Clinical trial NCT02266537: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-10-17
Enrollment: 97
Sex: MALE
Minimum age (years): 21
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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)


Eligibility criteria: 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

Primary outcomes:
measure: Sum of changes from baseline in the mean pupil diameters
timeFrame: Baseline, 60 and 80 min after administration of phenylephrine (PE)
Secondary outcomes:
measure: Change from baseline in mean diameter of both pupils
timeFrame: Baseline, 60 and 80 min after administration of phenylephrine (PE)
measure: Change from baseline in mean diameter of both pupils
timeFrame: one week after cessation of drug
measure: Concentration of the analyte in plasma
timeFrame: Up to 29 days after first administration of α-antagonists
measure: Number of participants with clinically significant changes in vital signs
timeFrame: Up to 8 days after last pupillometry
measure: Number of participants with abnormal changes in clinical laboratory parameters
timeFrame: Up to 8 days after last pupillometry
measure: Number of participants with Adverse Events
timeFrame: Up to 8 days after last pupillometry
measure: Assessement of global tolerability by investigator on a 4 point scale
timeFrame: 8 days after last pupillometry
Other outcomes:
Locations:
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