Dose Tolerance Study After Ocular Administration of Tiotropium in Healthy Male Volunteers

Study Overview
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Brief Summary
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Safety and tolerability after ocular administration

Official Title
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A Single Increasing Dose Tolerance Study After Ocular Administration of Tiotropium (Single Doses: 0.02 - 0.4 mcg) in Healthy Male Volunteers (Randomised, Placebo-controlled, Double-blind, Parallel Groups).

Conditions
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Healthy

Intervention / Treatment
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* Drug: 0.02 mcg tiotropium solution
* Drug: 0.04 mcg tiotropium solution
* Drug: 0.08 mcg tiotropium solution
* Drug: 0.16 mcg tiotropium solution
* Drug: 0.28 mcg tiotropium solution
* Drug: 0.40 mcg tiotropium solution
* Drug: Placebo solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males Age range from 21 to 50 years Within ± 20% of normal weight (Broca-Index) Written informed consent given Exclusion Criteria: Results of the medical examinations or laboratory tests are judged by the clinical investigator to differ significantly from normal clinical values Volunteers with known gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders Volunteers with disease of the central nervous system (such as epilepsy) or with psychiatric disorders Volunteers with known history of orthostatic hypotension, fainting spells or blackouts Volunteers with chronic or relevant acute infections Volunteers with history of allergy/ hypersensitivity (including drug allergy) Volunteers with known eye diseases (incl. glaucoma), with hyperopia (> 3 diopters) or with contact lenses Volunteers with intraocular pressure > 22 mmHg Volunteers with predisposition to narrow-angle glaucoma Volunteers with disturbed micturition Volunteers who have taken a drug with a long half-life (≥ 24 hours) within ten half-lives of the respective drug before enrolment in the study Volunteers who received any other drugs which might influence the results of the trial during the week previous the start of the study Volunteers who have participated in another study with an investigational drug within the last two months preceding this study Volunteers who smoke (> 10 cigarettes or 3 cigars or 3 pipes/day) Volunteers who are not able to refrain from smoking on study day Volunteers who drink more than 40 g of alcohol per day Volunteers who are dependent on drugs Volunteers who have donated blood (≥ 100 ml) within the last four weeks Volunteers who participated in excessive physical activities (e.g. competitive sports) within the last week before the study

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tiotropium dose group 1<br>0.02 mcg tiotropium solution | Drug: 0.02 mcg tiotropium solution<br> <br> Drug: Placebo solution<br> <br> |
| Experimental: Tiotropium dose group 2<br>0.04 mcg tiotropium solution | Drug: 0.04 mcg tiotropium solution<br> <br> Drug: Placebo solution<br> <br> |
| Experimental: Tiotropium dose group 3<br>0.08 mcg tiotropium solution | Drug: 0.08 mcg tiotropium solution<br> <br> Drug: Placebo solution<br> <br> |
| Experimental: Tiotropium dose group 4<br>0.16 mcg tiotropium solution | Drug: 0.16 mcg tiotropium solution<br> <br> Drug: Placebo solution<br> <br> |
| Experimental: Tiotropium dose group 5<br>0.28 mcg tiotropium solution | Drug: 0.28 mcg tiotropium solution<br> <br> Drug: Placebo solution<br> <br> |
| Experimental: Tiotropium dose group 6<br>0.40 mcg tiotropium solution | Drug: 0.40 mcg tiotropium solution<br> <br> Drug: Placebo solution<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in pupil diameter |  | baseline, after 24 hours | 
| Change in pupillary reflex |  | baseline, after 24 hours | 
| Change in intraocular pressure |  | baseline, after 24 hours | 
| Change in accommodation |  | baseline, after 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in blood pressure |  | on Day 1 before and 24 hours after treatment and within 8 days after treatment day | 
| Change from baseline in pulse rate |  | on Day 1 before and 24 hours after treatment and within 8 days after treatment day | 
| Change in 12-lead ECG |  | on Day 1 before and 24 hours after treatment and within 8 days after treatment day | 
| Changes from baseline in standard laboratory examinations |  | Baseline and within 8 days after treatment day | 
| Occurrence of Adverse Events |  | until 8 days after treatment day |