A Genotype Stratification Study for Pharmacokinetics and Pharmacodynamics of Amitriptyline in Healthy Male Subjects

A Single Dose, Double-blind, Genotype-based Stratification Study to Explore the Pharmacokinetics and Pharmacodynamics of Amitriptyline According to CYP2D6 and CYP2C19 Polymorphisms in Healthy Korean Male Adult Subjects

A total of 24 healthy Korean male subjects will receive a single oral dose of amitriptyline, 25 mg. Subjects will be enrolled in this study based on their cytochrome P450 2D6 and cytochrome P450 2C19 genotypes, and serial blood sampling will be done for plasma concentrations of amitriptyline, nortriptyline, and their metabolites. Various pharmacodynamic markers related to the adverse event of amitriptyline will be measured serially during the study.

Study Overview

• Status: Unknown
• Conditions: Depression
• Intervention / Treatment: Drug: Amitriptyline

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Shi Hyang Lee, MS; Phone Number: 82-2-3010-4622; Email: shlee@acp.kr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy male volunteer, age 19~45 years
• The result of Body Mass Index(BMI) is not less than 19 kg/m2 , no more than 28 kg/m2
• Subject who has the ability to comprehend the study objectives, contents and the property of the study drug before participating in the trial.
• Voluntarily signed the informed consent form

Exclusion Criteria:

• Presence of medical history or a concurrent disease that may interfere with treatment and safety assessment or completion of this clinical study
• History of relevant drug allergies or clinically significant hypersensitivity reaction.
• Smoked more than 10 cigarettes a day for past 3 months
• Not eligible due to other reasons including laboratory results

Study Plan

How is the study designed?

Design Details

• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Amitriptyline; Single oral dose of amitriptyline, 25 mg	Drug: Amitriptyline; Single oral dosing

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area under curve (AUC) of Amitriptyline, 10-Hydroxy-amitriptyline, Nortriptyline, and 10-Hydroxy-nortriptyline	0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 hour
Maximum concentration (Cmax) of Amitriptyline, 10-Hydroxy-amitriptyline, Nortriptyline, and 10-Hydroxy-nortriptyline	0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 hour

Collaborators and Investigators

• Sponsor: Asan Medical Center
• Investigators: Principal Investigator: Hyeongseok Lim, MD, PhD, Asan Medical Center, Ulsan University

Study record dates

Study Major Dates

• Study Start: August 1, 2015
• Primary Completion (Anticipated): October 1, 2015

Study Registration Dates

• First Submitted: August 5, 2015
• First Submitted That Met QC Criteria: August 7, 2015
• First Posted (Estimate): August 10, 2015

Study Record Updates

• Last Update Posted (Estimate): August 11, 2015
• Last Update Submitted That Met QC Criteria: August 9, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: amitriptyline; cyp2d6; cyp2c19
• Additional Relevant MeSH Terms: Behavioral Symptoms; Depression; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Antidepressive Agents, Tricyclic; Adrenergic Uptake Inhibitors; Amitriptyline
• Other Study ID Numbers: PGAM-001