Interaction Study of Timolol Eye Drops and Paroxetine Capsules

Study Overview
=================
Brief Summary
-----------------
The aim of the study is to investigate the effect of antidepressant paroxetine, on the plasma levels of timolol and its main metabolites after topical application of ophthalmic timolol products. This will be a phase I, randomised, 4-phase cross-over study in healthy volunteers. Healthy male volunteers aged 18 - 40 years will be enrolled. Placebo or paroxetine will be given for three days after which 1 drop of timolol product will be administered once in both eyes. The duration of the paroxetine or placebo treatment period will be 3 days. There will be four different treatment periods. A washout between the study periods will be at least 4 weeks.

Official Title
-----------------
The Effect of Paroxetine on the Plasma Levels of Timolol Using Ophthalmic 0.5% Timolol Eye Drops and 0.1% Timolol Eye Gel in Healthy Volunteers

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: Paroxetine
* Drug: Placebo
* Drug: timolol maleate
* Drug: timolol maleate


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: male 18 - 40 years of age be in good general health be willing to follow instructions provide a written informed consent have a BMI of 18.5 - 26 have systolic blood pressure at least 105 mmHg have haemoglobin at least 135 g/l. Exclusion Criteria: known hypersensitivity to timolol, paroxetine or any component of the study medications any contraindications to timolol treatment including asthma and obstructive lung disease any contraindications to paroxetine treatment have heart rate 50/min or less in rest any regular medication allergy requiring antihistamine or ocular or nasal treatment clinically significant abnormalities (from normal limits) in laboratory values: basic blood count, creatinine, ALAT, AFOS, gamma-GT, K, Na clinically significant EKG abnormalities assessed by the investigator blood donation within the last 60 days (the required time period between two donations for men given by RedCross Finland). participation in another clinical trial involving an investigational drug/device, or participation in such trial within the last 60 days

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Paroxetine<br> | Drug: Paroxetine<br>* Paroxetine 20 mg once a day during two treatment periods. One treatment period lasts for 3 days.<br>|
| Placebo Comparator: Gelatine capsule<br> | Drug: Placebo<br>* Gelatine capsule once a day during two treatment periods. One treatment period lasts for 3 days.<br>|
| Experimental: Timolol 0.5 % eye drops<br>The plasm levels of timolol will be measured after one drop of timolol has been administered into both eyes. | Drug: timolol maleate<br>* Oftan Timolol 0,5 % eye drop. One drop into both eyes on day 3 after taking paroxetine or placebo capsules for three days.<br>|
| Experimental: Timosan 0.1% eye gel<br>The plasm levels of timolol will be measured after one drop of timolol has been administered into both eyes. | Drug: timolol maleate<br>* Timosan 0,1 % eye gel. One drop into both eyes on day 3 after taking paroxetine or placebo capsules for three days.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary parameters will be timolol area under the plasma drug concentration-time curve (AUC0-12h) and highest drug concentration observed in plasma (Cmax). |  | 1 day | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Interaction, healthy volunteers, Interaction study for healthy volunteers