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

November 6, 2006
February 5, 2008
December 2006
October 2007   (final data collection date for primary outcome measure)
  • Dynamic pupillometry
  • Pharmacokinetics
  • AUC
Same as current
Complete list of historical versions of study NCT00397059 on ClinicalTrials.gov Archive Site
  • Cmax
  • Tmax
Same as current
Not Provided
Not Provided
 
Pupillary Changes as a Potential Biomarker for Escitalopram in Relation to CYP2C19 Polymorphism
Pupillary Changes as a Potential Biomarker for Escitalopram in Relation to CYP2C19 Polymorphism

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

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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Healthy
Drug: Escitalopram
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
16
October 2007
October 2007   (final data collection date for primary outcome measure)

Inclusion Criteria:

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

Exclusion Criteria:

  • Drug or alcohol abuse
  • Allergy towards escitalopram
Both
18 Years to 45 Years
Yes
Contact information is only displayed when the study is recruiting subjects
Denmark
 
NCT00397059
AKF-371, EudraCT no: 2006-001976-19
Not Provided
Not Provided
University of Southern Denmark
H. Lundbeck A/S
Principal Investigator: Kim Brosen, dr. med. University of Southern Denmark
University of Southern Denmark
February 2008

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