Pupillary Changes as a Potential Biomarker for Escitalopram in Relation to CYP2C19 Polymorphism

This study has been completed.

Sponsor:

ClinicalTrials.gov Identifier:

NCT00397059

First Posted: November 8, 2006

Last Update Posted: February 6, 2008

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

Collaborator:

H. Lundbeck A/S

Information provided by:

University of Southern Denmark

Tracking Information

First Submitted Date ^ICMJE

November 6, 2006

First Posted Date ^ICMJE

November 8, 2006

Last Update Posted Date

February 6, 2008

Start Date ^ICMJE

December 2006

Primary Completion Date

October 2007 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

Dynamic pupillometry
Pharmacokinetics
AUC

Original Primary Outcome Measures ^ICMJE

Same as current

Change History

Complete list of historical versions of study NCT00397059 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures ^ICMJE

Cmax
Tmax
T½

Original Secondary Outcome Measures ^ICMJE

Same as current

Current Other Outcome Measures ^ICMJE

Not Provided

Original Other Outcome Measures ^ICMJE

Not Provided

Descriptive Information

Brief Title ^ICMJE

Pupillary Changes as a Potential Biomarker for Escitalopram in Relation to CYP2C19 Polymorphism

Official Title ^ICMJE

Pupillary Changes as a Potential Biomarker for Escitalopram in Relation to CYP2C19 Polymorphism

Brief Summary

To study the impact of CYP2C19 polymorphism on escitalopram pharmacokinetics and pharmacodynamics measured as changes in pupil diameter

Detailed Description

Escitalopram, the therapeutic active S-enantiomer of citalopram, is a selective serotonine reuptake inhibitor (SSRI) used for treatment of depression and anxiety disorders. The antidepressant effect is probably due to a stimulation of the serotonergic neurotransmission caused by the inhibition of the presynaptic serotonin reuptake. This inhibition may also be responsible for the increased pupil diameter seen in volunteers treated with racemic citalopram. Based on escitaloprams pharmacodynamic properties it is expected to have the same affect on pupil diameter. A dose/response relationship has not yet been established but theoretically the pupillary changes might serve as a biomarker for the serotonergic effect of escitalopram.

Escitalopram is demethylated in part by the polymorphic cytochrome P450 enzyme 2C19 (CYP2C19); but the impact of CYP2C19 polymorphism on the total metabolism of escitalopram is still to be investigated.

Objective: The aim of this study is to investigate the pharmacokinetics and pharmacodynamics in CYP2C19 extensive metabolizers (EMs) and poor metabolizers (PMs) and to investigate whether change in pupil size reaction to a light stimulus can act as a biomarker for the serotonergic effect of escitalopram.

The study will be conducted as a randomized, double blinded; placebo controlled two phases cross-over trial with single and repeated doses of 20 mg escitalopram and equivalent placebo. Sixteen healthy volunteers (8 EMs and 8 PMs) will participate in the trial. Prior to the trial, approximately 400 volunteers will be phenotyped by omeprazole metabolic ratio in order to identify the CYP2C19 EMs and PMs.

During the two phases blood samples will be drawn and pupil sizes will be measured at fixed time points after drug administration.

Study Type ^ICMJE

Interventional

Study Phase

Phase 4

Study Design ^ICMJE

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

Condition ^ICMJE

Healthy

Intervention ^ICMJE

Drug: Escitalopram

Study Arms

Not Provided

Publications *

Not Provided

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Completed

Estimated Enrollment ^ICMJE

Completion Date

October 2007

Primary Completion Date

October 2007 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

Inclusion Criteria:

Healthy volunteer
Age: 18-45 years
Phenotyped for CYP2C19 activity

Exclusion Criteria:

Drug or alcohol abuse
Allergy towards escitalopram

Sex/Gender

Sexes Eligible for Study:

All

Ages

18 Years to 45 Years (Adult)

Accepts Healthy Volunteers

Yes

Contacts ^ICMJE

Contact information is only displayed when the study is recruiting subjects

Listed Location Countries ^ICMJE

Denmark

Removed Location Countries

Administrative Information

NCT Number ^ICMJE

NCT00397059

Other Study ID Numbers ^ICMJE

AKF-371
EudraCT no: 2006-001976-19

Has Data Monitoring Committee

Not Provided

U.S. FDA-regulated Product

Not Provided

IPD Sharing Statement

Not Provided

Responsible Party

Not Provided

Study Sponsor ^ICMJE

University of Southern Denmark

Collaborators ^ICMJE

H. Lundbeck A/S

Investigators ^ICMJE

Principal Investigator:

Kim Brosen, dr. med.

University of Southern Denmark

PRS Account

University of Southern Denmark

Verification Date

February 2008

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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