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

This study has been completed.
Sponsor:
Collaborator:
H. Lundbeck A/S
Information provided by:
University of Southern Denmark
ClinicalTrials.gov Identifier:
NCT00397059
First received: November 6, 2006
Last updated: February 5, 2008
Last verified: February 2008
  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 4

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:


Further study details as provided by University of Southern Denmark:

Primary Outcome Measures:
  • Dynamic pupillometry
  • Pharmacokinetics
  • AUC

Secondary Outcome Measures:
  • Cmax
  • Tmax


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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:
Citalopram
Dexetimide
Anti-Dyskinesia Agents
Antidepressive Agents
Antidepressive Agents, Second-Generation
Antiparkinson Agents
Autonomic Agents
Central Nervous System Agents
Cholinergic Agents
Cholinergic Antagonists
Molecular Mechanisms of Pharmacological Action
Muscarinic Antagonists
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Parasympatholytics
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents
Serotonin Uptake Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014