Ophthalmologic Examinations After Infusion of ZK200775

Ophthalmologic Examinations After 4-hour Infusion of ZK200775 in Healthy Elder Male Volunteers

ZK 200775 is an antagonist at the α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor and had earned attention a possible neuroprotective agent in cerebral ischemia. Probands receiving the agent within a stroke therapy related Phase I trial reported on an alteration of visual perception. In this trial, the effects of ZK 200775 on the visual system will be analyzed in detail.

In a randomised, placebo-controlled, double-blind study eyes and vision will be examined before and after the intravenous administration of ZK 200775. The following methods will be applied: clinical examination, visual acuity, ophthalmoscopy, colour vision, rod absolute threshold, central visual field, pattern-reversal visual evoked potentials (pVEP), ON-OFF and full-field electroretinogram (ERG).

Study Overview

• Status: Completed
• Conditions: Visual Acuity
• Intervention / Treatment: Drug: Sodium Chloride; Drug: ZK200775; Drug: ZK200775

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 13353
    • Charité Unviversitätsmedizin Berlin, Augenklinik Campus Virchow-Klinikum

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• The participant must be a voluntary proband
• Age between 55 and 65 years
• Body weight must not exceed the following value: Body height in cm minus 100 = body weight [kg] +/- 20%
• Male sex
• Written informed consent
• Physical examination: Probands must show normal findings without clinical relevance, mental and physical health is required;

Exclusion Criteria:

• Clinical history:

  • Substantial pre-existing medical condition
  • Known allergy to the employed effective components or galenic components

• Medicaments and drugs

  • Intake of systemically or locally acting drugs which conflict with the aim of the trial or that can influence the results (antipsychotic drugs, antidepressants, barbiturates and benzodiazepines)
  • A clinical history that hints to substance or alcohol abuse
  • Nicotine abuse of more than 10 cigarettes a day
  • Consumption of alcoholic beverages on the day prior to the examinations
  • Extreme physical stress (sports or work) within 8 days prior to the examinations
  • Blood donation within 2 months prior to the examinations
  • Relevant vaccination or stay abroad
  • Special or onesided alimentation (strict vegetarianism, low-caloric diet)
  • Simultaneous participation in another clinical trial

• Vital signs (after 3 minutes of rest)

  • Blood pressure with systolic values > 160 mmHg and / or diastolic values > 95 mmHg
  • Heart frequency: Values beyond 50-100 beats per minute

• Electrocardiogram

  • abnormal 12-channel ECG

• Laboratory findings

  • Hepatitis antigen (HBsAG), hepatitis C-antibodies or positive HIV-test

• Clinical pharmacology

  • positive drug test
  • clinically relevant abnormalities of the examined parameters
• Opinion of the investigator: when due to scientific or personal reasons or matters of compliance or safety a patient should not take part in the trial
• Opacification of optic media, retinal disease, optic nerve disease, amblyopia or color vision defects
• Status post intraocular surgery (exception: cataract surgery with implantation of a posterior chamber lens), laser coagulation
• Myopia > -5 diopters, hyperopia > +5 diopters
• Narrow angle glaucoma

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Sham infusion of sodium chloride 0.9%	Drug: Sodium Chloride; Intravenous infusion of sodium chloride over a period of 4 hours.
Active Comparator: Low dose arm; Infusion of 0.3 mg/kg/h ZK200775 over 4 hours	Drug: ZK200775; Intravenous infusion of 0.3 mg/kg/h of ZK200775 over a period of 4 hours.; Drug: ZK200775; Intravenous infusion of 0.75 mg/kg/h of ZK200775 over a period of 4 hours.
Active Comparator: High dose arm; Infusion of 0.75 mg/kg/h ZK200775 over 4 hours	Drug: ZK200775; Intravenous infusion of 0.3 mg/kg/h of ZK200775 over a period of 4 hours.; Drug: ZK200775; Intravenous infusion of 0.75 mg/kg/h of ZK200775 over a period of 4 hours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Visual acuity

Secondary Outcome Measures

Outcome Measure
Color vision (Panel D-15 test), dark vision (adaptometer), full-field electroretinogram

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany
• Collaborators: Bayer
• Investigators: Study Director: Thomas Staks, Dr., Bayer

Publications and helpful links

General Publications

• Bergholz R, Staks T, Ruther K. Effects of the AMPA antagonist ZK 200775 on visual function: a randomized controlled trial. PLoS One. 2010 Aug 12;5(8):e12111. doi: 10.1371/journal.pone.0012111.

Study record dates

Study Major Dates

• Study Start: December 1, 1996
• Primary Completion (Actual): April 1, 1998
• Study Completion (Actual): April 1, 1998

Study Registration Dates

• First Submitted: October 20, 2009
• First Submitted That Met QC Criteria: October 20, 2009
• First Posted (Estimate): October 21, 2009

Study Record Updates

• Last Update Posted (Estimate): October 21, 2009
• Last Update Submitted That Met QC Criteria: October 20, 2009
• Last Verified: October 1, 2009

More Information

Terms related to this study

• Keywords: ZK200775 is tested for its effects on vision on healthy probands.
• Other Study ID Numbers: 96048