Study Evaluating the Pharmacokinetics of Venlafaxine Extended-Release (ER) and Desvenlafaxine Succinate Sustained-Release (DVS SR) 50 mg in Healthy Subjects

A Randomized, Open-Label, Two-Period, Parallel Group, Crossover Study to Evaluate the Pharmacokinetics of Venlafaxine Extended-Release and DVS SR in Healthy Subjects Who Are Extensive or Poor Cytochrome P450 2D6 Substrate Metabolizers

The purpose of this study is to determine if the relative difference in Pharmacokinetics (PK) between extensive metabolizers (EMs) and poor metabolizers (PMs) is the same with desvenlafaxine SR and venlafaxine ER when a single dose is administered.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Desvenlafaxine Succinate Sustained-Release (DVS SR); Drug: Venlafaxine Extended Release (VEN ER)

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Wichita, Kansas, United States, 67211
      • Clinical Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy men and women aged 18 to 55 years. Healthy as determined by the investigator on the basis of medical history and physical examination, laboratory test results, vital signs, and 12-lead electrocardiogram (ECG).
• History of being a nonsmoker for at least 1 year.
• Subjects have to be either extensive CYP2D6 metabolizers with a normal complement of 1 or 2 fully active enzyme gene alleles or poor CYP2D6 metabolizers (lack of active enzyme gene alleles) via genetic testing of a blood sample.

Exclusion Criteria:

• Presence or history of any significant cardiovascular, hepatic, renal, respiratory, gastrointestinal, endocrine, immunologic, dermatologic, hematologic, neurologic, or psychiatric disease or any severe conditions of the ears, eyes or throat (such as glaucoma or increased intraocular pressure).
• Known or suspected alcohol abuse or consumption of more than 2 standard units per day (a standard unit equals 12 ounces of beer, 1½ ounces of 80-proof alcohol, or 6 ounces of wine) within the past 6 months.
• Known or suspected current abuse of prohibited drugs or other substances. Use of any hormonal therapy within 30 days before study day -1 until the end of the partial inpatient confinement period.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: DVS/VEN	Drug: Desvenlafaxine Succinate Sustained-Release (DVS SR); Drug: Venlafaxine Extended Release (VEN ER)
Active Comparator: VEN/DVS	Drug: Desvenlafaxine Succinate Sustained-Release (DVS SR); Drug: Venlafaxine Extended Release (VEN ER)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Concentration (Cmax) of Venlafaxine After Single Dose of Venlafaxine Extended-release (VEN ER) by Metabolizer Status	Cmax is a measure of drug metabolism and presented as least squares geometric mean with 90% Confidence Interval. Variations in drug metabolism among individuals can be due to differences in genetic expression (phenotype) of Cytochrome P450 (CYP450) enzymes. Enzyme CYP2D6 has 4 metabolizer phenotypes: poor (PM), intermediate (IM), extensive (EM), and ultrarapid (UM) metabolizers.	single dose
Area Under the Concentration-time Curve (AUC) of Venlafaxine After Single Dose of VEN ER by Metabolizer Status	AUC is drug level over time and measures drug metabolism. Variations in drug metabolism among individuals can be due to differences in genetic expression (phenotype) of Cytochrome P450 (CYP450) enzymes. Enzyme CYP2D6 has 4 metabolizer phenotypes: poor (PM), intermediate (IM), extensive (EM), ultrarapid (UM) metabolizers.	single dose
Maximum Concentration (Cmax) of Desvenlafaxine After Single Dose of VEN ER by Metabolizer Status	Cmax is a measure of drug metabolism. Variations in drug metabolism among individuals can be due to differences in genetic expression (phenotype) of Cytochrome P450 (CYP450) enzymes. Enzyme CYP2D6 has 4 metabolizer phenotypes: poor (PM), intermediate (IM), extensive (EM), and ultrarapid (UM) metabolizers.	single dose
Area Under the Concentration-time Curve (AUC) of Desvenlafaxine After Single Dose of VEN ER by Metabolizer Status	AUC is drug level over time and measures drug metabolism. Variations in drug metabolism among individuals can be due to differences in genetic expression (phenotype) of Cytochrome P450 (CYP450) enzymes. Enzyme CYP2D6 has 4 metabolizer phenotypes: poor (PM), intermediate (IM), extensive (EM), ultrarapid (UM) metabolizers.	single dose
Maximum Concentration (Cmax) of Desvenlafaxine After Single Dose of Desvenlafaxine Succinate Sustained-Release (DVS SR) by Metabolizer Status	Cmax is a measure of drug metabolism and is presented as least squares geometric mean with 90% Confidence Interval.Variations in drug metabolism among individuals can be due to differences in genetic expression (phenotype) of Cytochrome P450 (CYP450) enzymes. Enzyme CYP2D6 has 4 metabolizer phenotypes: poor (PM), intermediate (IM), extensive (EM), and ultrarapid (UM) metabolizers.	single dose
Area Under the Concentration-time Curve (AUC) of Desvenlafaxine After Single Dose of DVS SR by Metabolizer Status	AUC is drug level over time and measures drug metabolism. Variations in drug metabolism among individuals can be due to differences in genetic expression (phenotype) of Cytochrome P450 (CYP450) enzymes. Enzyme CYP2D6 has 4 metabolizer phenotypes: poor (PM), intermediate (IM), extensive (EM), ultrarapid (UM) metabolizers.	single dose

Collaborators and Investigators

• Sponsor: Wyeth is now a wholly owned subsidiary of Pfizer

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Actual): August 1, 2008
• Study Completion (Actual): August 1, 2008

Study Registration Dates

• First Submitted: July 29, 2008
• First Submitted That Met QC Criteria: July 31, 2008
• First Posted (Estimate): August 1, 2008

Study Record Updates

• Last Update Posted (Estimate): June 2, 2010
• Last Update Submitted That Met QC Criteria: May 26, 2010
• Last Verified: May 1, 2010

More Information

Terms related to this study

• Keywords: Healthy Subjects
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Antidepressive Agents, Second-Generation; Serotonin and Noradrenaline Reuptake Inhibitors; Desvenlafaxine Succinate; Venlafaxine Hydrochloride
• Other Study ID Numbers: 3151A1-4414