Study to Assess the Influence of Three Different α-antagonists and Placebo on the Extent of Weekly Phenylephrine-induced Mydriasis at Three Different Concentrations of Phenylephrine in Healthy Male Volunteers

Study Overview
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Brief Summary
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The study was aimed to evaluate the pharmacological effect of different α-antagonists on phenylephrine induced pupil size in healthy male volunteers as pharmacological basis for Intraoperative floppy iris syndrome (IFIS)

Official Title
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A Parallel Group Study With Three Different α-antagonists and Placebo Once Daily Over Three Weeks to Assess Their Influence on the Extent of Weekly Phenylephrine-induced Mydriasis at Three Different Concentrations of Phenylephrine in Healthy Male Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: Tamsulosin
* Drug: Alfuzosin
* Drug: Doxazosin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male Age ≥ 21 and ≤ 55 years Body Mass Index (BMI) ≥ 18.5 and ≤ 29.9 kg/m2 Signed and dated written informed consent in accordance with Good Clinical Practice (GCP) and local legislation Exclusion Criteria: Any finding of the medical examination (including blood pressure, pulse rate and Electrocardiogram (ECG)) deviating from normal and of clinical relevance Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders History of orthostatic hypotension, fainting spells or blackouts Chronic or relevant acute infections History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator Intake of drugs with a long half-life (> 24:00 hours) within at least one month or less than ten half-lives of the respective drug before enrolment in the study or during the study Use of any drugs which might influence the results of the trial up to seven days prior to enrolment in the study or during the study Participation in another trial with an investigational drug (≤ two months prior to administration or during the trial) Smoker (> 10 cigarettes or > 3 cigars or > 3 pipes/day) Inability to refrain from smoking on in-house trial days Alcohol abuse (> 60 g/day) Drug abuse Blood donation (≥ 100 mL within four weeks prior to administration or during the trial) Any laboratory value outside the clinically accepted reference range Excessive physical activities within the last week before the trial or during the trial The following exclusion criteria are of special interest for this study: Hypersensitivity to any alpha agonist, or to phenylephrine Supine blood pressure at screening of systolic < 110 mmHg and diastolic < 60 mmHg Ophthalmological criteria: Corrected visual acuity < 0.5 Refractive Error with a spherical equivalent > +6 or smaller - 6 D Elevated intraocular pressure (higher than 22 mmHg) Relevant anisocoria or pupil deformation History of eye surgery apart from laser trabeculoplasty less than three months previously or extraocular surgery such as strabismus surgery Topical ocular medication influencing IOP (intraocular pressure) or pupil size within 3 months prior to study-start

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 55 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: Tamsulosin<br> | Drug: Tamsulosin<br> <br> * Other names: Alna®;|
| Experimental: Alfuzosin<br> | Drug: Alfuzosin<br> <br> * Other names: Uroxatral® uno;|
| Experimental: Doxazosin<br> | Drug: Doxazosin<br> <br> * Other names: Cardular PP Uro®;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sum of changes from baseline in the mean pupil diameters |  | Baseline, 60 and 80 min after administration of phenylephrine (PE) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in mean diameter of both pupils |  | Baseline, 60 and 80 min after administration of phenylephrine (PE) | 
| Change from baseline in mean diameter of both pupils |  | one week after cessation of drug | 
| Concentration of the analyte in plasma |  | Up to 29 days after first administration of α-antagonists | 
| Number of participants with clinically significant changes in vital signs |  | Up to 8 days after last pupillometry | 
| Number of participants with abnormal changes in clinical laboratory parameters |  | Up to 8 days after last pupillometry | 
| Number of participants with Adverse Events |  | Up to 8 days after last pupillometry | 
| Assessement of global tolerability by investigator on a 4 point scale |  | 8 days after last pupillometry |