Drug Metabolism and Antidepressant

Depression Clinical Trial

— METADEP  

Official title:

Cocktail Phenotypic Approach to Explore Antidepressant Pharmacokinetic Variability: a Pilot Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02438072
• Other study ID #: CER-14051
• Status: Recruiting
• Phase: N/A
• First received: April 30, 2015
• Last updated: May 5, 2015
• Start date: December 2014
• Est. completion date: December 2015

Study information

• Verified date: May 2015
• Source: University Hospital, Geneva
• Contact: Celia Lloret-Linares, MD, PhD
• Phone: 0041 79 55 36 389
• Email: Celia.LloretLinares[@]hcuge.ch
• Is FDA regulated: No
• Health authority: Switzerland: Swissmedic
• Study type: Interventional

Clinical Trial Summary

We propose here to explore systematically the association between drug-metabolizing enzymes activity assessed by a phenotypical approach and antidepressant plasma concentration, efficacy and tolerance in the clinical setting. During one year, patients receiving antidepressant will be included in tis prospective clinical, naturalistic and descriptive pilot study.

Description:

• Objectives To describe drug metabolism variability in depressive patients using a phenotypic approach

• Study design Prospective, clinical, naturalistic, descriptive study During a consultation with their clinician, depressive patients will receive information.

During the visit V0 with an investigator: patients will be included:

• Verification of inclusion and non inclusion criteria

• Reminder participation conditions

• Inclusion, signature of consent

• Collection of clinical and demographic features Between V0 and V1, for patients with change in antidepressant therapy, will take place telephone interviews every two weeks, conducted by the clinician to evaluate treatment depression response (tolerance and efficacy)

During the visit V1, will take place:

• Phenotypic study

• Genetic study

• Dosage of current antidepressant drug

• Clinical evaluation: efficacy and tolerance

• Number of patients During one year, the protocol will be proposed to all patients with depression and decision of change in antidepressant therapy, and all patients with stability od prescription since almost 6 weeks. The inclusion of approximately 100 patients is expected.

• Name of the finished product Zyban®, Froben®, Antra®, Bexine®, Dormicum® Telfast®

• Name of the active substance Omeprazole (10 mg, A02BC01) Caffeine (50 mg, N06BC01) Flurbiprofen (10 mg, M01AE09) Dextromethorphan (10 mg, R05DA09) Midazolam (1 mg, N05CD08) Fexofenadine (25mg, R06AX26 ) Bupropion (20 mg, N06AX12)

• Duration of treatment One time during the study, one day (Visit 1)

• Time plan of research -Duration for the patient: The study will stop when the patient has performed the V1 study Minimal delay between V0 and V1: 6 weeks (5-7 weeks) : for patient with decision to change the treatment, 5 days for patients with stability of treatment since almost 6 weeks.

Maximal delay of participation for the patient: 4 months even when V1 was not performed

-Overall duration of inclusion: one year Maximal overall duration of the study: 12 months+4 months= 16 months Maximal duration for the analytical study since the beginning of the study= 16 months+6 months: 22 months.

Maximal delay for communication of the results: 2 years after the beginning of the study

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Patients with clinical diagnosis of depression and decision to change antidepressant therapy (augmentation or switch) OR Patients with clinical diagnosis of depression and stability of prescription since almost 6 weeks

2. Male and female aged from 18 to 70 years

3. Volunteers to participate to the study

4. Understanding of French language and able to give a written inform consent.

Exclusion Criteria:

Renal or hepatic impairment (Clearance below 60mL/min, AST or ALT over 3N) Sensitivity to any of the substrate drugs used ECG showing long QT interval (>0.46sec) No antidepressant dosage available Current pregnancy or desire to get pregnant

Criteria to perform V1 Sufficient compliance between V0 and V1 Six weeks period without change in antidepressant therapy

Study Design

Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Depression

Intervention

Drug:
• Omeprazole (10 mg, A02BC01)
The cocktail of drug substrates will be given one time, one day during the study, to explore the activity of CYP 1A2, 2B6, 2C9, 2C19, 3A4, 2D6, and the P-gp

Locations

Country	Name	City	State
Switzerland	Hôpitaux Universitaires de Genève	Genève

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Geneva

Country where clinical trial is conducted

Switzerland, 

References & Publications (2)

Bosilkovska M, Samer CF, Déglon J, Rebsamen M, Staub C, Dayer P, Walder B, Desmeules JA, Daali Y. Geneva cocktail for cytochrome p450 and P-glycoprotein activity assessment using dried blood spots. Clin Pharmacol Ther. 2014 Sep;96(3):349-59. doi: 10.1038/clpt.2014.83. Epub 2014 Apr 10. — View Citation

Hall-Flavin DK, Winner JG, Allen JD, Carhart JM, Proctor B, Snyder KA, Drews MS, Eisterhold LL, Geske J, Mrazek DA. Utility of integrated pharmacogenomic testing to support the treatment of major depressive disorder in a psychiatric outpatient setting. Ph — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CYP1A2 activity	paraxanthine/caffeine	>two hours after an oral intake of the cocktail probe drugs	No
Primary	CYP2B6 activity	4-hydroxybupropion/ bupropion	>two hours after an oral intake of the cocktail probe drugs	No
Primary	CYP2D6 activity	dextrorphan / dextromethorphan	>two hours after an oral intake of the cocktail probe drugs	No
Primary	CYP2C9 activity	4-hydroxyflurbiprofen/ flurbiprofen	>two hours after an oral intake of the cocktail probe drugs	No
Primary	CYP2C19 activity	5-hydroxyomeprazole/ omeprazole	>two, three and six hours after an oral intake of the cocktail probe drugs	No
Primary	CYP3A4 activity	1-hydroxymidazolam/ midazolam	>two hours after an oral intake of the cocktail probe drugs	No
Primary	P-gp activity	Limited sampling fexofenadine AUC	>two, three and six hours after an oral intake of the cocktail probe drugs	No
Secondary	Antidepressant Concentration		almost 6 weeks after the last treatment change	No
Secondary	Antidepressant tolerance	FISBER test	almost 6 weeks after the last treatment change	No
Secondary	Antidepressant efficacy	Tests: MADRS, Hamilton, QIDS-16	almost 6 weeks after the last treatment change	No