Pupillary Changes as a Potential Biomarker for Escitalopram in Relation to CYP2C19 Polymorphism - Full Text View

Sponsor:	University of Southern Denmark
Collaborator:	H. Lundbeck A/S
Information provided by:	University of Southern Denmark
ClinicalTrials.gov Identifier:	NCT00397059

Purpose

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

Condition	Intervention	Phase
Healthy	Drug: Escitalopram	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacokinetics/Dynamics Study Intervention Model: Crossover Assignment Masking: Double-Blind Primary Purpose: Treatment
Official Title:	Pupillary Changes as a Potential Biomarker for Escitalopram in Relation to CYP2C19 Polymorphism

Resource links provided by NLM:

Genetics Home Reference related topics: Help Me Understand Genetics

Drug Information available for: Benzetimide Dexetimide Citalopram hydrobromide Citalopram Escitalopram Escitalopram oxalate

U.S. FDA Resources

Further study details as provided by University of Southern Denmark:

Primary Outcome Measures:

Dynamic pupillometry
Pharmacokinetics
AUC

Secondary Outcome Measures:

Cmax
Tmax
T½

Estimated Enrollment:	16
Study Start Date:	December 2006
Study Completion Date:	October 2007
Primary Completion Date:	October 2007 (Final data collection date for primary outcome measure)

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.

Eligibility

Ages Eligible for Study:	18 Years to 45 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

Drug or alcohol abuse
Allergy towards escitalopram

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00397059

Locations

Denmark
Clinical Pharmacology, University of Southern Denmark
Odense, Denmark, DK-5000

Sponsors and Collaborators

University of Southern Denmark

H. Lundbeck A/S

Investigators

Principal Investigator:

Kim Brosen, dr. med.

University of Southern Denmark

More Information

No publications provided

ClinicalTrials.gov Identifier:	NCT00397059 History of Changes
Other Study ID Numbers:	AKF-371, EudraCT no: 2006-001976-19
Study First Received:	November 6, 2006
Last Updated:	February 5, 2008
Health Authority:	Denmark: Danish Dataprotection Agency; Denmark: Danish Medicines Agency; Denmark: The Regional Committee on Biomedical Research Ethics

Keywords provided by University of Southern Denmark:

Escitalopram
Pharmacokinetics
Pharmacodynamics

CYP2C19
Pupillometry
healthy volunteers

Additional relevant MeSH terms:

Dexetimide
Citalopram
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Parasympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs

Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Serotonin Agents

ClinicalTrials.gov processed this record on February 12, 2012