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

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

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)

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: Alfuzosin; Drug: Tamsulosin; Drug: Doxazosin

• Study Type: Interventional
• Enrollment (Actual): 97
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo
Experimental: Tamsulosin	Drug: Tamsulosin; Other Names: Alna®
Experimental: Alfuzosin	Drug: Alfuzosin; Other Names: Uroxatral® uno
Experimental: Doxazosin	Drug: Doxazosin; Other Names: Cardular PP Uro®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: November 1, 2005
• Primary Completion (Actual): February 1, 2006

Study Registration Dates

• First Submitted: October 16, 2014
• First Submitted That Met QC Criteria: October 16, 2014
• First Posted (Estimate): October 17, 2014

Study Record Updates

• Last Update Posted (Estimate): October 17, 2014
• Last Update Submitted That Met QC Criteria: October 16, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Pupil Disorders; Mydriasis; Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Urological Agents; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Tamsulosin; Alfuzosin; Doxazosin
• Other Study ID Numbers: 527.70