Interaction Study of Timolol Eye Drops and Paroxetine Capsules

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Paroxetine; Drug: Placebo; Drug: timolol maleate; Drug: timolol maleate

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Finland
  • Biomedicum
    • Helsinki, Biomedicum, Finland, 00014
      • University of Helsinki, Department of Clinical Pharmacology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Santen Oy
• Investigators: Principal Investigator: Janne Backman, MD, PhD, Department of Clinica Pharmacology, Institute of Clinical Medicine, University of Helsinki

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: April 7, 2009
• First Submitted That Met QC Criteria: April 8, 2009
• First Posted (Estimate): April 9, 2009

Study Record Updates

• Last Update Posted (Estimate): January 28, 2010
• Last Update Submitted That Met QC Criteria: January 27, 2010
• Last Verified: July 1, 2009

More Information

Terms related to this study

• Keywords: healthy volunteers; Interaction; Interaction study for healthy volunteers
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Enzyme Inhibitors; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Timolol; Paroxetine; Maleic acid
• Other Study ID Numbers: 73654; Eudra CT 2008-007324-26