Pharmacokinetic Study Comparing Tiotropium Easyhaler® and Spiriva® HandiHaler®

Study Overview
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Brief Summary
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Absorption of inhaled tiotropium is compared between five Tiotropium Easyhaler product variants and Spiriva capsules inhaled via HandiHaler without charcoal. Absorption of tiotropium is compared between one Easyhaler product variant administered with and without charcoal.

Official Title
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Comparison of Tiotropium Pharmacokinetics After Inhalation From Tiotropium Easyhaler® Product Variants and After Spiriva® Capsules Administered Via HandiHaler®; Study in Healthy Volunteers

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Tiotropium Bromide Monohydrate
* Drug: Tiotropium Bromide Monohydrate
* Drug: Tiotropium Bromide Monohydrate
* Drug: Tiotropium Bromide Monohydrate
* Drug: Tiotropium Bromide Monohydrate
* Drug: Tiotropium Bromide Monohydrate
* Drug: Tiotropium Easyhaler with oral activated 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, gastrointestinal, pulmonary, metabolic, endocrine, neurological or psychiatric disease Any condition requiring regular concomitant treatment Any clinically significant abnormal laboratory value 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 tiotropium bromide, atropine or its derivatives or lactose 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 4-period crossover study where the study subjects participate either in part 1 (20 subjects) or in part 2 (20 subjects). Parts can run in sequence or parallel. All study subjects receive single dose of Tiotropium Easyhaler on 3 periods and Spiriva HandiHaler on 1 period.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tiotropium Easyhaler Product variant D<br> | Drug: Tiotropium Bromide Monohydrate<br>* Tiotropium Easyhaler 10 µg/dose Product variant D<br>|
| Experimental: Tiotropium Easyhaler Product variant E<br> | Drug: Tiotropium Bromide Monohydrate<br>* Tiotropium Easyhaler 10 µg/dose Product variant E<br>|
| Experimental: Tiotropium Easyhaler Product variant F<br> | Drug: Tiotropium Bromide Monohydrate<br>* Tiotropium Easyhaler 10 µg/dose Product variant F<br>|
| Experimental: Tiotropium Easyhaler Product variant G<br> | Drug: Tiotropium Bromide Monohydrate<br>* Tiotropium Easyhaler 10 µg/dose Product variant G<br>|
| Experimental: Tiotropium Easyhaler Product variant H<br> | Drug: Tiotropium Bromide Monohydrate<br>* Tiotropium Easyhaler 10 µg/dose Product variant H<br>|
| Active Comparator: Spiriva HandiHaler<br> | Drug: Tiotropium Bromide Monohydrate<br>* Spiriva 18 µg/capsule inhaled via Handihaler<br>|
| Experimental: Tiotropium Easyhaler Product variant F administered with oral activated charcoal<br> | Drug: Tiotropium Bromide Monohydrate<br>* Tiotropium Easyhaler 10 µg/dose Product variant F<br>Drug: Tiotropium Easyhaler with oral activated charcoal<br>* The charcoal suspension will be administered orally with Tiotropium Easyhaler 10 µg/dose Product variant F<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak tiotropium concentration in plasma (Cmax) |  | between 0-72 hours after dosing | 
| Area under the concentration-time curve from time zero to 30 minutes (AUC30 minutes) |  | 0-30 minutes after dosing | 
| Area under the concentration-time curve from time zero to 72 hours (AUC72 hours) |  | 0-72 hours after dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to reach peak concentration in plasma (tmax) |  | between 0-72 hours after dosing |