A Study to Evaluate the Pharmacokinetics of Duloxetine in Chinese Han Healthy Subjects

A Open Single-dose and Multiple-dose Study to Evaluate the Pharmacokinetics and Safety of Duloxetine in Chinese Han Healthy Subjects

The primary objective of this study is to evaluate the pharmacokinetics of duloxetine hydrochloride tablets in Chinese Han Healthy Subjects. The single oral dose and multiple oral dose of the drug in the body and the effects of different dosages of the drug will also be evaluated.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: duloxetine; Drug: duloxetine; Drug: duloxetine

Detailed Description

This is an open, parallel assignment (low-dose, moderate-dose and high-dose), inpatient, sequential-group pharmacokinetics study of single oral administered and multiple oral administered to healthy Chinese male and female subjects at a single investigational site. All subjects are from the Chinese Han race.

Approximately 36 healthy male and female Chinese subjects will participate in this study. One half of the subjects enrolled in each dose group will be female. Twelve subjects will be enrolled in each of 3 dose level groups.

Safety will be evaluated from self-reported adverse events, scheduled physical examination, vital signs, 12-lead ECGs, and clinical laboratory test results.

Single-dose blood samples (5 mL) will be obtained within 2 hours before test article administration and at 1, 2, 3, 4, 5, 6, 8, 12, 15, 24, 36, 48, and 72 hours after test article administration.

Multiple-dose (subjects of moderate dose group finished first step single-dose 30mg trial, one week later, will be repeatedly administered duloxetine 30 mg 7days) blood samples (5 mL) will be obtained at 4th, 5th, 6th and 7th day before test article administration (to test the valley concentration)and at 1, 2, 3, 4, 5, 6, 8, 12, 15, 24, 36, 48, and 72 hours after last test article administration (7th day).

Cross-over (subjects of high dose group finished first step single-dose 60 mg generic duloxetine trial, one week later, will be administered single-dose innovator duloxetine 60 mg) blood samples will be obtained as same as first step.

• Study Type: Interventional
• Enrollment (Anticipated): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200030
      • Shanghai Mental Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy Chinese Han male or female determined by the investigator on the basis of medical history and physical examination
• Age from 18 to 45 years old at screening
• Body mass index (BMI) from 19~24 kg/m2 and body weight ≥ 50 kg at screening
• Normal clinical laboratory test results or 'no clinical significantly abnormal' results judged by the investigator at screening
• Subjects can comply with all requirements of the study according to study procedure
• A sighed and dated ICF (informed consent form) with approval by IEC

Exclusion Criteria:

• Participation in any drug trial within 1 month prior to enrollment into this study
• Known hypersensitivity to duloxetine hydrochloride or relative compounds
• Abnormal 12-lead electrocardiogram (ECG) results and increasing risk to participate this study determined by investigator
• Presence or history of any medical disorder, including cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematologic, psychiatric and neurologic system, or medical conditions that would significantly affect the absorption, distribution, metabolism, or excretion of investigational drug, or increase risk to administer investigational drug, or interfere explanation for data
• History of hepatitis B and/or HBsAg (+)
• Serum HIV antibody (+) or hepatitis C Antibody (+)
• Female subjects of childbearing potential with a positive human chorionic gonadotropin (HCG) test or lack of a reliable method of contraception
• History of blood donor within 3 months prior to enrollment
• History of drug abuse or alcoholism
• Use any drugs including traditional Chinese Medicine within 1 week prior to enrollment
• Any unsuitable subjects judged by the investigator

Study Plan

How is the study designed?

Design Details

• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: low dose group; single oral administer 15mg duloxetine	Drug: duloxetine; 30mg, oral administer; step 1: single dose; step 2: multiple dose, 7 days; Other Names: Generic duloxetine; Drug: duloxetine; 15mg, oral administer; Other Names: generic duloxetine; Drug: duloxetine; 60mg, oral administer; step 1: generic duloxetine; step 2: Innovator duloxetine; Other Names: generic duloxetine; innovator duloxetine
Experimental: moderate dose group/multiple dose group; single oral duloxetine 30mg, after that repeat 7 oral duloxetine 30mg/d	Drug: duloxetine; 30mg, oral administer; step 1: single dose; step 2: multiple dose, 7 days; Other Names: Generic duloxetine; Drug: duloxetine; 15mg, oral administer; Other Names: generic duloxetine; Drug: duloxetine; 60mg, oral administer; step 1: generic duloxetine; step 2: Innovator duloxetine; Other Names: generic duloxetine; innovator duloxetine
Experimental: high dose group/crossover group; single oral duloxetine 60mg, after that single oral innovator duloxetine 60mg	Drug: duloxetine; 30mg, oral administer; step 1: single dose; step 2: multiple dose, 7 days; Other Names: Generic duloxetine; Drug: duloxetine; 15mg, oral administer; Other Names: generic duloxetine; Drug: duloxetine; 60mg, oral administer; step 1: generic duloxetine; step 2: Innovator duloxetine; Other Names: generic duloxetine; innovator duloxetine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics as evaluated from blood concentrations of duloxetine	2 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety and tolerability as evaluated from reported adverse events, scheduled physical examinations, vital sign measurements, cardiac rhythm monitoring, 12 lead ECG and clinical laboratory results	2 months
Serum BDNF level as evaluated from blood sample	2 months

Collaborators and Investigators

• Sponsor: Shanghai Mental Health Center
• Collaborators: Jiangsu Nhwa Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Huafang LI, MD, PhD, Drug Clinical Trial Office, Shanghai Mental Health Center

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): November 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: July 5, 2009
• First Submitted That Met QC Criteria: July 6, 2009
• First Posted (Estimate): July 7, 2009

Study Record Updates

• Last Update Posted (Estimate): June 15, 2010
• Last Update Submitted That Met QC Criteria: June 11, 2010
• Last Verified: June 1, 2010

More Information

Terms related to this study

• Keywords: safety; depression; Chinese; pharmacokinetics; BDNF; duloxetine; antidepressant; antidepressive agents; psychotropic drugs; HAN
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Dopamine Agents; Serotonin and Noradrenaline Reuptake Inhibitors; Duloxetine Hydrochloride
• Other Study ID Numbers: 2006L01603; SMHC-106