Indacaterol/glycopyrronium) as a single dose in one of the four periods (cross-over) with concomitant charcoal administration (Carbomix granules). The total dose is 170 µg of indacaterol and 86 µg glycopyrronium (delivered doses). | Drug: Indacaterol/glycopyrronium<br>* In each period, subjects receive single dose of indacaterol/glycopyrronium consisting of 2 inhaled doses via Easyhaler or 2 capsules inhaled via Ultibro Breezhaler. In addition to study treatments, activated charcoal will be administered on each study period before and after study drug administration.<br>* Other names: Ultibro® Breezhaler® 85/43 µg inhalation powder, hard capsule with charcoal;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak indacaterol and glycopyrronium concentration in plasma (Cmax) | Pharmacokinetic parameters of indacaterol and glycopyrronium | between 0-72 hours after dosing | 
| Area under the concentration-time curve from time zero to 72 hours (AUC72) | Pharmacokinetic parameters of indacaterol and glycopyrronium | between 0-72 hours after dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to reach peak indacaterol and glycopyrronium concentration in plasma (tmax) | Pharmacokinetic parameters of indacaterol and glycopyrronium | between 0-72 hours after dosing | 
| Area under the concentration-time curve from time zero to 30 minutes (AUC30) | Pharmacokinetic parameters of indacaterol and glycopyrronium | between 0-30 minutes after dosing |