Metabolism of Methylphenidate and Enalapril Based on CES1 Genotype

Carboxylesterase 1 (CES1) Genotype Clinical Trial

Official title:

Metabolism of Methylphenidate and Enalapril Based on CES1 Genotype

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02135263
• Other study ID #: INDICES-WP2
• Status: Completed
• Phase: Phase 4
• First received: July 1, 2013
• Last updated: July 29, 2014
• Start date: April 2012
• Est. completion date: May 2014

Study information

• Verified date: July 2014
• Source: Bispebjerg Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Health and Medicines Authority
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether differences in the gene coding for the liver enzyme carboxylesterase 1 (CES1) means differences in the metabolism of two CES1 dependent drugs, enalapril and methylphenidate.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: May 2014
• Est. primary completion date: May 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• > 18 years old

• Caucasian

Exclusion Criteria:

• Chronic disease (except hay fever and eczema)

• Pregnancy

• Smoking

• High level of alcohol consumption (> 21 units per week for men and 14 for women)

• Known allergy towards methylphenidate and enalapril

• Permanent use of medication (contraception ok)

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Carboxylesterase 1 (CES1) Genotype
• CES1 Activity

Intervention

Drug:
• Methylphenidate
10 mg as a single dose followed by blood samples for the next 33 hours
• Enalapril
10 mg as a single dose followed by blood samples for the next 72 hours

Locations

Country	Name	City	State
Denmark	Department of Clinical Pharmacology, Bispebjerg University Hospital	Copenhagen

Sponsors (6)

Lead Sponsor	Collaborator
Bispebjerg Hospital	Duke University, Mental Health Centre Sct. Hans (Denmark), The Leiden Academic Center for Drug Research (LACDR), The Ministry of Science, Technology and Innovation, Denmark, University of Copenhagen

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Peak plasma concentration (Cmax) of methylphenidate		Predose, ½, 1, 1½, 2, 2½, 3, 4, 6, 8, 10, 24 and 33 hours post-dose	No
Primary	Time to peak plasma concentration (Tmax) of methylphenidate		Predose, ½, 1, 1½, 2, 2½, 3, 4, 6, 8, 10, 24 and 33 hours post-dose	No
Primary	Terminal half life (t½) of methylphenidate		Predose, ½, 1, 1½, 2, 2½, 3, 4, 6, 8, 10, 24 and 33 hours post-dose	No
Primary	Area under the plasma concentration versus time curve (AUC) of methylphenidate		Predose, ½, 1, 1½, 2, 2½, 3, 4, 6, 8, 10, 24 and 33 hours post-dose	No
Primary	Peak plasma concentration (Cmax) of enalapril		Predose, ½, 1, 2, 3, 4, 5, 6, 9, 24, 48 and 72 hours post-dose	No
Primary	Time to peak plasma concentration (Tmax) of enalapril		Predose, ½, 1, 2, 3, 4, 5, 6, 9, 24, 48 and 72 hours post-dose	No
Primary	Terminal half life (t½) of enalapril		Predose, ½, 1, 2, 3, 4, 5, 6, 9, 24, 48 and 72 hours post-dose	No
Primary	Area under the plasma concentration versus time curve (AUC) of enalapril		Predose, ½, 1, 2, 3, 4, 5, 6, 9, 24, 48 and 72 hours post-dose	No
Secondary	Metabolomic profile	Four samples for each participant during the methylphenidate trials (as indicated above). Metabolomics will be assessed with focus on lipids (lipid platform) and with use of usual concentration measures (eg nanomolar (nM))	Predose/pre-meal, predose/post-meal, 2 and 6 hours post-dose	No